Wildfires in Western North America have become more frequent and intense in recent years. Wildfire smoke can cause adverse health impacts creating an urgent public health concern. This study compares wildfire smoke preparedness and response plans developed by jurisdictions and institutions in western North America, including counties, cities, states, provinces, and universities. We used qualitative content analysis methods to assess the characteristics of 20 wildfire smoke preparedness and response plans. The majority of the plans included strategies related to air quality monitoring, household-level exposure reduction, and risk communication. Wildfire smoke poses a bigger risk to susceptible and/or vulnerable populations, however, 25% of the plans did not include strategies related to targeted outreach for at-risk populations. Since wildfire smoke plans are a relatively new strategy within emergency response, a “gold” standard set of components has yet to be established, therefore,  significant variations of included plan components exist. To improve these plans, it is crucial to enhance targeted outreach programs for vulnerable populations, develop a standardized framework for preparedness, and integrate plans with existing public health frameworks. Additionally, training for first responders on health impacts and investing in air quality monitoring are essential. Future research should focus on evaluating the effectiveness of outreach strategies, conducting longitudinal health studies, and analyzing the economic impacts of wildfire smoke preparedness. By addressing these recommendations and pursuing further research, jurisdictions can enhance their wildfire smoke preparedness and response plans, ultimately protecting public health more effectively.

In the age of the internet, literature is consumed in unprecedented ways. Modern social movements often call upon those of the past through key quotes and references to influential literary works. Quotes can go viral, seen outside of their context by thousands of people and become associated with these movements or rediscovered by new communities. For instance, key figures in post-WWII literature such as author and civil rights activist James Baldwin have had their words re-immortalized within the context of contemporary movements such as Black Lives Matter. Baldwin’s era of literature was one of marked social change and evolution within the literary world that parallels our society today, making it significant to understand how quotes from this period can reappear and spread across social media. To analyze the reception of post-war literature on Twitter, we utilized a dataset of over 40 million tweets quoting or referencing James Baldwin, as well as similar datasets quoting four other influential authors of the time including David Foster Wallace and Kurt Vonnegut. We focused on the patterns of text reuse (i.e., the repetition of known quotes) in tweets from 2006-2023, examining key moments of reception and exploring the context of virality for key quotes. During this context-finding process, we also developed a novel method for conducting self-identified user demographic analysis. We implemented clustering algorithms on both tweets and user bios, supplemented the resulting clusters with manual merging processes, and experimented with various visualization strategies. Our results yielded clear quote usage patterns for certain demographic groups, demonstrating the efficacy of the novel demographic extraction method. These methods can be expanded for further demographic-focused social media research and help us understand how cultural movements evolve today.

Little is known about how male and female Pieris rapae behave during territorial behaviors, making this project particularly significant. Through our previous experiment, we have uncovered intriguing insights into the unique behaviors exhibited by male P. rapae when interacting with pseudo-females (males in disguise). Our observations suggest a complex interplay between competitive instincts and courtship behaviors. Specifically, male Pieris rapae display distinct responses when encountering pseudo-females, indicating a potential recognition of the sex of the interacting butterfly. This recognition may trigger competitive behaviors like a territorial move if perceived as a rival male or foster a display of courtship if perceived as a potential mate. Additionally, we aim to study how female P. rapae interact with other females to determine if there are any behavioral differences in these interactions. By studying the intricacies of both male and female courtship and/or territorial behaviors in P. rapae, this project seeks a deeper understanding of the factors shaping mating systems and reproductive success in this species and beyond.

Chiral molecule sensing has important biochemical applications for detection of disease, as well as cognitive and neurodegenerative disorders. Circular dichroism (CD) has emerged as a powerful spectroscopic tool for probing post-synthetic ligand exchanges of chiral molecules onto originally achiral quantum confined CdS morphologies, manifesting in chirality corresponding to the electronic transitions of the nanocrystals. In this work, we first describe making water soluble quantum dots (QDs) and nanorods (NRs) via ligand exchange with glycine. After this exchange, aqueous chiral thiol solutions are then titrated into glycine capped achiral CdS, and the optical properties are monitored via UV-vis, photo-luminescence (PL), and CD spectroscopies. Preliminary results show we can controllably produce measurable chirality equal to or exceeding previous literature values whilst using orders of magnitude less L-cysteine than previously reported. Moving forward, we intend to correlate growth in CD with changes in PL across a myriad of cysteine derivatives. Additionally, we plan to examine the impact of NR aspect ratio on normalized maximum CD absorption (g-factor).   

King County’s population growth over the past two decades has significantly shifted area demographics. The influx of a large volume of highly-paid residents has led to a housing shortage, driven up housing costs and area median income, and displaced long-time residents and businesses — a process known as gentrification. Residential gentrification often coincides with commercial gentrification, where local, minority-owned businesses are replaced by high-priced specialty stores or chains. Commercial gentrification impacts residents of the surrounding neighborhood and people countywide who rely on local businesses for socialization and community building. Despite its impacts, business displacement is understudied compared to the residential effects of gentrification. The 2024 Population Health Initative’s Applied Research Fellowship project sought to close this gap and examine the scope of commercial gentrification in King County with an analysis of business-level data from Data Axle, a data analytics firm, to quantify business openings and closures by size and industry from 1997 to 2023. This research examines which of King County’s communities and industries appear to be most impacted by recent commercial gentrification. To better understand spatial trends in businesses, we used King County’s 61 Health Reporting Areas (HRAs) and also focused on unincorporated King County as a whole. For our industry-level analysis, we identified three essential services: grocery stores, pharmacies, child care providers, and four categories of third places: retail, entertainment, eating and drinking, and services establishments. Our research showed the limitations to using this data to calculate King County’s top employers by business size. Moreover, despite significant population growth in King County since 1997, grocery store and child care provider numbers remained relatively stable, with the number of pharmacies increasing; despite 8 of 61 HRAs having two or fewer pharmacies. Third place services, eating and drinking, and entertainment establishments increased since 1997, while retail establishments decreased

Human liver microsomes, or HLMs, play a key role in drug metabolism because they contain important cytochrome P450 (CYP) enzymes that are critical in oxidation and hydrolysis processes. We hypothesized that the variability in CYP enzyme concentration and activity among individuals will contribute to differences in metabolic capacity. In this study, my goal was to characterize HLMs from a bank of individual donors with different genetic backgrounds. I assessed their drug-metabolizing capabilities, with an emphasis on CYP-mediated pathways. I used bicinchoninic acid assays (BCA) to quantify protein content, carbon monoxide heme spectra (P450 spectra) to determine CYP enzyme concentrations, and a cytochrome c reduction assay to measure P450 reductase activity. For conducting these experiments, we used HLM samples from five different individuals from the UW Human Liver Bank. From the first subset of samples, I found that the ratio of CYP protein to total protein content varied across individuals with different clinical presentations. The differences among individuals in our findings emphasize the importance of HLM characterization in preclinical drug trials to understand the need for the personalization of pharmacological treatments. The implementation of such characterization can have a tremendous effect on predictions of drug responses and optimization of drug dosages, ultimately improving drug efficacy and safety.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder marked by repetitive behavioral patterns and challenges with social interaction. Gastrointestinal symptoms are a common comorbidity of ASD, and individuals with the disorder tend to have a distinct gut microbial community composition and circulating metabolomes. Elevated levels of gut-derived metabolite 4-ethylphenolsulfate (4-EPS) are associated with ASD mouse models and children with ASD. Administration of 4-EPS to conventional mice induced atypical myelination and anxiety-like behaviors. 4-Ethylphenol (4-EP), its precursor, is produced by gut microbiota before host-mediated sulfation; however, its microbial biosynthetic pathway remains unknown. We propose a pathway involving stepwise conversion of plant-derived complex polysaccharides to 4-EP. My project aims to identify a gut microbial enzyme that completes the first step of this proposed pathway: a hydroxycinnamoyl esterase. After extensive literature review and biochemical study, candidate enzymes from resident gut microbes were identified and selected using bioinformatic tools. In vitro and in vivo experiments will be used to assess their activity towards model and dietary substrates. Remaining substrate and product concentrations will reveal species and strain specific enzymatic activity and substrate uptake. If the results are negative, this bioinformatics to experimental analysis pipeline will be repeated on new candidate enzymes. This work complements ongoing lab investigations to demonstrate the complete enzymatic pathway in a single species. Elucidating the microbial biosynthetic pathway of 4-EPS will contribute to detangling the gut’s role in ASD, regardless of if it is causal to the disorder or simply a biomarker. More importantly, studying the biochemistry and metabolism of gut microbiota supports the efforts to fill fundamental gaps in understanding the gut-brain axis. 

Autosomal Dominant Alzheimer’s Disease (ADAD) can result from a pathogenic variant in the PSEN2 gene, which encodes an integral membrane protein called Presenilin 2. This variant has been shown to result in a harmful change in the balance of amyloid-β types in neurons, which has been hypothesized to increase risk of dementia. The diverse capabilities of Presenilin give reason to hypothesize that there may be other effects of the variant protein that are connected to ADAD pathogenesis. Reduced spine density, a feature of ADAD pathology, may be caused by overactivity of synaptic pruning. This activity is mediated by resident innate immune cells in the brain called microglia. We sought to explore the effects of PSEN2 variants on microglia-neuronal interactions via the assessment of synaptic pruning in a human induced pluripotent stem cell (hiPSC) derived in vitro model. We differentiated CVIA2 isogenic and PSEN2 N141I variant hiPSCs into both microglia and neurons. Utilizing a coculture of both wild-type neurons and microglia with the PSEN2 N141I variant, we performed immunocytochemistry for synaptic proteins Synapsin 1 and PSD95a. We then imaged the microglia and neurons using confocal microscopy. We assessed differences in synaptic pruning by quantifying immunofluorescent signal of Synapsin in microglia. Specifically, we looked at the colocalization of synaptic protein expression with signal from microglia-specific protein Iba1. We hypothesized that the variant microglia would contain a significantly different amount of signal for Synapsin compared to that of a control sample of wild-type microglia and neurons, implying a change to synaptic pruning function. If altered microglial synaptic pruning activity is shown to play a role in ADAD pathogenesis, targeting microglia could become a possible therapeutic treatment for patients.

Cancer Cachexia is a condition characterized by muscle wasting, functional impairment and decreased quality of life that leads to 30% of cancer-related deaths. Cytokines, proteins secreted by both the body and tumors that drive inflammatory response, are potential therapeutic targets and biomarkers for tracking disease progression. However, their role in cancer cachexia and relationship with physical function, patient-reported quality of life, and body composition have not been fully characterized. We hypothesized that in cancer patients, inflammatory cytokines would be elevated in patients with weight loss compared to weight-stable patients and inflammatory cytokines would be negatively correlated with muscle function, patient-reported outcomes and body composition. Body composition was assessed by Dual-energy X-ray absorptiometry (DEXA) and X-ray computed tomography (CT). Muscle function was assessed by stair climb power, hand grip strength and one-repetition maximum (1RM) muscle strength of different muscle groups. I assessed 55 cytokine plasma levels with Mesoscale Discovery Assay kits. Preliminary analyses show that in patients with cancer, interleukin (IL)-6 is negatively correlated with CT skeletal muscle mass (r=-0.36, p<0.05, n=53), IL-8 is negatively correlated with body weight (r=-0.40, p<0.01, n=53), body mass index (r=-0.41, p<0.01, n=53), CT skeletal muscle mass and subcutaneous adipose tissue (r=-0.49, p<0.05, n=53). Tumor Necrosis Factor-Alpha was negatively correlated with hand grip strength (r=-0.30, p<0.05, n=53). IL-5 was positively correlated with Anderson Symptom Assessment Scale (ASAS) fatigue (r = 0.40, N = 47, p = 0.005) and ASAS total (r = 0.45, n = 47, p = 0.002). Certain cytokines are linked to worse muscle mass and function, while others correlate with better patient-reported outcomes, suggesting inflammation’s role in cachexia is complex. More research is needed to distinguish these differences for targeted therapies treating specific attributes of cachexia.

Traumatic spinal cord injuries (SCI) are devastating and lead to permanent and irreversible functional impairments. While the primary injury causes immediate damage, the progression of secondary injury is characterized by neuroinflammation. Microglia, the resident immune cells of the central nervous system, can further contribute to tissue damage. Although extensive research has been done focusing on microglial activation at the lesion site, their presence in regions distal to the injury at the chronic stage (4-6 weeks after injury) remains understudied. Here, we aimed to investigate the correlation between microglial activation in the lumbar region caudal to the injury site and cervical region rostral to the injury site with different grades of injury severity. We hypothesize that as injury severity increases, microglial activation in the surrounding region will increase as well. Contusion injuries were created at T8/9 in Long Evans rats using three impact forces: 200 kilodynes, 200 kilodynes and 2-second dwell time, and 250 kilodynes and 2-second dwell time. After 8 weeks post injury, our histological analyses revealed a significant increase in microglial activation in the caudal region, with activation levels reaching 136.03%, 205.08%, and 254.81% of sham levels in the 200, 200/2s, and 250/2s groups, respectively (n = 5/group). The most severe injury had the highest microglial inflammation. We anticipate a similar trend in the cervical region rostral to the injury. Combined, our data indicate a significant microglial response in regions distal to the injury, which correlates with impaired functional recovery. We believe that modulating microglial responses in the regions distal to the site of SCI could provide a novel approach to reducing chronic secondary injury and enhancing recovery following traumatic SCI.

Soluble peptides from the HIV-1 (Human Immunodeficiency Virus) envelope heptad repeat-2 domain, known as HIV fusion inhibitors, can inhibit viral entry by blocking formation of the gp41 6-helix bundle required for membrane fusion and infection. However, this treatment is unfeasible because it requires twice-daily subcutaneous injections with high risk and cost. The Lieber Lab is working to engineer hematopoietic stem and progenitor cells (HSPCs) to express HIV fusion inhibitors in vivo, potentially offering sustained protection against HIV. In my work I used SIVmac239 (Simian Immunodeficiency Virus) challenged Rhesus Macaques sera and developed viremia (from another study by Lieber lab). My goal was to test whether anti-gp41 antibodies from these animals cross-reacted with synthetic gp41-derived fusion inhibitor peptides, specifically C46-v2o, C34-SFT, and Enfuvirtide(T20). If antibodies interfered with fusion inhibitors, their therapeutic effect would be severely compromised. In my project, I developed an Enzyme-Linked Immunosorbent Assay (ELISA) to measure antibody titers. These peptides were coated, then blocked with 3% bovine serum albumin, and incubated with diluted Macaque serum to allow antibody binding. I used anti-monkey immunoglobulin-G conjugated with Horseradish Peroxidase for detection of antibody binding. I optimized the serum dilution to 1:200 to reduce background signal and concluded SIV-challenged Macaques had detectable antibody levels against C46-v2o and C34-SFT, but not T20. Ongoing work will determine more detailed IC50 antibody titers in serum samples. Notably, animals with high viral loads exhibited higher levels of antibodies against HIV fusion inhibitors. T20 is a promising candidate for sustained HIV inhibition, as no detectable antibodies means it’s less susceptible to pre-existing immune responses. These findings provide valuable insights into how fusion inhibitors interact with the immune system and help refine strategies for HSPC-based HIV therapies, bringing us closer to a long-term, self-sustaining approach for HIV prevention. 
 

For biomass derived molecules to serve as precursors for biofuel and other related energy sources, more stable and efficient catalysts are needed. Drawing inspiration from enzymes, our group has recently shown that a bifunctional acid–base metal–organic framework (MOF) with co-localized acid and base sites outperforms a MOF with randomly dispersed acid and base sites as a catalyst for the aldol condensation of biomass-derived carbonyls. These active acid–base sites are composed of a primary amine and carboxylic acid. However, to further improve catalytic activity a templated framework with secondary amine and carboxylic acid active sites can be developed. Relative to primary amines, secondary amines should favor the formation of the key enamine intermediate and increase catalytic rates. Framework synthesis and characterization show success of incorporation of the secondary amine, and preliminary catalysis results indicate how successful this secondary amine has been. Overall, this work expands on the previous introduction of metal-organic framework catalysts as an alternative to common industrial catalysts in the biomass upcycling process by exploring the utility of a new templated secondary amine acid–base MOF. 

Neuroethics explores the ethical paradigms surrounding neuroscience as it relates to new technologies, research and improved understanding of the brain and nervous system. A study within the Department of Neurosurgery includes human participants who have experienced a stroke. Participants get brain surgery to have intracranial electrodes implanted, have time for surgical recovery, then participate in follow up study sessions to gather neural and other data as they engage in rehabilitation therapy while being recorded and stimulated via the electrodes. From a neuroethics view, there is a limited understanding of why eligible people would choose to opt in or out of participating in this or similar studies. The neuroethics research group has done prior work to explore motivations for people who choose to participate in research and understand their experiences with implantable neural device research. However, few studies explore motivations surrounding a person’s decision to decline an invitation to participate in a research trial for which they are eligible. This project presents a literature review of potential  motivating factors in prospective participants’ decision to decline or participate in research. We will present how this literature review is used to construct a survey instrument to be administered to study decliners and a data analysis framework to interpret the survey results that we will gather. The results will have broad implications for understanding how people living with neurological conditions think about the potential risks and benefits of neurotechnologies that directly modify brain activity.

Prenatal lead exposure is associated with learning and behavior problems, reduced growth, and increased risk of miscarriages. The Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists recommend lead exposure screening for pregnant women due to the significant health risks lead poses to their developing fetus. However, there is no nationally recognized screening tool, leading to inconsistent practices and potential gaps in care across the country. This project aimed to address this gap by identifying state-specific screening resources for clinicians and creating a tool to help healthcare providers more easily access these resources. Through web searches, emails, and phone calls to 50 state health departments, 20 state-level screening resources were identified, along with county-level resources in three counties with childhood lead poisoning prevention programs. These resources were compiled into an interactive map directing clinicians to screening resources in their region. This tool is being reviewed for potential use by the Pediatric Environmental Health Specialty Units, an organization that provides free pediatric and reproductive environmental health consultation services to clinicians. The tool addresses the barrier to accessing screening resources, ideally increasing lead screening rates and improving pediatric health outcomes. The findings highlight the need for a national screening tool and provide insights into regional differences in recommended screening practices.

Microbial odors are essential for attracting mosquitoes to their hosts, but their role in attraction to other nutrient sources remains unknown. Sugar sources provide nutrients that lengthen the lifespan of both male and female mosquitoes and increase the vectorial capacity in host-seeking female mosquitoes. Microbial odors have been shown to act as proxy signals for the availability and composition of certain nutrients, such as amino acids and mineral ions, found in nectar and fruit sap. As microbes are abundant in flowers and fruits, we hypothesize that Microbial Volatile Organic Compounds (mVOCs) from these nutrient sources play an important role in the feeding behavior of mosquitos. To test this, we analyzed the microbial community of a known attractive fruit, Mangifera indica ‘Keitt.’ Microbial species were identified from our environmental samples through amplicon sequencing of the 16S and 26S regions. Isolates of the most abundant and relevant species were cultured for mVOC collection and chemical analysis via Gas Chromatography and Mass Spectroscopy (GC-MS). Behavioral assays were then performed with Aedes aegypti mosquitoes to observe the effect of microbial odors on the attractiveness of nutrient sources. Through the identification of behaviorally-relevant microbial compounds, we can gain a stronger understanding of the ecological dynamics of mosquito chemoreception and microbial community signaling, which can help inform future mosquito-control measures.

The Red-legged Honeycreeper, Cyanerpes cyaneus, is a member of the passerine bird family Thraupidae (tanagers) and is part of a group commonly called Neotropical honeycreepers.  Along with other honeycreeper species, C. cyaneus is a nectarivore, meaning that floral nectar is a large component of its diet.  It is expected that C. cyaneus, like other avian nectarivores, exhibits specialized adaptations to the tongue and bill and specialized feeding mechanisms for feeding on nectar, but this remains unexplored.  This study analyzes the kinematics (movements in space) of the bill and tongue during nectar feeding in C. cyaneus to investigate how this species is adapted for nectar feeding.  The feeding kinematics of C. cyaneus are then compared to those of three frugivorous (fruit-eating), but opportunistically nectarivorous, tanager species: the Crimson-backed tanager (Ramphocelus dimidiatus), the Palm tanager (Thraupis palmarum), and the Blue-grey tanager (Thraupis episcopus).  These opportunistic nectar feeders were given access to nectar and their feeding kinematics were characterized and compared to those of C. cyaneus to determine how ancestral patterns of feeding kinematics could be co-opted for specialized nectarivory.  Birds were filmed in Panama using high-speed videography and footage was digitized using the DLTdv8 imaging tool. Data were subsequently processed in Microsoft Excel and RStudio.  By comparing the feeding mechanics of C. cyaneus with those of closely related opportunistic nectarivores, this research aims to not only uncover the nectar extraction mechanisms used by C. cyaneus, but will be the first study to examine the evolutionary trajectory of nectar-feeding biomechanics.  These anticipated findings will contribute to a more comprehensive understanding of the evolution of avian nectarivory.

Orientation Patch Count (OPC) is a method of research used by biologists and paleontologists to analyze the complexity of an animal’s feeding surface while inferring their diets; diet and tooth complexity have evolved in concert with one another, which is why this method has been used on reptilian and mammalian (denticular) species. However, it has not been extensively tested on edentulous (toothless) clades. Therefore, my research examines the OPC of an edentulous species - specifically the endangered Madagascar big-headed turtle (Erymnochelys madagascariensis) using  three CT-scanned specimens. Three primary programs were used in order to analyze the quantitative morphometricsof the species: Slicer for processing and editing CT scans from the University of Washington’s Friday Harbor Lab, MeshLab for editing 3D models, and RStudio for data analysis. This research contributes to a broader study on turtle species led by paleontologist Brenlee Shipps, who will apply these findings to extinct beaked clades, specifically dicynodonts.

Dilated Cardiomyopathy (DCM) is a heart disease characterized by the thinning and dilation of the heart's walls, which leads to a decrease in blood pumping ability and can progress to heart failure. Many genetic mutations, primarily in components of the sarcomere, have been implicated in causing DCM. One such mutation is the beta myosin heavy chain mutation E525K. This project aims to understand the molecular mechanism by which E525K leads to disease progression using stem cell-derived cardiomyocytes and a unique multi-level approach to characterizing contractility and cell morphology. Here we show that the E525K mutation can lead to both hyper- and hypocontractility depending on the scale of the analysis. We found that in isolated cells, E525K mutants experienced a 65% decrease in sarcomere shortening and that in engineered heart tissues, the max force produced by tissues with mutant cells was 39% lower than WT tissues. Meanwhile, in isolated myofibrils with the mutation peak force was increased by 45% when stimulated with pCa 4.0 calcium. Morphological analysis showed that mutant cells on average have fewer, smaller, less organized sarcomeres than WT cells. This demonstrates that E525K myosin, though linked to DCM, which is associated with hypocontractility, exhibits both hyper- and hypocontractile effects. Cardiomyopathy affects an estimated 1 in 500 people worldwide and is a major cause of heart failure. Novel pharmacological treatments that activate or inhibit myosin are becoming available; however, cardiomyopathy’s genetic nature complicates treatment. Our findings highlight that the underlying mechanisms causing cardiomyopathy can vary greatly even between patients showing similar disease phenotypes. From a clinical perspective, this complicates what medications should be used, demonstrating that a deeper understanding of the underlying mechanism by which cardiomyopathy-related mutations cause disease is imperative to diagnose and treat patients optimally.

Increased mitochondrial oxidative stress causes fatigue and metabolic dysfunction in muscle tissue. It is unclear whether the oxidative stress is due to elevated production or impaired consumption of reactive oxygen species (ROS). The purpose of this study is to test whether the capacity of the antioxidant defense system is impaired or the mitochondrial ROS production rate is elevated in response to chronic changes in mitochondrial oxidative stress. To experimentally manipulate mitochondrial oxidative stress, we use an inducible mouse model to knockdown superoxide dismutase 2 (SOD2) in skeletal muscle and heart to increase oxidative stress, and exercise training to decrease oxidative stress. Knockdowns (KD) or littermate controls (CON) performed a six-week voluntary wheel running (EX) or sedentary control intervention (SED). Following completion of the intervention, I isolated heart and skeletal muscle mitochondria using differential centrifugation. I measured mitochondrial hydrogen peroxide (H₂O₂) production rate and tested the antioxidant capacity by treating isolated mitochondria with Auranofin (AFN) or 1-chloro-2,4-dintrobenzene (CDNB), which inhibit the thioredoxin and glutathione S-transferase components of the mitochondrial antioxidant defense system, respectively. KD heart and skeletal muscle had similar absolute H₂O₂ production rates compared to CON, but normalized to oxygen consumption the KD had significantly higher H₂O₂ production. Since absolute H₂O₂ production under vehicle conditions was not different, this suggests that the antioxidant capacity adapts to meet the changes in mitochondrial H₂O₂ production. We will collect data from the exercise-trained cohort next month. I expect to see an increase in H₂O₂ production rate and antioxidant capacity in both groups due to the increased mitochondrial biogenesis from exercise training. These results demonstrate that chronic increases in mitochondrial oxidative stress decrease mitochondrial H₂O₂ production capacity from skeletal muscle.

Body dysmorphic disorder (BDD) is a relatively common debilitating psychiatric disorder, marked by a preoccupation with one's physical appearance and associated with significant morbidity and mortality. This preoccupation is due to one's perceived flaws that are not noticeable to others, causing extreme distress and functional impairment. Previous neuroimaging studies have shown how aberration in visual processing is central to BDD. BDD participants often exhibit an unusual focus on high-detail image information (high spatial frequency processing) versus broad image information (low spatial frequency processing), leading to perceptual disturbances. Other research has shown hypoactivation of early cortices, such as V1 and V2, can be found in BDD participants compared to healthy controls when viewing low spatial frequency information. Hypoactivation in visual cortices extends across multiple stimulus categories, indicating a fundamental deficit in integrating low-spatial frequency information. This study aims to isolate and examine low-level visual processing using fMRI and visual mapping techniques to precisely localize the stage of the visual hierarchy where visual processing is altered in BDD. We aim to recruit n=30 participants (n=15 with BDD, n=15 healthy controls), all of whom will undergo clinical diagnostic interviews and behavioral assessments characterizing spatial frequency processing, ending with a spatial frequency processing task involving both low-level and high-level spatial frequency processing. We hypothesize that the results of our research will show that those with BDD will display reduced sensitivity to low spatial frequency stimuli in early visual cortices. If our hypothesis is confirmed, these findings will reveal potential new biomarkers of perceptual dysfunction in BDD, informing intervention efforts to address more fundamental perceptual deficits and identify potential risk markers for early detection of this disorder.

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a fatty acid β-oxidation disease associated with severe hypoglycemia and sudden death. MCADD is caused by biallelic pathogenic variants in the ACADM gene, which codes for a dehydrogenase specific to carnitines C6 through C12. MCADD is included in newborn screening (NBS) and characterized by elevated medium-chain acylcarnitine fats, annotated as C6, C8, and C10:1. Diagnostic testing is performed in plasma. Acylcarnitine results in dried blood spots have been described to differentiate carriers from affected individuals to reduce false positive NBS. Disease sensitivity and specificity, particularly to differentiate carriers from true positive cases, has not been well described in plasma. We posit that MCADD diagnosis will be more accurate if additional ratios beyond the primary disease markers, C6, C8, and C10:1 acylcarnitines, are considered. This study is a retrospective data review of NBS cases that were positive for possible MCADD and diagnostic testing was performed at Seattle Children’s Hospital. Cases are sorted into four groups: MCADD with homozygous disease variants, compound heterozygous MCADD, carriers of MCADD, or true negative. In collaboration with the biostats core service, linear regression models and receiver operator characteristic curves will compare acylcarnitine species and ratios by group. Preliminary results demonstrate that the primary markers associated with MCADD, C10/C2, C10/C6, C8/C2, C8/C10, and C8/Free carnitine, clearly discriminate affected individuals from control cases in plasma. Analysis is in process to compare the different genotypes of affected MCADD from carriers. Uncovering the diagnostic accuracy of plasma acylcarnitine profiles may influence future testing plans and improve the cost-effectiveness of healthcare services. DNA testing remains costly and slow. Additional biomarkers that provide a conclusive diagnosis of MCADD without requiring genetic testing may lead to more equitable patient care.

Changing patterns of human land use near coastal zones have increased the abundance of aquatic habitats where mosquito and midge larvae develop. Salt-tolerant species, such as Aedes togoi mosquitoes and Dicrotendipes enteromorphae midges, have evolved distinct anatomical and physiological mechanisms that allow them to thrive in saltwater environments while also being able to develop in freshwater. While much is known about how freshwater-confined species maintain salt and water homeostasis (i.e. osmoregulation) in dilute freshwater, these processes remain largely unexplored in salt-tolerant species. The main goal of this research was to describe and compare the osmoregulatory strategies of Ae. togoi and D. enteromorphae larvae reared in seawater and freshwater, focusing on how they maintain ion and water balance in saline conditions. Based on information from other salt-tolerant insects, I hypothesized that the rectum of these species is the main organ that excretes salts and will have higher expression of ion pumps compared to other osmoregulatory organs of the larvae. This increased expression would support the secretion of hyperosmotic (salty) urine, a critical adaptation for survival in saltwater. Using immunohistochemistry and fluorescence microscopy, I localized key ion-transport pumps within the rectum and other osmoregulatory organs of Ae. togoi and D. enteromorphae larvae. I identified a high expression of Na⁺/K⁺-ATPase (sodium/potassium pump), and V-type H⁺-ATPase (proton pump) enriched in the anal gills, renal tubules, and the rectum. My findings suggest that the coordinated function of many osmoregulatory organs, and not just the rectum, allows for salt-secretion by marine insects, and this establishes an initial framework of cellular mechanisms among marine insects. This research has implications for predicting future species distributions with rising sea levels, as well as the potential to identify novel targets to control salt-tolerant mosquito populations to mitigate disease transmission in coastal regions.

