Osteoporosis is the most common metabolic bone disease in the United States and worldwide. Genome-wide association studies (GWAS) have identified numerous loci associated with bone mineral density (BMD), however, the target genes at most of these loci remain unknown. Multiple GWAS have identified the TNFRSF11B-COLEC10 locus to be associated with BMD. TNFRSF11B, tumor necrosis factor receptor superfamily, member 11B, is a gene that encodes for osteoprotegerin (OPG), a key regulator of bone resorption. COLEC10, collectin subfamily member 10, encodes a C-lectin family protein involved in neural crest cell migration, endocrine function, and the nervous system, though its role in bone remains unknown. While TNFRSF11B is presumed to be the target gene at the TNFRSF11B-COLEC10 locus, we have obtained preliminary data that loss of COLEC10 in zebrafish results in altered bone morphology. However, these animals were mosaic for mutations in COLEC10, preventing a uniequivocal determination of its role in bone. The purpose of my study is to map genotype-to-phenotype relationships in COLEC10 and TNFRSF11B germline mutant zebrafish. Mutants for COLEC10 were generated by ENU mutagenesis as part of the Sanger Mutation Project. Mutants for TNFRSF11B were generated by our lab using CRISPR. I will genotype both mutants using Polymerase Chain Reaction (PCR) and gel electrophoresis. I will scan the adult fish (90 days post fertilization) using micro-computed tomography (microCT), and then utilize FishCuT for the segmentation and analysis of the vertebral column of each zebrafish. The primary outcomes will be the tissue mineral density (TMD), volume (Vol), thickness (Th), and length (Le), in the centrum, haemal arch, and neural arch of each vertebra. By determining whether COLEC10 is a gene of major effect compared to TNFRSF11B, my research will help to elucidate COLEC10’s skeletal function and its potential role as a casual gene underlying genetic risk for osteoporosis.

In 1972, Washington State implemented the Marine Mammal Protection Act (MMPA), following which there was a drastic spatial expansion of pinniped populations throughout the region. Harbor seals, specifically, had been impacted prior to this act, with a reduction in population due, in part, to state-financed population control. Since 1970, there has been a 7 to 10-fold increase in population sizes. Predation from pinnipeds can decrease salmon population sizes, leading to negative impacts on Pacific salmon as pinniped populations grow. This is especially concerning for endangered species of salmonids, such as ESA-listed Chinook salmon, which show little recovery since federal protections have been placed on them. I reviewed historical and modern literature to find available harbor seal population data from years before and after the implementation of the MMPA. I used documentation regarding injury and human-caused death of marine mammals, including reports from the National Oceanic and Atmospheric Administration (NOAA), to relate encounter frequency with species abundance. I used R to generate maps showing the distribution of pinnipeds throughout Puget Sound to illustrate the spatial expansion of this species. I expect to find an increase in pinniped populations, particularly an accumulation of harbor seals in areas of abundant food resources and areas less impacted by human development. This study, compiled with further research, will be helpful for the future conservation of impacted salmonids and understanding the ecological responses to the management of pinniped populations.

Gender disparities persist in male-dominated fields, with women often underrepresented in STEM fields such as computer science. We examine “sense of mattering”– the perception of one's contributions and work being valued and recognized by others– as a factor that may help explain women’s underrepresentation in male-dominated fields. We investigate whether manipulating sense of mattering in a hypothetical computer science class influences actual participation, interest, and anticipated performance in group tasks. Participants (n=200) recruited from the University of Washington’s Psychology Research Pool will be randomly assigned to either a high or low peer recognition condition via an online survey wherein participants engage in a group chat with peers to complete computer science tasks. Participants will contribute to this chat using both prewritten and open-response options. Participation will be analyzed for language content and response length and perceived interest and anticipated performance in computer science will be assessed through a self-report measure. We hypothesize that heightened peer recognition will lead to greater participation, interest, and anticipated performance outcomes for all participants, with a stronger effect for women than men. Future directions for this study include exploring other channels through which sense of mattering could be influenced (e.g., teacher behaviors) and investigating its relevance in disciplines beyond computer science. Examining the potential significance of mattering may pave the way for interventions that foster environments that better appreciate women's contributions.

Using temperature reconstruction to understand how the Earth’s climate responded to external forcing from factors such as CO2 in the past can inform predictions about future climate change due to global warming. This project aims to examine a recent paleoclimate data assimilation study of the past 24,000 years from the Last Glacial Maximum (LGM) to the present day. Paleoclimate data assimilation combines both proxy data and climate model simulations to address the discrepancies in climate reconstructions produced by each. For the LGM to present, discrepancies between model simulations and proxy data include the timing and characteristics of climate events like deglaciation. While data assimilation helps to resolve some of these discrepancies, it also makes assumptions about the uncertainty of the proxy data used. Processes that introduce proxy uncertainty such as bioturbation–sediment mixing by marine organisms–and calibration errors are often not characterized as time scale-dependent which could potentially introduce bias and affect the accuracy of these data assimilation studies. We examine the proxy uncertainty within this data assimilation to identify timescale-dependent errors and measure their impact on the accuracy of the temperature reconstruction. We do this by producing a set of pseudoproxies, which are synthetic datasets of different sediment proxies such as δ¹⁸O, to create hypothetical systems of past climate. By isolating and controlling different uncertainty characteristics, we are able to measure their overall impact on the climate reconstructions.

This study investigates the physical mechanisms driving spatiotemporal variability of

barrier layers in the Western Tropical Pacific (WTP) along 149°E, with a specific focus on the

La Niña phase of the El Niño-Southern Oscillation (ENSO). Barrier layers, which separate the

surface mixed layer from the thermocline, regulate ocean-atmosphere interactions and influence

climate dynamics. This research assesses the relative contributions of freshwater input from

precipitation, and wind stress on barrier layer formation and thickness. Data were collected

during a research cruise in January 2025 aboard the R/V Thomas G. Thompson from an

Underway Conductivity Temperature and Density (UCTD) sensor for temperature profiles, and

public-source meteorological data for atmospheric conditions (ERA5). Seven stations, spaced

two degrees apart in latitude, were sampled along a transect from 4°N to 15°N. Each station

provided data to analyze barrier layer thickness, with spatiotemporal variability determined by

comparing different formation mechanisms across stations. Spearman Correlation analyses were

used to determine dominant factors influencing barrier layer thickness and variability. We found

that barrier layer thickness in the WTP shows a general positive but statistically insignificant

relationship with freshwater (ρ 0.32 and p-value 0.48), and a general negative but statistically

insignificant relationship with wind stress (ρ 0.18 and p-value 0.70). During La Niña conditions,

these effects are expected to drive variability, with thicker layers forming in regions of high

precipitation and weak wind stress. Increased freshwater input enhances stratification, while

strong wind stress likely promotes surface and subsurface mixing, leading to barrier layer

thinning. Understanding these dynamics has implications for improving ocean-atmospheric

interaction climate models in the tropical Pacific.

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) is an emerging global human health concern and a risk factor for cardiovascular diseases and atherosclerosis. While the pathogenesis of MAFLD is complex and multifactorial, scientific evidence suggests environmental factors play a role in the development of the disease. Prior studies indicate exposure to particulate matter (PM) leads to MAFLD. A major constituent of ambient PM is diesel exhaust particles (DEPs). This study aims to explore the association between exposure to DEPs and the development of MAFLD using a murine model vulnerable to MAFLD development. DEPs cause oxidative stress through the generation of reactive oxygen species within the body. Male and female low-density lipoprotein receptor knockout mice were exposed to filtered air or freshly generated DE for 18 weeks while fed a high-fat or Chow diet. Plasma and liver tissue were harvested for biochemical measurements. The levels of a panel of lipid markers (triglycerides, cholesterol, free fatty acids) and glucose were measured in plasma and liver via colorimetric assay kits. Liver oxidative stress (8-isoprostane; nuclear factor erythroid 2-related factor 2, and 3-nitrotyrosine) was quantified via ELISA and Western blot (WB), respectively. Levels of peroxisome proliferator-activated receptor alpha (PPARα) were assessed via WB. We found statistically significant increases in plasma glucose and plasma and liver cholesterol in DE HFD male mice, and plasma triglycerides in DE HFD female mice. We expect to find increased liver oxidative stress and decreased liver PPARα protein, providing insight into the metabolic pathways associated with MAFLD that are disrupted by DE. Our findings will lead to a better understanding of air pollution as a risk factor for MAFLD and inform targeted interventions for affected populations.

Individuals with diabetes experience a unique set of challenges as metabolic disease impairs the proper regulation of glucose homeostasis. Glycogen stores in the liver are mobilized in response to islet hormones, insulin and glucagon, to address changes in circulating blood glucose levels. Individuals with diabetes are known to have lower hepatic glycogen levels and repairing these levels in preclinical mouse models of metabolic disease improves the diabetic state, suggesting hepatic glycogen storage may be a rational therapeutic target. With the use of a mouse model of increased hepatic glycogen by overexpression of a protein called Ppp1r3b ( Ppp1r3bhepOE), I explored the hypothesis that increasing hepatic glycogen levels affects the hormonal response and hepatic post-receptor signaling in response to nutrient feeding. Using oral gavage mixed-nutrient meals (consisting of varying glucose and/or alanine), I monitored plasma glucose and hormone levels from mice under different feeding conditions. I collected blood glucose and plasma samples from the tail vein and used ELISA to quantify circulating insulin and glucagon levels. In comparison to a control AAV group, the Ppp1r3b OE mice showed significantly elevated glycogen levels and following an overnight fast increased blood glucose levels. Furthermore, after conducting a 5 hour fast, the Ppp1r3b OE group had lower insulin levels without changes in glucose, signifying increased insulin sensitivity.  Yet, after an insulin tolerance test, Ppp1r3bhepOE mice did not decrease blood glucose to the same extent as controls, perhaps due to increased liver-derived glucose output. Lastly, to measure post-receptor signaling I administered either insulin or glucagon to control and Ppp1r3bhepOE mice and measured the glycemic response and activation of relevant hepatic signaling intermediates. My preliminary evidence reveals the importance of hepatic glycogen in energy metabolism and lays the foundation for future studies investigating how the alteration of glycogen storage could optimize energy expenditure in metabolic disease.