Soil-transmitted helminths impact over 1.5 billion people worldwide, disproportionately affecting school-aged children and pregnant women. Hosts issue a “weep and sweep” Type II immune response to expel helminth parasites from the intestines. Ruptured epithelial cells secrete the cytokine interleukin (IL)-33, which recruits innate lymphoid type 2 cells (ILCs)2 and CD4+ T-helper type 2 (Th2) cells. ILC2s release IL-13, encouraging stem cell differentiation into tuft and goblet cells to facilitate tissue repair and worm expulsion. Anemia is prevalent in helminth-rich environments because of elevated rates of malaria and malnutrition. Despite correlations between anemia and helminth infection, the impact of anemia on the Type II immune response in the small intestines remains unknown. Using N. brasiliensis (Nb), a bloodsucking hookworm-like parasite, I observed that one week post infection, iron-deficient (ID) mice were less capable of expelling worms compared to iron-sufficient (IS) mice. Through tuft cell immunofluorescence staining in the small intestine, I observed comparable hyperplasia in IS and ID-Nb infected mice but noticed differences in cell localization: ID-Nb infected mice had decreased numbers of tuft cells in the crypts compared to IS-Nb mice. This suggests that ID Nb-infected mice could be experiencing decreased migration/proliferation of tuft cells, compared to their IS-infected counterparts. Using EdU, a synthetic nucleotide tag that labels newly synthesized DNA, we can understand cellular proliferation patterns in IS vs. ID Nb mice. Co-staining for tuft cells permits us to merge events and track unique vs. universal trends in cell behavior, including cells’ migration patterns. I hypothesize that ID-Nb mice will have decreased cellular proliferation and migration compared to IS-Nb mice, ultimately impacting worm burden. These findings offer insights into the mechanism behind negative outcomes in anemic hosts, and could contribute to dietary intervention or therapies targeting the epithelium to alleviate burdens of helminth infection.

In healthy cells, NRF2 is an essential transcription factor for regulating oxidative stress. However, when constitutively activated in cancer cells, it can lead to tumor cell proliferation and metabolic rewiring. When NRF2 is activated, it increases cysteine consumption in the cells through increased expression of the SLC7A11 cystine/glutamate antiporter. We discovered a dose dependent decrease in proliferation when exposed to higher cystine concentrations, unique to cells with NRF2 activation. To understand the kinetics of this proliferation defect, I am developing a tool to visualize and track cell proliferation using a live-cell imager. I will first genetically encode Nuclear Red Fluorescent Protein (NucRFP) into our NRF2-activated cells, using single-cell cloning and flow cytometry to isolate and establish clonal populations that stably express NucRFP. Then, I will use the live-cell imager to incubate cells with NucRFP expression, titrating different concentrations of cystine. Stable NucRFP expression will allow me to quantify cell growth overtime in different concentrations of cystine media to better understand cell growth. This research will generate insights into the consequences of cystine stress that inform the development of targeted treatments for NRF2 activation in cancer cells.

Circadian clocks have evolved as a powerful adaptation in response to daily environmental changes, allowing optimally timed sleep-wake cycles. The solar light-dark (LD) cycle is the dominant zeitgeber (time-giver) for entrainment (synchronization) of sleep and wake to external cues. While our lab has found that humans sleep less and later the days prior to the full moon phase where moonlight is available in the early night, moonlight was found to be an unreliable cue in determining lunar modulation of sleep for the light-polluted city population. Thus, my project investigates whether lunar cycling on activity patterns remains present without photic moonlight exposure using a diurnal non-human primate model: captive titi monkeys (Plecturocebus). The California National Primate Research Center collected titi monkey data (n=16) between 2022 to 2024 using AX3 from Axivity, a wearable data log that measures acceleration to monitor physical activity. I am using the statistical software R to derive activity onset and sleep onset/offset as phase markers of activity. Additionally, I am fitting different cosine models to a 30/15-day period, respectively lunar and semilunar, to analyze the periodic data for activity across the lunar month. We expect to see phase markers of activity oscillate with the monthly lunar phase, showing how the lunar cycle influences circadian rhythms in diurnal non-human primates, even in the absence of moonlight. This study may reveal a novel finding on lunar rhythms on activity patterns and could incur interest on how endogenous processes have adapted to the lunar cycle. Further molecular work could elucidate the neural mechanism behind lunar modulation of sleep and provide insights on improved treatment of dysregulated sleep.

Women with inflammatory bowel disease (IBD) report changes in symptoms due meses and hormonal contraception. However, research on the impacts of menopause on IBD symptoms and progression in women is limited. We systematically reviewed existing literature to describe the impact of menopause, menopause transition, and hormone replacement therapy (HRT) on IBD activity, symptoms severity, and progression. Our search strategy included terms related to menopause and IBD. PubMed, CINAHL, PsycINFO, Embase, and Web of Science were searched. Two reviewers screened all records. Findings were reported using narrative synthesis. Out of 1568 identified records, we reviewed 107 full text reports and included 14 studies (5 cohort, 3 case-control, 5 cross-sectional). IBD participant sample sizes ranged from 37 to 1367. Five studies examined the relationship between menopause/menopause symptoms and disease activity, with four reporting no relationship and one reporting more bothersome menopause symptoms in women with active IBD, compared to those in remission. Seven studies examined the impact of HRT on IBD risk or symptoms: HRT associated with increased risk of IBD (n=2), no change in IBD symptoms (n=3), and improvement of IBD symptoms (n=2). Five studies examined menopause onset age for IBD patients: earlier menopause onset in IBD participants compared to age-matched controls (n=4), no difference in menopause onset (n=1). Few studies have examined the effects of menopause, menopause transition, or HRT among IBD patients. Inconclusive results were found for the relationship between menopause and HRT and IBD progression, symptoms, and risk. Some evidence suggests that women with IBD may have an earlier onset of menopause compared to controls. However, there is a need for continued research on the relationship between IBD disease activity and menopause symptoms to create tailored interventions to improve women’s health in IBD across the lifespan.

Intimate partner violence (IPV) is a widespread problem across the U.S. that typically begins in adolescence which can cause severe struggles for the impacted individuals. IPV can be mitigated through some preventative factors, such as education and understanding of IPV. The purpose of this study is to evaluate rejection sensitivity (RS)-- the tendency to strongly react to rejection, including the dismissal or refusal of ideas, people, or offers-- as a mediator between comprehensive sexuality education (CSE) and IPV. I designed this study to use a cross-sectional online survey to measure levels of RS, themes of CSE from middle and high school education, and levels of IPV that individuals have experienced. It includes a representative sample based on Unites States census data of 340 participants who range from 18-25 years and have had a romantic relationship lasting at least two months. The data is analyzed through a mediation model, with RS as the mediator, as well as testing the direct effects of CSE on IPV using R Statistical Software. Analysis models the three pathways: path a-- CSE to RS, path b-- RS to IPV, path C-- direct effects of CSE on IPV (CSE to IPV). I anticipate that RS will act as a mediator between CSE and IPV such that higher levels of CSE will be associated with lower IPV levels through the mediation of RS. Additionally, I hypothesize there will be a direct effect of CSE on IPV. This study aims to improve the understanding of potential preventative factors of IPV as well as inform future interventions, such as CSE. Keywords: intimate partner violence, rejection sensitivity, comprehensive sexuality education

During inflammation, myeloid-biased hematopoietic stem cells (myHSCs) are crucial for replenishing myeloid cells and platelets. Excessive activation of myHSC during aging and chronic inflammation results in the loss of their regenerative function. We have shown that Semaphorin-4A is a neutrophil-derived molecule that confers myHSC resilience to inflammatory stress and safeguards their epigenetic state, preserving their regenerative function. Sema4AKO mice exhibit excessive myHSC expansion and myeloid bias compared to their wild type (WT) counterparts, particularly in the context of aging. Given that myHSC are positioned at the top of hematopoietic hierarchy, we asked whether myHSC molecular defects due to the absence of Sema4A are “passed down” to mature progeny. In preliminary analysis of aged WT and Sema4AKO mice, we mapped the neutrophil maturation pathway via whole bone marrow RNA Sequencing. Notably, we found that in aged Sema4AKO mice, this process was significantly dysregulated. Moreover, the neutrophil transcriptional signature was abnormal and consistent with excessively activated, pro-inflammatory state. This suggests that neutrophils produced from KO mice may have defective function. To investigate this, we are using a murine ligature-induced periodontitis model to monitor alveolar bone loss as a readout of neutrophil function. Periodontitis is an oral disease that leads to alveolar bone loss and promotes inflammation, specifically production of myeloid cells. The ligatures are placed on the left second maxillary molar and are left on for 8 days. After this incubation period, the mice are euthanized, and bone loss is measured. Since the ligatures are only placed on one side of the mouth, the other side acts as an internal control for bone loss. In our preliminary studies in WT mice, we observed that as expected, ligature-induced periodontitis causes bone loss. Having established this model in our lab, we are starting experiments to examine the impact of Sema4AKO on neutrophil function.

Post-Traumatic Stress Disorder (PTSD) is one of the most common mental disorders in the world. People with PTSD often have difficulty managing time or have witnessed a traumatic event in the past. PTSD is also associated with memory issues which are characterized by intrusive memories that can cause re-experience aspect of the traumatic event. Through the use of computational models, we aim to investigate the differences in memory retention in spaced vs massed practice presentations. We hypothesize that mass practice will lead to less accuracy in recognition and less intrusive thoughts during retention. Through recruiting healthy adult participants with no history of PTSD or other stress-related psychiatric disorders we get a base data avoiding discrepancies. Participants view visual stimuli as images, either neutral or triggering which are presented in pseudo-order and are asked to rate them based on their valence ranging from neutral to extremely negative. The images are presented under two conditions: mass and space presentation. For spaced presentation, different versions of the triggering image category are presented in no particular order with neutral and filler images in between. For massed presentation, all versions of the triggering image category are presented one after the other with no neutral or filler images in between. 24 hours after the initial presentation of the images, participants are tested on memory retention in the form of image recognition. Participants are asked about the difficulty of recalling the image and how often they think about the image. Having collected data during AUT 24, we were able to understand there is a correlation present between memory retention in mass and spaced recognition in terms of traumatic and non-traumatic events. By collecting data through WIN 25, we will have greater accuracy in terms of significant data.

Over the years, the relationship between universities and corporations have become more and more intertwined through research and building funding, student opportunities, and company influence on administrators and faculty. My research explores the connections between the University of Washington (UW) and Boeing, a large transnational weapons manufacturer, and the impacts these connections have on research, education, and students' future career prospects. In this project, I ask: how are student’s educational experiences and career opportunities impacted by the university’s close connection to the Boeing company? I am focusing on a potential student to Boeing pipeline–a process for where students are primed to work at Boeing through their educational experiences at UW. I address this question through a variety of methods and sources, including a comprehensive analysis of all publicly available information on UW websites, including individual websites run by UW research labs, interviews with engineering students, Public Records requests, and a review of relevant Critical University Studies literature. My findings indicate that there is significant evidence towards the existence of a student-to-Boeing pipeline at UW. Boeing has given an extensive amount of money to the university, placed employees/affiliates in professorships, and is vastly overrepresented in internship and capstone opportunities available to students through the University of Washington. Furthermore, my research found a correlation between departments with a high amount of funding from Boeing with higher rates of student employment at Boeing after graduation. I argue that the student-to-Boeing pipeline has fundamentally changed the education of UW Engineering students to better fit Boeing’s needs, and it upholds the military-industrial complex. This project contributes to broader debates in critical university studies about the mission of public universities in providing students an unbiased education and universities' role in combating the climate crisis.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by challenges in communication, social interaction, and restricted repetitive behaviors and interests (RRBs). Studies have alluded that a relationship exists between RRBs and difficulties with emotional regulation in ASD individuals. However, a better understanding of this relationship is not only critical for improving therapeutic approaches for individuals with ASD, but also to understand the underlying mechanisms of the disorder. In this study, we aim to explore the relationship between emotional control and compulsive and ritualistic behaviors in youth aged 8–17 years with and without ASD as well as look at sex as a confounder. Emotional control will be assessed using Behavioral Rating Inventory Executive Functioning T-scores, and the presence of Compulsive and Ritualistic Behaviors were assessed from the Repetitive Behavior Scale-Revised subdomains. We will compare emotional control scores between participants with and without these behaviors (based on clinical cutoff). To do so, first, we will conduct an ANOVA to assess the impact of Group (ASD vs TD), Sex (M vs F), and Compulsive behavior (Above/Below Clinical Cutoff) and their interactions on Emotion Control (dependent variable). Second, we will conduct the same analyses with Ritualistic behaviors on Emotion Control.  We hypothesize that youth with compulsive and ritualistic behaviors will demonstrate lower emotional control than those without (main effect of RRBs). We also predict that males will have lower emotional control than females (main effect of sex) and that autistic youth will have lower emotional control than their typically developing peers (main effect of diagnosis). This research has the potential to reveal insights regarding the interaction between emotional regulation and RRBs in youth with ASD, highlighting the importance of interventions targeting emotional control. Such interventions can improve emotional regulation and also address compulsive and ritualistic behaviors.

Cardiac Electrophysiologists (EP) use various devices to diagnose and treat heart rhythm disorders. Unfortunately, these devices can be defective and are subject to recalls by the U.S. Food and Drug Administration (FDA) to protect the patient. This study aims to better understand the rates of these recalls from 2014 to 2024 and thereby evaluate the safety of these devices, compare the safety vis a vis previous decades, and assess the safety of new devices as they are introduced for clinical use. We evaluated the number of FDA advisories related to implantable cardiac devices from 2014 – 2024; total the number of devices recalled under these advisories, determining the most prevalent malfunctions, and analyzing trends compared to rates from 1990-2000. The data shows that Permanent Pacemakers and Implantable Cardioverter Defibrillators (ICD)  have become safer compared to the past, although more units were affected per device advisory. Newer technologies of Leadless Pacemakers, Subcutaneous-ICDs, Implantable Loop Recorders, and Cardiac Contractility Modulation have been impacted by malfunctions and their trend will be critical to follow over the years to come. The findings of this study provide information regarding the safety of these technologies that are valuable to both EP cardiologists and the millions of American patients who live with these devices.

Acute Pancreatitis (AP) is a sudden inflammatory condition of the pancreas that can lead to significant mortality. Despite its rising prevalence and associated healthcare burden, treatment options remain limited to supportive care, with mortality rates in severe cases reaching 30%. Activin A is a key contributor to AP, interacting with the ACVR2A receptor to regulate various pathophysiological processes, including inflammation through immune cell recruitment. This study hypothesizes that activin A binds to ACVR2A to activate the ERK pathway, leading to increased NF-κB expression and elevated production of pro-inflammatory cytokines, including TNF-α and IL-1β. Experiments were designed using the 266-6 immortalized pancreatic acinar cell line and RAW 264.7 macrophages. These cells will be cultured for western blot analysis, ELISA assays, and transwell migration assays following activin A stimulation. Lower ERK phosphorylation and reduced NF-κB expression are expected when cells are treated with ACVR2A inhibitors in combination with activin A, compared to activin A treatment alone. ELISA assays are anticipated to confirm increased TNF-α and IL-1β production in 266-6 cells following activin A treatment. Macrophage migratory capacity is expected to increase when exposed to conditioned media from activin A-treated 266-6 cells. These findings will provide insights into the role of activin A in AP pathophysiology, potentially identifying new therapeutic targets for mitigating pancreatic inflammation and immune cell recruitment.

Chlamydia, caused by the bacteria Chlamydia trachomatis, is one of the most common bacterial sexually transmitted infections of the urogenital and gastrointestinal tracts. Preliminary whole genome sequencing of C. trachomatis isolates from women and men who have sex with men (MSM) identified the gene pmpE. This gene encodes for a putative membrane protein that is a key locus of genetic variation between these two populations of isolates. Here, I performed deeper sequencing and structural analysis of natural pmpE variants to better understand how these genetically distinct strains exhibit their tissue tropism differences. PCR-based sequencing of C. trachomatis isolates was conducted against pmpE and ompA to initially type the strain, and then followed by whole genome sequencing to derive complete genomic information. Bioinformatic analysis showed that the cervical and rectal strains are sorted into two distinct clades based on pmpE. To predict possible functional differences, structures of pmpE sequence variants were computationally modeled using Alphafold v3, and analysis demonstrated that variations were confined to predicted surface-exposed loops. Based on the collective data, we hypothesize that two loops may provide functional differences in the ability of cervical versus rectal C. trachomatis strains to interact with tissue-specific host attachment proteins.

Neotrypaea californiensis, or burrowing shrimp, is a native pest for oyster growers in Washington. The shrimp create networks of interconnected burrows that displace and liquify sediment, suffocating oysters. The pesticide carbaryl was used for decades to effectively control shrimp populations. More recently, the Environmental Protection Agency (EPA) deemed carbaryl an environmental hazard, leading to a vital need for a shrimp control method with minimal non-target effects. Very little is known of the physiology of shrimp that allows them to tolerate environmental extremes. My study aims to understand the tolerance of Netotrypaea californiensis to high concentrations of salts that challenge their ability to regulate internal ions, pH, and metabolic wastes. Using a laboratory-based system whereby shrimp burrow in 6 inch deep sediment in seawater, my research findings revealed that the addition of high concentrations of sodium bicarbonate (NaHCO₃) caused shrimp mortality while high concentrations of regular sea salts did not. This suggested that an ionic imbalance—high levels of sodium and reduced levels of chloride—may be causing shrimp death. To investigate, I collected the gills, a critical organ that regulates systemic ion levels, of shrimp after NaHCO₃ exposure and quantified the abundance and localization of key ion pumps using Western blotting, immunohistochemistry and confocal microscopy. I found a significantly higher expression of Na⁺/K⁺ pumps in the gills with NaHCO₃ exposure, suggesting a major ion-regulatory disturbance caused by NaHCO₃. These data will expand our understanding of how salts that cause ionic imbalance in seawater can disrupt the internal levels of ions that are critical for most biological processes. Findings will be disseminated to Washington oyster growers to aid in the management of their crop.

Malaria is one of the most prevalent diseases worldwide, with nearly half of the world residing in regions at risk of transmission. It is commonly spread to humans through the bite of a female Anopheles mosquito infected with Plasmodium spp. parasites. When feeding, mosquitoes ingest biogenic amines at concentrations found in the blood of the host. Adult patients with severe malaria have altered concentrations of serotonin and histamine in their blood compared to healthy individuals. Previous work showed the ingestion of serotonin and/or histamine concentrations associated with adult patients with severe malaria influenced key mosquito behaviors, such as the tendency to take a second blood meal, flight behavior, and visual object inspection—traits that are related to the transmission of malaria. However, the mechanisms by which serotonin and histamine modulate mosquito behavior remain unclear. Given the known involvement of these biogenic amines in physiological processes, we hypothesize that the ingestion of varying serotonin and histamine concentrations in Anopheles stephensi mosquitoes will alter their distribution across tissues. Mosquitoes are fed with deuterated serotonin and histamine at levels associated with patients with severe malaria versus healthy individuals. These deuterated compounds serve as tracers to distinguish endogenous (natural) from exogenous (ingested) serotonin and histamine in the tissue. The mosquitoes are dissected to retrieve the head as a proxy for the brain, the midgut, and sensory appendages including maxillary palps, antennae, legs, and proboscis. All tissue samples are extracted and analyzed via liquid chromatography-mass spectrometry (LC-MS) to distinguish and quantify deuterated and non-deuterated serotonin and histamine. By viewing all aforementioned tissue regions and comparing endogenous versus exogenous biogenic amine levels in the samples, we hope to understand the modulation of biogenic amine distribution in An. stephensi tissue and offer insights into possible connections between neuromodulators and behavior in the mosquitoes.

The tongue base is a key structure in respiration and swallowing and morphological and functional adaptations to its volumetric changes are largely unknown. Thus, addressing this gap could enhance the understanding of breathing and swallowing disorders in the enlarged and reduced tongue base. Twelve Yucatan minipigs 8-to-9-month-old (half each sex) were analyzed. Six minipigs received a high-caloric chow pellet to reach a BMI>50 (enlargement group), while the others underwent surgical partial tongue base ablation (reduction group). Five weeks after surgery all minipigs were scanned using magnetic resonance imaging (MRI) synchronized with respiratory cycle gating. Mid-sagittal cross-sectional areas of the velopharyngeal and oropharyngeal airways, and retroglossal space during inspiration and expiration were quantified using ITK-SNAP. The volumes were also calculated using segmentation techniques. These measurements were compared between the enlargement and reduction groups in the inspiratory and expiratory cross-sectional areas to determine differences. Extrapolating from one minipig from the enlarged group observed larger mid-sagittal cross-sectional areas of the interested regions compared to the reduction group. The enlarged minipig observed greater differences in range and larger averages and medians for each cross-sectional volume. The enlargement group also had slower inspiratory and expiratory rates than the reduced group. Observations from one minipig from the reduced group were observed to have smaller cross-sectional areas, medians, and averages for all interested regions. Additionally, the reduced minipig had more frequent respiratory rates. The current analysis of the sagittal views from the obese enlarged tongue base versus the reduced tongue base minipigs revealed larger volumes within the enlarged group. This pattern currently suggests enlarged tongue base minipigs with larger cross-sectional volumes, but less inspiratory and expiratory rates. However, the reduced tongue base minipigs are anticipated to have smaller cross-sectional volumes and more frequent respiratory rates compared to the enlarged group.

Rising atmospheric carbon dioxide levels have driven research into efficient gas separation materials. Polymers of intrinsic microporosity (PIMs) is one promising solution due to their rigid, porous structures and processability, allowing them to be turned into thin films for membrane-based gas separations. My research focuses on enhancing the carbon dioxide selectivity of helicene-based PIMs through post-synthetic modification of these polymers. I have synthesized a small molecule model of the PIM to screen for amine substitution conditions and ensure the viability of post-synthetic modification on the larger helicene-based PIM. Characterization techniques, multinuclear NMR and mass spectrometry, have verified the synthesis and amination of my model system. By incorporating nucleophilic amines into PIMs, these polymers can feature enhanced binding to electrophilic carbon dioxide, thereby increasing the interactions with carbon dioxide over other mixed gases, leading to separation. In my future studies, I will extend these modifications to the helicene-base PIM, fabricate films and evaluate their properties. Surface area measurements using N₂ gas sorption methods and CO₂ absorption isotherms will quantify gas-binding affinity and separation performance.

Currently, monitoring the heart's electrical activity to diagnose cardiovascular disease requires the patient to have electrodes placed on their chest. A novel approach was proposed to record ECG (electrocardiogram) signals from human fingertips, which could offer a more convenient alternative for in-home use. A prototype device was designed to capture and process the ECG heart signals for real-time health monitoring. The development process included schematic design, printed circuit board (PCB) layout creation, hardware assembly, troubleshooting, and data acquisition and analysis. The device has three rounded copper electrode plates for collecting ECG from 3 fingers, with one serving as a noise-canceling electrode. ECG signals were successfully recorded from volunteers using these fingertip copper electrodes mounted on a PCB with biomedical signal amplifiers. Additionally, basic signal-processing algorithms have been implemented in MATLAB to remove noise and enhance ECG signal quality for parameter extraction. With further research and refinement, this prototype could evolve into a portable, user-friendly device suitable for at-home monitoring or clinical use as an alternative method for tracking heart activity.

The importance of accurately identifying infections and wounds is crucial for correct medical treatment. In serious cases, misidentification of infection can cause delay in the healing process and even result in death. Thus, there is a need to simulate the physiological progression of an infection so that medical trainees are better equipped to respond to a real skin wound/infection. Through UW Medicine’s Center for Research in Education and Simulation Technologies (CREST) lab, the dynamic tissue wound modeling and infection simulation project aims to meet this need. Motivation for this research project is rooted in the lack of acceptable physical simulation models despite the educational benefit they provide. The goal of this research project is to engineer high fidelity models of skin wounds and infections that dynamically alter their appearance to create a more realistic simulation for the trainer/trainee. My specific involvement is to create a model of a skin abscess that not only simulates an infection but, when given correct treatment, changes its physiology to reflect said treatment.

The external fertilization and transparent embryos of zebrafish make them an informative model of vertebrate embryonic development from the 1-cell stage. In this study, we examine the impact of de novo GTP synthesis on the formation of the embryonic somites, which are embryonic cells which develop into segmented blocks of muscle that run the length of the body. We hypothesize the de novo GTP synthesis is required for the correct patterning of somite borders in zebrafish embryos, and that this process facilitates the formation of a vertebrate body plan. Inosine monophosphate dehydrogenase 2 (IMPDH2) is the enzyme which catalyzes the conversion of inosine monophosphate (IMP) towards the de novo synthesis of GTP instead of ATP. To test the impact of de novo GTP synthesis on somite formation, we inhibited IMPDH2 function with mycophenolic acid (MPA) both before and after somite formation began. MPA caused stronger defects in the somite morphology and embryonic body shape when added to embryos before somite formation began, earlier in development. We performed in situ hybridization against xirp2a to assess the effect of inhibiting IMPDH2 function on the formation and patterning of the somite borders. MPA treatment decreased the definition of somite borders we could observe in the posterior tail. Inhibiting IMPDH2 with MPA produced somites with smooth, round borders instead of the chevron-shape typical of zebrafish. We next conducted immunohistochemistry against IMPDH2 to examine the expression and localization of this enzyme in embryonic cells when GTP conditions are low. In MPA-treated embryos, we observed increased expression of IMPDH2 across the entire embryo. We will next explore how GTP abundance affects activity of the clock, a mechanism which synchronizes gene expression of embryonic cells.

Large Language Models (LLMs) have demonstrated remarkable performance in code generation and problem-solving, but their effectiveness varies across problem domains and complexities. In this study, we assess the problem-solving capabilities of different LLMs on a subset of LeetCode problems, categorized by difficulty, topic, and computational complexity. Through a systematic analysis of LLM performance across question topics—such as dynamic programming, matrix, and binary search—we identify trends in their strengths and weaknesses. Our findings reveal that LLMs excel at problems likely included in their training data but struggle significantly with novel or unseen problems. By evaluating their performance across different algorithmic domains, we offer insights into the potential limitations in specific algorithmic domains and implications for AI-assisted coding, competitive programming, and software engineering education. 

Before a child says their first word, they begin to produce and practice sounds they hear. Early vocalizations play a crucial role in speech development and language acquisition. However, most research on infant vocalizations focuses on children in Western, industrialized societies. This study contributes to the growing body of literature on diverse linguistic environments, specifically examining emergent sounds in the Panãra community, an Indigenous group in the Brazilian Amazon with approximately 700 speakers. Ten infants aged 2-21 months wore recording devices that collected a recording of their language environment over a day. Alongside shared ethnographic observations, I manually annotated selected 30-second audio segments for a fine-grained analysis of child vocalizations. I am currently analyzing the frequency and types of child vocalizations (i.e. vocal play, canonical babbling, variegated babbling) in infants' speech, and I plan to explore how these vocalizations may differ across the age range studied. I predict that child vocalizations will become more complex with increasing age, following pre-speech vocal development stages broadly found across cultures. My findings will contribute to a broader understanding of how language learning varies across cultural settings, vocalization stages, and the role of the environment to language development. 

The kinetochore plays a key role during the cell division process, acting as an adaptor between the mitotic spindles and the centromere. The STU1 gene codes for a microtubule plus-end-tracking non-motor protein (Stu1) and facilitates the connection between the kinetochores and mitotic spindles during cell division. It also participates in a checkpoint that ensures proper connections between the spindles and kinetochores before the cell continues into anaphase. Stu1 contains multiple MELT motifs, which are conserved sequences of amino acids that are phosphorylated and targeted by the Mps1 kinase. Mps1 plays a major role in the regulation of segregation and spindle checkpoints. The impact of phosphorylation at the MELT motif on the function of Stu1 is not known. We used a previously constructed CRISPR vector and HDR template to mutagenize the codon within the MELT motif at position 719 in the STU1 gene of Saccharomyces cerevisiae. This mutation would result in a substitution of the amino acid threonine for glutamic acid within the Stu1 protein (stu1-T719E). Threonine is a neutrally-charged amino acid and is used in S. cerevisiae proteins as a phosphorylation site, but glutamic acid mimics a phosphorylation site as it has a constant negative charge. We transformed the CRISPR vector and HDR template DNA into S. cerevisiae cells and recovered transformants. To verify the success of the mutagenesis, we purified genomic DNA from transformed yeast, amplified the STU1 gene via PCR, and then sent for Sanger sequencing. It was found that mutagenesis was successful. This will allow us to move on to the next steps, which include phenotypic tests which will allow us to see if the mutation we made impacts cell division of S. cerevisiae cells. 

Depression is one of the most commonly co-occurring mental health conditions among individuals with autism spectrum disorder (ASD) for which there are not currently effective strategies to minimize onset. Given that early caregiver support in autism-specific and general areas of functioning predict the development of a range of adaptive social and behavioral patterns, leveraging caregiving processes in childhood and adolescence may represent one approach to decreasing the risk for psychological disorder. However, current research recognizes that the high levels of stress experienced by many families with an autistic child may undermine the quality of support caregivers are able to provide. As a result, there is limited understanding of caregiving strategies that will reliably confer resilience to depression and that will support the successful implementation of mental health-related interventions in autism. As such, this project assesses caregiver involvement in childhood and adolescence as a predictor of depressive symptomatology in autistic adults, and additionally to evaluate the family environment as a moderator of this relationship. It is hypothesized that there will be a negative association between caregiver involvement and severity of depression symptoms, and that the association will be stronger under conditions of high familial warmth but reversed in family environments characterized by high control or rejection. Taken together, family environment will account for appreciable variations in the effectiveness of parent involvement as protecting against the development of depression. This survey study will lay the groundwork for researchers and autism service providers to develop an informed approach to leveraging parent involvement as a preventative measure against depressive symptoms in adulthood.

The kappa opioid receptor (KOR) system is a promising target for substance use disorder, yet its role in long-term addiction regulation remains unclear. This project investigates how selective activation of the KOR/c-Jun N-terminal kinase (JNK) pathway activates the enzyme peroxiredoxin VI (PRDX6), triggering the release of reactive oxygen species (ROS) and resulting in long-lasting KOR inactivation distinct from its canonical Gαi pathway. I investigate whether JWT-101, a repurposed ligand, acts as a long-term KOR antagonist by inducing JNK-mediated ROS production, potentially offering new therapeutic avenues. KOR-Cre mice were injected in the prefrontal cortex with oROS-Gr, a fluorescent tag that senses ROS concentrations, for selective expression in KOR-positive neurons. Using high-resolution two-photon microscopy, I monitored ROS levels in live brain slices after 2 weeks from these mice. Bath application of JWT-101 led to increased fluorescence, indicating elevated ROS production and thus, JNK activation. To confirm JNK path specificity, I applied MJ33, an inhibitor of PRDX6. Fluorescence was reduced following MJ33 treatment, indicating that JWT-101 acts in a KOR/JNK manner. These findings suggest that JWT-101 induces KOR inactivation through ROS-mediated signaling. This research provides insights into KOR/JNK signaling in substance use disorders, with implications for developing targeted therapies for recovery and relapse prevention.

The research project involves designing and building circuits for a pulsed laser and photodetector for a speed of light time of flight measurement device and developing pedagogy and curricula for 200-level experimental laboratory and 400-level senior research project physics courses. We completed project-based learning on circuit principles, Kirchhoff’s Laws, RLC circuits, Thevenin and Norton equivalence, AC signal, phasors, RC filters, oscillators, impedance, diodes, transformers, operational amplifiers, metal–oxide–semiconductor field-effect transistors (MOSFET), and introductory optics and optoelectronics. We performed hands-on training on analog circuits logic and components, CAD design, prototyping, and practical physics applications of analog circuits. Technical lab responsibilities include learning to design analog circuits using a CAD program; ordering the printed circuit board (PCB); testing circuits for functionality, accuracy, and precision; testing the speed of light measurement device for precision with light passing through air and other mediums; and measuring the refractive index of different mediums. Physics education responsibilities include incorporating our work into BPHYS 231 Experimental Physics Speed of Light Lab; developing a pre-lab quiz and lab manual; and providing documented guidance for students on learning objectives, instructions on use of the new speed of light device, lab extensions for BPHYS 231 final projects, and research topics for BPHYS 433 Senior Project. Due to the large scope of this project, the research will continue through Autumn 2025.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that affects millions of people. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive stimulation typically used in psychiatric conditions such as depression and anxiety. rTMS works by using an electric current to generate a transient magnetic field, depolarizing neurons in a target region and creating lasting changes in brain connectivity via synaptic plasticity. Patients with AD show disruptions in the Default Mode Network (DMN), a network of brain regions typically active during rest and crucial for memory consolidation. We hypothesize that strengthening the DMN through rTMS targeted at the left Brodmann 8AV region, selected for being an easily accessible node of the DMN, will improve memory in AD patients. To test this hypothesis, we are conducting a single-blind, single-arm, randomized cross-over trial of rTMS on early-stage AD patients over a 12 week period with week 1 where we scan for the 8AV region via MRI, during week 3 and 8 being the placebo or treatment week. We measure our primary outcome of the participants’ speed of forgetting —a novel index of memory function—through an individualized, adaptive memory test. To eliminate potential confounding variables, we also measure depression and anxiety symptoms during the 1st, 8th and 12th week of the study. Additionally, functional MRI scans will be analyzed for potential structural or functional differences caused by treatment. Preliminary results from our initial participants have shown promising improvements, and we are hopeful that similar outcomes will be observed in the remaining participants. Successful results would provide a novel target for AD treatment using rTMS, and support further investigation of rTMS as a viable treatment option.

The health risks of particulate matter measuring less than 2.5 micrometers (PM2.5)  include: respiratory disease, cardiovascular issues, and cognitive impairments. Its presence near schools and colleges remains underexplored. This study examines the relationship between PM2.5 exposure levels and academic outcomes in community colleges located in historically redlined neighborhoods across four major West Coast cities: Los Angeles and San Diego in California; Portland, Oregon; and the greater Seattle area in Washington. Using data from the PurpleAir Network, state air quality indices, and community college governing bodies, we analyzed and compared PM2.5 levels near institutions located within historically redlined neighborhoods and institutions located outside those neighborhoods. Leveraging the Python programming language and Google Colab, we examined correlations between an institution’s demographic makeup and transfer rates relative to PM2.5 exposure. Data sets obtained were filtered between the hours of 8 AM and 1 PM during the months of January 2024 through December 2024. Our findings indicate a correlation between higher PM2.5 exposure and lower academic performance for colleges serving predominantly racially marginalized communities located within historically redlined neighborhoods. This research reinforces the role of environmental inequities in shaping educational disparities and highlights the need for targeted policies to address air quality in affected communities.

Brain cells depend on the extracellular matrix (ECM) for structural and functional support as well as sequestration and transport of key ions and neurotransmitters. Structural and compositional changes to the ECM occur in development and in response to injury and disease. Probing ECM structure and composition in real-time in a dynamic living brain would enhance our understanding of the ECM changes that drive disease. In our work, we use organotypic whole-hemisphere (OWH) brain slices to study the interaction between brain parenchymal cells and the ECM. We have applied multiple-particle tracking (MPT), an imaging technique that tracks movement of nanoscale probes with sub-micron resolution, to OWH slices exposed to different stimuli, including oxygen-glucose deprivation (OGD) and mitochondrial dysfunction by rotenone (ROT) exposure.  Our MPT data confirmed that ECM microstructure changes in a time and stimuli-dependent manner and this was associated with changes in cellular composition and morphology. In this study, we measured changes in expression of ECM transcripts using Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) of RNA isolated from OWH brain slices exposed to OGD and ROT. After exposure to 30 minutes of OGD or treated with 50 nM ROT, OWH slices were preserved at 2h and 24h in RNALater buffer for RNA isolation. The 2h time point aligns with the end of the MPT experimental window. Healthy unexposed OWH slices were controls. We measured expression of genes associated with ECM composition and remodeling including tenascin-R, aggrecan, neurocan, MMP9, and TIMP1; markers associated with cellular activation including Ki67, Cd45, Cd11B, and GFAP; inflammation markers including IL-1β, IL-4, IL-6, IL-9, and IL-10; and cell death markers including iNOS, nNOS, TNF-α, and Casp-3. Our results provide a quantitative measure of ECM composition that can be integrated with our MPT and imaging data to better define microstructural dynamics in the stimuli-exposed brain.

Ecological data from the Green River College main campus trails have recently shown a significant increase in fungi observations in recent months compared to previous years. In addition, the diversity of these fungi vary greatly in comparison to previous years, raising concerns of identification errors. This project works to manually sort fungi observed on Green River College into their proper taxonomic groups to observe the species abundance and diversity of September 2023-December 2023 compared to September 2024-December 2024. Results show that, although there were several errors with the initial identification of several species, the abundance, distribution, and variation of fungi had significantly increased in Fall 2024 compared to Fall 2023.

Tuberculosis (TB) remains a major global health challenge, causing over a million deaths annually despite being a curable disease. A critical issue is treatment non-adherence, as many patients struggle to complete the required six-month regimen due to a lack of support and access to reliable medical guidance. Improving treatment adherence can significantly increase recovery rates and save lives. This project develops an AI-augmented chatbot powered by GPT-based models to assist Spanish-speaking TB patients. This is done by providing accurate medical guidance, fostering empathy, and enhancing communication between patients and healthcare providers. Integrated into a Human-System Interaction (HSI) interface, the system employs three AI models: a two-step pipeline that classifies messages as informational or emotional to tailor responses appropriately, a few-shot model that generates responses based on examples from prior patient interactions, and a Retrieval-Augmented Generation (RAG) + few-shot model that retrieves relevant medical information from guidelines while maintaining conversational fluency. These models leverage the same underlying technology as ChatGPT, optimizing responses for accuracy, linguistic fluency, and empathy. As part of the research team, I contributed to model development and implementation, ensuring alignment with medical guidelines and human-centered design principles. The chatbot is currently undergoing external evaluation by a multidisciplinary team, including healthcare professionals specializing in TB treatment and AI researchers. Evaluators interact with the chatbot using personas as TB patients, asking medical and support-related questions to assess response quality. They rate the system based on medical accuracy, linguistic fluency, empathy, and other key criteria relevant to patient-provider communication. Insights from this evaluation will guide future refinements, with the goal of improving AI-driven patient support systems in clinical settings.

Dynamic marine environments require long-term spatiotemporal datasets to successfully monitor and understand patterns in ecosystem composition on a decadal scale. High-resolution photography is often used to compensate for the field logistical constraints associated with marine sites, such as personnel availability or weather conditions, and works well to quickly capture data in the field. However, these photos require extensive manual analysis after the fact. As a research mentee, I asked the question: “Can image annotation with machine learning models provide enough clear data to inform community ecology studies of sessile organisms in subtidal habitats?” Using images collected through transect/quadrat sampling by the Sebens Lab’s Salish Sea Long-term Monitoring Project (University of Washington Biology and Friday Harbor Laboratories), a variation of an open-source model (CoralNet) was trained in the identification of relevant sessile flora and fauna. I then used CoralNet to continue the work of the lab by generating sessile assemblage metrics for a single site in the Friday Harbor Laboratories Biological Preserve. This site included images from transects at two different depths, with sampling from 2014 and 2024. After being uploaded, CoralNet identified 200 random points per image to the lowest possible taxon. I then reviewed all annotations for accuracy and corrected them whenever necessary. This technique greatly reduced the time spent per identification, without sacrificing accuracy. Next, I calculated species richness and Simpson’s Diversity for each quadrat and transect, comparing between depth and year. My analysis showed significant increases in both metrics from 2014 to 2024 and no significant differences between depths, demonstrating a successful report on the dynamics of a subtidal marine community. Application of this method to the entire existing dataset (7 sites, 63 transects per year), and others, provides opportunities to streamline analysis of sessile community composition.

Cervical spinal cord injuries (SCIs) often result in impaired locomotion and forelimb mobility. Assessed with a forelimb locomotor scale (FLS), previous research demonstrated improved forelimb locomotion with task-specific physical therapy (PT) training following a unilateral 150 kdyne C6 SCI in a rat model. Improvement in locomotion was calculated using a recovery ratio, which measures the difference in FLS scores normalized to the animal’s baseline score. There was a significant improvement in the recovery ratio (3dpi-14wpi) for animals that underwent task-specific PT training (p ≤ 0.0014). The underlying molecular mechanisms behind this improvement are still unclear. A potential explanation for these functional changes is the task-specific PT-induced increase in brain-derived neurotrophic factor (BDNF) targeted at the injury site. Task-specific PT stimulates neurons, microglia, and astrocytes to release BDNF, promoting neuron survival, growth, and synaptic plasticity. These processes are crucial for mediating the effects of cervical SCI trauma. This study investigates whether BDNF expression in the spinal cord varies in rats that underwent task-specific PT training following cervical SCI. PT-trained rats are hypothesized to have increased BDNF within the spinal cord, especially proximal to the injury site, which would help mitigate SCI trauma and enhance forelimb locomotion and mobility. To this end, we performed immunohistochemistry staining and quantification of BDNF in the spinal cord and compared it across three groups: PT + SCI, SCI-only, and Sham. The expression levels of BDNF in neuronal cells, astrocytes, and microglia were then correlated with their FLS scores to determine if there was a positive correlation between BDNF expression and forelimb locomotion. This would indicate that BDNF supports synaptic plasticity and recovery from SCI-induced trauma.

Accurately describing a child’s language skills is difficult, but identifying children with atypical language development adds even more complexity. In an ordinary language assessment session, a Speech-Language Pathologist (SLP) will use both standardized, norm-referenced assessments and non-standardized assessments, like Language Sample Analysis (LSA). However, there is little research about how these different assessments relate to one another. To better understand this relationship, the language abilities of children (n=38) were assessed after turning 6-years-old and attending Kindergarten by SLPs using the following norm-referenced tests: a sound-in-words subtest from the Goldman-Fristoe Test of Articulation, 3rd Ed. (GFTA-3); core language subtests from the Clinical Evaluation of Language Fundamentals, 5th Ed. (CELF-5); and a nonverbal IQ subtest from the Kaufman Brief Intelligence Test, 2nd Ed. (KBIT-2). Then, a 10- to 20-minute language sample of the child’s spontaneous speech was collected for analysis. This project extends from previous research by including participants beyond clinical populations and using multiple sampling contexts to holistically capture the child’s naturalistic speech. I transcribed each language sample with Codes for Human Analysis of Transcripts (CHAT) and utilized Computerized Language Analysis (CLAN) software to automatically compute measures reflecting language skills from the language samples. I will conduct correlational analyses to inspect the associations between measures from norm-referenced tests and measures extracted from language samples. I expect to see significantly positive correlations between several CELF-5 measures and LSA measures of morphosyntactic development (i.e., grammar) that demonstrate a convergence between these two methods of assessment. Correlations between LSA measures and GFTA-3 measures are expected as well but to a lesser degree of association because they do not index identical elements of language. Overall, relationships discovered during this process will lend themselves to further understanding the information we gain from these common tools of language assessment.

The identification of synergistic drug combinations remains a significant challenge in oncology due to the large amount of existing drugs and complex interactions between these drugs. In this work, we propose an active learning framework applied to the NCI ALMANAC dataset to efficiently uncover promising drug pairs that conventional screening methods might overlook due to lack of time and resources to handle these nearly countless combinations. Building on established greedy sampling strategies—such as GSx, which selects samples based on maximal minimum distance in the input space, and GSy, which focuses on output diversity—we introduce modifications to potentially enhance sample selection diversity and predictive performance. First, we explore replacing the traditional greatest minimum distance criterion with a greatest average distance metric, hypothesizing that this adjustment captures the overall variability in the data differently than the traditional method. Second, we redefine the improved greedy sampling (iGS) approach by standardizing the distance metrics from both the input (GSx) and output (GSy) spaces using Z-score normalization (or alternative standardization methods) prior to their aggregation, rather than combining them multiplicatively. We conduct a comprehensive comparative analysis against traditional methods to evaluate improvements in model convergence, prediction accuracy, and the ability to identify rare but potent drug combinations. We also explore other active learning strategies as Query By Committee (QBC) and others. Our preliminary findings suggest that these tailored active learning techniques offer a promising pathway toward more efficient and insightful exploration of high-dimensional drug interaction landscapes.

Dementia, a growing global health concern, affects the nervous system and leads to severe cognitive impairment, with Alzheimer’s disease (AD) being the most common form, currently impacting nearly 7 million Americans. As life expectancy increases, the prevalence of dementia increases in corresponding fashion, driving research efforts like those of the Darvas Lab, where we study AD and other related dementias using adeno-associated viruses (AAVs) to induce neuropathologic changes. The TDP43 protein is involved in neuropathologic changes such as those in Frontotemporal Dementia (FTD) and in Amyotrophic Lateral Sclerosis (ALS), a primary motor neuron disorder. TDP43, primarily localized in the nucleus, plays a crucial role in regulating gene expression and RNA metabolism. TDP43 pathology in neurons involves the presence of TDP43 in the cytoplasm and its accumulation in cytoplasmic inclusions. To better understand the role of TDP43 in neurodegeneration, we use a mouse model where TDP43 proteins are introduced via AAV, a genetically engineered viral vector commonly used in research. This approach allows control over the timing of neuropathologic changes. Our prior AAV constructs included the Synapsin I promoter, which led to a severe ALS-like motor phenotype due to its expression in spinal motor neurons. However, this model could not be used to study the more subtle effects of dementia due to the extreme nature of the physical pathology. Therefore, our goal is to produce a new model to overexpress TDP43 using an AAV that is exclusive to the cortical brain regions relevant to FTD by instead including the CamKIIα promoter, which exclusively drives expression in the forebrain. I assessed behavioral phenotypes in our mouse model by conducting a Y-maze to evaluate effects on short-term memory, and analyzing neurological scoring to evaluate neuromuscular dysfunction. The development of a more dementia-focused TDP43 model will allow us to more specifically investigate its neuropathology.

The stimulation of the genioglossus muscle may prevent upper airway collapse in breathing disorders such as obstructive sleep apnea (OSA). Thus, the present study was to analyze the 3D-changes of the tongue base by electric stimulation of genioglossal muscle in relation to volumetric alterations of the tongue base in minipigs. Twenty 8-to-9-month-old Yucatan minipigs were used. Of them, 8 were controls, and 12 were experimental. Each experimental same-sex sibling pair was randomly assigned: 1. Normal-weight having surgical tongue base volumetric reduction. 2. Enlargement having significant obesity, BMI>50. All minipigs received surgical implantation of eight 2mm ultrasonic crystals in a cubic-shaped array in the tongue base. The distance change between each crystal pair indicated dimensional deformations for lengths, widths, and thicknesses responding to the stimulation. Increased distances indicated elongations while decreased indicated shortenings. Stimulations to the left genioglossal muscle were ramping up in range of 10-40V to reach the maximal amplitudes (tetany). Stimulation of the genioglossus muscle in controls induced left lengthening, anterior thickening and overall widening along with posterior thinning and right shortening. In contrast, the reduction group showed thickening and widening with left lengthening and minor right shortening. Elongations in the reduction group were larger than those in the control group (p<0.05). The enlargement group showed decreased dorso-ventral lengths compared to those of the control and reduction groups (p<0.05), along with antero-posterior thickening and widening. Stimulation of the genioglossus muscle induces distinctive deformational patterns between the normal and volumetric-altered tongue bases. For instance, shortening in length in the enlarged tongue due to obesity may suggest retraction of the tongue base inducing narrowing of the oropharyngeal airway. These results may contribute to understanding kinematic adaptations in the respiratory dynamics in relation to the volumetric alterations of the tongue base, a current approach to treat moderate and severe OSA. 

This research study explores the evolutionary adaptations of the TLR7 protein receptor in primates in relation to Flavivirus (Yellow Fever) recognition. TLR7, an important receptor in the immune system, is essential for recognizing single stranded RNA viruses such as Flavivirus. Given the growing prevalence of Yellow Fever in tropical climates, I hope to understand how environmental factors shape immune response. I hypothesize that ecological niches, particularly wet vs dry climates, play a crucial role in the evolution of the TLR7 receptor among primate species. Since Yellow Fever is transmitted by mosquitoes, which thrive in wet climates, these environments are likely driving the transmission of the virus. As a result, wet climates may exert selective pressure on the evolution of TLR7 to enhance immune responses against Yellow Fever in regions where mosquitoes are prevalent. To conduct comparisons of the TLR7 receptors, I will be running Blast, a bioinformatics software that compares genomic sequences across different species. This tool will allow for identification of both conserved and divergent regions in the TLR7 sequences from primate species, including humans, that inhabit wet and dry climates. These variations could reveal evolutionary adaptations influenced by ecological pressures. Through these sequence comparisons, I aim to explore how differences in TLR7 might affect susceptibility to Yellow Fever and other similar viral infections. Understanding how ecological conditions shape immune receptor evolution could also improve our ability to predict how different populations might respond to emerging infectious diseases.

Global interest in and demand for macroalgae farms has increased due to growing interest in seaweeds as food, biofuel, a possible source for carbon sequestration, and an economic asset for small island communities. However, the presence of farms can negatively impact marine mammals, with risks including entanglement, habitat exclusion, and behavioral changes. In this study, we conducted passive acoustic monitoring over three years (2021-2024) in developing macroalgae 5-line and catenary farms at Romero and Media Luna reefs off the southwest coast near La Parguera, Puerto Rico, to assess the long-term effect on bottlenose dolphin (Tursiops truncatus) movement and behavior in the region. Detections were automated using PAMguard software and manually confirmed with visual validation by trained acousticians. We observe higher interaction with farms at dawn and dusk, which corresponds with the crepuscular nature of T. truncatus. To date, we observe no entanglements, and our models indicate no significant long-term effect on the local bottlenose dolphins at low macroalgae biomass. As biomass increases, this may change. This research highlights the important trade-offs between economic development and conservation and the promise of passive acoustic monitoring as an effective, data-rich tool for managers. 

Microglia are innate immune cells in the brain that play an important role in maintaining homeostasis, carrying out immune surveillance, and modulating synaptic plasticity. Through the secretion of cytokines, along with physical functions like synaptic pruning and network refinement via phagocytosis, microglia support the health of neurons and help establish a functional neuronal network. In previous experiments, our lab demonstrated that when cultured with microglia, neurons exhibit more robust morphology and greater synaptic activity. However, it remained unclear whether the beneficial effects of microglia on neurons occur during physical contact between the two cell types, or if the supportive factors secreted by microglia are sufficient to drive this change. To investigate this, I compared the morphology and function of neurons directly co-cultured with microglia, to neurons treated with media conditioned by microglia. In the microglia-conditioned media treatment, I conditioned the microglia media for 24, 48, and 72 hours prior to treating the neurons to determine the optimal conditions for establishing a healthy neuronal environment. To evaluate these results, I conducted immunofluorescence staining for microtubule-associated protein tau (MAPT) and microtubule-associated protein 2 (MAP2), both of which are indicators of neuronal health. I analyzed fluorescence intensity and neurite length to quantify morphological differences in neurons between conditions. To investigate differences in synaptic activity, I carried out micro-electrode array recordings of neurons in each condition. Using data from these recordings, I analyzed the coordinated and overall electrical activity to measure the functionality of the synaptic network in each condition. Given that microglia perform both secretory and physical functions, I expected that neurons directly co-cultured with microglia would exhibit more robust phenotypic and functional characteristics. These experiments provide insight into healthy neuron-microglia interactions and reveal possible avenues towards their dysregulation in Alzheimer’s disease (AD), potentially guiding the development of therapeutics targeting such interactions.

Surf smelt (Hypomesus pretiosus) are ecologically and culturally important forage fishes that rely on intertidal beach habitat for spawning. However, the combined effects of rising sea level and human modification (e.g. seawalls, bulkheads, riprap) have put this habitat at risk of coastal squeezing, which could reduce available spawning areas along Puget Sound. This research aims to assess the vulnerability of surf smelt spawning beaches to climate change by combining field data collection with quantitative analysis. We evaluated existing risk assessment methods, such as the Coastal Vulnerability Index (CVI) to determine its applicability to Puget Sound. Additionally, we conducted beach surveys at productive spawning beaches to characterize the beach morphology. Our morphodynamic analysis included measurements of beach slope, sediment composition, pH, and water table depth from the high tide line to the waterline. Our hypothesis suggests that spawning beaches with a lower slope, smaller sediments, and a shallow water table will be more resilient to climate change impacts. Findings from this study will improve our understanding of climate-driven and anthropogenic threats to intertidal ecosystems and provide insight into habitat resilience, supporting conservation efforts for surf smelt populations.

The aim of this study was to examine the respiratory 3D deformational changes in the tongue base with normal weight and obesity in a minipig model. This study included 6 same-sex sibling pairs (3 pairs each sex) of Yucatan minipigs 8-to-9 months old. Of each pair, one minipig was normal weight with a BMI<35 and the other was fed a special diet reaching a BMI>50 (obese,). While under sedation, eight 2mm ultrasonic piezoelectric crystals with an extended skin button attached to the back were surgically implanted at the base of the tongue in a cubic-shaped arrangement. These crystals represented dorsoventral lengths, anteroposterior widths, and thicknesses. The 3D deformational changes of the tongue base were recorded during respiration using a Sonometric system together with synchronized electromyography and airflow recordings to identify respiratory phases. The amplitudes and durations of each dimensional change within the crystal-defined region concerning inspiration were calculated for 5- consecutive respiratory cycles per minipig. The total respiratory cycle duration was 1.87±0.38s in the normal-weight group and 3.2±1.01s in the obese group (p<0.05).  Similarly, the durations of the inspiratory phase in the normal and obese groups were 0.62±0.36s and 1.19±0.77s respectively (p<0.05). Deformational changes in the normal-weighted group included dorsoventral lengthening, anteroposterior ventral widening with dorsal shortening, and thickening in all dimensions. In contrast, the obese group showed dorsal lengthening with ventral shortening, widening in all dimensions, and anterior thickening with posterior shortening. Overall, larger dynamics were observed in the normal-weighted group compared to the obese group (p<0.05). These results demonstrate that obesity affects tongue base respiratory kinematics, with longer respiratory cycles and decreased deformational changes mainly ventrally and posteriorly. These findings enhance understanding of obesity's impact on the oropharyngeal function, with implications for breathing disorders.

Mycobacterium abscessus is a non-tuberculous mycobacterial (NTM) species that causes severe pulmonary infections, particularly in immunocompromised patients and those with preexisting lung diseases such as cystic fibrosis. Treating M. abscessus infections is challenging due to its intrinsic antibiotic tolerance and capacity to develop multidrug resistance. To identify novel molecules that can target this pathogen and enhance current treatments, we screened a library of FDA-approved drugs (n = 2,400). Our data shows that Netupitant, a drug commonly used to prevent chemotherapy-induced nausea and vomiting, exhibits potent antibacterial activity against a broad range of M. abscessus clinical isolates, including multidrug-resistant strains, with a minimum inhibitory concentration (MIC) ranging from 4 to 16 µg/mL. Furthermore, in combination with amikacin, a standard treatment for M. abscessus infections, Netupitant demonstrated strong synergistic interactions, as confirmed by checkerboard microdilution and time-kill assays. These findings highlight Netupitant’s potential as a novel therapeutic option for M. abscessus, particularly in combination with existing antibiotics. Future studies exploring its mechanism of action and in vivo efficacy could further advance antibacterial drug discovery for difficult-to-treat NTM infections.

On May 19, 2015, President Obama released the "National Strategy to Promote the Health of Honey Bees and Other Pollinators" to reduce pollinators' mortality rates when overwintering. This plan compelled honeybee researchers to search for trends in honey bee hives that did not survive the winter. The Varroa mite was one of the main focuses of this strategy as it has been shown to kill hives in the past. Here in the Puget Sound region, the Green River College Honeybees program verified that Puget Sound beekeepers face the same problems with Varroa; I joined the team in 2024. Given that Varroa has been problematic since the late 1980s, we wanted to research for another strategy. Managing honeybee colonies for Varroa infestations can improve survivability of honeybee colonies, but we had no information about how it affects honey production. In order to see the impact that different mite treatments had on a hive's honey production, we measured the hive's weight prior to treatment, along with the percentage of mites found in the hive. Here, we present data that demonstrates that if managed properly, not only can Varroa infestations be reduced, but honey production can be increased. What we did not expect, was that some treatments negatively affect honey production. This new methodology should provide more motivation for beekeepers to not only manage differently, but also work more collaboratively to prevent Varroa infestations from spreading. 

Menopause is a significant life transition that is experienced differently across cultures, with each cultural background shaping unique beliefs, expectations, and responses to menopausal symptoms. Among Somali and Indonesian older adults with a uterus, cultural factors play a particularly influential role in shaping the menopause experience, potentially affecting symptom recognition, coping strategies, and interaction with healthcare providers. The purpose of this qualitative study is to 1) explore menopausal symptoms, perceptions, beliefs, and experiences of aging and menopause among Somali and Indonesian older adults, and 2) examine how cultural factors shape their understanding of menopause, as well as how they interpret and manage the symptoms associated with this stage of life. We conducted a cross-sectional qualitative study using semi-structured interviews with 5 participants with a uterus: 2 Somali and 3 Indonesian individuals. We recruited participants through community networks within Somali and Indonesian populations living in Washington state. We included individuals who are 1) 60 years or older and 2) undergoing or have gone through menopause. We chose older adults for their reflective perspective, offering holistic insight into the long-term impact of menopause and their ability to share cultural wisdom and experiences. Our findings will inform healthcare providers in delivering culturally sensitive care to support individuals going through menopause in these communities. Additionally, this knowledge can inform the development of targeted interventions and educational tools that help bridge cultural gaps in menopause understanding, thereby promoting holistic, culturally sensitive, and inclusive care for older adults with menopausal symptoms in these communities. Addressing these deficits can lead to improved care for Somali and Indonesian adults with a uterus while also benefiting women more broadly by promoting a more comprehensive and inclusive approach to menopause support.

Relative Risk (RR) is a highly interpretable parameter in epidemiology and biostatistics, based on both binary input and outcome. It is frequently used in vaccine development to measure the relative efficacy between two treatment groups.
Researchers are often tempted to use generalized linear models (GLMs) to estimate the logarithmic RR with respect to a set of baseline covariates. However, this approach has inherent flaws, as GLMs do not account for variation dependence in Relative Risk on its nuisance parameters. Richardson et al. have developed an unconstrained and variation-independent doubly robust nuisance model using the log Odds Product (OP).
To expand on this work, we will explore alternative nuisance models—both those developed by us and those from other researchers—and compare their computational robustness to that of the log Odds Product (OP).
Additionally, using the brm R package (which streamlines the methods proposed by Richardson et al.), we will analyze a dataset where Relative Risk serves as the target of inference and compare these results to those obtained using regression methods.

Sound is a vibration that is created by an oscillating object and travels in periodic waves of pressure through a medium. Sound waves are characterized by properties such as frequency, amplitude, wavelength, and speed. The purpose of my research was to measure the effects the lower temperature and air pressure present in the stratosphere have on the properties of sound. To conduct this research I custom-designed an Arduino based sensor with a barometer and thermometer that was then attached to a weather balloon. The sensor also had a buzzer that repeated a tone at constant intervals along with a microphone that measured the amplitude of sound across various frequencies as it was necessary to consider the impact that the high wind speeds present in the stratosphere would have on the measurements. As the air becomes colder and less dense it also becomes less elastic causing it to transfer energy less efficiently which in turn leads to a decrease in amplitude. Frequency, however, did not change as it is determined by the source of the sound and does not depend on the properties of the medium. Understanding how changes in the properties of the medium affect the properties of sound opens a path to using sound to illuminate the properties of the medium. Additionally, broadening our understanding of how various atmospheric conditions present on our own planet affect the properties of sound deepens our understanding of how the various atmospheric conditions present on other planets will impact the properties of sound.

Europium (Eu) is a redox-sensitive rare earth element (REE). Eu stable isotopes are promising tracers across different scientific domains, giving quantitative insight to the processes where Eu anomalies are present. Studies on Eu isotopes remain scarce as the chemical separation of Eu from other REEs is challenging due to their geochemical similarities, as well as low concentration of Eu in standard geological materials . Recent development of a high-yield (99.4%) and low blanks (<20 pg, Wu et al., 2024) Eu purification scheme from geological materials using cation exchange resin and extraction chromatographic resin allows for an effective approach to better characterize Eu isotope compositions in various materials. We aim to investigate this method of purification and instrumental analysis technique to obtain  δ 153/151Eu values with a multicollector-inductively coupled plasma-mass spectrometry (MC-ICPMS) instrument. To achieve this, we will replicate the purification protocol established by Wu et al. (2024) with synthetic solutions and digested geological reference materials (GRMs), monitoring the relative intensity of Eu and other matrix elements. We collect pre- and postcut fractions of samples to determine the Eu yields and potential contamination from other elements using MC-ICPMS. To correct instrumental mass bias, Wu et al. (2024) used combined standard-sample-bracketing-internal-normalization method, with internal normalization using Nd and standard reference material NIST 3117a as the bracketing standard. Building on the protocol by Wu et al. (2024), we will additionally investigate the effect of column geometry, acid molarity, as well as instrumental analysis without element doping on yield and precision. The validation of the method used for accurate and precise Eu isotope analysis allows for increased applications of Eu isotope geochemistry.