Thermodynamic properties of conventional s-wave superconductors (i.e. superconductors with an isotropic gap Δ) are insensitive to weak disorder.  In unconventional superconductors with a p-wave and d-wave symmetry of the order parameter, disorder strongly suppresses superconductivity. Experiments indicate that the disorder improves the superconducting properties of aluminum, an s-wave superconductor with a significant gap anisotropy. This project aims to study the effect of a single impurity on the density of quasiparticle states in an s-wave superconductor with a strong gap anisotropy Δ→Δ(n). The density of quasiparticle states is expected to migrate from smaller to greater energies. By using numerical methods, I can reveal how the density of states changes. Understanding the behavior of the quasiparticle density of states can allow further exploration into several types of s-wave superconductors without the need to assume isotropy.

The spatial and temporal distribution of select harmful algae species in Clayoquot Sound on the west coast of Vancouver Island, BC, was investigated to understand their prevalence and potential risks to human health, aquaculture, and local economies. Harmful algae species, such as Alexandrium spp. (producing saxitoxins), Pseudo-nitzschia spp. (physically harmful to fish gills and producing domoic acid), and Dinophysis spp. (producing okadaic acid and dinophysotoxins), are known to cause harmful algal blooms (HABs) where toxins can accumulate in bivalves, leading to paralytic shellfish poisoning, amnesic shellfish poisoning and diarrhetic shellfish poisoning in humans when consumed. These blooms can disrupt aquaculture industries and result in serious economic repercussions. In addition, harmful algae can cause significant damage to marine animals, including fish kills and the disruption of trophic interactions, thereby threatening ecosystem stability. UWT researchers have been collecting water property data in Clayoquot Sound in the late summer/early fall annually since 2001 and phytoplankton samples since 2006. These data include CTD water property profiles and discrete water samples for nutrients and phytoplankton. Phytoplankton 10-meter vertical net tows (20 um mesh) were collected in addition to bottle samples at the surface and 10 m at the same stations every year. Samples were fixed and counted in the lab. This project aims to compile and map the distribution patterns of the three harmful algae species mentioned above and assess how that distribution has changed over the last 17 years. These results will also be compared with historical phytoplankton data for this region from Fisheries and Oceans Canada to compare distribution pattens.  We hypothesize that HABs will become more prevalent as water temperature increases. The study will provide valuable insights into the location and prevalence of select HABs in Clayoquot Sound, informing future monitoring plans and management strategies to mitigate potential negative effects.

Scaling and power law concepts are fundamental in undergraduate physics and have important applications in biology, including thermoregulation and metabolism. Because of this, scaling is emphasized in the introductory physics sequence for life science students. To inform instruction, we examined student understanding of scaling relationships, focusing on surface area, volume, and mass. Our study analyzed student responses to multiple-choice and free-response questions on quizzes given before and after lecture instruction. Preliminary findings indicate persistent difficulties in recognizing the linear relationship between mass and volume in uniform-density objects. Additionally, students struggle to track changes in surface area for three-dimensional objects. These challenges suggest gaps in conceptual understanding that may hinder students' ability to apply scaling principles across disciplines.

The retina possesses an intrinsic circadian clock that synchronizes directly to light without input from the brain or visual photoreceptors. Previous research has shown that removing this clock affects photoreceptor health as an animal ages. Furthermore, disruptions to these circadian rhythms, which are increasingly common in modern lifestyles, may exacerbate retinal degenerative diseases such as Retinitis Pigmentosa (RP), a condition that leads to progressive vision loss and affects millions worldwide. Examples of circadian rhythm disruptions include cross-time-zone travel, the use of backlit devices, and social and work obligations. This study investigates the impact of chronic circadian dysregulation (chronic jet lag) on the progression of retinal degeneration in two murine models of RP. We hypothesize that stably synchronized circadian clocks protect against progressive retinal degeneration, while chronic disruption accelerates disease progression. We used three mouse models: a healthy wildtype, mice heterozygous for mild RP, and mice exhibiting retinal white deposits and degeneration. These mice were subjected to either a control lighting schedule or chronic jet lag beginning at one month of age. We assessed retinal health at multiple time points using fundus imaging to quantify white deposit area, immunohistochemistry staining to measure the thickness and depth of the outer nuclear layer (ONL) of the retina, and qRT-PCR to quantify the abundance of Rhodopsin and Opsin transcripts. We used ANOVA and Tukey post-hoc analyses to compare measured values among groups. The results of this experiment provide preliminary data that can inform research into RP models in other organisms and contribute to understanding the implications of chronic circadian desynchronization in the progression of RP in humans.

Producing long-lasting, useful, and valuable biodegradable products is the future of sustainability. To support this effort, the Bura Lab aims to develop and improve an economically feasible process for converting thermomechanical pulp (TMP) into lignocellulosic nanofibers (LCNFs). LCNFs are a highly versatile and valuable product derived from carbohydrate and organic polymer compounds found in plants, cellulose and lignin. LCNFs are fibers, characterized by their 2-100 nanometer widths, suspended in a thick, gel-like solution that can be hot-pressed into biodegradable plastic products. LCNF bioplastics have enhanced barrier properties due to the hydrophobic properties of lignin, which allows for increased versatility and application in various industries. The current method for producing LCNFs is expensive, energetically costly, and uses 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), an environmentally hazardous chemical. The Bura Lab has developed an environmentally friendly and economically viable alternative to this process, utilizing inexpensive feedstock with mild pretreatment conditions and oxidation agents. My research focuses on the analysis of nanocellulose fibers from TMP feedstock using scanning electron microscopy (SEM). This technology is used to characterize fiber width and the range of diameters to determine the quality of nanocellulose produced. I use this data to understand the effects of varying chemical treatments on the fiber width and overall quality. 

Most real-world motor tasks involve a many-to-few input-output relationship, such as many neurons firing or muscles contracting to control a few degrees of freedom of the arm. The brain must form an internal model of outputs to inputs when there are fewer dimensions of feedback than dimensions of inputs to control ("redundancy"). However, motor learning is typically studied in laboratory contexts with one-to-one input-output tasks (Krakauer et al., 2019). To investigate how redundancy influences motor learning, I developed a novel virtual reality (VR) visuomotor perturbation task that can either be fully dimensioned or redundant. Participants are trained on a point-to-point reaching task controlled by hand movements in 3D space. In the 3D version of the task, the 3D cursor motion results from the 3D movements of the hand according to some unknown spatial rotation that the participant will have to learn in order to get to targets. In the redundant (2D) version, 3D hand motions are projected onto a 2D plane oriented somewhere in space that the participant has to learn. In both cases, targets are represented as infinite cylinders such that there is a task-irrelevant dimension, but in the redundant version of the task, the participant receives no visual feedback from this dimension. I hypothesize that providing 3D cursor feedback will enhance the learning of the task-relevant 2D plane by allowing participants to better map redundant hand movements in 3D space onto the constrained 2D plane. In contrast, restricting feedback to only the 2D plane will limit available sensory information, making it more difficult to learn the correct movement strategy. By comparing performance across these two tasks, I aim to clarify how task redundancy influences internal model formation and adaptation, with implications for designing more effective motor rehabilitation and VR-based training protocols.

Neuroendocrine bladder cancer (NEBC) is a rare and aggressive urothelial tract cancer. NEBC is characterized by high metastatic potential and poor clinical prognosis. Neuroendocrine cancers often exhibit characteristic genetic changes including loss of tumor-suppressing genes like TP53 and RB1 and amplification or activating mutations in proto-oncogenes, e.g., MYC. However, not all bladder cancers with these characteristic mutations progress to NEBC, suggesting other occult genetic or epigenetic drivers of disease progression. To investigate the clonal origins of NEBC tumor heterogeneity, our lab developed a genetically engineered mouse model by introducing orthotopic mutations observed in human tumors (TP53, RB1, and MYC) in murine bladders by lentiviral delivery of Cre recombinase. We found some of the resulting tumors had high levels of the pioneer transcription factor, FOXA2. To further explore the role of this gene in NEBC development, we conducted an overexpression experiment in which FOXA2 was expressed in mouse-derived bladder cancer cell lines. We performed RNAseq (RNA sequencing) analysis in a panel of syngeneic murine NEBC lines, including samples with FOXA2 over expression and parental controls. In the course of this work, we developed an informatics pipeline to interrogate clonal heterogeneity at the transcriptional level in genetically identical syngeneic tumor lines – a method which we termed clonal phylogenies from RNAseq (CPR) data. My role in this project involved designing and implementing a bioinformatics pipeline to analyze both single-cell and bulk RNAseq data. By integrating cross-species comparisons with computational analysis, we aim to uncover novel molecular mechanisms driving NEBC emergence. While our research is ongoing, this approach highlights a new bioinformatics method allowing deeper insights into human cancer biology.

With college students becoming more diverse, both ideologically and culturally, creating environments conducive to productive civil dialogue is vitally important. The Civil Discourse Project (CDP) uses participatory action research principles to understand and address inequity related to civil dialogue at the University of Washington. Co-led by student researchers and staff from UW Brotherhood (BI) and Sisterhood (SI) Initiatives, this three-part project (i.e., survey, data walk, focus group) empowers students of color to surface and address barriers to civil dialogue faced by other students of color within the BI and SI.  As a part of the CDP,  this study utilized the data walk community engagement method developed by the Urban Institute to invite BI and SI first-year students (n = 103) to jointly review previously collected survey data, interpret what the data meant, and discuss data-related experiences. Through small group discussions focused on select survey charts, the purpose of the event was to clarify the influence of identity and prior experiences in seeking out civil discourse. After the event, transcripts from small group discussions were analyzed using a six-step thematic analysis process to identify major themes. Several preliminary themes emerged from the study. Participants expressed hesitance about engaging in civil discourse, often due to the anticipation of a lack of active listening from peers or over or under-reliance on fact-based arguments.  Previous encounters with dismissive or heated exchanges also influenced their willingness to seek dialogue. These findings suggest that the quality of previous interactions, particularly in terms of listening and respect, plays a crucial role in ongoing engagement with civil discourse. The research also highlighted the value of using data to engage students and catalyze discussions grounded in objective, community-based information. These insights suggest that promoting respectful engagement and creating opportunities for collaborative dialogue could enhance civil discourse on campus.

This research explores the potential implementation of a docked micromobility parking system in Seattle, addressing the question: What would the implementation of a docked micromobility parking system in Seattle entail in terms of infrastructure, capital costs, and impact, and how might it contribute to challenges posed by the existing dockless system? The study evaluates how such a system might mitigate issues such as accessibility concerns, public space obstructions, and environmental inefficiencies stemming from the current dockless micromobility program. By analyzing case studies from cities with established docked systems and reviewing Seattle-specific permitting data, the research investigates the feasibility and benefits of integrating docking infrastructure. Preliminary findings suggest that while docked systems require significant capital investment, they can enhance compliance, reduce sidewalk clutter, and create equitable access to micromobility options. This study contributes to the broader discourse on sustainable urban transportation by proposing strategies to optimize micromobility systems for accessibility and environmental impact in Seattle's landscape.