In the paper "Planting Undetectable Backdoors in Machine Learning Models" by Goldwasser et al (arXiv:2204:06974), the authors establish the notion of "black-box undetectability" for machine learning models and prove it in many cases. This is a backdoor that is undetectable by merely looking at inputs and outputs of the model. The paper also introduces the concept of "white-box undetectability."  We aim to consider this stronger notion and outline how even with the knowledge of entire model weights, there may be undetectable backdoors in a model. More specifically, we establish an idea where one takes an innocuous model (say a Multi-Layer-Perceptron model) and enlarges it by adding "dummy" edges and using appropriate non-linear activation functions to effectively place a backdoor in the model. In our project, we establish a proof of concept by backdooring an MNIST classifier.

Carpenter syndrome is a congenital disorder mainly characterized by craniosynostosis – soft spots of the skull fuse prematurely resulting in skull elongation. MEGF8, a protein in the MEGF8-MGRN1-MOSMO (MMM) regulatory complex involved in Hedgehog (Hh) signaling, has been previously linked to Carpenter syndrome. Hh signaling, a core developmental pathway, plays many roles in skull development, including functioning as a guidance cue for cranial neural crest cells (foundational cells for skull bones) and regulating bone ossification (bone hardening). Despite the previous research linking MEGF8 and anomalous skull development, the role of the MMM complex and Hh signaling in skull development and the mechanism behind this abnormal skull development is still widely unknown. I’m exploring the mechanism by which elevated Hh signaling influences cell fates during the development of skull structures. I investigated a whole-embryo knockout mouse model to identify regions where overexpression of Hh correlates to abnormal skull phenotypes. I explored and measured these phenotypes via imaging a genetic Hedgehog reporter mouse line and skeletal stained embryos of various ages. These knockout mice were embryonic lethal because of a congenital heart defect associated with loss of Hh. We introduced an inducible Cre to conditionally knockout the MMM complex at a later age, avoiding heart defects. My findings identified the interparietal and parietal regions of the skull as areas of interest, visualized by over-ossification and lack of defined structural boundaries- nasal and palatal development was normally observed. These findings suggest that elevated Hh signals result in abnormal development of skull structures, similar to craniosynostosis, and are involved in intramembranous ossification (skull structures) rather than endochondral ossification (nasal/palate). From these findings, I’m investigating how Hh signaling plays a role in skull development and intramembranous ossification.

Cytochrome P450 enzymes (CYPs) are a family of proteins that play an integral part in drug metabolism. An example is CYP3A4, a specialized protein within the CYP family, involved in the oxidation of small drugs and toxins, like cannabinoids, to allow for their removal from the body. Understanding this reaction is important in evaluating how different expression levels of CYP3A4 in different individuals affect the efficiency of drug metabolism. In this project, I studied drug binding to recombinant, purified, CYP3A4 protein. The binding assays of CYP3A4 allow evaluation of the quality of the purified protein. Ultraviolet-visible spectroscopy (UV-Vis) was used to quantify the protein, and spectral binding through drug titration was used to characterize the binding affinities of different substrates. Drug titration enables us to observe the amount of ligand bound to the protein at various concentrations, displayed as a binding curve from which we can determine the spectral binding constant (Ks). The CYP active site contains a heme group. Upon binding, the ligand replaces the water molecule that is originally docked in the active site. This transfer reaction shifts the heme spin state and appears on the UV-Vis spectra as an increasing absorbance at the 380 nm wavelength and a decreasing absorbance at 420 nm. Inhibitors would have the reverse spectrum. In vitro studies with purified protein have several benefits when investigating protein function, such as simplifying the experimental system and reducing the limitations of complicated sample preparations from living organisms. Having a well-defined assay to determine recombinant 3A4 protein quality will contribute to the value of further in vitro activity and pharmacokinetic studies with this protein. 

As Cannabis use is becoming more widespread there is growing concern regarding the respiratory exposures of employees working in indoor cannabis processing facilities. Employees in these occupational settings are frequently exposed to volatile organic compounds (VOCs), particulate matter (PM), other respiratory irritants, and allergic sensitizers. These exposures are linked to work related illness and disease, such as occupational asthma. Notably, a fatality, in 2022, in a Cannabis worker due to occupational asthma highlights the urgent need for improved exposure controls. Cannabis processing workers experience prolonged and frequent exposure via inhalation with little knowledge on the respiratory hazards of this work. This study aims to evaluate the efficacy of a local exhaust ventilation (LEV) system to reduce exposure to airborne hazards during automated joint filling. Automated joint filling is a common process in Cannabis production facilities, using mechanized equipment pre-ground material is dispensed into pre-rolled cones. This method is preferred in the field as it increases both consistency and efficiency. Over a ~2-hour sampling period across eight batches of pre-rolled joints, we conducted gravimetric sampling for inhalable PM using two inhalable aerosol samplers (IOMs) positioned at the workbench and in the breathing zone. VOC exposure was assessed using thermal desorption tubes and photoionization detectors (PIDs), while continuous respirable PM concentrations were measured using a Nanozen DustCount monitor. Testing air concentration for PM and VOCs with and without the LEV mechanism is being conducted to determine its effectiveness at reducing exposure. We hypothesize that this may be an effective solution, as the LEV has controlled these agents significantly in other similar workplace settings. As this field grows due to recent state by state legalization of Cannabis, these findings hold great impact for workplace safety regulation and solutions. Additional research should be gathered on long-term exposure effects and preventive mechanisms.

Indium phosphide (InP) quantum dots are a high-performing semiconductor material used in optoelectronic applications due to their tunable electronic properties and low toxicity compared to cadmium-based quantum dots. However, InP quantum dots are currently synthesized at or above 180°C because of the high energy input required for nucleation and growth of the covalent nanocrystals. This study explores the synthesis of small InP clusters at lower temperatures by investigating reaction conditions that can produce InP with reduced energy consumption. Using the precursors indium carboxylate and P(SiMe₃)₃ in a nonpolar solvent toluene, we systematically investigate the evolution of InP clusters at room temperature and 60°C via UV-Vis absorbance spectroscopy. The formation of atomically precise InP clusters was observed at room temperature after 23 days. To speed up the reaction, we investigate adding a polar aprotic solvent or amines to promote the formation of InP at low temperatures. Including 20% of N-Methylpyrrolidone in the solvent mixture with toluene allows InP to be formed in 2 hours. Amine additives interact with the indium cations to modulate their reactivity, therefore we investigate adding varying equivalents both to the pre-formed atomically precise cluster, and to the indium and phosphorous precursors in toluene. We found that adding up to 100 equivalents of benzylamine per cluster did not promote the growth of InP clusters. Our findings contribute to the understanding of how InP forms at low temperatures for scalable, environmentally friendly production.

The increasing concern over global warming has driven interest in clean energy solutions, with piezoelectricity emerging as a promising alternative. Piezoelectric materials generate electric voltage under external mechanical forces, offering an innovative method for energy harvesting. This work derives a system of partial differential equations (PDEs) and their accompanying boundary conditions that describe the coupled elastic-electric behavior of an Euler-Bernoulli piezoelectric beam. Under the quasi-static approximation for the electrical field, the assumptions of Euler-Bernoulli beam theory, and the constitutive relations for the 3-1 piezoelectric coupling mode (i.e., voltage is generated in a direction perpendicular to external mechanical force), we develop a Hamilton’s variational principle to derive the governing equations and boundary conditions for the piezoelectric Euler-Bernoulli beam. The obtained equations consist of Gauss’s law of electrostatics and the Euler-Bernoulli beam equation that are coupled due to the piezoelectric effect: apparent electric charges that depend on elastic deflection appear in Gauss’s law, while apparent mechanical forces and moments that depend on the electric potential appear in the Euler-Bernoulli beam equation and its boundary conditions. The derivation from first principles, as well as the study of the governing equations constitutes a fundamental framework for analyzing piezoelectric beam behavior, with implications to the improvement of design of piezoelectric energy harvesters.

Glaciers have long been used as the bellwethers of climate change, given their ability to store gases, dust, microbes, and other environmental materials in their layers; tracking their recession has also been an important visual indicator of climate change. In this research, I examine how anions in newly exposed vary with depth. To do this, I took samples from exposed vertical ice faces on the Coleman glacier, on the north face of Mount Baker. Samples were thawed and analyzed using ion chromatography.  Trace amounts of chloride, nitrate, sulfate, and phosphate were found in each sample. The ion concentrations showed no trend with depth, and the ice itself appeared uniform. This is in contrast from vertical cores taken from solid ice in numerous other surveys, which show distinct annual layers and variation. This suggests that the ice at vertical faces has different properties from that at the top layers, including in its ability to trap environmental markers. Further research is needed to confirm this difference and examine which of these markers is most affected. Increased understanding of these markers could give more insight into how glaciers change over time and interact with their environment.

Multidrug-resistant cancers is responsible for over 90% of the metastatic cancer deaths which show enhanced drug transportation. Our group wanted to know how the acquired drug resistance impacts the flow of the MDR drug class, (Imidazoquinolinone, IMQ) by P-Glycoprotein (transporter protein in helping transport the drug). The experiments were performed by using melanoma cancer cell lines, prostate cells, and mouse genomes as the basis for observation. The cells were then introduced to three derivatives of IMQ, called Imiquimod (IMQ), Resiquimod (RSQ), and Gardiquimod (GDQ). The findings we hope to see were how effective each derivate of IMQ were in transport, hindering cell replication, and rhodamine concentration (compound dye in the cells to see how much of the drug is in the cells) with GDQ expected to have the lowest effect of drug resistance. The future of small molecular immunotherapy prodrugs heavily depends on the research and investigation of candidate compound classes and its derivatives to make sure that it is safe, effective, and the overall quality for the patients.

Dense-core vesicles are membrane-bound structures that carry neuromodulators such as insulin, dopamine, and serotonin. The peptides within dense-core vesicles are initially larger precursor proteins that undergo enzymatic processing to achieve their functional forms. During the defecation motor program in Caenorhabditis elegans, dense-core vesicles released from the intestine harbor neuropeptides that trigger neurons which activate enteric muscles, promoting the act of defecation. Failure of certain proneuropeptides to mature into neuropeptides results in decreased frequency of defecations. CPD-1, a conserved transmembrane carboxypeptidase, is a poorly understood processing enzyme that affects the defecation motor program. I built on our knowledge of EGL-21, another carboxypeptidase known to process neuropeptides and peptide hormones, to better understand CPD-1’s function. I show here that these two carboxypeptidases, EGL-21 and CPD-1, process neuropeptides necessary for successful defecation patterns. Mutants lacking egl-21 had decreased defecation frequency while worms lacking both egl-21 and cpd-1 had an even lower defecation frequency. Additionally, my results show that CPD-1 is expressed in intestinal cells and can compensate for EGL-21’s function. Finally, I am conducting experiments to determine whether one of CPD-1’s targets is NLP-40, an important neuro-like peptide released from the intestine that regulates defecation. These results contribute to our broader knowledge of peptide processing in dense-core vesicles.

This project seeks to investigate the viability of a multi-channel grating coupler (GC) as an approach for individual ion addressing in ion-trap architectures. A multi-channel design is desirable because it allows for one GC to be used for controllable, individual addressing of many ions. Current approaches for ion addressing include bulky optical systems or single channel GCs which both have notable shortcomings. Optical arrays employing large lens and laser systems require complex, error-sensitive setups, challenging the scalability of those systems. Single channel GCs reduce the complexity and footprint of the optical setup, but they are unsuitable for individual addressing of ions within a chain. Single channel GCs provide the ability to globally address N ions using one integrated structure, or individually address N ions using N integrated structures. Both of these solutions are not optimal as global addressing lacks the specificity required for complex quantum operations, and using one grating structure per ion entails a massive footprint for large ion chains, much larger than the chain itself. A multi-channel GC allows many ions to be individually addressed by one compact integrated structure and, with optimization, multi-channel GCs can achieve high coupling efficiencies and low insertion losses, allowing for accurate and reliable addressing of ions. To design a multi-channel GC for this purpose, we first develop an idealized analytical model by deriving the relationship between the incident angle of guided light into a grating structure and the output angle of diffracted light into free space. Using this analytical model, a conceptual design for a multi-channel GC is formulated. Finally, the GC design is optimized using finite difference time domain (FDTD) simulation software. We will present the results of our idealized analytical model and results from optimization of a full FDTD simulation of our structure.

The hearing aid experience is not a one-size-fits-all situation. Rather, each hearing aid user and their environment is unique. This project aimed to customize the listening experience of hearing aid users by reconstructing daily sound scenes based on real-world data during hearing aid fine-tuning. Older adults with mild to severe hearing loss were recruited and randomly assigned to the experimental or control group. All participants were fitted and sent home with hearing aids for an initial field trial of two weeks. During this period, they were instructed to collect information on the sound scenes that they identified as most important to their communication needs, including communication intent, listening effort, and acoustic recordings of the scenes. Following the initial field trial, participants were invited back for hearing aid fine-tuning. Participants in the experimental group conducted self-directed adjustment of their hearing aid gain for the individualized sound scenes reconstructed in the lab based on the audio recordings collected during the initial field trial. In contrast, participants in the control group made adjustments in two non-individualized, generic acoustic environments. Following fine-tuning, the participants were sent out again for three weeks, before returning for final outcome assessments. These included speech recognition performance in background noise and questionnaires on the subjective benefits of the hearing aids. For my role, I conducted detailed analyses of the survey data collected during the two field trials and the final outcome questionnaire results. Additionally, I managed the equipment inventory to support the field trials. It is anticipated that the experimental group will demonstrate greater clinical outcomes based on speech recognition testing and subjective questionnaires than the control group. If this is confirmed, it would provide the first evidence for leveraging real-world data in individualized hearing aid fine-tuning.

Most human activities engage multiple brain regions simultaneously, but our ability to study this is limited by our capability to run experiments. Electrophysiology is the data-collecting technique of placing electrode probes into the brain to record the electrical activity of neurons. Currently, researchers performing electrophysiology use one or two probes. However, to record activity across many regions, researchers must use multiple probes which introduce new kinds of challenges such as ensuring accurate and reproducible positioning of several probes to target specific areas in the brain, managing probe movements to avoid collisions with each other, and preventing probes from breaking during insertion. Brain-wide coverage will require five, ten, or more probes, amplifying the challenges researchers face with just one or two probes at a time. Over the past two years, I have been developing an automation platform that can solve these challenges in electrophysiology. A key innovation is the integration of a computer-vision-based probe tracking system being developed in collaboration with the Allen Institute. This probe tracking system ensures probes can be accurately positioned on brain regions repeatably and detect when probes fail to insert into the brain, so movements are stopped before damage occurs. The automation platform will also route and manage electrode probes during experiments, preventing collisions with each other and the rig. Together these improvements ensure that electrophysiology experiments can be performed in a reliable, safe, and reproducible manner, but perhaps the biggest improvement the platform provides is efficiency. On average, it takes 15 minutes to insert one probe into the brain, meaning brain-wide experiments using eight probes may need two hours to insert manually, increasing stress on subjects unnecessarily. With automation parallelizing the process, we can reduce insertion times from 15 minutes per probe to 15 minutes flat making brain-wide electrophysiology a viable tool in neuroscience.

Humans have limited ability to regenerate tissue lost from traumatic injury or amputation. Growth factors have the potential to induce the regrowth of damaged tissues, such as bones and joints in a mouse model of digit amputation. However, to achieve this in a clinical setting, a minimally invasive drug delivery system that permits the controlled release of multiple growth factors is needed. To this end, we are using micron-sized, bioactive hydrogels (microgels) to investigate the spatiotemporal release of growth factors in the presence of an external magnet, which helps direct microgels to the wound site. Optimizing the drug release profile requires an understanding of the biophysical properties of the microgels and their surrounding tissue. We hypothesize that the magnetic force needed to translocate a microgel is directly related to its size and stiffness and to the tissue microenvironment’s pore size and stiffness. Meanwhile, the release rate for growth factors is expected to be inversely related to microgel diameter and stiffness. To investigate these hypotheses in silico, we developed two computational finite element (FE) models. First, we used COMSOL Multiphysics to characterize the magnetic force exerted on a microgel by a permanent magnet. Magnetic forces were measured by varying the distances between the microgel and magnet. Second, we used FEBio to model microgel movement through tissue, taking into account how microgel and tissue mechanical properties (e.g., Young’s modulus, Poisson’s ratio) influence translocation. Future work will compare simulation results to in vitro data of microgel translocation and protein release. By using FE analysis to model biomaterial behavior, we will be able to better predict drug dosing at the wound site to induce musculoskeletal tissue regeneration.

Liver fatty acid binding protein (FABP1) is highly expressed in the liver, kidney, and gut and is known for its role in binding endogenous lipids. FABP1 has also been shown to bind drugs and modulate metabolism in the liver. A high frequency single nucleotide polymorphism (SNP T94A) in FABP1 is shown to correlate with nonalcoholic fatty liver disease. We hypothesize that this SNP also affects drug binding. To evaluate drug-FABP1 binding, I measure equilibrium dissociation constants (K_ds) by fluorescent displacement assays for both FABP1 wild-type and T94A using two fluorescent probes, 11-(dansylamino)undecanoic acid (DAUDA) and 8-anilino-1-naphthalenesulfonic acid (ANS). FABP1 has a large binding pocket that can accommodate 2 ligands simultaneously in a ‘high affinity’ and ‘low affinity’ binding site. When DAUDA-FABP1 or ANS-FABP1 are titrated with a drug, a drug-FABP1-probe ternary complex is formed rather than the probe being fully displaced. This complicates data analysis and suggests that endogenous lipids may change the affinity of drugs for FABP1. Therefore, I use multiple fluorescent probes with different binding affinity to obtain drug K_d values. I use singular value decomposition (SVD) to isolate individual fluorescent components from the overall observed fluorescence spectra. I then estimate drug and probe K_ds for FABP1 T94A and T94T by fitting the fluorescent change due to binding to dynamic models in COPASI software. From forward and reverse titrations, DAUDA K_d for FABP1 wild-type was found to be 0.194 µM while ANS binds more weakly (K_d = 1.38 µM). From DAUDA displacement assays, diclofenac was found to have a K_d of 3.90 µM for wild-type FABP1 and 3.78 µM for T94A. I anticipate measurement of K_ds for 8 other drugs using both DAUDA and ANS in the coming months. The developed methods will enable evaluation of FABP1’s role in drug disposition.

The Sensors, Energy, and Automation Lab (SEAL) aims to gamify undergraduate research by instituting a leaderboard, awarding points for tasks, assigning ranks for accomplishments and published papers, and framing research directions as Quests. Individuals receive a character sheet with a health bar, while groups compete against one another in Racetrack- a software for team challenges. Gamification in educational settings is well-studied: gamifying learning can boost students’ motivation, retention, and challenge appraisal. However, research indicates that the efficacy of gamification varies dramatically, particularly personality traits like extraversion, which correlate more positively with success in software with leaderboards. Significant gaps exist in gamification literature; existing research primarily studies gamification in classrooms, not workplaces or research environments. Further, the studies fail to incorporate modern approaches to psychology. The socio-psychological model suggests personalities and behaviors differ depending on the environment, meaning people may exhibit different personality traits in gamified environments. Moreover, gamer motivation, a personality test tailored to predicting player personality with strong correlations to the Big Five (psychological scale for key personality traits), has yet to be tested in gamification studies. By accounting for contemporary psychological theory, SEAL aims to rigorously test the hypothesis that gamification is an effective structure in lab organizations through multi-year longitudinal study on a scale never seen in gamification literature. SEAL’s large cohort and gamified structure offer a perfect platform to analyze the role of demographic and personality type in gamification outcomes. Our preliminary results explored collected qualitative and quantitative data on demographics, gamer motivation personality, and perceptions of the SEAL system by anonymously surveying 81 associates. Our longitudinal study contributes to the growing literature on gamification; a solution potentially improving productivity in research ecosystems.

Societal industrialization and post-industrialization are associated with birth rate reduction. This decline coincides with the increase in accessibility to education, contraception, and employment for people with capacity for pregnancy. In a post-industrial society such as the United States, more people are electing to not parenting. However, an individual’s choice to remain childfree is still deviant from the expected social norms of female-presenting individuals. The mounting stresses of finances, political restrictions of bodily autonomy, and lifestyle lead many individuals to seek community and kinship outside the traditional understanding of family. We aim to describe the experiences and conceptualization of family of cisgender women, a demographic with presumed capacity for pregnancy, as well as a societal expectation of pregnancy and motherhood. Cisgender women of reproductive age, navigate the crux of societal expectation to reproduce while also experiencing factors that disincentivize traditional family-making and the increased accessibility to choose to remain childfree. Existing literature has looked into the reasoning of electing to not parent, however, there is a lack of research into understanding the individual’s schemas about family and their perceptions about their own autonomous decisions. The boundaries of societal expectations of kinship are evolving alongside the societal and political pressures that discourage people from having children. Therefore, we are conducting qualitative semi-structured interviews with cisgender women in Seattle to describe the conceptualization of kinship in a population with reduced barriers to remaining childfree and increased stresses that discourage people from having children. This research will illuminate how they understand and live the paradoxical pressures between the expectation of family-making and their decision not to parent and raise children.

Latine people constitute the largest minority in the US, yet the prevalence of diabetes within the Latine community is nearly twice that of White Americans. Latine populations also experience food insecurity at higher rates than the national average, which heightens their risk for chronic conditions like type 2 diabetes (T2D). While nutritional counseling is critical for T2D care, there is limited research on the barriers to effective counseling, especially for minoritized identities. Understanding how Latine patients relate to counseling and barriers to adherence is an urgent health concern with significant implications for addressing health disparities. This study investigates both micro (e.g., provider pathologization of culturally relevant foods) and macro (e.g., food access) barriers to following nutritional guidance for Latine people with T2D. Previous research in South Asian communities shows providers pathologize culturally relevant foods, leading to poor metabolic control, increased complications, higher healthcare costs, and lower quality of life. Food insecurity exacerbates outcomes, with food-insecure diabetic patients reporting less control over their diets despite understanding dietary requirements. However, these barriers remain unexplored for Latine people with diabetes in the US healthcare context. Through a qualitative study in Greater Seattle, we seek to understand the experiences of Latine people managing T2D by conducting structured interviews on barriers to following nutritional counseling. Content analysis uncovers themes related to micro and macro barriers. We aim to enhance culturally competent healthcare to overcome barriers preventing Latine people with T2D from following nutritional guidance. By amplifying the voices of Latine patients, we can inform providers on more effective ways to interact with this population and develop tailored care plans.

The widespread use of makeup raises concerns about bacterial contamination, which can lead to acne, rashes, pink eye, and staph infections. Despite these risks, hygiene practices in cosmetic use, especially in public settings, are often overlooked. This study investigates bacterial contamination in both personal makeup products and in-store testers to assess potential health risks. Swab samples were collected from used personal cosmetics and store testers at popular beauty retailers, focusing on mascaras, foundation bottles, lipsticks, and sponges. Samples were transferred to nutrient-rich media plates, incubated at 37°C for 24–48 hours, and analyzed through colony-forming unit (CFU) counts and Gram staining for bacterial classification. Preliminary results suggest that store testers contain higher bacterial loads than personal products, emphasizing the need for improved hygiene practices in retail environments. These findings could encourage cosmetic brands and retailers to implement better sanitation protocols, such as stricter single-use applicator policies or improved packaging designs, to limit bacterial contamination and promote safer cosmetic use.

My research project focuses on age-related changes in muscle function. We have previously designed and used novel young and naturally aged in vitro three-dimensional engineered muscle tissues (3D-EMTs) using donated myoblasts from the Study of Muscle, Mobility, and Aging (SOMMA) to investigate this. A question raised in this research is the how closely force measured in 3D-EMTs correlates to in vivo force of intact skeletal muscle. To address this, I stimulated young and aged mice's gastrocnemius muscles to contract (Aurora Instruments) measuring maximum force, contraction/relaxation kinetics, and fatiguability. Mice were then sacrificed and hindlimb muscles dissociated to isolate skeletal muscle myoblasts for cell culture. Myoblasts were amplified and used to generate young and aged rodent 3D-EMT. We tested in vitro 3D-EMT muscle mechanics using a Magnetometric Analyzer for engiNeered Tissue ARRAY (MantARRAY, Curi Bio). In vitro muscle force data was compared to in vivo force data from the same mouse. Results generated by this project helped identify the correlation between in vivo and in vitro force measurements and how they are impacted by age. This study also allowed us to bank multiple cell lines for future high throughput studies to utilize these rodent 3D-EMT models to study the progressive loss of muscle mass and function known as sarcopenia. The results from this project and the cellular models created will be used in the future to investigate potential targets for therapeutic interventions to treat sarcopenia in an ever-expanding aging population.

Plasma, a fluid consisting of highly charged particles, is the single most abundant state of matter in the universe, yet our understanding of its properties remains incomplete. One common method of generating plasma is by inducing a large voltage difference between two charged electrodes in a low-pressure environment, referred to as direct current (DC) plasma. Understanding the relationship between plasma temperature and spectral line intensity as a function of external parameters, such as voltage, pressure, and position, is crucial to optimizing plasma-based processes. This study analyzes these dependencies systematically to help build a further understanding of the spatially dependent properties of DC plasmas. We extract electron temperature from spectroscopic measurements by analyzing line intensities assuming a Maxwell-Boltzmann electron energy distribution. The intensity of spectral lines is related to electron energy via the Boltzmann factor, allowing for temperature determination through a logarithmic plot of intensity ratios versus upper energy levels. By varying voltage and pressure, we identified trends in intensity and temperature, providing insights into plasma behavior. Our results suggest that higher discharge voltages correspond to an increase in electron temperatures, indicating a direct relationship between voltage and temperature. These results provide a greater understanding of plasma-based processes, paving a path toward greater efficiency in applications such as semiconductor manufacturing, surface treatment, and materials processing.

In their books Pihkal and Tihkal, Dr. Alexander and Ann Shulgin describe their experiences ingesting 234 psychoactive compounds, most of them newly synthesized by Dr. Shulgin. The goal of this project is to use natural language processing techniques to map the semantic space of the Shulgins’ qualitative comments and determine what commonalities, if any, exist between compounds of similar molecular structures. I first created a TF-IDF matrix to determine the importance of each word for each compound. I then applied three clustering techniques (k-means, DBSCAN, and affinity propagation) to group compounds based on their meaning and used UMAP after each technique to graph the clusters in two dimensions. Unfortunately, despite attempting different combinations of pre/post processing and hyperparameter tuning, each method resulted in only weakly associated clusters. My next analytical method is using Sentence-BERT modeling to compare the semantic meanings at the sentence level. Since sentences hold more meaning than single words, I anticipate that this technique will differentiate the compounds to a greater extent, therefore leading to more visibly divided clusters. I also have the compounds clustered by similarity in molecular structure and determined the most common words associated within each group. By quantifying the subjective experiences of these psychoactive compounds and mapping them to molecular structures, this knowledge could allow us to synthesize molecules to obtain a desired effect on a patient’s consciousness. This could in turn aid in synthesizing new medications to treat mental health disorders.

Formalization is the process of translating human-written mathematical proofs into a form that can be verified by a computer. A popular tool for this is Lean, a proof assistant that represents proofs as code. However, the process of formalizing proofs in Lean can be slow and time-consuming. Our research explores so-called "autoformalization" strategies, which aim to automate the generation of Lean proofs. We propose a tree-based search framework to formalize mathematical theorems in Lean using Language Models. This approach explores potential proof steps as branches in a tree, using AI models to suggest "tactics" at each node. This has the benefit of avoiding hallucinations by rigorously checking that AI suggestion represent valid Lean code. We employ both Large Language Models such as Claude Sonnet 3.5 and specialized fine-tuned Small Language Models such as Lean-Dojo. We use Pantograph to interact with Lean, leveraging its native support of Monte Carlo tree search. We assemble a small set of simple and medium-difficulty mathematical theorems to benchmark against, called nanoF2F. Additionally, we benchmark our system on the well-established miniF2F benchmark created by OpenAI.

Wildfires are capable of altering landscapes, devastating forests, and communities, and are increasing in frequency and intensity. However, the hazard extends well past the burn phase as burn scars are at high risk for the generation of debris flows and flooding in the days, weeks, and years after a fire. Conconully, WA, experienced severe post-fire debris flows and flooding in 2022 following the 2021 Muckamuck fire. Witnessing the effects of both the fire and the subsequent debris flow on my community motivated me to explore why these events occur, to investigate how they initiate, and help inform future warnings or mitigation strategies to increase resilience in the face of these hazards. Whether these floods and debris flows were initiated by shallow landslides, or storm runoff remains unknown, and could alter how post-fire hazard or evacuation warnings are issued. In this study, we employ geospatial analysis to identify areas affected by the fire and correlate these with the origins of the debris flows and flooding. Additionally, we use meteorological data and historical records of similar incidents over the past century, to identify thresholds for flooding initiation both before and after fires. By focusing on this topic, we hope to shed light on the long-term consequences of fires on communities and initiate a dialogue about the ongoing risks they face.

Erbium(III) doped cerium oxide nanocrystals are promising candidates for spin qubits in quantum computing and information science applications. Our goal is to tune the synthesis and composition of Er-doped CeO2 nanocrystals for monodispersity and desirable optical properties, particularly the intensity and lifetime of near-infrared emission features unique to Er3+. We optimized previously reported methods for making Er-doped CeO2 by altering the concentration of erbium, presence of water, and the amount of time allowed for the reaction to progress. These nanocrystals were then analyzed using several techniques, including transmission electron microscopy, X-ray diffraction, and photoluminescence spectroscopy. Our results indicated that by omitting water from the synthesis, the sizes of the nanoparticles decreased significantly. Additionally, smaller concentration of erbium(III) dopant in the nanoparticles correlated with a longer lifetime of photoluminescence intensity.