Porphyromonas gingivalis is a Gram-negative bacterium that is a major contributor to periodontal disease. It is also linked to the development of systemic inflammatory diseases like rheumatoid arthritis. Outer membrane vesicles (OMVs) modulate cell-cell interactions between P. gingivalis cells and export cargo to the cell’s surroundings, but their biogenesis mechanisms remain unclear. Peptidylarginine deiminase (PAD) is an OMV cargo protein that catalyzes the post-translational citrullination of many P. gingivalis proteins. Others have reported that inhibiting PAD in P. gingivalis decreases OMV production and increases biofilm density. A study from our lab found that the deletion of lpxF was also affecting biofilm formation and OMV production in a similar manner. The inclusion of the C4’ phosphatase on lipid A inhibited OMV production, reducing biofilm dispersal. This is presumably due to the reduced delivery of OMV cargos that drive dispersal. We hypothesized that strains with different lipid A structures will have different OM proteomes because of the differences in trafficking and stable interactions with membrane lipids. To begin investigating these potential interactions between outer membrane proteins and LPS, I optimized an outer membrane (OM) isolation protocol so that I can consistently isolate OM from P. gingivalis regardless of strain. I followed up the isolations with Western blots as a quality check so that the samples could be prepared for comparative proteomics analysis. OM, OMV, and whole cell fractions from strains 33277 WT/ΔlpxF and 381 WT/ΔlpxF were sent to a core facility for the comparative proteomics analysis by LC-MS-MS. Our preliminary results suggest that PAD activity is reduced in ΔlpxF because the citrullination of proteins decreased versus WT in whole cells. This led us to our hypothesis for future studies; that lipid A structure influences PAD activity.

Chloramphenicol (CAP) is a synthetic antibiotic used to treat various bacterial infections in animals and humans. However, case studies and clinical trials have revealed that CAP can induce severe blood disorders, genotoxicity, and carcinogenic effects. Consequently, in 1997, the United States and several other countries prohibited its use in food-producing animals and imposed strict regulations on its application in human healthcare. Despite regulations, CAP remains prevalent in food, especially in imported seafood like shrimp, posing a risk to human health. To address this issue, we aim to develop a CAP contamination-detection assay using two engineered DNA strands: a CAP-specific aptamer and a blocker. Using NUPACK, a Python package for thermodynamic analysis of nucleic acids, we created scripts to design, select, and evaluate candidate DNA strands from our sequence library. We are developing a two-phase assay to assess their specificity and sensitivity to CAP. In the first phase, blockers are tagged with a fluorophore, and aptamers are conjugated with biotin and a corresponding quencher. These sequences are incubated in streptavidin-coated wells, and the aptamer-blocker separation is measured via fluorescence when aptamers more favorably bind to CAP. In the second phase, the released blockers are collected, amplified, and detected using recombinase polymerase amplification (RPA) with exonuclease III and target-specific probes. Unlike the first phase, the aptamers remain biotinylated with no fluorophore-quencher conjugation, as target-specific probes have their fluorescence mechanism. In the future, this assay will be streamlined and used in conjunction with point-of-care applications to detect other small molecules.

As the native range of key timber species in Western Washington, such as Pseudotsuga menziesii (Douglas-fir) and Thuja plicata (Western redcedar), contracts due to climate change, land managers who rely on these species face increasing challenges. Assisted migration (AM) of Sequoia sempervirens (coast redwood) has been proposed as a strategy to sustain working forests in Washington while supporting the conservation of redwoods, which are also vulnerable to climate-related stressors within their native range. However, for AM to be a viable management tool across Washington’s forests, it is critical to assess not only the species' projected future performance but also how mature redwood stands currently fare under existing climatic conditions. This study evaluates the timber volume, site index, and carbon sequestration of coast redwoods in comparison to Washington’s native timber species. I conducted forest inventories using 29 variable-radius plots across 10 stands in Western Washington, encompassing both redwood and non-redwood sites. To estimate potential timber volume, I measured tree height and diameter, calculating average tarif numbers to derive cubic volume estimates. Site index was created through core sampling, with average annual basal area increments analyzed to assess growth. Preliminary results indicate that coast redwoods exhibit strong potential for timber production in Washington. At age 30, redwood stands at two sites averaged diameters of 19.8 inches and heights of 104.9 feet, while non-redwood species averaged diameters of 16.4 inches and heights of 90.6 feet on adjacent sites. These findings will help inform land management strategies, supporting adaptation to shifting climatic conditions and promoting resilient working forests.

Carbon fiber reinforced polymer (CFRP) is a composite material consisting of carbon fiber and cured resin layers. Its usage is especially prominent in Washington state, whose aerospace sector generates over 70 billion dollars in revenue each year and supports more than 250,000 jobs. Despite its relatively high material value of more than $40 per pound, around two million pounds of CFRP waste are sent to landfills in Washington each year. Assessments show that the costs of this waste and its disposal are a significant financial expense for manufacturers, potentially exceeding hundreds of thousands of dollars. Additionally, the complex and high-temperature manufacturing process required to produce CFRP is extremely energy intensive and generates high levels of greenhouse gas emissions. My research seeks to identify the current state of CFRP recycling in the Washington aerospace sector and examine its potential to address these industry-wide economic and environmental concerns. Through conducting market analysis of aerospace manufacturers in Washington, I will collect data on current levels of CFRP recycling and understand to what extent these recycling processes are effective in reducing environmental impact and improving business profitability. I aim to identify the main barriers that manufacturers face when attempting to implement recycling processes, in order to establish what developments would be necessary to expand the adoption of CFRP recycling across the industry. I anticipate that by identifying these developments and the processes required to achieve them, there will be opportunities for increased collaboration between aerospace manufacturers and CFRP recyclers. With Earth’s resources rapidly depleting and demand for CFRP steadily rising, CFRP recycling is a critical solution that will ensure that aerospace manufacturing can be sustainable, circular and economically feasible.

Although much has been explored regarding introductory physics students' everyday ideas about energy, it is often still taught in much the same way as it was 30 years ago (e.g., balls falling off cliffs, roller coasters, skateboarding). During that same time period, the climate crisis and society’s energy consumption has become a culturally important topic that is largely neglected in physics courses. At a community college in the Pacific NW, instructors introduced activities from Levy et al. (2023)  “An Energy Unit Fueled by Climate Change” to the physics curriculum, aiming to explicitly tie energy topics to climate change issues. Post implementation of the unit, we asked students to share their views of the relevance of and relationship between energy topics in physics and their society, specifically in the context of climate change. Using a phenomenographic qualitative analysis, we examined students' written reflections and coded their responses into similar themes. In this presentation, we share the results of our analysis and recommend a more robust integration of the culturally relevant topic of climate change into introductory physics education.

Mutations, which arise spontaneously, are the foundation of genetic variation and play a key role in evolution. Understanding mutation dynamics has relevance for public health, as antibiotic resistance in bacteria often results from genetic mutations that allow them to thrive in the presence of drugs that would typically inhibit their growth. Our research builds on the Luria-Delbrück method, originally designed to estimate mutation rates phenotypically, by using Next-Generation Sequencing (NGS) to measure base-level mutation rates in Escherichia coli that confer resistance to rifampicin. Rifampicin targets the β-subunit of RNA polymerase, and resistance arises from single nucleotide mutations in the rpoB gene. My team and I conducted experiments by inoculating E. coli populations, exposing them to rifampicin at specific times, and sequencing resistant mutants to calculate mutation rates for each base change. Interestingly, our data revealed that identical base changes at different genomic positions can have significantly different mutation rates. However, our mutation rate estimation does assume that every mutant cell has the same probability of establishing a lineage in the presence of rifampicin. If a certain mutant has a lower probability of lineage survival, its mutation rate will be underestimated. Thus, to determine whether the mutation rate variability we found is due to actual differences and not survival differences, I developed an assay to measure the probability that a mutant fails to establish a lineage. To date, I have isolated nine distinct rifampicin-resistant mutants and tested the extinction rates of two, finding no observable extinction, supporting the accuracy of our mutation rate estimates for these mutants. This research refines mutation rate calculations and enhances our understanding of bacterial adaptation, with implications for developing strategies to predict and mitigate antibiotic resistance. Additionally, it contributes to evolutionary biology by revealing the complexities of mutation and survival in microbial populations

Pseudomonas aeruginosa PA14 and Escherichia coli K12 are gram-negative bacilli that produce outer membrane vesicles (OMVs). Gram-negative bacteria have a cell wall composed of an inner and outer membrane with a layer of peptidoglycan. OMVs are spherical buds that bleb and detach from the outer membrane of bacteria, and contain material that was previously within the periplasmic space, such as proteins, nucleic acids, and virulence factors. OMVs are produced for various reasons, including nutrient acquisition, signaling, protection, and horizontal gene transfer. Other work has aimed at identifying the structure and function of these vesicles, as well as mechanisms of their production. This study concentrates on the creation of methods to produce and isolate OMVs, with a particular focus on ensuring separation from extracellular substances that inhibit direct quantification. To test how biogenesis could be increased, growth conditions were changed. Results indicated that media had a larger influence than temperature or incubation period on OMV biogenesis. In addition, a direct quantification method of OMVs was developed using spectrophotometry, whereas previous studies relied on indirect quantification methods, like protein or lipid assays, or incredibly expensive equipment for direct quantification assays. Gel electrophoresis was used to optimize and identify biological molecules by being able to separate them based on size and charge throughout the gel. Our work will contribute to the research methods of OMVs, and support the potential for them to be used biomedically for mechanisms of drug delivery.

Mitochondrial fusion is essential for cellular function, metabolism, apoptosis, and stress responses. Mitochondrial outer membrane fusion is mediated by two mitofusin paralogs, Mfn1 andMfn2, which are large GTPases that remodel cellular membranes. Membrane fusion likely proceeds through two distinct steps, first tethering two organelles and second lipid mixing; however, much of the mechanism is poorly defined. Previous studies have solved crystal structures of a partial construct of the mitofusins, revealing a GTP dependent conformational change ; however, this is not a complete analysis as at least two states in the catalytic cycle are missing. Our project aims to quantify the conformational changes of Mfn2 throughout the entire mechanism of GTP hydrolysis. To achieve this, we are utilizing a novel transition metal Förster Resonance Energy Transfer (tmFRET) developed by Dr. Gordon and Dr. Zagotta. This system utilizes a noncanonical amino acid as the donor and a transition metal as the acceptor to measure changes as small as 3Å. Currently, we’re mutating the cystines to develop a single donor-acceptor pair, while keeping the stability and GTPase function of Mfn2. Our main approach is to introduce targeted mutations in key cysteine residues and analyze their effects on the protein’s enzymatic activity. Using molecular biology, we design DNA plasmids encoding the mutations,and express and purify the mutant proteins.  Finally we measure the GTPase activity using malachite green assays. Our current findings suggest some mutations have trivial impact on MFN2’s GTP hydrolysis, suggesting that it’s viable. The further goal of our project is to keep only one solvent accessible cysteine while maintaining protein function. This research will further elucidate the mechanism of mitochondrial fusion and its role in disease pathogenesis. Explanding the biophysical understanding of membrane remodeling.

As the aorta ages, the risk of cardiovascular diseases like high blood pressure, aortic aneurysms, and heart failure increases. Previous research has shown that both mitochondrial dysfunction and cellular aging (senescence) contribute to these problems. However, how these two processes interact is not well understood. We hypothesize that the interactions between mitochondrial dysfunction and senescence in aortic smooth muscle cells (SMCs) can lead to harmful changes that promote disease. To test this, we study SMCs from patients undergoing heart surgery. We will measure mitochondrial function using high-resolution respirometry (Oroboros Oxygraph), assess senescence through gene expression (qPCR) and β-galactosidase staining, and examine cell changes using qPCR and immunofluorescence. Understanding this connection could help identify new ways to prevent or treat age-related aortic diseases. Early data shows significant difference in mitochondrial function and cell expression function in different aging disease groups. We are currently studying the effects of mitochondrial targeted and senescence targeted drugs. 

Alzheimer’s disease (AD) is characterized by microvascular (MV) changes due, in part, to basement membrane (BM) alterations. Collagen IV (Col IV), a key BM structural protein, is often found near amyloid-beta (Aβ) deposition in AD, but their relationship remains unclear. Our project investigates how Aβ binding and removal using lecanemab (mAb158) affects MV structure and Col IV in 5xFAD mice, an AD model with extensive brain Aβ deposition. We hypothesized that Aβ removal disrupts Col IV, increasing MV damage and hemorrhage risk. Six-month-old 5xFAD male mice were treated weekly for eight weeks with mAb158 10mg/kg, mAb158 20mg/kg, or isotype control. A fourth group consisted of wild-type (WT) mice (n=4/group). We stained brain sections with hematoxylin and eosin (H&E) for acute hemorrhages and Prussian blue (PB) for subacute hemorrhages. Additionally, I performed immunohistochemistry using collagen hybridizing peptide (CHP) for Col IV degradation and antibody 6E10 for Aβ deposition. In our preliminary results, H&E and PB indicated no acute or subacute hemorrhages in any of the groups. CHP levels were highest at 10 mg/kg, while 20mg/kg and isotype groups had levels similar to or slightly lower than the WT group. Contrastingly, Aβ decreased at 10 mg/kg but increased at 20 mg/kg, and was consistently higher in the lower cortex than in the upper cortex. All non-WT mice exhibited extensive Aβ deposition, suggesting that the late start to treatment reduced efficacy. Concurrently, our co-investigator observed increased blood-brain-barrier (BBB) leakage at 20 mg/kg, but not at 10 mg/kg. Overall, this pilot informs how Aβ-targeting antibodies affect Aβ deposits, Col IV structure, and BBB integrity during AD treatment. Ongoing studies with younger 5xFAD mice (n=10/group), treated from four-months-old for 12 weeks, will further define effects of Aβ on MV structure.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) occurs when a streptococcal infection triggers an abnormal immune response, leading to neuroinflammation in the basal ganglia, causing sudden-onset OCD and other neuropsychiatric symptoms. Current treatments include antibiotics, cognitive-behavioral therapy, selective serotonin reuptake inhibitors, and anti-inflammatory medications (NSAIDs, corticosteroids). While antibiotics target infection, they often fail to resolve persistent immune dysfunction. Some patients experience recurring symptoms, suggesting an autoimmune-driven mechanism beyond direct infection. Despite growing research, PANDAS remains controversial. Some clinicians support an autoimmune model, linking streptococcal infections to neuropsychiatric symptoms; others argue that evidence is inconclusive or that PANDAS is not a distinct disorder. Skeptics cite inconsistent diagnostic criteria, patient variability, and limited large-scale clinical trials. Additionally, the lack of a clear biomarker and symptom overlap with other childhood-onset OCD and tic disorders create diagnostic uncertainty. Intravenous Immunoglobulin (IVIG) has shown promise in modulating immune responses, reducing autoantibody activity, and lowering neuroinflammation, offering a complementary therapy. However, placebo-controlled trials remain limited, and the synergy between IVIG and antibiotics remains underexplored. This literature review seeks to fill that gap, evaluating the combined efficacy of IVIG and antibiotics in treating PANDAS-associated OCD. It examines whether dual therapy leads to better clinical outcomes than monotherapy and identifies which antibiotics work best with IVIG. Drawing from existing studies on similar conditions and neuroinflammatory mechanisms, this research synthesizes clinical trials, case studies, and immune-response data to explore the therapeutic synergy of these treatments. Preliminary evidence suggests IVIG and antibiotics together may better address both infectious and immune components, potentially improving outcomes. However, further research is needed to optimize treatment protocols, refine diagnostic criteria, and expand knowledge on immune-brain interactions in pediatric neuropsychiatric disorders. Future implications include refining diagnostic criteria, identifying biomarkers, and expanding research on the immune-brain connection in pediatric neuropsychiatric disorders.

In recent years, soft end-effector prototypes for agricultural harvesting applications have seen a rise in research and development from numerous sources. Soft robot manipulators in agriculture are necessary because of delicate produce requiring a wide area of force application to reduce bruising, as opposed to small points of contact through rigid gripper materials. Novel designs for delicate and clustered fruits and berries such as blackberries, strawberries, and blueberries are of highest demand. This is because of their small size, fragility, and the narrow windows of fruit harvest due to ripeness. These limitations for berries and vine plants necessitate the use of manual labor as opposed to assisted labor for harvesting other fruits and vegetables like apples and pears, and full harvest automation of other fruits and grains like corn and wheat. As novel proof-of-concept designs describe solutions to these limitations, sensing mechanisms for control loop compensation such as visual and tactile are required to control the parameters required when harvesting fruits. These parameters of surface roughness, overall ripeness, blemishes, etc. require thorough and precise sensing capabilities to reduce fruit waste and resulting costs. The purpose of this paper is to discuss the state of novel agricultural end-effector prototypes for harvesting non-automated produce. This review describes the materials and methods of actuation for end-effectors of small, difficult to automate, and/or delicate agricultural needs with focus on sensing methods, variability and scalability to differently sized produce, and cost-effectiveness. End-effector design prototype and case study research papers are used to produce conclusions through analyzing qualitative data and subjective results. Design improvements, future considerations, and gaps in research are covered to aid the advancement of the most promising prospective designs and potential innovation.

Hypoxic ischemic encephalopathy (HIE) is a neurological condition resulting from reduced blood and oxygen flow to the brain and is a leading cause of morbidity and mortality in neonates. Limited treatment options necessitate accessible and scalable interventions to improve outcomes in newborns impacted by HIE. Extracellular vesicles (EVs) have been previously shown to attenuate oxidative stress and inflammation in the brain. Further research suggests that EVs secreted by astrocytes, a brain cell type involved with the inflammatory and injury response, may elicit neurotrophic or neuroprotective properties. In this study, I isolated, characterized, and evaluated the therapeutic potential of astrocyte-derived EVs (AEVs) in an ex vivo model of hypoxic-ischemic (HI) brain injury. AEV characterization via protein assays and nanoparticle tracking analysis showed that we were able to produce AEV particles about 100 nm in size at concentrations up to 10^11 particles/mL. To assess their therapeutic efficacy, I administered AEVs at varying doses (5, 12.5, 25, and 50 µg) to neonatal rat brain slices exposed to oxygen-glucose deprivation (OGD), an ex vivo model for HI injury. Following 24h of exposure, I evaluated cell viability. Our results indicate that AEVs decrease cytotoxicity in a dose-dependent manner. To further elucidate AEVs’ mechanisms of action, we conjugate AEVs with quantum dots to track AEV localization and cell-type specific uptake in brain tissues. Understanding AEV interactions with neural cells provides insight into both the roles of AEVs and different brain cells in modulating inflammatory responses and promoting neuroprotection. By characterizing AEVs and their therapeutic potential, these findings contribute to the growing body of research on EV-based therapeutics and lay a foundation for developing reliable and scalable therapies with the potential to advance treatments for neurodevelopmental disorders and aid brain injury recovery. 

Controlled fusion would provide clean, abundant energy on Earth and propulsion for space travel. However, we still have much to learn about plasmas, the fusion medium, before we achieve these goals. Simulations play a key role in studying plasmas. Kinetic simulations resolve particles and their collisions individually, so they are computationally expensive. Their alternative, fluid simulations, are less expensive to run  but can't capture as much complexity as kinetic models. This work investigates a hybrid model called Parallel Kinetics Perpendicular Moments (PKPM) that is part of the Princeton code, Gkeyll. PKPM uses kinetic methods parallel to the magnetic field and fluid methods otherwise. Its goal is to get kinetic-like results with lower computational cost. This study investigates how PKPM simulations handle plasma transport compared to fully kinetic simulations. The initial conditions of the two simulation types are identical and consist of an initial sinusoidal perturbation in the temperature of the plasma that is parallel to the magnetic field. The perturbation relaxes over time, leading to a reduction in thermal conductivity. This study compares the reduction in thermal conductivity of the plasma between fully kinetic and PKPM simulations for varying levels of collisionality. The reduction in thermal conductivity is calculated from the change in amplitude of the temperature distribution over time. The PKPM and kinetic results match relatively closely in this case. While more research is needed on how PKPM handles other plasma dynamics, it shows promise as a way to resolve kinetic effects more quickly and with less computational resources. 

Regenerative braking is a well-tested and ubiquitous technology currently used in electric and hybrid vehicles. It recovers electrical energy while stopping or slowing a vehicle rather than simply wasting the energy as heat losses. However, another much-less studied source of untapped energy also exists in vehicle suspension systems, where shock absorbers also dissipate kinetic energy as heat. This study investigates the practicality of regenerative shock absorbers for transforming oscillatory motion (vehicle bouncing) into recoverable electrical energy. In our study, a motor-driven oscillation system simulates vehicle-like suspension movements in controlled experiments. We have created an experimental regenerative electric shock design that uses oscillatory linear actuation of a series of magnets passing through a series of coils to convert mechanical energy into recoverable electrical energy. We have examined the electrical current, voltage and power characteristics and are able to quantify energy-recapture efficiency over broad operating conditions ranging from single-frequency vibrational modes to more complicated and realistic pulse (sudden impact) conditions. Our findings advance knowledge of the feasibility of using regenerative suspension systems to charge auxiliary electronics or augment vehicle power and identify an alternate method of energy recapture for the automobile industry that maximizes vehicle efficiency without sacrificing ride enjoyment.