The ventral tegmental area (VTA) contains dopamine (DA) expressing neurons, which are critical for reward processing in the brain. DA neurons are tightly regulated by inhibitory GABA-expressing neurons; these GABA neurons have recently been found to be present in distinct subpopulations in the VTA. Opioids disrupt this regulation by inhibiting VTA GABA neurons via mu-opioid receptors (MORs), leading to increased DA activity and reinforcing drug-seeking behavior. However, the distribution of MORs across distinct VTA GABA subpopulations remains unclear. This study uses multiplexed in situ hybridization to map MOR (Oprm1) expression in genetically distinct GABA populations characterized by their expression of Pnoc, Crhbp, and Cbln4. Preliminary findings suggest differential Oprm1 expression, with Pnoc and Cbln4 populations showing high Oprm1 expression patterns, while Crhbp contains little Oprm1 expression. These results highlight the heterogeneity of VTA GABAergic neurons and provide insight into the mechanisms underlying opioid addiction, which may inform future therapeutic strategies.

Manduca sexta is a model lepidopteran insect organism which has been widely used in the field of chemical ecology due to its impressive olfactory senses. Odorant reception plays an important role in locating nectar sources, mating, and ovipositioning. Insects detect volatile chemical compounds (VOCs) present in their complex environment primarily through their sensory organ antenna. Each antenna is made up of thousands of olfactory receptor neurons (ORNs) and each neuron detects specific odor molecules with specific odorant receptor proteins. The whole genome sequencing of Manduca sexta has identified the major chemosensory receptor proteins: odorant (ORs), ionotropic (IRs) and gustatory (GR) but the role of each receptor is still unclear. In this project, we are investigating the role of female-biased odorant receptors OR5 and OR6, which might be involved in detecting VOCs present in their environment and play an important role in mating and oviposition. To investigate the role of these ORs, we have generated mutant strains by using a CRISPR/Cas9 approach and we are checking their effect on odor detection and oviposition behavior by comparing them with wild type strains. We are also performing an RNA-FISH experiment to visualize the ORs and locate the olfactory sensory neurons in the female antennae. In addition to this, we are also working on developing a neurogenetic tool which will allow us to measure the neuronal activity in response to different olfactory stimuli by generating a pan-neuronal BRP-GCaMP6s transgenic line.

All mammals experience a slowdown of cardiac pacemaker rate with aging. The main mechanisms to explain that phenomenon are related to alterations in the ionic currents that underlie the diastolic depolarization phase of the action potential. We have previously reported that pacemaker cells from old mice have reduced L-type calcium currents. We further explore the mechanism underlying that reduction, testing cell hypertrophy and alteration in the scaffolding of L-type calcium channels as potential mechanisms. To test for cell hypertrophy, we combined immunostaining and high-resolution imaging to map the HCN4-positive pacemaker region of isolated upper heart explants from young and old mice. We compared cell length, width, and area between young and old cells. We also determined these morphological parameters in HCN4-positive enzymatically dissociated pacemaker cells. We found no significant difference in cell dimensions or area between ages, ruling out hypertrophy as a potential mechanism. We used mass spectrometry to identify expression changes in scaffolding proteins essential for calcium channel organization at the plasma membrane. Through this approach, we identified a large reduction of caveolin 3 as a possible mechanism. Caveolin is a protein essential to forming signaling microdomains between calcium channels and other proteins. Using western blotting, we confirmed a 50% reduction of caveolin 3 in isolated pacemaker tissues from old animals. Using proximity ligation assay and super-resolution microscopy, we showed altered recruitment of L-type calcium channels into caveolae. Our findings suggest that the age-associated decrease of L-type calcium current is caused by a reduced insertion of these channels in caveolae.

The heart's primary function is to pump blood to supply oxygen and nutrients to the body. The biomechanical principles of the heart are determined by specializations at the organ, tissue, cellular, and molecular levels. Little is known about how these specializations have adapted to sustain high heart rates in animals with extreme biology, as is the case of the hummingbird, whose heart rate above 1000 bpm makes it the endotherm with the highest heart rate observed in nature. We hypothesize that the hummingbird heart has evolved several adaptations at all the abovementioned levels to i) generate fast firing rates, ii) optimize electrical-contraction coupling, and iii) sustain fast contraction-relaxation cycles. Using different histological and imaging approaches, we have started to characterize the architecture of the hummingbird’s heart for the first time in a research lab. To describe the overall dimensions and structure of the hummingbird heart, we generated CT scans and 3D reconstructions of iodine-labeled Calypte anna hummingbird hearts. To characterize the organization of the tissue, we present data using hematoxylin-eosin and lectin stainings in fixed paraffin-embedded slices of the hummingbird heart. Our preliminary results showed that hummingbird ventricles have a cell density of 110 cells per 5000 µm2, around 7-fold larger than mouse ventricles. Ventricular cells in the hummingbird are 8-fold smaller with a cross-sectional area of 41 ± 4 µm2. Hummingbird hearts also have a higher capillary density with 18.0 ± 0.6 capillaries per 2500 µm2. Our results provide a foundation for structural and functional characterization of the hummingbird heart at an organ, tissue, and cellular level while opening avenues for further investigation of extreme cardiac physiology.

In vivo genome editing of hematopoietic stem cells (HSCs) offers a promising approach for treating hemoglobinopathies and HIV/AIDS. The Lieber Lab has developed helper-dependent adenoviral (HDAd) vectors that preferentially transduce primitive HSCs in mobilized CD46-transgenic mice, humanized mice, and rhesus macaques following intravenous injection. However, off-target transduction (including other blood cell lineages and various organs) remains a critical challenge, potentially compromising safety. Moreover, the comparison of PGK and the relatively strong Ef1α promoters revealed that the editor expression level influences editing outcomes, especially in multiplex editing approaches. To address these limitations, the project’s goal is to engineer a highly active HSC-specific promoter that maximizes on-target gene editing while minimizing off-target effects, improving both the safety and efficacy of HDAd-based therapies. I first generated GFP reporter plasmids containing roughly 2 kb of proximal promoter sequence from five genes highly expressed in HSCs: CD164, cKit, DSG2, PROM1, and PROCR. These constructs were introduced into human CD34⁺ cells via nucleofection, and the cKit and PROCR promoters showed the strongest GFP expression in the HSC-enriched (CD34⁺/CD45RA⁻/CD90⁺) subset. To further enhance promoter activity, we linked the top-performing promoters to distal HSC enhancers that, according to ENCODE/Hi-C analyses from Dr. David Hawkin’s Lab, regulate cKit (2 enhancers), CD164 (4 enhancers), and PROM1 (2 enhancers). Engineered promoter-enhancer constructs yielded 3- to 4-fold higher GFP expression than Ef1α in CD34⁺/CD45RA⁻/CD90⁺ cells, with the cKit promoter + CD164-3 and PROM1 enhancers showing the highest activity. Building on these findings, we have incorporated these HSC-specific promoter–enhancers into helper-dependent adenoviral (HDAd) vectors driving an ABE8e-base editor for γ-globin reactivation. Ongoing work is focused on evaluating the specificity and efficacy of these HDAd vectors in humanized mice and CD46/βYAC-transgenic mice, with the ultimate goal of achieving safer, more effective in vivo genome editing in HSCs.

Acetylcholine (ACh), a neurotransmitter known for its roles in neuromuscular function and cognition, has recently been implicated in immune regulation, particularly in the context of Type-2 immunity. The Type-2 response combats parasites at mucosal and cutaneous sites and plays a role in allergic diseases like asthma and food allergy. In the intestine, Type-2 inflammation involves a dramatic remodeling of the intestinal epithelium via the activation of intestinal epithelial stem cells (ISCs), which results in the hyperplasia of specialized effector-like secretory cells such as goblet and tuft cells. These epithelial cells then produce factors that talk back to the epithelium, such as Ach, and factors that promote Type 2 immune responses, such as the cytokine interleukin-25. Tuft cells are the only intestinal epithelial cells that express choline acetyltransferase, the enzyme for ACh synthesis. Recent work suggests that during helminth infection, tuft cells release ACh in response to IL-13 signaling, implying a role for ACh in regulating epithelial responses. However, its specific function in epithelial remodeling and Type-2 immunity remains unclear.This project aims to investigate ACh’s epithelial intrinsic role in Type-2 immune responses using an in-vitro enteroid model of the intestinal epithelium. Enteroids, 3-D cultures derived from stem cells, model the epithelium without immune cells, allowing for a focused examination of epithelial-intrinsic factors in immune responses. By culturing and treating enteroids from wild-type and tuft cell-deficient mice with ACh, we will assess its effects on goblet cell proliferation, inflammation, and stem cell renewal during injury regeneration responses. I hypothesize that ACh enhances the pro-Type-2 inflammatory response in enteroid epithelial cells, leading to heightened immune activity. This research will advance our understanding of the neuro-immune axis in the gut and may have implications for parasitic infections and allergic inflammation.

The obligate intracellular bacterium Chlamydia trachomatis is one of the leading causes of sexually transmitted bacterial infections. Despite its great prevalence and systemic impact on women's reproductive health, no vaccine has been developed. As an obligate intracellular parasite, Chlamydia trachomatis infection occurs within a host-derived vacuole, and Chlamydia have evolved numerous pathways for evading cellular immune defenses. Recent work has highlighted a mechanism through which intracellular Chlamydia interferes with a cell-intrinsic, interferon-gamma (IFN_γ) activated pathway. Our lab discovered a secreted CT virulence factor (GarD) that is important of preventing the IFN_γ -dependent recruitment of ubiquitin to CT-containing vacuoles, and we hypothesize that a gene of unknown function (ct134) immediately upstream of garD may also play a role in this immune evasion pathway. In this project, we used a new genetic system to produce a double knockout mutant for these genes, and we investigated in a cell culture model the fitness and susceptibility of mutants in cell stimulated with human IFN_γ. We expect this work to either define a broader role of this gene locus in mediating chlamydial anti-IFN_γ defenses. In addition, we generated a homologous double knockout lesion in the mouse-tropic pathogen Chlamydia muridarum, and we hypothesize that the C. muridarum homologs of ct134 and garD fulfill this phenotype will support future studies focused on investigating the in vivo role of these genes in Chlamydial infection and virulence in the upper genital tracts of infected female mice.

Hyalella azteca are freshwater amphipod crustaceans abundantly found throughout North America and are frequently used in toxicology for water and sediment toxicity testing. As freshwater bodies change due to anthropogenic climate change, understanding chronic, sublethal impacts to aquatic life is critical. Amphipods are known to have a higher tolerance to heavy metals (i.e. Cu²⁺) and road salt (i.e. NaCl) compared to other aquatic invertebrates, however, these contaminants may have subtle, sublethal consequences on their ability to smell and detect chemical cues for survival and reproduction. This research identifies the combined impacts of environmentally relevant levels of Cu2+ and NaCl, on the olfactory system and olfactory-related behaviors of H. azteca. H. azteca underwent acute 96 hour exposure to control, Cu2+ (30 µmol/L), and combined Cu2+ (30 µmol/L) and NaCl (5 ppt) contaminated freshwater. I recorded daily measurements of survival, and utilized qPCR to examine changes in the expression of key olfactory genes that we predicted would be modulated in response to these multiple stressors. I assessed the olfactory-associated foraging behavior to determine changes in their detection of an attractive food cue when exposed to Cu2+ and NaCl, which would indicate olfactory impairment. Preliminary results show that amphipod survival is not impacted by Cu2+ and NaCl contamination but changes to their olfactory system occur. Therefore, U.S. Environmental Protection Agency water quality standards for heavy metals and salt may not mitigate long-term, sublethal effects on aquatic animal populations as it relates to this important sensory modality.

Certain species exhibit the remarkable ability to regenerate their appendages, a process that requires complex metabolic pathways to facilitate the cellular proliferation needed to regrow tissue. Among these species, Xenopus tropicalis, the Tropical Clawed Frog, serves as a great model for regeneration studies because of its transient regenerative capacity. X. tropicalis tadpoles exhibit the ability to regenerate their tails, but this capability is gradually lost after metamorphosis. This unique characteristic allows for direct comparison of regenerative and non-regenerative processes within the same species. Previous work from the Wills lab indicates that genes encoding the enzymes of the pentose phosphate pathway (PPP), which generates precursors of biosynthetic molecules such as nucleotides and lipids, are highly expressed during tadpole tail regeneration. Although tail regeneration has been well studied, the variation in hind limb regenerative capacity across developmental stages and the metabolic pathways involved remains unclear. Hence, I performed a live imaging study to determine the developmental progression of hind limbs and assess their regenerative potential. This data suggests a decrease in success as the tadpole gets older. Immunohistochemistry staining of mitotic cells in developing limbs shows that proliferating cells decline as regeneration competency decreases. I hypothesized that genes for the PPP enzymes would also be expressed during successful limb regeneration, which was confirmed by in-situ hybridization. Together, these findings indicate that the regenerative capacity in limbs of X. tropicalis is stage-dependent and that PPP genes are expressed during all stages of regenerative capacity. This provides insights into the role of metabolic reprogramming in appendage regeneration, with the potential for translating it into non-regenerative species like mammals.

This investigation is based on the famous intermediate axis theorem, often called the tennis racket theorem. This theorem describes why objects with three distinct moments of inertia, around three different axes, have an unstable rotation around the intermediate axis (the axis with the intermediate moment of inertia) while the axes that have the largest and smallest moment of inertia have a stable rotation. This phenomenon can be observed in rotations of everyday objects like tennis rackets and phones. By videotaping rotations of different objects with three distinct moments of inertia around three axes, and visually examining the intermediate axis, one can notice the instability of the intermediate axis compared to the stability of rotations about the other two axes. We mathematically analyzed the motion around three axes using Euler’s equations of rotations, the equations governing the dynamics of a rigid body undergoing rotational motion. We solved the differential equations demonstrating the instability around the axis with the intermediate moment of inertia. This behavior was also simulated in MATLAB using Euler’s equations of rotations. Our graphs of velocity as a function of time for rotation around the three axes, demonstrated and justified the visual observations from the videos. These experimental and computational approaches can lead students to a comprehensive understanding of the intermediate axis theorem.

Fluoride intake is essential for dental health, yet excessive consumption can lead to fluorosis, a condition negatively affecting teeth and bones. Tea, one of the most widely consumed beverages globally, naturally accumulates fluoride, making it a significant but often overlooked dietary source. Black tea is the most popular type of tea consumed in the U.S. In this study we compared fluoride levels across six brands of black tea and investigated how brewing conditions and water sources affect fluoride concentrations in tea. We brewed black tea from six locally popular brands (Lipton, Tazo, Fortnum & Mason, Twinings, Tetly, and Harney & Sons), using two water sources (distilled water and Seattle tap water), with four samples for each brand using both water sources. We brewed 50 mL of water at 100°C, then we let each sample of the tea sit for 5, 10, and 20 minutes. Ion chromatography was used to measure fluoride concentrations at each time interval. We compared these values to the U.S. Environmental Protection Agency's (EPA) recommended fluoride level of 4.0 mg/L. Our results help characterize the variation between brands and the influence of brewing duration on fluoride release. These findings contribute to a better understanding of fluoride exposure from tea consumption, helping consumers make informed choices about their dietary fluoride intake.

Beaver dams can function as natural filters helping decrease pollution in streams, creeks, and rivers. Beaver dams slow down the water flow in a creek or river, forming ponds that help trap excessive nutrients. An excess of nutrients such as phosphate and nitrate can cause eutrophication, leading to increased algal blooms that can produce toxins and ultimately deplete oxygen in the water. This study investigates the ion levels of chloride, fluoride, phosphate, nitrate, sulfate, and bromide upstream and downstream of the major beaver dam at Pipers Creek in North Seattle's Carkeek Park over the course of a year to better understand the long-term impacts of the dam. We collected three water samples at each of eleven sites along the creek, eight upstream from the dam, and three downstream. Ion chromatography was used to measure the concentrations of anions at each site. The results of this study help elucidate the role of beavers in moderating water quality and provide important baseline data documenting seasonal variations in the nutrient load at Pipers Creek. These findings can also be used to better understand the impact of new beaver dams in other freshwater systems.

Low-income communities are often disproportionately exposed to air pollution. High concentrations of pollutants such as particulate matter under 2.5 µm (PM2.5) and human aerosol emissions, including carbon dioxide (CO2), have been linked to various health and cognitive issues. Performance arts, including singing and playing instruments, produce human aerosol emissions and are considered high risk for airborne disease transmission. Our study evaluated the accumulation of CO2 and PM2.5 in high-risk environments (band classrooms) in low-income public schools in King County (WA), to determine whether there is a correlation between accumulation rates and Title 1 designation. Title 1 designation, which provides government funding for schools with a high percentage of students from low-income households, was used to represent low-income communities. We compared four middle schools that qualified for Title 1 designation to one school that did not qualify. Concentrations of CO2 and PM2.5 were measured using the Aranet4 Home CO2 sensor and a PurpleAir Classic sensor for PM2.5. We took a baseline measurement of both concentrations when the classroom was unoccupied. We then analyzed the change in concentration rates when classes were in session, taking into account classroom size and number of students. Our data showed concentrations above recommended levels at 1,370 ppm (parts per million) for CO2 in one of the Title 1 schools suggesting that Title 1 schools may be at greater risk of poor indoor air quality, though additional studies are needed. This additional exposure to pollutants and human aerosol emissions in already high-risk environments like band classrooms may lead to increased airborne disease transmission, highlighting the disparity in healthy learning environments. These classrooms require additional measures to maintain healthy concentrations of CO2 and PM2.5 to reduce the risk of airborne disease transmission particularly in low-income communities. 

Stiffness measures derived from MR Elastography have shown value in guiding treatment decisions and monitoring effectiveness of therapies for liver disease but it requires extra hardware, longer scan duration and is susceptible to motion and breathing artifacts. Recent studies have revealed a strong linear correlation between water diffusion and tissue stiffness, demonstrating that Diffusion Weighted MRI (DWI) can be used to estimate stiffness values in liver tissue. DWI-derived stiffness values may help evaluate treatment-induced changes in breast cancer but to our knowledge, this has not yet been tested. The purpose of my ongoing study is to calibrate DWI estimates of tissue stiffness for the breast by optimizing DWI parameters (diffusion weightings, or ‘b-values’) and  calibration coefficients (a, b), evaluating the potential of stiffness measures for monitoring response to neoadjuvant chemotherapy (NAC) in breast cancer. We collected baseline and early treatment MRI exams from 25 patients undergoing NAC in this IRB approved study along with their treatment outcomes based on pathologic response post completion of NAC. I evaluated  the stiffness values obtained from different b-value pairs (low b-values: 100/200; high b-values: 800,1500,2000 s/mm²) and calibration coefficients(a,b=-9.7,13.9:-10.8,17.5:-8.8,21.2) and compared it to the invasive breast cancer stiffness values reported in literature. I also evaluated the performance of the optimized parameters to predict treatment response. The optimal b-value pairing (b=200,1500s/mm²) and coefficients a=-9.7,b=13.9 produced stiffness values consistent with literature. Using this approach, the performance for predicting treatment outcomes between responder and non-responder groups was AUC=0.84. These preliminary findings suggest that DWI based virtual elastography could serve as a non-invasive tool to assess tumor stiffness and track treatment efficacy, potentially improving breast cancer management.

Aquacultures are an environmentally responsible way of breeding and harvesting a variety of marine organisms. Challenges to aquacultures include the introduction of nonnative pathogens and parasites to wild fish as well as intense changes to the physical environment. Monitoring the environment for impacts of aquaculture is costly and time-consuming, so finding a cost-effective rapid monitoring solution is important. This project tests the feasibility of monitoring the diversity of meiofauna species present in the sediment via DNA sequencing. Meiofauna species are marine organisms between 0.06 mm and 1 mm in size that live in marine sediment. DNA sequencing is quicker and cheaper than current monitoring practices, and since changes to the physical environment affect meiofauna species diversity, observing the change in species diversity is a potential alternative to monitoring aquaculture health. Through samples taken before and after the introduction of a sablefish net pen aquaculture, analysis of both physical sediment samples and meiofauna samples will determine the feasibility of implementation. By looking at the total organic carbon content and grain size distribution of the sediment samples, we can determine the physical changes to the environment caused by aquaculture. Suppose the DNA sequencing results show shifts in species diversity that match the physical changes. In that case, we can confirm there is evidence supporting the feasibility of implementing monitoring via meiofauna DNA sequencing. 

Forest management systems have a dramatic impact on Puget sound ecosystems. Not only does lumber-focused forest management reduce habitat for animals, but the disturbance of the forest floor and removal of canopy cover also impacts many plants and fungi. This study compares moss communities under different states of forest management, exploring how the loss of shade and impact of human management affects the diversity of moss species. I have designated several sites based on their current conditions and state of management and have surveyed moss communities in each site for species richness and diversity. By comparing the data between sites, we can see trends in how moss communities respond to forest management and logging. All sites are based in the Green River College learning forest, which is managed by the college’s forestry program. This is a small fragment forest, but it is extremely diverse with well over 100 flower and bird species. It’s vital that we understand the effects of management on these smaller fragments as well as larger plots. Here we report the differences in moss communities based on taxonomy, sun exposure, and management treatment. By understanding trends in how moss communities are impacted overall, as well as seeing which species of moss are disproportionately affected, we can identify species that are more at risk from human impact. Moss is a vital part of our forests, from maintaining soil moisture and temperature to slowing erosion, it’s important for us to understand how these diverse plants are affected by forest management systems so we can better protect our forests and all the things living there.

As individuals experiencing homelessness age, their healthcare needs become increasingly complex. People over age 50 are the fastest-growing group experiencing homelessness, yet there is little knowledge about specific subgroups, particularly older homeless veterans. The aim of our study was to explore the experiences of older veterans and non-veterans experiencing homelessness, with a focus on contextualizing the unique barriers to accessing healthcare and maintaining stable housing in each group to better understand how these factors impact healthy aging. Using a qualitative research design, we developed a semi-structured interview guide in collaboration with key informants from Compass Housing Alliance. We recruited participants aged over 50 who have recently exited homelessness and are living in Permanent Supportive Housing (PSH). We conducted forty-five-minute interviews with veterans (6-10 participants) and non-veterans (6-10 participants). The questions focused on daily living, work, healthcare, connection & community, access to structural support services, and perceived impact on aging well. We recorded and transcribed these semi-structured interviews, which we coded to identify key themes. Additionally, all participants completed a basic survey to capture demographics such as length of time homeless, age, and gender. After the initial thematic analysis, we had a second session with participants to check the accuracy of the identified themes. The qualitative approach of this study provides new data directly from those with lived experience. This study offers critical insights into the unique challenges faced by aging veterans in comparison to non-veterans in PSH, exploring gaps in healthcare access, limitations of healthcare services, and the role of housing stability for older adults. This research is significant to policymakers, healthcare providers, and housing organizations seeking to tailor support to the heterogeneous groups within the aging homeless population.

Antibiotic resistance is an increasingly critical concern for the treatment of bacterial infections, rendering new therapy options progressively more necessary. Gram positive bacteria are common infectious agents in skin and soft tissue infections, pneumonia, urinary tract infections, bacteremia, and more. A novel antibiotic candidate, MRS-2541 has been demonstrated to inhibit Gram positive methionyl-tRNA synthetase and decrease bacterial loads of both methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pyogenes in mouse thigh infections to the same degree as currently recommended therapy. This study aims to further characterize the activity of MRS-2541 against Gram positive bacteria including Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus lugdunensis, Staphylococcus saprophyticus, Staphylococcus aureus, MRSA, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus salivarius. I conducted this study by first determining the preliminary minimum inhibitory concentration of MRS-2541 in growth media against each of the aforementioned organisms. I then use these results to guide time kill assays that characterize MRS-2541’s synergy with another antibiotic often used to treat Gram positive infections outside of the United States. Preliminary results demonstrate that MRS-2541 inhibits the above-mentioned organisms. Synergy experiments with MRS-2541 and existing antibiotics will be performed and results will be presented at the symposium. These results will further define the spectrum of activity as well as synergy of MRS-2541, allowing new insight into its candidacy for clinical trials. As a novel antibiotic candidate, the development of MRS-2541 will help address the increase in antibiotic resistance among Gram positive bacterial infections.

Transient ischemic attack (TIA) patients can still experience a recurrent stroke due to platelet-rich thrombi despite being on dual antiplatelet therapy (DAPT) consisting of acetylsalicylic acid (ASA) and a P2Y12-inhibitor. One pattern these patients have was an elevated von Willebrand Factor level (VWF), a blood clotting protein that tethers platelets to the endothelium. VWF unfolds under shear, exposes its A1 domain to which surface receptor GPIb-IX-V of platelets can bind. DAPT targets platelet activation by inhibiting thromboxane A2 synthesis and blocking ADP binding to P2Y12, but it does not directly address shear-mediated activation of platelets via VWF. Even with DAPT, platelets can still bind to VWF via GPIb-IX-V under a high shear rate. To understand the interplay between elevated VWF levels, DAPT, and platelet thrombus formation under shear flow, we used a microfluidic device to analyze platelet-rich plugs for (1) platelet activation, (2) aggregation size, and (3) contractile versus drag forces to withstand embolization. Those characteristics are measured in a healthy platelet-plug control and a platelet-plug doped with 6-fold VWF level, both with and without DAPT. We found platelet-plugs with DAPT still maintain activation, and activation level becomes higher when DAPT is combined with elevated VWF level. Platelet-plugs with DAPT and/or elevated VWF have larger aggregate size than control, and aggregate size is highest when DAPT is combined with elevated VWF level. While contractile force dominates in control, it becomes similar to drag force with DAPT and/or elevated VWF. We suspect the large size, reduced contractile force and maintained activation of platelet-plugs with elevated VWF can make the plug prone to embolization caused by the drag force. This result can shed light on the limitations of DAPT when VWF level is elevated, and introduces the possibility of screening patients for high VWF to tailor antiplatelet therapies. 

The angiopoietin-Tie2 signaling pathway is central to regulating vascular stability, remodeling, and permeability. Angiopoietin-1 (Ang1) promotes pAKT activation and vascular stability and regeneration, whereas Ang2 antagonizes these effects, leading to leaky vasculature. Although Tie2’s association with α5β1 integrin has been implicated in mediating these divergent outcomes, the requirement of direct F-domain ligand binding for integrin recruitment remains unclear. Here, we report the development and mechanistic evaluation of a de novo designed Tie2 mini binder (Tmb) that selectively targets the Tie2 receptor without engaging α5β1 integrin. Using an AI-based protein design pipeline, we designed Tmb with high affinity (KD ≈ 0.65 nM) for Tie2, as confirmed by CryoEM analysis, which demonstrated that Tmb accurately recapitulates its designed structure. When conjugated to multivalent scaffolds, Tmb effectively clusters Tie2 receptors, recapitulating the signaling profile of native Ang1. Notably, high valency Tmb constructs (e.g., H8T) robustly activated pAKT and induced nuclear FOXO1 exclusion, mirroring the pro-survival and vascular stabilizing effects of Ang1, despite lacking the capacity to bind α5β1 integrin directly. Detailed cellular assays revealed that Tie2 clustering leads to the formation of two distinct complexes: a Tie2–α5β1 integrin complex that facilitates focal adhesion assembly and cell migration via pCAS recruitment, and a Tie2–tight junction complex (comprising ZO1, claudin-5, and occludin) that underpins vascular barrier integrity. Importantly, competitive binding studies demonstrated that integrin recruitment to the Tie2 complex does not require direct F-domain engagement. In human iPSC-derived diabetic blood vessel organoids, treatment with Tmb-based Tie2 agonists ameliorated diabetic vasculopathy phenotypes by reducing pathogenic collagen IV deposition, restoring tight junction organization, and lowering nuclear FOXO1 levels. These findings provide novel insights into the mechanistic interplay between Tie2, integrin, and junctional proteins, and underscore the therapeutic potential of synthetic Tie2 agonists in vascular repair and diabetic vasculopathy.

As climate change increases temperature, Pieris rapae caterpillars' feeding habits may be affected. As their feeding habits are altered, P. rapae may begin to migrate to different plants; this can be detrimental for agriculture because these defoliating caterpillars are pests. P. rapae caterpillars are known to feed on Brassica species, including collards and kale. It is also shown that caterpillars increase their feeding rate at higher temperatures (Kingsolver 2000). However, little is known about how temperature influences their feeding preferences. In this experiment, we find the consumption rate of P. rapae 4th instar larvae eating kale (Brassica oleracea var. sabellica) and collards (Brassica oleracea var. viridis) to find consumption preference between these two plants at 14°C, 23°C, and 35°C. Larvae were placed on a moist filter paper in petri dishes containing 2 collard and 2 kale leaf disks placed in an alternating fashion. Petri dishes were placed in three separate incubators set to the three temperatures. We predicted that P. rapae would have a preference for collards since they are reared on collards in the lab and they would increase their consumption of the preferred plant. We also examined the percentage per hour of each leaf eaten and compared this data between types of leaves and temperatures. The data showed that as temperatures increased, the consumption rate of P. rapae caterpillars also increased. Though, there was no change in preference as the P. rapae caterpillars consistently preferred collards over kale. This suggest that higher temperatures from climate change will increase the rate at which caterpillars eat, but will not affect preference. It is important to consider the change in consumption rate of caterpillars with temperature when aiming to prevent crop damage in the face of climate change.

Safe drinking water in schools is crucial for children's safety and academic performance. While Seattle Public Schools has tested for some contaminants, such as lead, the district's responsibility for ion-specific testing for anions such as phosphate, bromide, nitrite, nitrate, chloride, sulfate, and sulfite is less clear. High concentrations of anions pose potential health risks, including reduced oxygen in red blood cells, higher risks of tumors in children, and diarrhea. This research investigated the anion concentration in water fountains across seven high schools in the Seattle Public Schools. Twenty-one water samples were collected from seven public high schools and analyzed for anion concentration using ion chromatography. Results were compared to the Environmental Protection Agency's (EPA) maximum contaminant level (MCL). All test samples were below the EPA's MCL. These results suggest that the drinking water in these schools does not pose potential risks to students from anion contamination. While regular monitoring and management are still necessary to maintain safe drinking water, Seattle Public Schools have met the safety requirements for anion concentration in their drinking water. 