Aging is characterized by functional decline and increased disease susceptibility, making it essential to study its mechanisms for developing treatments. However, human-based research presents ethical, logistical, and financial challenges, leading to the use of animal models such as rodents and non-human primates. House crickets (Acheta domesticus) offer a promising alternative due to their short lifespan, well-defined organ systems, and ease of rearing. Based on lifespan and age-related decline, a 4-week-old cricket corresponds to a young adult mouse (~3 months) and a human in their 20s, while a 10-week-old cricket is comparable to a geriatric mouse (~24 months) and a human in their 70s. This study examines age-related cognitive decline in crickets using the Y-maze, a widely used cognitive assessment tool in rodents. The Y-maze measures spontaneous alternation, defined as the frequency of sequential entries into three different arms, divided by total arm entries. A higher alternation rate indicates better working memory and decision-making ability, while a lower rate suggests cognitive deficits. Previous experiments showed a significant age-related decline in alternation (p = 0.019), with geriatric crickets exhibiting lower rates than young adult crickets, suggesting age-related cognitive decline. However, the single 10-minute trial design may have introduced confounds such as fatigue or habituation, potentially skewing results.To improve data reliability, a refined Y-maze protocol will implement a two-phase trial. Crickets at 4, 6, 8, and 10 weeks (10 males, 10 females per group) will undergo a 5-minute test phase followed by a 5-minute main trial. One-way ANOVA will compare alternation percentages across age groups, while two-way ANOVA will assess sex-related differences. This study provides a clearer understanding of cognitive function across age groups, strengthening the validity of house crickets as a model for aging research and laying the groundwork for further translational studies.

Reactive ion etching (RIE) is a critical nanofabrication technique used to pattern silicon substrates for various applications such as computer chips and biomedical devices. The process uses high-energy plasma and electromagnetic currents to direct free ions at a silicon substrate, causing chemical reactions that remove target material. One major challenge in RIE is maintaining etch depth and uniformity, particularly as the etch deepens, making it harder to direct ions precisely. The Bosch process addresses this issue by alternating etch and deposition steps in a cyclic manner, where a thin polymer film is deposited after each etch phase. This process is critical to industry, where it is commonly used to make MEMS devices such as accelerometers and medical sensors. In this project, we aimed to optimize the aspect ratio—the ratio of feature depth to feature width—of silicon substrates by fine-tuning various Bosch process parameters, including etch time, deposition time, pressure, gas flow, DC bias, and number of loops. We conducted etch processes on test substrates made using standard nanofabrication processes. Afterwards, we measured the quality and geometry of the etched features using a combination of metrology tools such as a microscope, contact profilometer, and reflectometer, along with scanning electron microscopy (SEM) for detailed analysis of feature sidewalls and trench angles. To efficiently explore the complex relationship between these parameters and their impact on the aspect ratio, we use JMP software to design a set of experiments. This tool enables us to systematically evaluate the effects of multiple variables and identify the optimal etch recipes for enhancing the aspect ratio. This research provides valuable insights into optimizing the Bosch process for broader applications, potentially enabling the fabrication of devices with unique features that would otherwise not be possible in our facility.

Washington state has one of the lowest cardiovascular disease (CVD) mortality rates in the nation, yet significant disparities in CVD burden and access to high-quality cardiovascular care persist and little is known about the effect of socioeconomic and cardiovascular care access factors on CVD burden and outcomes disparity. Here we investigate how the distribution and accessibility of comprehensive cardiovascular care impacts cardiovascular outcomes and burden across the Washington State counties. To assess cardiovascular healthcare accessibility, we catalogued hospitals offering cardiovascular services, determined physician density, and calculated the distance of care types to the county population center. The strength and relationships between these accessibility metrics, selected socioeconomic, and behavioral risk factors were compared against select cardiovascular disease outcomes. Data was obtained from public health records and healthcare datasets and were assessed using linear, logarithmic, and logistic regression models. Area Deprivation Index (ADI), Median Income, and College Education were the top socioeconomic (SES) predictors that positively correlated with improved cardiovascular disease outcomes and burden across counties. While proximity of cath lab and emergency services were not strongly correlated with improved cardiovascular outcomes and mortality, proximity of coronary intervention and cardiothoracic surgery were moderately predictive of cardiovascular disease outcomes and mortality. Surprisingly, the density of primary care, emergency services, critical care, and cardiology physicians was weakly correlated with improved cardiovascular outcomes, while the density of neurologists was moderately correlated with improved cerebrovascular outcomes and the density of cardiothoracic surgeons was moderately correlated with improved cardiovascular outcomes. Cardiovascular outcomes, burden, and healthcare resources vary widely across Washington state counties. Overall, higher SES and immediate accessibility, availability, and proximity of specialized cardiovascular care were most highly associated with improved cardiovascular outcomes and higher median ADI percentiles across counties, highlighting the critical need for targeted and specialized cardiovascular care and expansion of accessible interventional services.

Glioblastomas (GBMs) are highly aggressive brain tumors with poor patient prognosis, necessitating improved preclinical models to evaluate therapeutic strategies. My lab develops cerebral organoids from human pluripotent stem cells, seeded with primary patient tumors to model GBM progression and therapeutic screening. Developing biologically relevant neural organoids provides a platform for integrating patient-derived GBM samples, enabling disease modeling and treatment testing. This study aims to optimize the embedding, cryosectioning and immunofluorescence (IF) staining protocols used to screen key molecular markers and cell populations within the organoids to validate their suitability for GBM tumor engraftment. Fixed organoids, along with embryonic and adult mouse brain tissues, are embedded in OCT to preserve structure and cryosectioned (12–20 μm). IF staining is optimized by adjusting fixation time, permeabilization, blocking reagents, and antibody concentrations to improve specificity and reduce background fluorescence. Markers analyzed so far include SOX2 (neural precursors), PAX6 (radial glia), FOXG1 (forebrain), and TUJ1 (neuronal differentiation). Mouse brain cryosections from newborn (P0) and adult (P56) stages serve as positive controls to validate antibody specificity and distinguish true signals from autofluorescence or non-specific staining. Images are acquired via Olympus scanner and analyzed using OlyViA and NIH Fiji (Enhanced ImageJ). Current efforts focus on optimizing section thickness for clearer images and refining blocking conditions to minimize non-specific binding. We expect the detected fluorescent markers will mirror known cellular and tissue expression patterns, confirming that the organoids exhibit normal human fetal neurodevelopmental characteristics and are biologically relevant for GBM modeling. Future work will expand marker validation to include GFAP (astrocytes), DCX (neurogenesis marker), TBR2 (intermediate progenitors), OLIG2 (oligodendrocyte progenitors), PTPRZ1 (radial glia), IBA1 (microglia) and other cell lineage-specific markers. Establishing reliable staining and imaging conditions is a crucial step toward developing our organoid model to be suitable for exploring GBM tumor biology and potential therapeutic responses.

As incidences of opioid use disorder (OUD) have surged to an astonishing 2.5 million individuals, trends of concurrent opioid and psychostimulant use have also risen to a dire degree. Despite this growing number of polysubstance related overdose deaths, current research has primarily focused on the effects of single-substance drug exposure–creating a knowledge gap in our understanding of polysubstance use and corresponding treatment modalities. Thus, we aimed to investigate the differential effects of fentanyl and methamphetamine (METH) polysubstance exposure compared to single substance exposure on drug-induced hyperlocomotion and social interaction in male and female Sprague Dawley rats (n=40). We initially hypothesized that polysubstance exposure to fentanyl and METH would generate distinct behavioral effects on locomotor behavior compared to single-substance exposed animals. We found that in polysubstance and METH-only rats, METH-induced locomotion increased over time in males, but not in females. Additionally, we observed that polysubstance exposure exacerbated fentanyl-induced locomotion in males compared to their fentanyl-only counterparts. We further hypothesized that polysubstance exposure would amplify drug-induced social deficits compared to METH-only and fentanyl-only groups. Seeing how recent literature suggests that psychedelic drugs may have substantial therapeutic and prosocial effects, we also hypothesized that the psychedelic compound R-(-)2,5-dimethoxy-4-iodoamphetamine (DOI) would reverse social deficits observed in both single and polysubstance exposure. We found that social deficits emerged in our polysubstance males and females. We additionally observed a social deficit in our METH-only treated females, but not males. We are currently investigating if the effects of DOI may reverse these deficits. Considering these sex-specific findings, it is crucial that we continue investigating the diverging impacts between males and females to develop targeted therapeutic interventions for polysubstance use.

Per-Arnt-Sim (PAS) domains are ubiquitous protein modules that enable cells to detect and respond to environmental signals. For instance, circadian rhythm regulators leverage PAS domains to sense stimuli and initiate protein-protein interactions critical for maintaining biological oscillations. Structurally, the sensory region of PAS domains detects environmental cues—such as fluctuations in phosphorylation levels—while the effector domain converts these signals into cellular responses, including altered gene expression or protein interactions. Inspired by this natural framework, our project aims to design de novo sensory domains that selectively recognize tyrosine phosphorylation, a key post-translational modification in cellular signaling, through association/dissociation between bound and unbound states regulated by the phosphorylation/dephosphorylation cycles. During the design phase, we prioritized synthetic peptide targets for initial proof of principle and systematically deployed computational pipelines: (1) Rosetta introduced phosphotyrosine modifications into pre-designed protein-peptide heterodimer scaffolds; (2) iterative LigandMPNN with Rosetta FastRelax optimized binding interfaces to accommodate the phosphotyrosine modifications; (3) RFdiffusion Partial Diffusion enhanced the structural diversity around promising designs with the aim of improving affinity and specificity; and (4) Chai-1 and AlphaFold enabled in silico folding and structure-based filtering of final candidates. High-confidence designs will be expressed and purified from E. coli, and then undergo in vivo characterization via size exclusion chromatography (SEC) binding assays and enzyme-linked immunosorbent arrays (ELISA) to quantify their binding affinity, specificity, and the function of phosphorylation-dependent switching. Validated scaffolds will then be integrated with pre-designed effector domains to assemble fully de novo PAS domains. This modular platform establishes a foundation for designing phosphorylation-sensitive biosensors. Future adaptation to natural phosphorylation sites could yield programmable tools for interrogating signaling networks, advancing synthetic biology, and enabling precise manipulation of cellular communication pathways.