The focus of this research was to test the effectiveness of a silicone-based paint in the marking of Pieris rapae in a manner that was non-invasive and durable. Previous studies have tested other marking methods but have faced challenges such as harm to the organism. By using a paint made from red cabbage (Brassica oleracea), I aim to minimize the harm to larvae in current marking methods while retaining durability under moist conditions. This experiment examined both the durability and health effects of cabbage-based paints on P. rapae caterpillars. Preliminary experiments tested a water-based version, which did not appear to affect survival but faded under moist conditions, and a silicone-based version, which withstood moisture but raised concerns about potential effects on health due to the additional ingredients required for the silicone base. My research continued testing the cabbage paint with a cosmetic-grade dimethicone base and aimed to determine the extent that the cabbage paint may have on caterpillar health and survival. Survival experiments were conducted on 4th and 5th instar caterpillars to determine larva mortality rates when exposed to the pigment. Weight change experiments were conducted from the 4th instar to pupation to be used as a metric of the overall health of the larvae. I conclude that the silicone-based cabbage pigment is a promising marking method for larger caterpillars, offering improved durability and minimal impact on overall health compared to many conventional methods. These findings contribute to the development of safe durable marking techniques suitable for ecological research on soft-bodied insects.

Obesity is linked to reproductive dysfunction through defects in the hypothalamic-pituitary-gonadal (HPG) axis that arise by unknown mechanisms. Importantly, rodents fed a high-fat diet (HFD) develop similar hypogonadism and reduced ovulatory capacity. During HFD feeding, CNS immune cells (microglia) become activated in the hypothalamus, promoting inflammation, and altering neuronal function indirectly and via cell-cell contacts. Surprisingly, however, genetic ablation of this microglial inflammatory response exacerbates rather than improves HFD-induced HPG axis dysfunction including altering the activity of hypothalamic neurons that express the key reproductive neuropeptide GnRH. Therefore, we hypothesized that increased microglial inflammatory signaling during HFD feeding helps maintain GnRH neuron integrity. To test this hypothesis, we used immunohistochemistry (IHC) to assess microglia-GnRH cell-cell interactions in the hypothalamus of 15-week HFD-fed female mice with microglia-specific deletion of IKKβ (IKKβ-MGKO), a critical regulator of the inflammatory NF-κB pathway. IHC studies using GnRH and Iba1 (microglial marker) revealed fewer cell-cell contacts between GnRH neurons and microglia in the preoptic area of the hypothalamus (POA) of IKKβ-MGKO mice compared with controls. In addition, we found that IKKβ-MGKO mice have reduced levels of Iba1 and total numbers of microglia but no changes in microglial cell morphology as determined by Sholl analysis. These findings suggest that HFD-induced microglial inflammatory signaling promote cell-cell interactions with GnRH neurons that may contribute to maintenance of HPG axis integrity and female reproductive function during diet-induced obesity.

The Western Honey Bee (Apis mellifera) is responsible for approximately 80% of agricultural pollination in the United States, making them an incredibly important resource. The Varroa mite (Varroa destructor), is one of the biggest threats to honey bee populations worldwide. The Honey Bee Research Team at Green River College has investigated these mite populations in the Puget Sound Region for the past decade. In the spring of 2024, I joined the Research Team and was taught the processes of determining the mite infection percentage in honey bee hives using the sugar shake method. If there were more than seven mites on a test sample of one hundred bees, it was time for treatment of the hive. If there was a 7% infection (7 mites on 100 bees) or more, 70.6% of the colonies died; if less than 7% infection, 96% of the colonies survived. While this data mimics data in the rest of the country, we report here a more detailed understanding of mite populations and why it is important to know when it is best to perform management and treatment. Having proper management practices is essential for the future of our honey bee populations as well as changing beekeeping culture. This research is still ongoing and has led to the question of what the most effective way for honey bees to survive a mite infection and survive over the winter. As research continues, new methods of treatment will be developed and tested.

Despite the development of effective COVID-19 vaccines, countries with high rates of HIV infection still have limited vaccine access and inadequate access to antiretroviral medications essential for controlling HIV. Studying COVID-19 vaccination in people living with HIV (PLWH) is needed to improve vaccination strategies in immunosuppressed populations. Previously, in pigtail macaques (PTM) we showed that COVID-19 repRNA vaccination elicits durable and protective immunity against SARS-CoV-2 infection. Here we utilized the simian immunodeficiency virus (SIV)-infected PTM model of HIV/AIDS to test the hypothesis that COVID-19 repRNA vaccination is less durable during immunosuppression. Nine PTM were enrolled into the SIV naive (n=4) and experimental SIV-infected (n=5) cohorts. SIV-infected PTM were infected with 10,000 units of SIVmac293M seven weeks prior to the first vaccination. All PTM were given 2-4 COVID-19 repRNA immunizations, encoding the SARS-CoV-2 WA.1 Spike protein, to reach maximal immunogenicity and monitored for 26 weeks for vaccine durability. Vaccine recall was evaluated by administering a booster immunization after immunity responses waned. Blood and bronchoalveolar lavage samples were collected every 2-4 weeks. SIV-infected animals were monitored for SIV disease progression, including measuring CD4 counts in peripheral blood. Enzyme-linked immunosorbent assays (ELISAs) were used to quantify longitudinal Spike-specific binding IgG antibodies. Preliminary data shows that COVID-19 repRNA vaccination elicited robust anti-Spike IgG antibodies in both PTM groups, with diminished responses in some animals within the SIV-infected group.  Anti-SARS-CoV-2 neutralizing antibodies were also generated in both groups and interestingly, more durable in SIV-infected animals. Ongoing analysis includes evaluation of IgM and IgA binding antibodies. Collectively, this study suggests SIV-associated immunosuppression impacts vaccine-induced humoral memory, which could, in turn, impact long-term protection from COVID-19. These findings are crucial for improving vaccine regimens for PLWH and other immunosuppressed individuals.

Duchenne Muscular Dystrophy (DMD) is a severe neuromuscular disease caused by mutations in the dystrophin gene and characterized by progressive muscle wasting. Dystrophin protein is essential for the stabilization of muscle fibers; without it, continuous muscle damage eventually has devastating consequences in the skeletal, cardiac, and respiratory systems. While prior AAV-mediated editing strategies have been effective in targeting these mutations, there are significant immunological concerns from the uninterrupted expression of bacterial gene editing components. This project utilizes the mdx mouse model of DMD to address these concerns by developing methods to turn gene editing on and off using novel drug-responsive pA regulator vector constructs. I have been part of this project from the start, contributing to the assembly of the expression constructs using bacterial cultures and standard cloning techniques relying on restriction enzymes and high-fidelity cloning kits to piece together our editing constructs. Initial data was acquired from cell culture tests where I helped perform quantitative dual-luciferase reporter assay analyses. Subsequent in vivo experiments were performed by delivering adeno-associated viral vectors, carrying our constructs, into mdx mice via retro orbital injection. Activation of editing activity was achieved via three intraperitoneal injections of Tetracycline.  During analyses, I played a significant role in processing muscle tissues to extract proteins, DNA, and RNA for quantitative assays. Ultimately, our cell culture tests identified two lead pA regulator sequences exhibiting favorable activation levels at therapeutically relevant Tetracycline doses. Initial in vivo tests are promising, showing drug responsive editing and dystrophin expression in mice. We anticipate that our follow up tests will restore sufficient dystrophin expression and improve muscle function, without persistent editing activity. Overall, the outcomes of these studies could have significant implications for a multitude of genetic conditions amenable to genome editing and may help accelerate translation of effective methods towards clinical trials.

Viral evolution theory hypothesizes that specialist strategies increase fitness by reducing interspecific competition, while generalist viruses increase fitness by accessing multiple hosts. However, specialism may come at the cost of infecting few hosts, while generalism may reduce fitness in any single host. These tradeoffs have been demonstrated in Infectious hematopoietic necrosis virus (IHNV), an aquatic rhabdovirus infecting multiple salmonid species. High rates of viral replication have been observed for specialized subgroups in their respective hosts, while lower rates of replication across multiple hosts have been observed for the generalist subgroup. However, the host-virus mechanisms underlying these replicative differences are unknown. Here, I aim to characterize the early innate immune response of sockeye salmon, the ancestral host of IHNV, to specialist and generalist subgroups at target tissues. Specifically, I seek to test whether sockeye salmon display distinct transcriptomic responses to IHNV specialist and generalist subgroups in the kidney 2 days post-exposure (dpe). To accomplish this goal, RNA was extracted and sequenced from kidney tissue of individuals 2-dpe following exposure to specialist (n=9), generalist (n=9), or control (n=4) IHNV treatments. Overexpressed and underexpressed genes will be identified between each subgroup and control samples. These genes will then be used for pathway enrichment to compare differences in transcriptomic response. Replicative rates have shown a difference between specialist and generalist subgroups of IHNV 2-dpe in the kidney; therefore, we expect to observe differences in the number and magnitude of over- or underexpressed genes and enriched pathways between hosts exposed to specialist and generalist subgroups. Results from this study will aid in characterizing evolutionary mechanisms underlying viral specialism and generalism, understanding host innate immune response and evasion strategies, and identifying biological markers associated with response to viral exposure. This knowledge will be critical in predicting future disease outbreak and informing disease mitigation strategies.

Protein subunit vaccines are highly used today as an alternate vaccine platform to older vaccines such as live-attenuated viruses. They contain a protein antigen of the virus or bacterium that can be recognized and targeted by the immune system, and an adjuvant that amplifies the immune system response to this protein by widely putting the immune system on alert. The most commonly used adjuvants pose the risk of possible adverse reactions and are not created to target specific immune pathways, but rather stimulate general inflammation. To design a vaccine adjuvant that generates a more targeted immune response, we are using the self-assembling protein nanoparticle, I53-dn5, to display a CD40 binder that mimics the T Cell ligand, CD40L, by binding to B cell surface receptor CD40. We aim to create a particle that can replicate the binding interaction between B and T cells in the lymph node responsible for triggering antibody maturation, and B cell proliferation and differentiation. We hypothesize that this multivalent display of CD40 binder will generate potent B cell responses allowing us to respond to an antigen more effectively than current adjuvants. We are utilizing computational protein design methods like RFDiffusion, ProteinMPNN, and AlphaFold2 to optimize this display, and testing these designs in vitro for stability and ability to elicit downstream signaling effects of the CD40/CD40L interaction. This research holds two promising innovation potentials. The first is creating higher potency adjuvants by stimulating specific signaling pathways for use with protein subunit vaccines. Secondly, these materials can be used as a more stable and potent molecule in biochemical assays such as being an alternative to feeder cell lines in B cell support culture.

Over a hundred years after the Spanish Flu, the influenza A virus (IAV) remains a leading cause of respiratory infections and mortality worldwide. The proliferation of IAV causes many of the symptoms associated with IAV clinical disease. However, the severity of acute lung injury (ALI) from IAV is primarily driven by the host's immune response to infection. The mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated protein kinase (ERK) signaling cascade is a highly conserved pathway that is activated during lung injury and inflammation in both rodents and humans. Two MEK isoforms, MEK1 (Map2k1) and MEK2 (Map2k2), activate downstream effectors, ERK1 and ERK2, and control critical cellular processes, including the intensity and duration of inflammatory signaling. Our prior research revealed that MEK2-deficient mice exhibited improved weight recovery and overall fitness during IAV infection, suggesting that MEK2 is a host response exacerbating ALI during IAV infection. During IAV infection, excessive pro-inflammatory cytokine production drives immune cell recruitment into the lungs, leading to collateral tissue damage that impairs organ function and exacerbates disease. We hypothesize that MEK2 enhances immune cell recruitment to the lungs, enhancing inflammation, which may occur through exuberant chemokine signaling. To investigate this, we infected MEK2-deficient and wild-type mice with mouse-adapted IAV (H1N1, PR8) and collected cells from bronchoalveolar lavage (BAL) and lung homogenates. Using flow cytometry, we found reduced immune cell recruitment, including decreased numbers of monocytes, dendritic cells, monocyte-macrophages, CD4+ T-cells, CD8+ T-cells, and B-cells. Next, we assessed levels of key chemokines known to attract monocytes and lymphocytes by measuring their gene expression in the lungs and protein levels in the BAL. Investigating MEK2’s impact on chemokine signaling will elucidate the mechanism by which MEK2 perpetuates lung inflammation and injury during IAV infection and will guide the development of future host-directed therapies for IAV-induced lung damage.

Transcriptional repression plays a critical role in the regulation of various biological processes, including developmental pathways and disease progression. Corepressors are proteins recruited by partner proteins to negatively influence the transcription of genes. TPL is a corepressor from the model plant Arabidopsis thaliana, and is known to play a pivotal role in transcriptional repression. My project aims to identify other proteins that work with TPL to form a transcriptional repression complex at a single engineered locus. To further understand the function of corepressors, we built a synthetic repressor system, dCas9-TPL, designed to specifically repress the transcription of the RUBY reporter gene. When expressed, the RUBY reporter turns Arabidopsis thaliana pink. In previous phases of this research, we utilized the EMS (ethyl methanesulfonate) mutagenesis protocol to create a population of plants containing many random mutations. Screening these plants for increased RUBY expression, I successfully Identified promising homozygous lines where plants demonstrated bright pink flowers and unique phenotypes such as early flowering, light avoidance, and small stature. Last quarter, I sent five lines to be sequenced and each line displayed distinct mutations that I can further explore to pinpoint the exact TPL interactor responsible for its unique phenotype. I am also investigating known TPL interactors such as SPT4, SPT5, and MED21 by creating transgenic lines within my control dCas9-TPL + RUBY line. Through genetic screening, I have validated the phenotypes among these control experiments. By investigating the intricate network of interactions between these regulatory proteins, I aim to gain a deeper understanding of how gene expression is coordinated across different cell types and how this process controls complex developmental pathways.

Plants' defense mechanism against herbivory is integral to both resistance in nature and the global food supply. Glycine max or soybean, is one of the most widely grown crops in the world, and suffers substantial losses from pests, including many Lepidopteran species. Related legumes, including cowpea, and common bean, can respond to Lepidopteran herbivory by detecting Inceptin-11 (In11), a short peptide found in larval oral secretions. The protein responsible for this ability, Inceptin Receptor (INR), is not found in soybean. The aims of this project are two fold, firstly introducing INR into soybean lines and testing for improved resistance to Lepidopteran herbivory, and secondly studying the effects of INR on defense gene expression in soybean, in order to better understand mechanisms of herbivory resistance. The first step in this project was to create soybean lines which consistently express INR. This was done by sending our INR construct to collaborators, who used it to inoculate multiple soybean lines, then breeding the corresponding lines until response to In11 was seen in all offspring. We will then test larval beet armyworms (Spodoptera exigua) on both INR- and INR+ lines. We expect the INR+ lines to have significantly lower S. exigua growth, indicating an improved immune response. We are also infiltrating INR- and INR+ lines with both In11 and flg22 (a well studied bacterial elicitor) for RNA sequencing of the early immune response. We expect genes involved specifically anti herbivory mechanisms being upregulated when compared to flg22. These two prongs allow us not just to demonstrate the viability of stable transgenic herbivory resistant lines, but to uncover the molecular mechanisms involved in that resistance, allowing for future scientists to better engineer the next wave of pest resistant crops.

Essentialist beliefs about gender modality, which conceptualize being transgender as an inherent and unchanging aspect of an individual, stand in contrast to perspectives that emphasize the social construction and fluidity of gender identity. These contrasting beliefs about the transgender identity are meaningful, as they shape the attitudes and behaviors among and towards trans individuals, who historically and currently face discrimination. To understand how trans people make sense of both cisgender and transgender individuals’ beliefs about the trans identity, I am conducting 12 semi-structured interviews with University of Washington students ages 18-25 who identify as transgender and/or non-binary. I analyze how specific assumptions, expectations, and cognitive worldview perspectives impact experiences and identity formation through a double consciousness perspective, a concept that has adapted from the writings of W.E.B. Du Bois about the impacts of racism. Double consciousness is an instinctive social awareness to uphold two identities, one that is “true” to oneself, and one that is constructed to conform in accordance to societal expectations in an act of self-protection. This can lead to feelings of inauthenticity and loneliness in a society that has rigid expectations for how gender should be represented. Therefore, certain assumptions and essentialist explanations about the social category of transgender, may motivate trans people to hold an additional social awareness to anticipate how cis people will react to their identities under the cis gaze. My data provides insight into the forces behind trans prejudice and offers transphobia mitigation recommendations, while centering transgender and non-binary voices in the research. Additionally, this research provides theoretical contributions, important for understanding the processes motivating essentialism and double consciousness. I conclude with directions and suggestions for future research.

Queer animality is an alternative framework of being disrupting how Spanish colonialism marginalized the third-gender spiritual figure of the quariwarmi. I argue that animality in Andean spirituality and culture illustrates queerness as a decolonial force despite the repression of indigeneity through the Spanish colonial regime. Seen through this lens, queer animality becomes a radical, fluid embrace of difference, emphasizing how the intersection of queerness and animality threatens dominant power. Indigenous spirituality and embodiment of animality are an active resistance to colonialism because they refute the Western gender binary and fear of the nonhuman. I analyze historical documentation of sodomy in Cuzco and depictions of Andean constellations in conjunction with artwork to demonstrate the intersection of queerness and animality. Contemporary Peruvian artistry pays homage to a queer past, uplifting oppressed bodies through a reclamation of animality. Peruvian artist Javi Vargas uses queer animality to highlight an alternative future, critiquing the colonial influences of masculinity on Peruvian historical figures. Spanish missionaries deliberately suppressed androgynous identities by demonizing sodomy, driving the quariwarmi underground. The jaguar constellation chuquichinchay appears when the quariwarmi is present, and this presence of Andean spirituality intimidates the colonial agenda when manifesting itself through a gendered and animalized power. The radical renditions of notable Peruvian and Andean figures as queer and animalized contribute to the vision of an alternative future where marginalized bodies are honored and celebrated. This exploration of speculative imaginings is crucial when queerness is being erased from the archive, displaying a sustained resistance to colonial oppression. In the context of contemporary Peruvian art, queer animality therefore represents a transformative outlook on identity, establishing that beyond the human, there is a liberatory future. 

This research project explores relationships between queer activist organizations and the business community in Portland, Oregon, during the early 1990s. By examining the fight against Ballot Measure 9, which would have curtailed LGBT rights in Oregon if it had passed, this paper shows how queer activism was shaped and developed during the late 20th century, by both internal and external concerns. As they led the charge against Ballot Measure 9, queer organizations in Portland actively sought to engage businesses for their monetary support and tacit endorsement of LGBT rights. By comparing and contrasting the experiences of one queer organization that was developed specifically for this fight and one that had long-standing grassroots ties, this paper illuminates the scope and variety of queer-business connections. My focus on the opposition movement to Measure 9, composed of queer organizations and their business allies, also demonstrates the critical nature of these alliances to the political success of queer organizations, starting in the 1990s, with an impact reaching well beyond the specific context of this specific ballot measure. This project, centered around extensive archival research that was supported by Pacific Lutheran University’s Benson Summer Research Fellowship, offers a new layer of understanding to American queer activism during this period, with implications that still shape current-day affairs in both the U.S. queer community and the U.S. business community.

Injustice has permeated the criminal legal system and its punitive regime for as long as this society has existed. The rapidly expanding American carceral state arose from a myriad of retributive policies and legislation that became prevalent throughout the last quarter of the twentieth century. There is currently an abundance of research focused on the effects of incarceration on people of diverse racial, ethnic, and socioeconomic backgrounds. A crucial gap in prison reform research remains the effects of this system of punishment on LGBTQ+ people. My research endeavor aims to address that fact and reveal how individuals with queer sexual or gender identities have been impacted by this system within Washington State. The institutions that exact punishment in this state operate both on a heteronormative apparatus and a gender binary. My thesis involves placing formerly incarcerated LGBTQ+ people at the forefront of prison reform research to highlight their distinctive adversities and establish policy proposals to ameliorate them. I conducted interviews with people who fit this demographic to bring to light their lived experiences and discover what practices, policies, and changes they want to see implemented. The findings illustrate a need for reform in areas including programming opportunities, support systems, healthcare accessibility, gender-affirming care, therapeutic services, housing assignments, reentry assistance, and equitable treatment overall. Incarcerated LGBTQ+ individuals are subjected to exacerbated punishment from correctional staff and other incarcerated individuals, which leads to difficulties with interpersonal dynamics and an overall suppression of identity. Faced with heightened vulnerabilities while incarcerated, LGBTQ+ people maintain resilient attitudes as they reenter society and positively transform their lives. The voices of this community in this research illuminates the necessity of addressing LGBTQ+ rights within prison reform efforts.

Substance use disorder disproportionately affects sexual and gender minority (SGM) youth compared to their heterosexual and cisgender peers, a disparity which is driven by unique stressors and systemic inequities. This systematic review synthesizes 122 empirical studies to explore the factors contributing to elevated rates of substance use among SGM youth and to identify gaps in existing prevention and intervention efforts. Findings reveal significant disparities, with SGM youth experiencing heightened vulnerability due to stressors such as expectations of rejection, interpersonal and structural discrimination, familial rejection, and other challenges of navigating a heteronormative world. These challenges are compounded by individual-level covariates including race, ethnicity, and socioeconomic status, which are often overlooked in existing research. A key finding is the paradox of community. While SGM-affirming spaces provide essential support, they are often closely associated with substance use. Despite sparse availability of targeted interventions, existing studies underscore the necessity of culturally relevant affirming approaches that address the unique needs of this population. Recommendations for youth, schools, practitioners, and families are provided, emphasizing the importance of fostering inclusive environments, reducing stigma, and building pathways to resilience and mental health. This review highlights an urgent call to action to address these disparities through innovative and inclusive prevention and intervention strategies.  

Determining the genus of a graph—the smallest surface on which it can be embedded without edge crossings—is a fundamental problem in graph theory with applications in circuit design, transportation networks, and data visualization. Existing genus computation methods often require extensive case-by-case analysis, and the problem is NP-hard in general. To address this, we developed and analyzed PAGE, a novel algorithm that efficiently determines a graph’s genus by enumerating non-backtracking closed directed trails and optimizing search iterations. We established an upper bound on its runtime as O(n(4m/n)^(n/t)) for graphs of girth t and implemented performance optimizations using hash sets for cycle tracking and adjacency list storage for rotation systems. We then conducted empirical comparisons against existing methods, including SAGEMath and MULTI_GENUS, demonstrating PAGE’s superior scalability, particularly for large 3-regular cage graphs. These results suggest PAGE’s potential to improve genus computation, contribute to open problems in topological graph theory, and enhance applications in fields requiring efficient graph embeddings.

In this work, we present two new geometric properties of ellipses that emerged while studying problems related to mass transportation. The first property states that if we shrink the ellipse proportionally and consider any tangent to the smaller ellipse, the two points where this tangent intersects the original ellipse always sum to the point of tangency. This reveals a fundamental symmetry in how ellipses scale and interact with their tangents. The second property describes a special set of interior points that arise by tracing how tangents from a fixed boundary point behave across a family of smaller ellipses. We prove that this set forms another ellipse, exactly half the size of the original, centered at the midpoint between the origin and the fixed boundary point. These findings offer new insights into classical geometry and may have potential applications for problems in mathematics and other fields. 

In this project, we study the order polytopes of generalized snake posets, a particular family of polytopes (geometric shapes with flat sides) defined in recent work by von Bell and coauthors. We specifically investigate triangulations of these polytopes, which are subdivisions of the polytopes into simplicies (arbitrary-dimensional generalizations of the triangle). To do so we examine their secondary polytopes. The secondary polytope of a polytope is a related polytope in which each vertex corresponds to a triangulation of the original polytope and each edge corresponds to a bistellar flip (a specific type of transformation between triangulations), capturing the combinatorial relationships between different triangulations in a geometric object. Von Bell and coauthors conjecture that the secondary polytopes of order polytopes of snake posets have multiple unusually nice properties similar to those of the associahedra, a well-known family of polytopes that admit nice combinatorial descriptions and appear in many areas of mathematics. The overall goal of this project is to prove these conjectures. Collaborating with fellow undergraduates Molly Bradley (University of Pennsylvania), Mario Tomba (Dartmouth), and Katherine Tung (Harvard), I have written code to compute details of the smallest examples of these secondary polytopes, proved related theorems/results, proposed some new conjectures based on observed patterns in the examined examples, and made partial progress towards proving multiple of the von Bell conjectures. This project is ongoing, and we continue to explore multiple ways to approach the conjectures and more broadly understand the secondary polytopes.

Image processing using dithering finds important applications for data compression, data encryption, data security and cryptography. Dithering is used for the design of high-quality printers, computers and game consoles. Digitization and compression of images often involve reduction of color palette which gives rise to color bands due to quantization errors. Dithering involves the application of noise to randomize quantization errors which helps preserve key features of images when converted to black and white and other color reduced formats. We applied mathematical matrix-algebra based methods for image digitization, image recognition and image processing. We wrote Python programs to study image quality before and after application of different algorithms for dithering including thresholding, randomization, ordered methods like Bayer’s method, void and cluster methods, error diffusion methods like Floyd-Steinberg techniques, etc. This project offered excellent hands-on opportunities to integrate programming in python with matrix algebra methods for image processing and provides insights into how different dither algorithms enhance visual capabilities along with compressing image size. Dithering introduces some textural contours and color shifts but preserves most features in image data. We also find that in addition to enhancing image quality, dithering modulations offer powerful techniques for digital watermarking and image embedding indicating their key role in data security.

The Mars Rover Sojourner is an autonomous robotic vehicle that was used by NASA for space exploration on Mars. The Mars Sojourner landed in a location called Ares Vallis in 1997 where it explored and took several photos and collected data. Google Maps and network routing programs, often use the popular Dijkstra's algorithm used to find the shortest and most cost-effective routes between various nodes on a graph. Here, we used the free open Cyberbotics Webots code to simulate the Mars Sojourner which was designed to successfully navigate over the rocky terrains of Mars. Robotic simulation software like Webots offers an excellent testing platform to study the stability and routing of autonomous navigation vehicles on different terrains prior to their deployment in outer space. The robotic Mars Sojourner was equipped with a GPS sensor which kept provided measurements of position using geodetic coordinates involving latitude and longitude. We used the Haversine formula to calculate distances between various places it traversed on Mars. We used a python code to map the shortest optimized route to go from point A to point B on Mars using Dijkstra’s iterative algorithm. Such studies are important for future development of robot motion controller software that can be effectively used for cost effective autonomous navigation in outer space.

Autism is a neurodevelopmental condition characterized by social-communication differences and restricted, repetitive behaviors (American Psychological Association, 2013). While racial disparities in autism prevalence have been documented, not much research has examined how these differences appear in autism screening measures. This study investigates racial differences in Autism Spectrum Quotient (AQ) scores among non-autistic Asian and White adults to assess potential biases in autism screening. Using data from three NIH-funded studies (COBRA, BEAM, and The Korean Study), AQ scores from 166 participants (n=102 White, n=64 Asian) will be analyzed through t-tests and Repeated Measures Analysis of Variance (ANOVA) to compare total and subscale scores. Preliminary observation suggests that non-autistic Asian participants may be more likely to score higher on the AQ, raising concerns about false positives in autism screenings. Understanding these differences will help improve diagnostic accuracy, reduce disparities, and promote equitable access to neurodevelopmental resources.

Asian Americans are victims of anti-Asian racism, but recent studies have also shown that they have a different role in perpetuating anti-Blackness and White supremacy. Our research aimed to specifically examine whether White and Asian Americans perceive a difference between anti-Blackness and White supremacy. We ran a qualitative study where anti-Blackness and White supremacy were defined for Asian and White American participants, who were then asked to write about their racial group’s relationship with those phenomena. We defined anti-Blackness as the belief that Black people are inherently inferior to others, and the corresponding practice of them being given insufficient power. Similarly, we defined White supremacy as the belief that White people are inherently superior to others and the corresponding practice of them being given disproportionate power. A few research assistants and I rated the similarity between the responses on anti-Blackness and White supremacy on a Likert scale from 1 to 7, with 1 indicating “not similar at all,” and 7 indicating “very similar.” We then performed a two-sample t-test (a type of statistical data analysis in psychological research) on this data to compare the responses between the Asian and White American participants. As expected, we found that the Asian American participants rated anti-Blackness and White supremacy as being more distinct than the White Americans did. The p-value for this data analysis was a statistically significant 0.004. These findings establish a foundation for future studies on the Asian American role in anti-Blackness and White supremacy. I have also conducted data analysis and ran participants for two such studies, which examined whether reminders of anti-Blackness caused Asian Americans to take more responsibility for anti-Blackness and show more solidarity with African Americans more than reminders of White supremacy.

First-generation college students (FGCS), those first in their families to pursue or complete a college degree, are a widely studied demographic across psychological research. However, much of the literature on FGCS examines their mental health and life experiences through a deficit framework, focused on systemic obstacles to success and categorizing students as “at risk”. Additionally, some research fails to recognize the importance of intersectionality, viewing FGCS’s mental health as separate from its systemic, social, and institutional contexts. To better highlight the assets and intersecting identities of FGCS, this strengths-based presentation explores existing literature about their mental health experiences, describes their risk and protective factors in developing mental health symptoms and conditions, and proposes mental health initiatives for FGCS and, specifically for, Latine FGCS. I use insights from interviews with Latine FGCS as illustrative examples to further demonstrate the importance of considering context and intersectionality in this area of psychological research.

Overgeneral Autobiographical Memory (OGM) is a common symptom of depression and Post-Traumatic Stress Disorder (PTSD). Instead of remembering specific details, individuals with OGM can only describe past events from their lives in general terms. The "trauma hypothesis" suggests that OGM emerges because individuals suffering from PTSD tend to reduce the number of details they retrieve about their memories to avoid remembering their trauma. However, this hypothesis does not fully explain how this avoidance is learned, or why avoidance spreads from traumatic memories to all autobiographical memories. To this end, we propose a computational model of OGM that integrates theories of memory retrieval and trauma with reinforcement learning. In this model, multiple episodic memories are nodes in an interconnected network, and memories are retrieved when visiting that node in the network. The more nodes that are visited, the more detailed that autobiographical recall will be. On the other hand, visiting more nodes comes with an increased risk of encountering a traumatic memory, which comes with negative emotional valence. The decisions about whether to visit another node or terminate the retrieval process are made using reinforcement learning, which takes actions based on predicted outcomes. By obtaining a greater understanding of OGM through this model, we hope to improve treatments for PTSD that specifically targets its effects on memory. 