The auxin hormone is necessary for many essential plant functions. Corepressors from the TPX family hold auxin response genes (ARGs) OFF unless auxin levels are high. TPX proteins are brought to ARGs through interaction with Aux/IAA adaptor proteins, which can bind to auxin-regulated transcription factors. Plant pathogens interfere with the auxin transcriptional pathway, making a plant more susceptible to infection. Oomycetes, for example, are a common plant pathogen commonly found as a mold growing on ripe tomatoes and strawberries. Oomycetes inject RxLR effector proteins into plant cells to reprogram the immune response. RxL21 is one of these effectors, and it contains a binding site for TPX proteins that is very similar to what is found in the Aux/IAA proteins. We hypothesize that RxL21 competes with Aux/IAA for recruitment of TPX proteins and keeps auxin genes on during an infection. I tested this hypothesis by performing a cytoplasmic split ubiquitin assay (Cyto-SUS), which is a protein-protein interaction assay done in yeast. Through this assay, we detected weaker TPX-Aux/IAA interaction when RxL21 was present, suggesting that competition for TPX protein interaction is occurring. I also tested whether the RxL21 competition would alter transcription of an ARG using a fluorescence-based assay in yeast. I observed much greater fluorescence when RxL21 was present, suggesting that RxL21 competition with Aux/IAA for recruitment of TPX results in increased transcription of ARG. In future experiments, I will further test our hypothesis by expressing RxL21 and other effector proteins in specific cell types in the model plant Arabidopsis thaliana. These experiments will allow me to quantify the impact of the competition for TPX corepressors on a developmental process. The results of this work could guide the design of new, broad-spectrum strategies to protect plants from pathogens.

According to the Centers for Disease Control and Prevention, the U.S. has more than 2.8 million antibiotic-resistant infections each year. The rise of multidrug resistance in bacteria poses an urgent clinical threat contributing to these various infections. UPAB1 is a specific strain of a notoriously drug-resistant bacteria Acinetobacter baumannii associated with catheter-associated urinary tract infections (CAUTI). UPAB1 infects the urinary tract through the introduction of a foreign object, such as a catheter. In response, the immune system coats the catheter with fibrinogen, a glycoprotein complex that assists in wound healing. UPAB1 uses its bacterial adhesin proteins, such as Abp2D, to bind to fibrinogen, deplete essential nutrients, and infect the urinary tract. By designing Abp2D inhibitors as de novo miniproteins, we hypothesize that A. baumannii will be prevented from establishing a bacterial infection and allow us to offer a potential alternative in combating antibiotic resistance in CAUTIs. Targeting UPAB1 Abp2D, we first developed designs of Abp2D inhibitors utilizing computational software like RoseTTAFold Diffusion (RFdiffusion) for miniprotein backbone design, ProteinMPNN for sequence design, and AlphaFold2 (AF2) for structure prediction of the sequences to validate and filter. Afterwards, in the laboratory, we expressed and purified the miniprotein designs. We are currently testing these designs as Abp2D inhibitors via E. coli cultures to determine their success in binding to UPAB1 Abp2D.

The growing demand for sustainable materials has driven research into biodegradable alternatives to petroleum-based plastics. Global plastic production has surged to 367 million metric tons as of 2018, with projections indicating a threefold increase by 2050. The persistence of petroleum-based plastics has led to the accumulation of nearly 5 billion metric tons of plastic waste in oceans and ecosystems since the 1950s, presenting significant environmental challenges. This highlights the need for sustainable alternatives, such as algae-based bioplastics. Photosynthetic algae, such as spirulina, can be processed through hot pressing to produce bioplastics with mechanical properties comparable to conventional plastics. Moreover, algal bioplastics are biodegradable, and algae’s ability to capture atmospheric carbon positions this material as a promising eco-friendly alternative. The chemical composition of algae includes protein, carbohydrates, lipids, as well as vitamins, minerals, and pigments. My research aims to analyze the role of lipids on the formation and performance of the resulting bioplastic. Algae cells were disrupted using mechanical force, followed by lipid extraction using a chloroform-based solvent. The extracted lipids were characterized using Fourier Transform Infrared (FTIR) spectroscopy, revealing consistent peaks associated with lipids. The lipid free algae was then hot pressed to evaluate the mechanical strength of the bioplastic in the absence of lipids. Future work will aim to further analyze the microscopic structure of lipid-free bioplastics to determine the role of lipids in their formation and cohesion. Additionally, this research is expanding to extract other macromolecules, such as proteins and carbohydrates, to investigate their contributions to bioplastic performance. Gaining insight into the roles of lipids and other macromolecules will enable the precise design and optimization of bioplastic materials.

The conservation of global marine mammal abundance has been considered largely successful as the widespread ban of the industrial harvest of pinnipeds and large cetaceans has led to their strong recovery in abundance. However, it remains unknown whether the story of their conservation applies to marine mammals that were not heavily harvested such as oceanic dolphins. Here, I plan to fill this knowledge gap by presenting a meta-analysis of global abundance trends of oceanic dolphins by conducting a systematic literature review of government reports, journal articles, and marine biodiversity data sets to gather abundance trend data. I expect to find data for roughly 25% of all 38 oceanic dolphin species, mostly represented by line-transect surveys and mark-recapture evidence in coastal waters. Using a Bayesian multi-population state-space model, I intend to estimate abundance trends for each dolphin population, in addition to the uncertainty in population changes and varying survey methods. I seek to summarize abundance trends of populations by species and regions to identify which of these have declining or highly unknown abundance trends. I expect dolphins with restricted geographic ranges, especially coastal species, to have the strongest declines, and dolphins that occupy high seas to have the least known trends. I aim to highlight which taxa and areas need further conservation and monitoring attention. These findings represent a crucial first step in gaining insight from rising dolphin populations, which can be used to help reverse the decline of other populations.  

Following an extensive history of industrial activity in Commencement Bay, Washington, the health of marine ecosystems continues to be affected by persisting pollutants. Commencement Bay has been identified as a Superfund Site, in which the Environmental Protection Agency (EPA) is tasked with cleaning up locations contaminated with hazardous materials. In an effort to gauge just how effective these recovery efforts have been, this study, part of the Puget Sound Foraminifera Project at the Burke Museum, investigates how the density and diversity of benthic foraminiferal assemblages have changed over time. Foraminifera, a diverse and widespread order of shelled marine protists, can be utilized as a reliable measure of marine ecosystem health due to their innate sensitivity to environmental changes. Samples collected by the Washington Department of Ecology (WDOE) from 2014 and 2022 allow for a comparison of diversity indices that are indicative of the success in the bay’s recovery. To quantify this success, calculations of the Shannon Index and the Simpson Index were completed for each sample, supporting our determination of the Foraminiferal Benthic Index (FBI) of the region. The FBI was defined using measures of abundance, diversity, and percentages of tolerant species present in each sample to quantify the extent of adversity. With 2022 density and diversity averages that are statistically similar to those of 2014, we can conclude that clean up efforts have not yet made sufficient measurable improvements in the Foraminiferal Benthic Index over the previous eight years.

Anthropogenic climate change is expected to shift the range of numerous species, including coast redwood (Sequoia sempervirens) at a rate faster than natural migration patterns. Assisted migration (i.e., human movement of species) is one strategy proposed to maintain survival of coast redwood, which are limited to a native range of approximately 50 km stretch on the west coast of California. To determine survival of the crucial seedling stage in the Pacific Northwest, 845 seedlings were planted in a controlled greenhouse experiment to test the survival of redwoods against drought and competition with implications for range expansion into Washington. I recorded seedling height, stem length, root length, root collar diameter, vigor and dry biomass of stems and roots of 694 seedlings included in this study. I then analyzed data to determine if differential investments in aboveground versus belowground biomass alter survivability in drought and competition of different native and non-native species; coast redwood, Douglas-fir (Pseudotsuga menziesii) and western redcedar (Thuja plicata). We predict that an increase in relative root investment, categorized as relative mass of root compared to stem mass, will correlate with longer survival of redwood seedlings in drought conditions. Douglas-fir were found to have significantly higher root:shoot ratios than redwoods and western redcedar  with further variation within species genetic identifications. Prolonged redwood survival compared to Douglas-fir and western redcedar was observed and may provide survival implications for planted conifers in the Pacific Northwest.

Over 200,000 doctors and nurses in the U.S. who use live X-ray imaging (fluoroscopy) to guide medical procedures are exposed to harmful radiation. Over time, this exposure increases their risk of cancer, cataracts, and other health problems. The current solution, which involves wearing heavy lead aprons, provides some protection but does not entirely block radiation. Furthermore, these heavy lead aprons often cause long-term problems, such as chronic back, neck, and joint pain in over 50% of users. Over the past two years, I have helped develop a new portable radiation shield designed to provide full-body protection while reducing physical strain. This shield features telescoping poles that adjust for ergonomic positioning and support large lead sheets while remaining compact, easy to maneuver, and compatible with sterile environments. To evaluate its effectiveness, a phantom model is used to measure scattered radiation during live X-ray imaging. Two shielding methods are tested: a standard lead apron and the portable shield we have created. Radiation sensors are placed at the head, neck, chest, and legs to compare exposure levels. A paired t-test determines whether the portable shield significantly reduces radiation compared to the lead apron. At least 30 test trials per shielding condition are conducted to ensure accurate results, with a target of ≥95% radiation reduction. Based on our initial calculations, I expect a 15-fold decrease in radiation exposure with our portable shield compared to traditional lead aprons. This research evaluates a new way to protect healthcare workers from harmful radiation exposure while reducing physical strain and helping improve safety in medical settings. 

All organisms regulate genes for proper cell development, healthy environmental response, and prevention of disease. One way to regulate genes is through transcriptional repression, specifically through corepressors that bind to repressors to inhibit expression of genes. The TPL/TPR corepressor family is crucial in Arabidopsis thaliana for regulating auxin-dependent genes during embryogenesis, root and shoot axis formation, differentiation, and environmental responses. Due to functional redundancy among the TPL/TPR gene family, partial mutations in the family do not create full loss of function. However, knocking out multiple family members is lethal. My research aims to induce loss of function for TPL in specific tissue. To achieve this, I started with a plant strain that is mutated for three of the five family members through insertional mutagenesis by T-DNA, leading to a partial loss of function, with two remaining genes remaining functional. Then I constructed a single TPL copy under the control of an integrase-based molecular switch, which when expressed, inverts the promoter of the TPL gene, turning it off. This construct, assembled through Golden Gate cloning, includes a YFP-tagged TPL gene and an mScarlet reporter that allows me to confirm TPL expression (YFP) or its absence (mScarlet) through fluorescence microscopy. I have integrated this construct with the controllable TPL switch into Arabidopsis, and my next goal is to use a CRISPR/Cas9 system to mutate the remaining two TPL genes for full loss of function. I will then utilize the integrase control switch system for specific TPL repression in the lateral roots. Such a study helps synthetic biologists understand the necessity of TPL in specific tissues, avoiding full knockout lethality. With corepressors existing among different eukaryotes, this study has broader implications in understanding human repressors, such as TBL-1 that are linked to dysregulation of gene expression in diseases like cancer.

Under acute genotoxic stress, such as chemoradiation, stem cells can undergo cell cycle arrest at the G1/S phase to avoid apoptosis. This protective state, called quiescence, is reversible once stress-free conditions allow re-entry into the cell cycle to regenerate daughter cells. We have previously demonstrated a common mechanism by which two types of stem cells—Drosophila germline stem cells (GSCs) and human-induced pluripotent stem cells (hiPSCs)—enter quiescence. Recently, we found Cyclin E (CycE) associated with the outer mitochondrial membrane (OMM) in both GSCs and hiPSCs. We are interested in studying the interaction between CycE mitochondrial localization domains and mitochondrial proteins responsible for CycE localization.To map the CycE mitochondrial localization domain, I have generated four CycE truncations tagged with GFP: ΔN-terminus, ΔCyclin Box_N terminus, ΔCyclin Box_C terminus, and ΔC-terminus. I have tested these constructs in various cell lines, including Rcc4, HCT116, MCF10A, HEK, and HeLa, and found that HCT116 exhibits mitochondrial localization of CycE. I will compare the localization of wild-type CycE-GFP versus mutant CycE using immunofluorescent staining of CycE and mitochondria in HCT116, as this cell line is well-suited for transfection studies. We have shown that mitochondrial CycE is degraded in quiescent stem cells through PINK1/PARKIN-mediated mitophagy. We propose that CycE degradation is necessary for quiescence entry. In Drosophila GSCs, we observe that upon irradiation, cells overexpressing non-degradable CycE continue cell division, whereas control cells undergo quiescence. Understanding the mechanism by which Cyclin E localizes to the OMM will enhance our knowledge of how it prevents quiescence entry, thereby contributing to the development of anti-cancer treatments.

Exposure to air pollution, the fourth leading risk factor for global attributable deaths, has been linked to the development of several noncommunicable diseases. The incidence of thyroid diseases in the United States continues to increase yearly, estimating that over 12% of Americans will develop it during their lifetime. While thyroid disorders are not yet recognized as a noncommunicable disease, they promote the onset of other chronic diseases. Diesel exhaust (DE), an important source of particulate matter and other toxic compounds within traffic-related air pollution, generates reactive oxygen species (ROS) which can lead to oxidative stress in the body. Oxidative stress is the imbalance of ROS and antioxidants in the body and is associated with numerous diseases. The purpose of this study is to assess the effects of DE-induced oxidative stress in plasma and the thyroid, specifically examining how effects differ based on sex and a high-fat diet (HFD). We exposed male and female mice (low-density lipoprotein receptor knockout mice) to filtered air or DE for 18 weeks, while fed HFD or Chow. In plasma, we measured the activity of the antioxidant enzyme paraoxonase-1 (PON1) and the concentration of the acute-phase serum amyloid A (SAA) protein via ELISA. In thyroid tissue, we extracted RNA and used RNA-Seq to assess DE-induced transcriptional reprogramming. We expect that DE exposure will result in higher levels of inflammation (SAA) and lower levels of antioxidants (PON1). We expect that these effects will display sex differences and will be more pronounced in HFD-fed mice fed. Our transcriptomics analysis will help identify new genes and pathways affected by DE, diet, or both. Our results will improve our understanding of the link between air pollution and thyroid disorders, guiding future research and interventions to address the growing health concern of thyroid disorders and related noncommunicable diseases.

People who identify as Black and African American face disproportionate mental health and addiction burdens, but they access existing evidence-based services at lower rates than their White counterparts. There has been historical harm from unethical research practices and questionable interpretations of research data generated from the black community; these have resulted in sustained distrust in research and healthcare among Black individuals. Whereas culturally tailored approaches can improve engagement, Black individuals remain underrepresented in research and often feel excluded. Our study explores: What do Black young adults perceive as essential for building trust in research and healthcare, and what priorities do they identify as critical for improving mental health and engagement within their communities? Our data are from an ongoing parent study examining the effects of daily and racial stressors on alcohol and cannabis use among Black young adults. We will use the qualitative data collected from participants of the parent study. Participants are 78 Black adults aged 18-25 (M_age=22.1, 50% female, 56% full-time students) recruited from Seattle, WA, and Dallas, TX. Each participant completes a 30-minute, one-on-one semi-structured virtual interview. The recorded interview is transcribed and coded for themes that answer our research questions. Interview questions are designed to understand participants' recommendations for building trust between the Black community and scientists and healthcare providers, and important or timely mental health needs in the Black community. First, participants highlighted the importance of researchers' cultural competency, increased diversity of healthcare providers and researchers, and clear, transparent communication between scientists/providers and Black individuals. Participants emphasized the need for accessible medical language, informed consent, and improved health literacy to build trust. Second, participants identified pressing research and healthcare needs, including destigmatizing mental illness, addressing racial and generational trauma, and increasing access to culturally competent care. Implications for research and practice are discussed.

Understanding complex disease processes requires visualizing both nanoscale details and their impact on larger structures. The Vaughan group has developed a method that achieves this using conventional optical microscopes by physically expanding tissue via hydrogel chemistry, enabling sub-diffraction-limit resolution. This approach preserves physiological context through fluorescent labeling of macromolecules (DNA, proteins, carbohydrates). Using mouse renal glomeruli—spherical kidney filtration units (~70-100 µm in diameter)—as a model, I demonstrate the method’s ability to capture nanoscale features, specifically global variations in basement membrane thickness (100-2000nm), with validation that the expansion process does not introduce significant distortion.

An aneurysm occurs when a blood vessel wall abnormally bulges in one spot. If it is left untreated and ruptures, it can be one of the highest causes of strokes and other neurovascular diseases. Current clinical treatment involves radiologists manually measuring the diameter of the aneurysm using computed tomography (CT) or magnetic resonance imaging (MRI) scans. However, the growth of aneurysms has been proven to be another indicator of aneurysm ruptures. To accurately track the progressive growth of aneurysms, we proposed a deep learning-assisted pipeline to segment and register aneurysms in different CTA scans. To train the model, we took a data set from Beijing Tiantan Hospital of 54 patients with more than two follow-ups and individually labeled each aneurysm with its parent vessels using a 3D slicer. Using the trained model, we segmented the image scans of 168 patients and performed rigid registration to align different scans. We calculated the Average Surface Distance (ASD) in parent vessels to show the boundary consistency in our methods. Under two radiologists' evaluations, 12 and 14 aneurysms were growing, with only 1 reaching consensus. In our 3D visualization, we found that the one confirmed by the two doctors was growing. However, the rest of the aneurysms showed little change, which might indicate a high false positive rate in clinical measurements and more accurate results with our proposed pipeline. Further work will be focused on a more quantitative comparison of aneurysm growth. An automatic segmentation and registration process will improve the efficiency and accuracy of medical evaluation for patients with neurovascular diseases, which can transform the future of medical imaging analysis and lead to greater insight, diagnosis, and treatment of neurovascular diseases.

Heroin, a commonly used opioid, has played a significant role in the escalating opioid crisis, highlighting the urgent need to better understand the neural mechanisms underlying its addictive properties. Despite well-documented sex differences in opioid use disorder (OUD), the majority of preclinical research has been conducted in male animal models, limiting our understanding of how biological sex influences addiction-related behaviors. This study investigates the role of sex differences in heroin-induced locomotor sensitization and hormonal adaptations in a rodent model. Using a rodent model, we administered intravenous heroin and tracked activity to assess sensitization to the effects of heroin on locomotion. Following treatment, the rats underwent 20 days of withdrawal from heroin. Blood samples were collected throughout treatment and withdrawal to track changes in serum hormone levels. Our findings indicate that female rats show locomotor sensitization at an earlier time point and exhibit a greater degree of escalation compared to males. This suggests potential sex-specific mechanisms influencing opioid addiction vulnerability and progression. We aim to continue quantifying gonadal hormone fluctuations throughout heroin exposure and withdrawal with additional cohorts of animals. Future experiments aim to use fiber photometry to image estradiol activity in the brain during sensitization, providing a real-time insight into its role in opioid-induced changes in behaviors.

All organisms develop from a single, symmetrical cell. That symmetry must be broken at several points during embryogenesis to develop into a complex, intricate form of life. The earliest symmetry breaking event in vertebrates is the formation of the dorsal organizer, a signaling center that establishes dorsal-ventral and anterior-posterior axes. β-catenin signaling is highly conserved in the dorsal organizer and utilized during cancer proliferation. However, the mechanisms employed in selective β-catenin stabilization are still not fully understood, due in part to limited vertebrate embryological models. Established model organisms for development, like fish and frogs, pre-pattern their dorsal organizer through maternal determinants, which is lacking in mammalian model organisms who break symmetry with self-organization. Remarkably, the African Turquoise Killifish, Nothobranchius furzeri, lack a pre-pattern. This presents a strong model organism, N. furzeri, to investigate mechanisms of self-organization. In this work, I explore the metabolic shifts and mechanical forces as two potential drivers of selective β-catenin stabilization. To investigate whether fluctuations in intracellular pH (pHi) stabilize β-catenin, I created a Tol-2 mediated transgenic pHi reporter line. Using light sheet microscopy, I observed that pHi fluctuations occur after β-catenin is stabilized in the incipient dorsal organizer. This ruled out pHi as the initializing factor of β-catenin stabilization. Next, I will explore whether mechanical forces drive embryonic symmetry breaking. This model posits that local microtubules-generated forces are transduced by focal adhesions into biochemical signals, enabling selective β-catenin stabilization. To evaluate this model, I will develop a transgenic toolkit to visualize microtubules polymerization and focal adhesion signaling with pharmacological and dominant negative approaches. These experiments will elucidate the mechanism responsible for symmetry breaking in N. furzeri and potentially conserved regulators of Β-catenin signaling, foundational to our understanding of development and cancer research.