The King County Brightwater Treatment Plant includes a marine outfall pipe anchored to the seafloor that discharges highly treated effluent from the Seattle metropolitan area into Puget Sound, Washington. Since 2009, as part of an eelgrass survey study, King County biologists have collected annual video footage of the outfall pipes from which they witnessed the abundance of organisms colonizing the pipe at all depths. Consequently, in 2012, King County biologists launched a ten-year project assessing the effectiveness of the high-density polyethylene (HDPE) outfall pipe at providing habitat for marine organisms and the composition of organisms it houses. Using a  remotely operated vehicle (ROV), they placed thirty plates of HDPE material adjacent to the outfall pipe at 100ft, 300ft and 600ft depths. Sets of replicate plates were then retrieved after 2, 5, and 10 years of deployment, at which time King County staff immediately took photos of each plate for analytical assessment. In this study, we analyzed the photos for percent live cover and composition of marine organisms inhabiting the pipe material, all across depths and time intervals. We hypothesized that the wastewater outfall pipe can function as a habitat; and the extent to which different organisms, their identifications and abundance, likely vary by depths due to the environmental conditions at different levels of depths. We found that percent live cover increased over time but did not vary across depths, and that certain phyla consistently dominated cover on the plates but dominant groups varied across depths. These findings allow experts in the field to consider using outfall pipes to provide additional habitats for marine organisms, and to assess communities of organisms at depths that are less accessible. 

Harmful algal blooms (HABs) are threats to a number of species in marine environments. One hypothesis states that excess nutrients in water lead to accumulations of certain plankton species that produce toxins. This can explain some illnesses such as paralytic shellfish syndrome in humans who consume impacted shellfish. HABs can be identified directly, but given the delays involved in analyzing results, other indicators may be used to predict presence of HABs as well. Possession Sound is an inlet of the Puget Sound located between Whidbey Island and the coasts of Everett and Mukilteo, Washington, connecting to the Snohomish River, as well as Saratoga Passage and Port Susan to its North and the main Puget Sound basin to its South.  Since HABs can occur in freshwater and saltwater for different reasons, Possession Sound’s status as a salt-wedge estuary makes it notable as a study site. To investigate the nature of HABs in Possession Sound, I analyzed plankton density data, chlorophyll-a levels, and phosphorus concentration data I collected in 2024 as well as data collected by the Ocean Research College Academy from 2016-2024. Chlorophyll-a concentrations were measured with a YSI EXO Sonde. Phosphorus concentrations of water samples were collected using a Niskin bottle and measured by the University of Washington Marine Chemistry Lab. I analyzed the progression of each parameter temporally and spatially. I expect to see clear spikes in certain plankton species, especially dinoflagellates, that align with similar-timed chlorophyll-a and phosphorus spikes. However, I predict that trends will be the least prominent in phosphorus concentrations due to its greater prevalence in freshwater than in saltwater. Understanding which plankton species are most responsible for HABs and temporal alignment of potential drivers can allow for better prediction of HABs in Possession Sound.

Zostera marina (eelgrass) is one of the many important biological features of Possession Sound, acting as a substrate for many microorganisms, a filter of greenhouse gases, and as protection for many species. The Possession Sound has been marked as a Seagrass Sanctuary by the Department of Natural Resources, which protects and monitors nearshore eelgrasses within the basin. By looking at what kinds of species are found in a marine environment, researchers can assess an ecosystem's overall health. Environmental DNA (eDNA) is a data capture technique used by researchers that picks up DNA traces left behind by organisms, and shows their presence/absence in a given area. The study site, Mount Baker Terminal, lies inside the Possession Sound basin near Everett, Washington, and contains a large eelgrass bed. I collected 10 samples using passive filters submerged at various depths inside and outside the eelgrass bed in 2024 and processed at a WDFW lab. I analyzed these data and 40 additional samples collected by the Ocean Research College Academy from 2021-2024 using similar methods. I hypothesized that there would be more species such as crustaceans, fish, and other plants inside the eelgrass because of its ability to protect and maintain a nutrient-dense environment. These data will help shed light on species richness in each environment, which has potential implications for understanding the overall health of the ecosystem and the critical role eelgrass plays in the estuary.

Possession Sound, located between the city of Everett and Whidbey Island, is a part of both a key economic area and a bustling marine environment. Because of the marine activity, scientists study all sorts of parameters involving the water including noise. Numerous studies have assessed ambient noise in marine environments to investigate the influence of tidal forces on ambient noise. These reports found that tidal noise or “flow noise” is observed around the 0-100Hz range with the most significant impacts observed centered around 25hz. The Ocean Research College Academy operates a SoundTrap ST400 STD hydrophone mounted to Mount Baker Terminal that takes recordings daily for most of the year. Mount Baker Terminal is a small marine terminal operated by the Port of Everett, located just north of the town of Mukilteo. Using data collected from the hydrophone, I took measurements of ambient noise in root mean square amplitude centered around the 25hz range and compared that to NOAA tidal data at Everett, Washington. Using these data I investigated the potential presence of a relationship between the tides and ambient noise. When the initial measurements of root mean square amplitude were compared to tidal data from the area the results showed that tides had no significant impact on the ambient noise at Mount Baker Terminal. Investigating the effects of tides on ambient noise can be crucial to future acoustic research done by researchers in the area as results could be affected by noise created or affected by tides. Future analysis should investigate the impacts of other natural contributors to the soundscape such as rain and wind.

The Eastern North Pacific gray whales (Eschrichtius robustus) have a long migration from their breeding grounds in Mexico to their feeding grounds in Alaska. A subgroup of the Eastern North Pacific stock, nicknamed the Sounders, deviate from the migratory path most gray whales follow to feed in the Salish Sea, typically between the months of March and May. Other studies show that gray whales feed on benthic organisms such as ghost shrimp. Studies conducted in the Arctic area of the gray whale migration route have seen sea ice playing an important role in the gray whales being able to enter the areas where they feed. One working hypothesis is that gray whale shifts in migration patterns are the direct result of climate change; this could explain why some of the Eastern North Pacific gray whales enter and feed in Possession Sound. I analyzed sightings data, shared by the Whale Museum and recorded in Possession Sound, WA from 2000-2022. These data, most of which were compiled by the Orca Network, were filtered to identify the number of visitations each month over the study period. Early analysis shows a phenological shift in the time of the gray whale's arrival and departure from Possession Sound. The shift shows an increase in the number of months gray whales are present in Possession Sound, from a March to May visit to a year-round presence. Although these results cannot explain the reason for the phenological shift, future research must look into related shifts in the Arctic ice formation as well as ambient air and water temperature shifts. Future research calculating density of ghost shrimp in Possession Sound will also indicate why this location is favored.

Ocean acidification is the reduction of pH in seawater due to increased carbon dioxide from fossil fuels in the atmosphere and other anthropogenic factors. Ocean acidification causes shellfish such as oysters to experience difficulty building their shells. Acidification trends in the North Pacific Basin are well documented, yet pH trends in Possession Sound, a salt-wedge estuary located in the Salish Sea is less documented. Possession Sound receives discharge from the Snohomish River and has human activity along the shoreline. In this study, the average change of pH in the middle of the North Pacific Ocean was measured and compared to the average change of pH in Possession Sound since 2016. I analyzed data collected from ARGOS Floats located in the central North Pacific Ocean. For Possession Sound, I used data collected from a  YSI EXO Sonde in partnership with the Ocean Research College Academy (ORCA). I collected data on 12 research cruises in 2024. I expect to find a slightly greater decrease in pH within Possession Sound than the North Pacific Basin due to the additional anthropogenic factors present in the Sound. Preliminary analysis shows a slight seasonal change in pH in Possession Sound, but little to no change yearly. I expect the data to show a steady decrease in pH for Possession Sound and the North Pacific Ocean basin every year since 2016. Calculating acidification rates and learning how they differ in various geographical locations, with separate factors, will increase understanding of the impacts of ocean acidification, which may be used in conservation efforts. 

Initial work from our lab has demonstrated that decision-making in OCD patients varies along the approach-avoidance behavioral axis depending on their response to deep brain stimulation (DBS) treatment. Patients who do not respond to DBS exhibit heightened risk aversion and consistently make avoidant decisions, while responders balance risk and reward in their decision-making process. In contrast, patients who receive excessive stimulation display disinhibited behavior, making choices that maximize reward regardless of potential risk. While this 2D task has provided valuable insights into approach-avoidance behavior in OCD, it does not fully capture the naturalistic behavioral responses observed in daily life. To address this limitation, we are developing a virtual reality (VR) task designed to quantify approach-avoidance behavior in a dynamic 3D environment. Participants complete probabilistic decision-making trials while wearing a VR headset, allowing for precise tracking of eye movements, hand positioning, and body dynamics. This project aims to provide a naturalistic task to analyze movement velocity and behavioral trends to identify neural biomarkers associated with approach-avoidance tendencies. This work will act as a stepping stone, enabling deeper insights into how neuromodulation regulates these behaviors. We are currently finalizing the development of this VR task and will demonstrate the feasibility of using this task to collect unique behavioral data on approach-avoidance behaviors. In the future we hope to use this task to identify biomarkers of approach-avoidance behavior and use that information to further refine neuromodulation treatment for psychiatric disorders.

Dopaminergic signaling within the striatum plays a crucial role in modulating reward and aversion, shaping behaviors such as food-seeking and consumption. While striatal dopamine release has been implicated in reinforcement learning and decision-making, the spatial and temporal dynamics of dopaminergic activity along the anterior-posterior axis of the striatum during consummatory behavior remain poorly understood. We investigated the role of dopamine in the striatum during the consumption of multiple solutions by employing a trial-based multi-spout behavioral paradigm with head fixed mice. To record the dopamine activity in the ventral and dorsal striatum, we utilized multi-site fiber photometry to record the fluorescent biosensor GRAB-DA2m along the anterior-posterior axis. Food restricted mice were given varying concentrations of sucrose as rewarding stimuli, while water restricted mice were given varying concentrations of sodium chloride as aversive stimuli. Our results revealed that dopamine responses scaled more across concentrations in the anterior regions of the striatum compared to the posterior regions. Additionally, we found more distinction between dopamine responses for the various concentrations of the aversive solution compared to the rewarding solution. Lastly, posterior striatal dopamine responses had a more rapid onset upon stimulus consumption, whereas anterior regions exhibited delayed responses, highlighting region-specific temporal differences in dopaminergic encoding. These findings refine our understanding of dopaminergic circuitry within the striatum and how dopamine-mediated responses to rewarding and aversive stimuli regulate feeding behaviors. By exploring this pathway, we offer potential insights into the mechanisms underlying disorders characterized by dysregulated reward including eating disorders and obesity.    

The ability to pattern three-dimensional microscale cultures opens new avenues for examining the effect of nonplanar mechanical environments on mammalian cells and tissues. Our lab has developed a method for generating suspended tissues with spatial control using open microfluidic principles called Suspended Tissue Open Microfluidic Patterning, or STOMP. STOMP utilizes spontaneous capillary flow and capillary pinning to pattern suspended, multi-region tissues. Using similar microfluidic principles as STOMP, we have developed a method to pattern large (cm-scale) models via semi-open microfluidic channels called Suspended Nonplanar and Planar, or SNaP, geometries. I design these devices with computer-aided design, fabricate components on stereolithography 3D printers, pattern devices with standard pipettes, and culture resulting tissues for short- and long-term time periods to model biological scenarios. With the broad statement that human tissue is generally nonplanar in mind, my research focuses on three different geometries of tissue, 1) a sinusoidal wave, 2) a transwell-like mogul, and 3) a multi-region dome, where each nonplanar geometry enables a different biomedical investigation. The sinusoidal wave construct allows us to ask if cells embedded in tissues with varying frequencies of undulation experience changes to cell morphology due to the topology of their environment; the transwell-like mogul enables investigation of cell proliferation of cells grown at or within an air-liquid interface; and the multi-region dome facilitates the study of tissue interfaces where a diseased region of cells meets a healthy region of cells, all within a single contiguous tissue. I am currently exploring these questions through multiple cultures where different device versions and/or multiple cell types are engaged to collect biological readouts which demonstrate SNaP as a translatable platform for the investigation of questions in biomechanics and regenerative medicine.

Electrochemical water splitting is an effective method for generating hydrogen gas (H2) and an attractive means for energy storage. During this process, hydrogen and oxygen bubbles form on the electrode surfaces often lower the efficiency of gas production. The overarching goal of this study is to probe and better understand the nucleation process of small H2 and O2 nanobubbles on the electrode. To do this, we use ultrasensitive fluorescence microscopy to monitor the transient adsorption and desorption of single fluorophore molecules, such as Rhodamine 6G (R6G), on the nanobubble surface. My project aims to study how different fluorophores interact differently with the bubble surface and how they may interact with each other when multiple fluorophores are co-adsorbed on the bubble surface. This research may help us better understand bubble-molecule and molecule-molecule interactions at confined spaces for enhanced chemical labeling of the nanobubble surface. Moreover, it may also help us better understand the chemical nature of the gas/water interface, which has direct implications for more efficient gas productions and energy conversion and storage.

Biodiesel, "an alkyl ester of fatty acid" and type of biofuel, can be used for fueling vehicles and can be produced via transesterification, the process of using the alcohol methanol along with a base catalyst (usually sodium hydroxide) to break down oils and fats that have many triglycerides into fatty acid methyl esters (FAMEs) and glycerol. The viscous triglycerides are broken down into ester bonds and free fatty acids (FFAs), which are not ideal for biodiesel synthesis because FFAs have high melting points, unlike FAMEs. Thus, biodiesel synthesis should be conducted in a manner that reduces the number of FFAs while having a high breakdown of triglycerides into ester bonds. Transesterification that involves alkali/alkyl (like the bases sodium hydroxide (NaOH) and potassium hydroxide (KOH)) as a catalyst can cause soap-FFA reactions, resulting in "emulsification" challenges (Cheng et al 2013) (Hasan et al 2017). KOH and NaOH both can cause soap formation if they interact with triglycerides and esters. Furthermore, KOH produces more soap that NaOH, but KOH also helped produce more biodiesel than that from NaOH at 0.2 mol concentration (Van Gerpen et al 2006). What are the effects of NaOH and KOH on the fuel value of the biodiesel produced over the course of eight weeks? If KOH is used to synthesize biodiesel, then the biodiesel's fuel value form KOH will be higher than that form NaOH. Although the research project is currently in progress, the anticipated result is that KOH better catalyzes transesterification (via causing more heat combustion of ethanol) than NaOH for producing biodiesel. The results' significance determines which catalysts are used to produce more biodiesel. This is because the amount of biodiesel produced can be used for daily life purposes like faster transportation without having to refuel automobiles as frequently.

Proteins in the NFкB family are transcription factors that modulate the expression of genes relating to immunity and inflammation. One protein within this family is the p50/RelA heterodimer which includes a structured DNA-binding domain and a Transcription Activation Domain (TAD) which is intrinsically disordered, or naturally lacking secondary and tertiary structure. Previous studies have shown that interactions between the DNA-binding domain and TAD affect DNA binding affinity and specificity. With the goal of further assessing and comparing the interactions between intrinsically disordered and structured domains in proteins of this family, we have worked to troubleshoot and optimize protocols relating to expressing and purifying human p50/RelA protein. I analyzed the efficiency of multiple chromatography steps and introduced changes to improve yield. Optimization of the expression and purification protocols will enable future investigations into the DNA binding activity of this protein.

Members of the gut microbiota produce an array of bioactive metabolites that impact many aspects of host metabolism, immunity, and behavior. However, the mechanisms by which these metabolites are generated remain poorly understood and the biosynthetic enzymes are largely understudied. Recently, our laboratory discovered a family of gut microbial amidases that were found to affect hunger-related biological pathways in malnourished children. These amidases hydrolyze N-acyl ethanolamines (NAEs), lipid messengers with known roles in satiety, visceral pain, and inflammation. Using one of these family members as a model amidase, I am exploring and defining the catalytic mechanisms that are responsible for NAE hydrolysis and the production of a new class of gut microbial metabolites, N-acyl amino acids (NAAAs). I used computational models to predict specific residues that might be important for the amidase activity. I then cloned mutant enzymes into an E. coli expression vector, induced recombinant protein expression, and tested the ability of the purified mutant enzymes to hydrolyze labeled NAEs using liquid chromatography - tandem mass spectrometry (LC-MS/MS). These analyses have pinpointed residues that are important for substrate recognition and binding. My work is advancing our understanding of the selectivity of these intriguing gut microbial enzymes and the regulation of NAAAs in the gut lumen. These efforts are expected to generate the knowledge required to engineer more selective enzymes that produce metabolites of known bioactivity.

Neuronal and endocrine cells store and secrete molecular cargos like neurotransmitters and metabolic hormones through the regulated secretory pathway. Dense-core vesicles (DCVs) originate from the trans-Golgi network and undergo a maturation process involving peptide processing and cargo sorting before being stimulated to release their cargos outside the cell. Dysregulation of this process leads to a wide range of neurological and metabolic disorders; yet the molecular mechanisms underpinning it remain poorly understood. Vesicular traffic are largely coordinated by the Rab family of GTPase proteins.  Previous work identified the conserved proteins TBC8 and RUND1 as regulators of DCV maturation in Caenorhabditis elegans; and both proteins bind active GTP-bound RAB2. TBC8 is the putative RAB2 GTPase activating protein (GAP) which promotes conversion of GTP-RAB2 into GDP-RAB2, thereby inactivating the Rab. RUND1 interacts with both active GTP-RAB2 and TBC8, yet its precise function remains unknown. This study aims to characterize the biochemical function of TBC8 and RUND1 in regulating RAB2 activity. Using purified proteins, we demonstrate that TBC8 greatly promotes RAB2 GTP hydrolysis, indicating it is the bona fide RAB2 GAP. Additionally, we show that RUND1 strongly inhibits TBC8-stimulated RAB2 GTP hydrolysis, suggesting RUND1 may compete with TBC8 for RAB2 binding. Given this interplay between RUND1 and TBC8 in binding RAB2, we hypothesize that RAB2 exhibits exclusively pairwise interactions with its partners. To test this, we will use mass photometry to study whether RUND1 and TBC8 can bind RAB2 simultaneously or if one complex is preferentially formed. Based on our current findings, we propose a model where TBC8 promotes RAB2 inactivation by stimulating GTP hydrolysis and RUND1 blocks RAB2 inactivation by TBC8, prolonging the activate state of RAB2.

Pulling apart DNA during replication induces DNA strands to wrap around each other, producing positive supercoils ahead of the replication fork. Positive supercoils hinder further DNA replication, and are removed by Type II Topoisomerases (Top2s), a group of essential enzymes that cleave positive supercoils to relax DNA for easy separation. Errors in supercoil resolution are linked to diseases like cancer and autoimmune disorders. A key question in the field is the mechanism by which Top2s locate positive supercoils. We recently discovered that GapR, an essential DNA binding protein conserved across α-proteobacteria, binds positive supercoils and stimulates the activity of bacterial Top2s DNA Gyrase and Topoisomerase IV. We hypothesized that GapR recruits Top2s to positive supercoils by direct interaction. We investigated this mechanism by using a Bacterial Two-Hybrid assay to screen for GapR interaction with Top2 subunit and identified an interaction between GapR and the A subunits of DNA Gyrase and Topoisomerase IV. Additionally, we discovered that GapR interacts with Top2 A subunits, and not with Top2 B subunits, in a gel shift assay. In collaboration with the David Baker lab, we generated predictions of the GapR-Top2 interaction which together support a model of interaction between GapR and the Top2 A subunit that is mutually exclusive to the Top2 B subunit. In our current work, we aim to identify the mechanism of direct interaction between GapR and Top2s aided by mass photometry and biochemical experiments to reveal a previously unknown mechanism of Top2 recruitment. Because GapR is conserved by alphaproteobacteria, our research could reveal a target for inhibition by antibiotics. If such Top2 recruiters are more broadly conserved, our work provides a novel pathway to target with anticancer therapeutics as human Top2 inhibitors are important chemotherapy drugs.

Hydrogen sulfide (H₂S), known for its distinct smell of rotten eggs, is recognized as the third endogenous gaseous signaling molecule, alongside nitric oxide and carbon monoxide. Often described as a double-edged sword, H₂S exhibits both cytoprotective and cytotoxic properties depending on the biological context. A 2018 study suggested that H₂S enhances the efficacy of doxorubicin (Dox), an anticancer drug, by promoting apoptosis and reducing colony formation in HepG2 cells, even restoring drug sensitivity in resistant cells. However, my preliminary experiments indicated a protective role of H₂S in HepG2 cells under stress, particularly when treated with NaSH (an H₂S donor). Rather than inducing apoptosis, H₂S appears to support cell proliferation and regulate reactive oxygen species (ROS) production. My research project aims to identify H₂S -dependent pathways in HepG2 cells under oxidative stress. Using Dox as a stress inducer, I conducted viability and cytotoxicity assays, demonstrating that supplementation with 250 µM NaSH at 0 and 12 hours significantly restored cell survival. To investigate the molecular mechanisms, RNA-seq analysis identified 2,996 differentially expressed genes in the H₂S + Dox group compared to Dox alone. Principal component analysis (PCA) revealed distinct transcriptomic profiles, while KEGG enrichment analysis highlighted significant alterations in genes within the PI3K-Akt pathway. To further validate these findings, I plan to perform flow cytometry and western blot analysis. While the role of H₂S continues to be debated, my data suggest a protective function in liver cells against Dox-induced stress via the PI3K-Akt pathway. Understanding these mechanisms could pave the way for new therapeutic strategies aimed at maintaining or increasing H₂S levels to support cell health in diseases characterized by oxidative stress, such as cancer and diabetes.

The small ubiquitin-like modifier protein, SUMO, regulates the activity of many cellular processes through covalent modification of proteins. These modified targets include the protein components of chromatin; histones H2A, H2B, H3, and H4. Chemical modification of histones directly regulates gene expression, necessitating an understanding of the role of each type of modification. The identification and role of histone SUMOylation has been described for H4 in human cells; however, SUMOylation of H2B in human cells has been recently observed but not yet characterized. SUMO is shown to impose a predominantly repressive effect on many cellular processes and proteins that it targets. Therefore, I am working toward identifying the role of H2B SUMOylation to either add to this narrative or describe novel functions of SUMO. To accomplish this, I have purified wild-type histones and SUMO-histone fusions through bacterial expression followed by size-exclusion and affinity chromatography. The purification of several of these proteins has not been described yet; therefore, I designed the purification for these proteins using unique methods, like solubilizing tags, to obtain the product. I reconstituted the purified proteins into octamers, the protein complex that DNA wraps around, and purified the octamers away from other oligomeric forms of the histones via size-exclusion chromatography. I further reconstituted the octamers into mononucleosomes by condensing DNA around them to mimic SUMOylated nucleosomes in chromatin. I hope to then subject the mononucleosomes to in vitro biochemical assays to observe changes in the modifications that regulate other chromatin-associated proteins. A better understanding of the complex dynamics at play during gene expression and repression is needed to identify stronger, safer, and more sustainable therapeutics. Furthermore, SUMO is implicated in a wide array of diseases, such as Alzheimer’s. Therefore, the results of this study will increase our understanding of gene regulation and provide insight towards treating related diseases.

Cardiac-specific promoters, such as NK2 homeobox 5 (NKX2.5), are essential for driving gene expression during early heart development, making them valuable for studying neonatal congenital heart diseases. However, the large size of the NKX2.5 promoter limits its use in adeno-associated virus (AAV) delivery systems, restricting vector space for therapeutic genes. This study aims to develop a compact hybrid NKX2.5 promoter that retains cardiac specificity while enhancing its efficiency in early-stage cardiac research and gene therapy. To achieve this, we replace the enhancer region of NKX2.5 with a shortened cytomegalovirus (CMV)-derived enhancer, preserving cardiac specificity while reducing promoter size. The hybrid promoter is then cloned into an AAV vector to drive green fluorescent protein (GFP) expression for assessing transcriptional activity and tissue specificity. Following AAV injection into pregnant mice, we will harvest early-stage embryos to evaluate GFP expression in cardiac tissues, comparing the hybrid promoter’s efficiency against the original NKX2.5-driven GFP expression. This study addresses current limitations of cardiac-specific promoters by developing a streamlined version optimized for gene delivery in neonatal models. Our findings strives to enhance gene therapy strategies for congenital heart diseases and provide insights into early cardiac gene regulation.

This study utilizes design research to explore how storytelling informs the design, usage, and knowledge production of a digital archive repository housing digitized memory objects. Ranging from ao dai to math booklets, these memory objects are grounded by narratives of Vietnamese diasporic identity and experiences shared by community researchers as part of Sarah Nguyen’s Sharing Stories, Sharing Trust (SSST) workshop series. To understand how story-driven approaches translate and transform digital archive design, I draw upon multiple methodologies such as case study analysis of existing community-based applications of digital archives and thematic analysis of SSST workshop discussions (formatted as observational memos). I also draw from user interviews with community researchers using a semi-structured, narrative-driven protocol. These analyses inform the design of a digital repository prototype that foregrounds story-driven design whilst exploring possibilities for the preservation and sharing of Vietnamese diasporic experiences.

“In Africa, whenever an old man dies, a library burns down.” –Amadou Hampâté Bâ. Malian writer, historian, and ethnologist Amadou Hampâté Bâ’s quote underlines elders as keepers and purveyors of knowledge, culture, and wisdom. As “libraries” worth prioritizing and preserving, Black grandmothers’ stories and cultural inheritances (material possessions, cultural traditions, rituals, language, etc.) have been integral to the matriarchal traditions and culture characterizing people of African descent. Yet, at key periods, African Americans have experienced threats to our collective ability to document, preserve, and pass down our “libraries” because of a lack of financial resources and technological support. Black grandmothers experience multidimensional oppressions and rarely have a chance for self-representation. What are the ways black grandmothers experience erasure in the digital age, and within their communities through displacement? How are we responding? How can researchers mitigate, document, and disrupt their erasure? To conduct this work, we collect oral histories, document cultural inheritances, and create data visualizations to digitize their "libraries." We document, preserve, and amplify Black culture and history by sharing the lived experiences of Black grandmothers. The Black Grandmother Worldmaking Library is a collaborative, community-based model for gathering, archiving, and digitizing distinct aspects of our “libraries” beginning with the stories and cultural inheritances of Black grandmothers experiencing mass displacement in Seattle’s Central District and along the Gullah Geechee Corridor. The project offers a readily accessible digital resource for Black grandmothers to contribute to and control the stories we tell about their lives. The Black Grandmother Worldmaking Library aims to repair what we are taught about Black grandmothers, to reclaim their narratives and culture using firsthand accounts, and to preserve their legacies.

I am currently assisting PhD student Jessica Luo in her research of the Sanmen Wu sound system, a language of the Wu family found in Southeast China. As Jessica writes an article that summarizes the sound structure of Sanmen Wu, I analyze utterances produced by speakers of the language. In my self-guided research, I focus on the sound quality of the consonants and their variations to determine underlying pronunciation. I also connect these variations to historical sound changes from Middle Chinese, its ancestor, into Sanmen Wu. I observe that Sanmen Wu speakers tend to freely alter pronunciations of certain consonants. For example, a speaker may say 部 [pu] or [bu] meaning ‘part,’ the latter only appearing after another spoken word. These two syllables contrast only in voicing, where [p] is voiceless and [b] is voiced. I use Praat, an industry-standard speech-analysis program, to read diagrams that depict the acoustics of these consonants to verify my findings. I am also creating a set of rules that predicts this alternation. One of the conditions is as follows: words with alternating voicing in their consonants change when pronounced within a sentence (‘medially’). Eventually, I will explain these rules, and I predict my explanation is related to the evolution of Sanmen Wu into its current stage. I reason that because the Wu language family stems from Middle Chinese, both of which require contrastive voicing to create distinct words, Sanmen Wu also contains the original underlying variation that exists in Middle Chinese. As such, I attribute this variation to an inherent part of the language rather than random circumstance. Ultimately, I intend to foster a thorough understanding of Sanmen Wu phonology and provide a foundation for further exploration of this topic.

The title of this project references Stuart Hall’s memoir, Familiar Strangers and encapsulates the experience many artists have when portraying family members they have never met but feel like they know through photographs. Drawing from Tina Campt’s definition of the haptic–how viewers touch or are touched by family photos–I look to Black artists’ uses of photos to express their relationship to themes of family, diaspora, memory, and history. How do Black artists use hapticity and embodiment to engage with family photos and produce alternative ways of conceptualizing identity? How do they view family photos as sites of memory activation? Why and when have these artists returned to family photos as source material?  This focus on hapticity reveals how Black visual artists recreate, re-enact, and revise family photos in their work to produce micro-histories that might otherwise be lost. I analyze artist statements, arts and culture literature, and academic articles to identify individual artists’ approaches to family archives. The featured 19 artists span the African diaspora, and I use Safia Elhillo’s home is not a country as a framework to situate the socio-political contexts of their work, which include the legacy of transatlantic slavery, transnational migration, diaspora, colonialism, racial apartheid. Many of the artists have gained significant attention as they portray family history and collective memory in their practice. This work can guide future exhibitions and continue the ongoing conversation on family photography in Black visual art.

Zanele Muholi is a queer, Black, nonbinary South African photographer who produces work depicting the lived emotional experiences of Black queer South Africans, specifically highlighting individuals who have lived through corrective sexual abuse. While corrective abuse against queer and Black people has been documented throughout the art historical canon, many depictions acknowledge only the physical pain, completely omitting the emotional toll this abuse causes. Acknowledgement of the range of emotion of queer and Black individuals in the art world is unfortunately extremely limited, especially when considering depiction of victimized forms; however, Zanele Muholi creates artwork that counters this inadequacy. Through the medium of black and white photography, captured with a “loving” lens, Muholi subverts the concept of corrective sexual abuse by emphasizing the true emotional impact it has through a focus on facial expression and body language, humanizing their subjects to decolonize and reclaim the long-exploited image of the black body from historical degradation under apartheid; they simultaneously challenge accepted gender presentation by depicting queer South Africans who fall outside of the accepted gender binary, making unavoidable the humanity of those who have endured this kind of abuse. Muholi’s work is intended for a wide audience; they want to provide an avenue for queer Black individuals to see themselves in the art world, however; they also want their work to be experienced by those who may be unaware of their communities’ struggles to humanize them to the world. By examining a selection of Muholi’s works alongside historical and contemporary examples of Black pain, and investigating responses to the artist, this paper proves that Muholi’s work questions how Black pain is depicted in media and pushes the boundaries of accepted gender presentation and sexual orientation in the museum space, ultimately creating a fuller picture of the queer Black lived experience.

Maintaining the integrity of genetic material and preventing changes over time is essential for normal cellular function. This genomic stability is directly affected by the DNA replication process. Replication must be both accurate and efficient; mutations that affect DNA replication can cause genomic instability and changes in the genetic makeup of the cell. Through a genomic instability screen in mice, researchers discovered a single base pair mutation in a highly conserved gene required for unwinding DNA during DNA replication. The presence of this single base pair substitution, called Chaos3, in both copies of the gene causes female mice to develop mammary tumors. We have found that in the yeast Saccharomyces cerevisiae, the corresponding Chaos3 mutation decreases activation or “firing” of some replication origins—the sites where DNA replication begins. Chaos3 does not affect all early firing origins in the genome; rather, origins near centromeres are specifically affected, thereby delaying replication of those centromeres, causing chromosome loss. We found that when an affected origin is replaced with an unaffected one, firing levels are restored to wild type function and that chromosome loss is rescued. To further understand what components are essential for timely DNA replication, and why only a subset of origin sequences are sensitive to the Chaos3 allele, I am focusing on the origin sequences directly. I am mutating the origin sequence itself and separately deleting different genes whose products have potential interactions with origin sequences. My research aims to advance the understanding of the role these genes play in the activation of origins for timely DNA replication and how the Chaos3 mutation may be interrupting normal function of these processes. This knowledge can help identify key molecular mechanisms that drive cancer development in higher eukaryotes.

Regulatory T cells (Tregs) play an integral role in self-tolerance and the preventing autoimmunity by suppressing the immune response. As such, inducing Treg expansion is a promising avenue for treating autoimmunity. Previous studies have shown that treatment with an interleukin-2 (IL-2) mutein Fc.Mut24 causes more robust Treg expansion than wildtype IL-2 and is effective at preventing autoimmunity in the non-obese diabetic (NOD) mouse model. In this study, we identified the synergistic roles of the T cell receptor (TCR) and IL-2 receptor in IL-2 Fc.Mut24-mediated Treg expansion, leading to the question of how TCR stimulation is affected during treatment. Classical dendritic cells (cDCs) present antigens to the TCR on Tregs, leading to an increased Treg population to suppress autoimmunity. This study aims to elucidate the role of interactions between Tregs and cDCs during IL-2 Fc.Mut24 treatment using in vivo mouse models. Through the uLIPSTIC (universal labelling immune partnerships by sortagging intracellular contacts) model, we reveal the effect of IL-2 Fc.Mut24 on the frequency of short-range and transient Treg/cDC interactions. Using Zbtb46-DtR bone marrow chimeras to deplete cDCs, we may begin to understand the extent to which cDCs are necessary for the robust Treg expansion typically seen during IL-2 Fc.Mut24 treatment. Preliminary results of cDC depletion do show reduced Treg expansion. We expect to find that IL-2 Fc.Mut24 promotes immunosuppressive Treg/cDC interactions in vivo, as indicated by increased frequency of interaction and cDC-dependent Treg expansion. The findings from this study will contribute to a greater understanding of how IL-2 mutein therapies mechanistically combat autoimmunity, potentially paving the way for identifying new applications to treat disease.

Copy number variation (CNV) is associated with genetic disorders in humans. One particular kind of CNV is a gene triplication in which the central copy is inverted. How such structures arise is poorly understood but is of great interest because of their association with cancer and other genetic disorders. We find similar amplified structures in budding yeast Saccharomyces cerevisiae, and therefore, we can use yeast to understand the mechanism that generates them. The Brewer and Dunham labs have proposed Origin Dependent Inverted Repeat Amplification (ODIRA) as a model that explains inverted CNVs. To understand which proteins/enzymes contribute to amplification, we are implementing gene deletions to observe the effect on the production of these ODIRA amplification events. ODIRA events are rare and thus large sample sizes are required to detect them. To streamline their identification, I am developing a system that uses color as a visual indicator of CNV. When a single copy of the bacterial gene, VioA, is expressed in yeast it produces light purple colonies; in multiple copies, the colonies are a darker shade of purple. I am inserting a single copy of the VioA gene into a region of the yeast genome that undergoes inverted triplication events. Simply scanning plates for dark purple colonies will enable me to screen for ODIRA events quickly and measure their frequency. Using this visual indicator will allow me to rapidly screen different yeast mutants and determine the role they play in the ODIRA amplification mechanism.

Merkel cell carcinoma (MCC), a rare skin cancer, is mostly driven by integration of the Merkel cell polyomavirus which encodes T-antigen (T-Ag) proteins. Previous research has shown that T & B cells target T-Ag. Indeed, patients with virus-driven MCC produce T-Ag-specific antibodies that are useful to track disease progression. These antibodies do not play a direct role in MCC immunity as T-Ag proteins are intracellular. Our group has recently found that in tumors, T-Ag-specific B cells with germinal center or antibody-secreting phenotypes strongly predict improved MCC outcomes. These intratumoral B cell phenotypes reflect a robust cancer-specific T cell response. In contrast, T-Ag-specific B cells in the blood of MCC patients are predicted to predominantly have a memory or naive phenotype, and it is unknown if they contribute to anti-tumor immunity. We used fluorescently labeled T-Ag-proteins and flow cytometry to assess B cell responses in blood at the time of MCC diagnosis. In total, we analyzed samples from 23 patients whose MCC recurred within 3 years of diagnosis and 24 samples from stage- and age-matched MCC patients whose disease did not recur. We found no difference in the frequency of all circulating B cells (regardless of T-Ag-specificity) between patients who did and did not develop MCC recurrence. In contrast, higher frequencies of total memory B cells (CD27+IgD-IgM-) were associated with an increased risk of disease recurrence (HR 3.67 [1.58- 8.55], p=0.003). Intriguingly, T-Ag-specific memory B cells were also more abundant in the blood of patients who ultimately developed MCC recurrence (HR 2.82 [1.22- 6.53], p=0.012). Together, our results demonstrate that higher frequencies of circulating memory B cells associate with worse MCC outcomes. These findings suggest that the functional state of total and T-Ag-specific circulating B cells reflect their immune response within MCC tumors.

Preterm birth is a leading cause of neonatal morbidity and mortality, with intra-amniotic infection and inflammation being major contributors to early preterm labor (PTL). Despite ongoing research aimed at reducing inflammation in neonates, most studies have focused on post-delivery while few have been done prior to delivery. IL-1 is a central upstream mediator of inflammation in the amniotic cavity and the neonate. IL-1 is a key cytokine that is responsible for induction or propagation of the cytokine cascade responsible for PTL. Rytvela, an interleukin-1 receptor antagonist made up of seven D-amino acids, acts as a selective antagonist of IL-1 signaling, which could be used to act as a therapeutic approach to reduce inflammation and prevent PTL. The purpose of this experiment is to determine if interleukin-1 (IL-1) is a key molecular target for the development of antenatal therapeutics to prevent PTL and fetal injury. We hypothesize that Rytvela administered intravenously to the mother will cross the placenta and be detectable in the amniotic fluid and fetal plasma, suggesting that Rytvela could effectively block IL-1 signaling in the fetus and therefore reduce fetal inflammation. Maternal blood plasma samples were drawn at Day 1, 2, 6 and 10 post infusion. To confirm the transfer of Rytvela to the fetus, we used liquid chromatography-mass spectrometry (LC-MS) to detect the drug, looking at integration, peak identification, and backlog pressures to see if Rytvela is detectable in maternal plasma. Rytvela was detected and luminex plates were run to measure cytokine levels. After GBS infection, Il-1 beta and Il-23 concentrations increased. After Rytvela administration, the concentration of the pro-inflammatory cytokines decreased. Future directions will involve measuring cytokine levels at these time points and correlating them with Rytvela infusion to evaluate the drug’s impact on maternal-fetal inflammation

As digital platforms increasingly influence financial markets, the role of social media engagement in shaping stock performance has gained growing attention. This study investigates the link between social media activity and stock prices, focusing on Reddit, a prominent platform for individual investors to share opinions. Analyzing daily data on the most frequently discussed stocks on Reddit, we examine how discussion volume and sentiment of investors drive stock price movements. Our findings reveal that both discussion volume and positive sentiment are significantly associated with rising stock prices. Additionally, we observed a nonlinear relationship between sentiment, mentions, and stock performance. Specifically, discussion volume exhibited a negative nonlinear relationship with stock prices, while positive sentiment showed a positive nonlinear effect. These results provide insights for investors and financial analysts, highlighting the value of monitoring social media trends to inform investment strategies. f

Social media algorithms shape how people consume information, but their potential influence on political attitudes remains uncertain. This research examines whether TikTok's "For You" page algorithm influences American users' political attitudes toward China by prioritizing positive narratives of China, including support for the People's Republic of China (PRC) policies and strategic objectives. While U.S. policymakers have expressed concerns that TikTok, owned by ByteDance, a Chinese technology company, may subtly influence public opinion, it remains debated whether its algorithm actively shapes user perceptions. To investigate this, we randomly assigned 60 American TikTok users to three groups: a control group with randomized content exposure, a treatment group exposed to pro-China content, and another to anti-China content. Participants completed surveys before and after their TikTok usage to measure changes in trust, favorability, and perceptions of China's role in international orders. If the algorithm operates purely for engagement optimization, we expect a polarization effect, where participants shift in opposite directions based on their respective content exposure. However, if the algorithm is actively shaping narratives, a uniform shift toward pro-China sentiment across all groups may indicate external influence. Using ANOVA and Difference-in-Differences regression, this study evaluates whether TikTok's algorithm passively reflects user engagement patterns or actively shapes political attitudes. The findings contribute to discussions on social media influence, information manipulation, and digital platforms' role in shaping public opinion.

Given a set of goods and a set of individuals, one might ask what the optimal way to divide the goods among the individuals is. This is known as a bargaining problem. Bargaining theory is a set of mathematical tools which can help us answer these sorts of questions. Assuming that the individuals’ preferences can be represented numerically, a bargaining solution concept tells us the optimal division of goods, called the solution to the bargaining problem, among the individuals. In some cases, solutions to bargaining problems involve randomly choosing how some or all of the goods are distributed. Of interest to us is the fact that the solutions to these bargaining problems may fail to be continuous, in a certain sense. If the strengths of the individuals’ preferences are changed even slightly, it may be the case that the optimal division of goods changes drastically. Broadly speaking, the goal of this project is to understand when and why this phenomenon occurs. I begin by formally defining what it means for the preferences of the individuals, as well as the sets of solutions to the associated bargaining problems, to be close to one another. I then prove that under certain conditions, small changes in individuals’ preferences cannot result in large changes in bargaining solutions. I am currently still working on proving that if these conditions fail to hold, then one can slightly modify the individuals’ preferences in such a way that the associated bargaining solutions change quite substantially. We hope that these results can be applied to justify randomization amongst options in collective decision making problems, particularly those related to experimental design.

Corn, a crucial agricultural commodity, serves as a fundamental input. Its economic importance has made government subsidies a vital policy instrument to stabilize corn supply and prices To investigate the relationship between corn subsidies and prices, we compiled yearly data on U.S. corn prices, subsidies, exports, production, and inflation from 1980 to 2023. Employing linear and nonlinear regression models, we analyzed the role of corn subsidies in shaping corn prices while controlling for other factors. Our results suggest a statistically significant negative relationship between subsidies and corn prices. Interestingly, this negative relationship weakens at higher subsidy levels, revealing a curvilinear relationship. This implies that while subsidies can lower prices to benefit consumers and stimulate the economy, excessive subsidies may reduce the magnitude of price decreases and dampen producers’ incentives by further suppressing prices and revenue. Our findings offer valuable insights for policymakers, showing the need for careful calibration of subsidies to balance consumer benefits with producer sustainability. We also suggest potential avenues for further exploration to extend this work

Since the ban on sports betting was struck down by the supreme court in 2018, 38 states have legalized betting in some form. In the third quarter of 2023, sports betting generated over $500 million in tax revenue for state governments. Many of the impacts that seem obvious when thinking about the consequences of legalizing sports betting have already been studied, so in this paper I analyze effects that are further downstream in the causation chain. Specifically, I look at how the legalization of sports betting has affected marital relationships as measured by state-level divorce rates, mental health outcomes as measured by depression rates, and substance abuse issue measured by the number of alcohol related hospitalizations and rehabilitation center bookings. I utilize the staggered rollout of legalization across the country to conduct a difference-in-differences analysis to accurately measure the magnitude of each of these effects. Additionally, I investigate the potential additional damages caused by the legalization of online gambling compared to only in-person gambling. Of the 12 states who have yet to legalize any form of sports gambling, most of them have some form of legislation on the table to decide the future of sports betting in their respective states. Within these legislative sessions, and eventually if these measures are on state ballots,legislators and voters will be asked to personally weigh the pros and cons that are associated with the legalization of sports betting and this paper's aim is to be a small part in helping inform these decisions.

Periodontitis is a severe inflammatory disease that damages the gingiva and has been linked to systemic diseases, such as diabetes, heart disease, and respiratory disease. These serious health complications express the importance of studying oral microbiota and their interactions. This research investigates the growth dynamics of Fusobacterium nucleatum and Porphyromonas gingivalis, two gram-negative anaerobic bacteria that play a significant role in inducing the progression of periodontitis, under mono- and co-culture conditions. By collecting monoculture and co-culture growth curves along with cell counts, and LIVE/DEAD BacLight staining we are identifying their optimal growth phases and interactions. With this information, we seek to optimize these cultures for downstream experiments, including bulk and single-cell RNA sequencing, to identify unique genes signatures from cell-cell interactions implicated in periodontal disease progression. Understanding these dynamics will contribute to future studies on the persistence of periodontal infections and broader research on gene expression.

Xylazine is a veterinary sedative that has become a common adulterant in fentanyl products due to its ability to prolong the euphoric effects of fentanyl. Adulterated drug mixtures containing xylazine have been linked to an increased risk for respiratory depression and fatal overdose. Existing treatments for overdose such as naloxone do not work against xylazine and there is currently no FDA approved reversal agent for xylazine toxicity. Monoclonal antibodies (mAbs) are a promising therapeutic option to reverse drug overdose and can be used to target small molecules by sequestering them in the bloodstream and preventing their passage into the brain. Previously, we made a series of xylazine haptens and formulated them into vaccines where they were found to induce strong antibody responses, reduce brain to serum ratio of xylazine, and mitigate respiratory depression in Sprague-Dawley rats. Based on the protective effects of our xylazine conjugate vaccines, we hypothesized that we can create an effective reversal agent by isolating xylazine specific mAbs. In this study, we immunized mice with xylazine conjugate vaccines to generate antibodies specific against xylazine. We then used the secondary lymphoid organs of the vaccinated mice to establish stable mAb producing cell lines using hybridoma technology. Hybridomas were screened with ELISA and lead candidates were selected and sequenced for further characterization. We will conduct in-vitro characterization assays to quantify binding affinity, functional activity, and thermostability of our lead mAbs. Furthermore, in-vivo studies will assess the efficacy of our mAb lead candidates in rodent models.

Chlorpyrifos (CPF) is a widely used organophosphate pesticide effective in controlling agricultural pests by inhibiting acetylcholinesterase, leading to the accumulation of acetylcholine and continuous nerve stimulation. CPF exposure has been linked to increasing autism risk and gut microbiome dysbiosis. However, the underlying mechanism linking CPF to autism remains unclear, and the role of the gut microbiome in CPF-induced neurodevelopmental toxicity remains elusive. Using a high-throughput social behavior assay, we found that embryonic exposure to CPF caused lasting social deficits in zebrafish. We then screened seven common gut microbiome metabolites and found that butyrate effectively rescued CPF-induced social deficits. Butyrate is a known inhibitor of histone deacetylases (HDACs). We discovered that valproic acid, an inhibitor of Class I and IIa HDACs, phenocopied butyrate’s rescue effects. Meanwhile, trichostatin A, an inhibitor of Class I, II, and IV HDACs, and nicotinamide, an inhibitor of Class III HDACs, did not. We are currently conducting multi-omics analyses; including metagenomics, metabolomics, RNA sequencing, and CUT & RUN, to further elucidate the mechanisms underlying CPF’s neurodevelopmental toxicity and butyrate's rescue effects. In the long run, our work will help to uncover how CPF exposure contributes to autism risk and to inspire new therapeutic approaches for alleviating autism-related social deficits.

Historical archaeologists understand toys in the material record to explicitly mark past activities of children. This project focuses on the play activities of enslaved children on North American plantations through the toys they left behind. We used data from the Digital Archaeological Archive of Comparative Slavery (DAACS) to explore the material evidence for identity formation and socialization of enslaved children based on existing studies on enslaved childhoods. Specifically, we investigated the following questions: what materials and manufacturing techniques were most frequently used in the creation of the toys of enslaved children on North American plantations? Based on the associated costs of these materials, what is the range of expense exhibited by enslaved children's toys? What role might toys have played in enslaved children’s agency or passivity in socialization? To address these questions, we queried the DAACS repository concerning object specifications like material and manufacturing technology for toys excavated from North American plantations. This data was imported into RStudio, where we used programming packages to clean it and create visualizations to convey trends. Our pilot project (48 toys) found that porcelain and a molding technique were most frequently used, materials with varying expenses were present, and some toys exhibited post-manufacture modifications. We now have data on 599 toys from 41 sites on 13 plantations, greatly improving our representation of enslaved children in the material record. In this poster we present the result of our analysis of this large data set and compare the locations. The findings of this research will help to fill in gaps of a larger conversation about the relationship between childhood play and race, and more broadly contribute to archaeology’s attention to past social dynamics.

TBC domain containing kinase (TBCK) is an understudied protein with three domains: a pseudokinase; Tre-2, Bub2, and Cdc16; and rhodanese, and is highly expressed in the brain. Homozygous mutations in TBCK cause a rare neurodegenerative disorder in children, which clinically presents as syndrome infantile encephalopathy, brain atrophy, cerebellar hypoplasia, and muscle hypotonia. Two mutations in particular, Arg126Stop and Arg511His in the pseudokinase and TBC domains respectively, are commonly found among TBCK patients. The progression of the disease is characterized by a global regression in brain development, severe intellectual disability, and premature death in acute cases. The pathogenic mechanism underlying TBCK syndrome is unclear, but past studies show that TBCK patient neurons demonstrate aberrant metabolite buildup in the lysosome likely resulting from abnormal lysosomal activity. Immunoprecipitation mass spectrometry was performed for wild type TBCK in both N terminal and C terminal tags, revealing a preliminary list of both known and unknown interactors for TBCK. To further investigate the early developmental implications of mutant TBCK, CRISPR/Cas9 directed mutagenesis is being used to generate two induced pluripotent stem cell (iPSC) lines harboring the Arg126Stop and Arg511His mutants for subsequent differentiation into neural progenitor cells (NPC) and neurons. Immunofluorescent imaging of the mutant NPCs will confirm the recapitulation of growth and lysosomal defects present in patient cells. To analyze the effect of TBCK mutation on lysosomal function/content, we will immuno-isolate lysosomes through lysosome immunoprecipitation (Lyso-IP) and identify proteomic changes through mass spectrometry. While providing a crucial in vitro cell model of two common patient mutations, these experiments will offer critical insight into cellular dysfunctions that contribute to TBCK disease states.

Copepods are an essential link between micro- and macroscopic trophic levels in Salish Sea food webs. The distribution of copepods across spatial and temporal scales is well-known and is partially attributed to physical oceanic processes. However, few studies have characterized copepod densities at different tidal heights in the San Juan Channel. This study investigates copepod densities at depths of 0-25m and 0-50m during high and low slack tides when tidal currents are at their lowest velocity. Higher overall copepod densities were expected during slack high tide due to the influx of oceanic water from the Strait of Juan de Fuca. Samples were collected over four days in the northern San Juan Channel during September 2024. Twelve vertical plankton tows were performed with six replicates for high and low tides respectively. Samples were diluted and randomized using a plankton splitter, creating 5ml aliquots to calculate copepod density. Copepod densities from 0-50m depth during slack high tide were significantly higher (p-value < 0.001) than all other samples. No difference in copepod density was found between 0-25m and 0-50m depths during slack low tide. Increased tidal height resulted in higher copepod densities for low and high slack tides. Our findings suggest the physical processes within the San Juan Channel, such as the influx of colder, saltier waters during slack high tides increase copepod densities in the top 50m of the water column. These shifts in copepod densities may impact the feeding behavior of higher trophic levels in the San Juan Channel food webs.

Frontline communities across and beyond the United States are continuously affected by the US nuclear legacy: from mines to test sites to radioactive waste disposal and beyond. Activists advocating for reparations and community safety often have to engage in their own research to provide the evidence the government requires as proof of radioactive harm. Most of this evidence exists only within physical documents that are behind multiple barriers, sometimes only recently declassified, and scattered across US nuclear sites. My research goal focuses on the creation of a living digital archive to help facilitate the digitization and sharing of important documentation among frontline communities. I use GitHub’s Collection Builder platform to create the foundation for an archive that can grow over time: including the first collection, the metadata schema, and information regarding the archive and how to get involved. My work includes selective digitization of documents of the now defunct UW Radiation Ecology Department, which was primarily funded by the US Atomic Energy Commission (AEC) and involved in a multitude of nuclear operations. These materials are housed in the UW Libraries Special Collections. Based on preliminary findings, I expect to find important evidence in this material of neglect to the harm of long-term exposure to low levels of radiation, and the specific testing done and results produced by the UW Radiation Ecology Department. My research also prototypes an archive that community researchers can continue to build and involves community feedback that helps shape the design. It is a step in the process of achieving necessary safety measures that protect people and ecosystems from continued radioactive harm.

Non-syndromic orofacial cleft (OFC), comprising cleft lip, cleft palate, or a combination of the two, is among the most common structural birth defects. OFC has both genetic and environmental underpinnings, though the genetic contribution is only partially understood. Members of the same gene regulatory networks associated with OFC are candidates to harbor the “missing heritability” for OFC. Van der Woude Syndrome (VWS) is an autosomal dominant condition characterized by cleft lip and/or palate, and lip pits. Mutations in IRF6, encoding the transcription factor Interferon Regulatory Factor-6, account for approximately 70% of VWS cases, mutations in GRHL3, a transcriptional target of IRF6, account for 5%, and it was recently found that mutations in PRKCi, encoding a kinase, account for 5% more. Published data support that IRF6 is phosphorylated and thereby activated by RIPK4. However, the kinases PRKCi and IKK1 are also required upstream of IRF6 activity. Regulatory interactions within this kinase cascade are unclear. The goal of this project is to shed light upon the kinase cascade encircling IRF6 to illustrate genetic causes of VWS and non-syndromic OFC and ultimately improve patient outcomes. I hypothesize that IRF6 phosphorylation is dependent upon RIPK4, which is activated by IKK1 and downstream of PRKCi activity, and all components are necessary for IRF6 activation. To test this hypothesis, I am conducting experiments injecting mRNA products from our genes of interest into zebrafish embryos and detecting phosphorylation activity within the harvested protein through immuno-precipitation and mass spectrometry analysis to determine protein-protein interactions. I anticipate that in the absence of RIPK4, the pool of Differentially Expressed Genes (DEGs) will align with the pool of DEGs in the absence of IKK1 and IRF6 respectively. Implications of these findings will ultimately give a stronger understanding of the molecular foundations of VWS and non syndromic OFC.

Poor sleep quantity and quality are associated with increased risk of negative health outcomes such as chronic conditions, depression, and anxiety, which ultimately impact overall well-being. The present study aims to investigate the association between perceived stress and sleep quality among college students. A sample of 113 college students in the United States completed an online survey that asked questions about their sleep and perceived stress. Perceived stress was assessed using the Perceived Stress Scale (PSS; Cohen et al., 1983) and sleep quality measured through the Pittsburgh Sleep Quality Index (PSQI; Buysse et al., 1989). Sociodemographic data were also collected. Results indicate that college students with higher perceived stress reported poorer sleep quality. Given that perceived stress and sleep were correlated, we conducted additional analyses to compare levels of stress and sleep quality among different sociodemographic groups. We found that international students exhibited lower perceived stress and better sleep quality compared to domestic students. Furthermore, college students who reported lower family income, and those whose native language was not English experienced higher perceived stress and poorer sleep quality across both groups. Taken together, the data demonstrate an association between perceived stress and sleep quality and highlight differences in both variables based on immigration situation, as well as linguistic and socioeconomic factors. Further longitudinal studies could be helpful to determine the temporal relationships among these variables and the long-term role that they play in health. 

Neonatal hypoxic-ischemic encephalopathy (HIE) occurs when the brain receives insufficient oxygen and blood supply before or during childbirth. HIE is a leading cause of neonatal mortality and morbidity that may also affect later brain development, specifically gyrification - folding of the cerebral cortex creating gyri and sulci. The nonhuman primate (NHP) brain is gyrified, similar to humans, making NHPs a highly translatable model to examine brain development after injury, which has not been well-studied in HIE. In our nonhuman primate (NHP) model of neonatal HIE, we induced injury through in utero umbilical cord occlusion (UCO) for 20 minutes, mimicking the cause of HIE in humans. Twenty-two term-equivalent pigtailed macaques (Macaca nemestrina) underwent UCO and were randomized to no treatment (n = 11) or treatment with therapeutic hypothermia and erythropoietin (TH + Epo [5x1000 U/kg]; n = 11), while non-UCO animals served as controls (n = 7). All animals were delivered via cesarian section. Injury severity was determined by physiological parameters (Apgar score), lactate, and pH levels after resuscitation. To evaluate the impact of injury on gyrification, we will utilize magnetic resonance imaging (MRI) taken 6-months post-injury to measure the gyrification index (GI). GI will be calculated by taking brain’s inner-to-outer hemispheric ratio; the inner trace following the contours of the gyri and sulci, and the outer trace following the circumference of the cerebral cortex. We hypothesize that global and regional GI will be altered in animals exposed to UCO, corresponding with decreased brain volume and greater injury. We also hypothesize that treatment will mitigate some of these changes, leading to a GI closer to control. These results will help determine whether hypoxia-ischemia alters the trajectory of cortical development, as well as the association between injury severity, brain volume, and gyrification.

This study aims to understand users’ needs in designing a mobile application that assists Cardiopulmonary Resuscitation (CPR). This study is designed through a two-stage online interview, beginning with a screening survey that asks about participants’ occupations and experience with CPR, followed by the main interview that asks about their challenges when performing CPR and their opinions on the most efficient type of feedback. Eight participants who completed the survey included CPR instructors, paramedics, firefighters, and medical students with experience ranging from 3 to 20 years. The participants rated maintaining compression depth as more challenging (7.63 out of 10) compared to maintaining compression rate (5.25 out of 10) when performing CPR, with 10 representing the highest level of difficulty. Participants also reported that visual feedback would be more beneficial for compression depth and auditory feedback for compression rate. Therefore, these findings suggest that an effective assistive CPR device should have real-time visual feedback to aid in-depth consistency while auditory cues support rhythm accuracy similar to a metronome. By leveraging these findings, the proposed application has the potential to enhance CPR effectiveness, improve user confidence, and ultimately increase patient survival rates.

Decision During Drinking (D3 study) is currently developing a mobile app aimed at reducing negative alcohol-related outcomes with a focus on young adults. D3 offers modules to educate users on identifying cues that influence their decisions, understanding their values after drinking, and engaging in practices to avoid such experiences. I have aided in the design of the prototype of the D3 program, both creating new features and adapting previously developed features. The current study assesses core aspects of human centered design on two of the D3 study features I helped to create in Figma. The first is an activity that compares participants’ perception on alcohol expectancies to alcohol’s physiological effects. The second is a “roadmap” planning tool that guides users to create action plans to cope with specific drinking cues, linking each plan to personal values. By using an iterative design approach from research participants’ feedback, I refined the user interface (UI) to improve the features. I am adapting measures on usability (i.e. System Usability Scale) to assess the metrics for these features specifically. Data is being collected from online surveys on the usability of these features. I predict that the final usability score would be higher than the industry-standard threshold (e.g. score of ≥ 70), so the features will provide a seamless and intuitive user interface. Based on the improvements, if deemed usable, these feature designs could be applied to other clinical app developments. 

Pregnant women infected with influenza A virus (IAV) are at higher risk of morbidity, mortality, and poor fetal outcomes. However, the difference in the pathogenesis of IAV between pregnant women and non-pregnant women remains inadequately understood, primarily due to the lack of animal studies that use a translational model of infection. I hypothesized that higher IAV viral load and Type I interferon concentrations would be observed in the lungs and bronchoalveolar lavage of pregnant pig-tail macaques compared to non-pregnant macaques, and that correlating these metrics would yield different results across groups. We inoculated pregnant (n=11) and non-pregnant female (n=18) pig-tail macaques (Macaca nemestrina) with IAV H1N1 (A/California/07/2009) and euthanized them at 5 days post-inoculation, when we expected to observe peak lung pathology. We tested pulmonary function at baseline and study endpoint and conducted clinical assessments daily. I extracted RNA and performed quantitative polymerase chain reactions on the samples to calculate viral load. I also performed enzyme-linked immunosorbent assays to quantify concentrations of Type I interferons (IFN-α, IFN-β). Lastly, I analyzed pulmonary physiology data and clinical assessment scores as a reliable measure of disease severity. A bi-modal distribution of viral load was observed in the lungs of pregnant animals (high>9e5 copies/mg; low<2e4 copies/mg), which was not observed in non-pregnant animals.  When correlating viral load at 5 days post-inoculation with Type I IFN in the lung of the pregnant animals, I found a significant positive correlation between IFN-β and viral load in both the lungs (ρ=0.8, p=0.03) and BAL (ρ=0.9, p=0.02). These results suggest that despite a strong IFN-β response in the lung, a high viral load persisted in the pregnant animals. Next steps could explore whether the kinetics of the pulmonary innate immune response is delayed in pregnancy, which impairs viral clearance.