Attention restoration theory (Kaplan & Kaplan, 1989) which has shaped our understanding of the benefits of nature, centers around the idea that certain qualities of nature innately capture our focus and encourage restoration. Based on this theory, it seems unlikely individuals would feel predominantly bored in nature. Using data from a larger study of University of Washington undergraduates' nature encounters, the goal of this research is to investigate how often individuals experience boredom in nature and to better understand the characteristics of those who may be prone to boredom. Participants who reported having spent time in nature over the past week were queried about whether they had felt bored during the experience. 101 (8%) said they “always” or “often” felt bored in nature, a contrast to 1154 (92%) who said they were “never” or “sometimes” bored. This group represents a unique subset of the data and preliminary findings show they self-reported higher levels of stress, depression and anxiety. This group also seems to have different trends regarding phone usage in nature. 64% of participants who were “often” or “always” bored reported looking at their phone for over half their time in nature, compared to only 20.3% of participants who didn’t report high levels of boredom. Additionally, 74% of participants with high levels of boredom reported using their phone for more than just checking maps, taking photos of nature and identifying plants or animals, compared with just 55% of the rest of the sample. This research has important implications for identifying what kinds of nature interaction may be more or less engaging and beneficial to the wider population, as well as understanding who may be more prone to boredom in nature. 

This study investigates the sensory adaptations of nocturnal and diurnal rodent species, focusing on the relationship between orbital structures and whisker morphology. We hypothesized that nocturnal rodents would exhibit larger orbital dimensions, including maximum orbit length (MOL), due to their need for enhanced light-gathering capabilities in low-light environments. Our analysis of various rodent species, including Peromyscus maniculatus, Rattus norvegicus, and Sciurus carolinensis, revealed significant differences in orbital measurements, with nocturnal species consistently displaying larger orbits (p < 0.001). Our data collection involved taking six linear measurements from skulls (four related to orbit size using ImageJ software and two cranial size proxies using digital calipers) and analyzing whisker morphology, followed by statistical analyses including histograms, boxplots, Pearson correlation test, and phylogenetic analysis to explore relationships among traits in diurnal and nocturnal species. Additionally, while whisker length showed a stronger correlation with body size in diurnal species compared to nocturnal ones, the differences in whisker morphology were less pronounced and not statistically significant. Phylogenetic analyses indicated that certain traits, such as interorbital width, are influenced by evolutionary relationships rather than solely by activity patterns. These findings suggest that while visual adaptations in nocturnal rodents are prominent and likely enhance their survival in dim conditions, the role of tactile sensory structures is more complex and may be shaped by a variety of ecological pressures. Overall, this research contributes to our understanding of how different lifestyles influence sensory system evolution in rodents and has implications for fields such as evolutionary biology and biomimetics.

The He6-CRES collaboration experiment aims to take precision measurements of nuclear beta decay spectra to search for exotic currents of the weak interaction, which would indicate a deviation from the Standard Model of particle physics. The sources used for the investigation of beta decay in the experiment are helium-6 and neon-19, which are created via use of a Tandem Van de Graff particle accelerator. For neon-19, a 12 MeV proton beam is incident upon the target gas sulfur hexaflouride. At this energy scale, it is possible for unstable isotopes, in addition to neon-19, to be created. As such, it is necessary to place upper limits on possible contaminants. The focal point of this project is the determination of the maximum amount of radioactive contaminants that are created when producing neon-19, and the methods in doing so.

According to the CDC, there are over 42,000 female deaths from breast cancer a year in America. In particular, triple negative breast cancer is a clinical subtype that lacks estrogen, progesterone, and HER2 expression, making it more aggressive and harder to treat compared to other subtypes. There is an increased demand for targeted treatments such as immunotherapy, but little is still known about the disease’s immunological progression. Thus, we aim to integrate multiplexed imaging techniques with computational algorithms to capture immune distributions and uncover unique immune spatial architectures. We will study the immune interactions  between neutrophils and different T cell populations as they play an important role in immune signaling in the tumor microenvironment. This is important as neutrophil interactions are currently not well understood. Using a cohort of multiplexed immunofluorescence (mIF) images, we will characterize helper, cytotoxic, and memory T cells as well as neutrophils using the following biomarker panel: CD3, CD4, CD8, CD45RO, CD66b. Custom-trained CNN-based models using spectrally unmixed data for each marker is used for phenotyping with high accuracy. We annotated cells from our dataset to generate the training dataset for these phenotype classifier models. After phenotyping, we utilize spatial point pattern analyses (e.g., G-Function) to identify spatial interactions such as clustering effects between the immune cell phenotypes. We also compute patient level metrics such as the median nearest neighbor distance between pairs of phenotypes and custom-designed inter-phenotype clustering scores. Finally, we utilize Kaplan Meier analyses and log-rank test to correlate the above spatial metrics with recurrence-free survival.

Mutations in the RAS gene family are common in various cancers and are estimated to occur in approximately 19% of cancer patients. We utilize the model organism C. elegans to study RAS genes because it sends signals in the worms the same way it does in humans. C. elegans only have one RAS family gene, encoded by let-60, making it simpler to study than the three in humans. The let-60 G13E mutation is a gain of function (gf) mutation also found in cancer patients and is characterized by a glycine to glutamic acid amino acid mutation at residue 13. The mutation is phenotypically marked by neoplasias - pathologically abnormal growths of tissue, effectively constituting tumors. Despite genetic uniformity of C. elegans in the controlled laboratory environment, not all let-60 gf worms develop neoplasias. Preliminary findings show that the penetrance of neoplasias is approximately 81% in the MT2124 strain, which developed the let-60 gf mutation via mutagenesis, and 93% in the ARM219 strain, which developed the mutation via CRISPR technology. Previous reports have identified chaperones as affecting RAS activity, My study aims to identify the effects of heat shock proteins hsp-17/CRYAB  and hsp-70/HSPA5 in C. elegans on the penetrance of neoplasias driven by the let-60 gf worms. Neoplasias shorten lifespan, so I measured their effects on survival in worms with and without the let-60 gf mutation, sorting them by tumor count. I hypothesized that the genetic backgrounds with a lower penetrance and expressivity of let-60 gf will have fewer tumors on average and observe a longer lifespan compared to strains with a higher penetrance of the mutation. Understanding the role of heat shock proteins in neoplasia penetrance could provide insights into potential therapeutic targets for RAS-related cancers.

Stone wool, with its exceptional insulation and fire resistance properties, is an effective material for reducing the energy consumption and environmental impact of buildings. Adhesives such as phenol-formaldehyde resins are used in conventional stone wool systems to provide mechanical strength to the system but require high temperatures and energetic costs during their curing process while also emitting harmful emissions during their uncured and curing phases. Our research aims to develop a non-toxic and fully degradable binder system utilizing algal biomatter, xanthan gum, and bacterial nanocellulose. We investigate the rheological properties of biobinders at different concentrations and evaluate the effects of thermal processing on the mechanical properties of the biobinder. Additionally, we use scanning electron microscopy (SEM) to study the distribution and microstructure of biobinder in the composite systems and Fourier transform infrared (FT-IR) spectroscopy to analyze the bonding interactions between each component at different temperatures. In this work, we obtain a better understanding of the interacting mechanisms between each biopolymer and their effects on biobinder mechanical performance, which shows great potential for reducing the environmental impacts of mineral fiber insulation materials.

Platelet transfusions are critical for bleeding patients or patients at risk of bleeding. For this purpose, platelets are either stored at room temperature or in the cold (1-6 degrees C). Cold-stored platelets (CSPs) have a longer shelf life, can reduce bacterial contamination, and may be more effective than room temperature-stored platelets (RTPs). However, CSPs can form aggregates, ultimately making them unusable. What causes these aggregates and how to prevent them is poorly understood. This study aims to identify potential factors related to aggregate formation in CSPs. We obtained CSP units manufactured in plasma between 3/16/22 and 9/25/24 from 88 unique donors. The units were sent from South Texas Blood and Tissue, TX to Swedish Medical Center, WA. Using this data, we analyzed the rates of aggregates among donors of different sex, age, and blood groups in 88 unique samples. The same criteria for aggregates used for RTPs were applied to CSPs. Of the 88 donors in our sample, 36.4% were female and 63.6% were male. Of the 88 unique samples, 47 had formed aggregates. Donor ages ranged from 17 to 85 years. The average donor was 53 years and the median age was 56 years. Our sample consisted of donors with type A- (6.82%), type A+ (70.5%), type O- (1.14%), and type O+ (21.6%) blood. We found no significant difference between donor characteristics and aggregates. We also compared aggregate formation to the time between CSP collection and shipment, time spent at the hospital blood bank, and total time of storage. We found no significant associations between aggregate formation and any of the time variables. In summary, there were no significant differences between our variables and aggregates in CSPs collected in plasma. These findings can be used to explore alternate factors associated with aggregate formation in CSPs.

The global pandemic of obesity has increased the prevalence and burden of metabolic diseases, including type 2 diabetes and cardiovascular disease. Obesity and its comorbidities are frequently associated with hypogonadism (low levels of testosterone (T) in men), and both preclinical and clinical evidence support a causative role of hypogonadism in predisposing individuals to metabolic diseases. However, the mechanisms remain unknown. One potential mechanism arises from our recent discovery that in mice, surgical castration (reducing T levels) amplifies the pro-inflammatory response to consumption of a high-fat diet, specifically leading to activation of astrocytes within the hypothalamus, a brain region critical for regulating whole-body metabolism. Concomitantly, there is a striking reduction of the anti-inflammatory neuropeptide neurokinin B (NKB; encoded by the Tac2 gene) in the same brain region. Therefore, we hypothesized that T limits astrocyte inflammation via enhanced NKB-neurokinin-3 receptor (NK3R) signaling. Using primary astrocytes harvested from newborn mice, we found that T and dihydrotestosterone (DHT; a non-aromatizable androgen) increase the expression of tachykinin genes like Tac2. Further, androgen treatment blunted the proinflammatory response of primary astrocytes to lipopolysaccharide (LPS), a sepsis-inducing bacterial cell wall component. To assess the anti-inflammatory capacity of NK3R signaling, we co-incubated astrocytes with the NK3R agonist Senktide and LPS, finding a significant attenuation of proinflammatory cytokine expression. Together, these data suggested that androgen receptor signaling might constrain astrocyte inflammation through induction of NKB-NK3R. However, the ability of DHT to reduce cytokine expression in response to LPS was preserved in the presence of Osanetant, an NK3R antagonist, indicating that the anti-inflammatory actions of androgens are independent of NK3R signaling. These findings form the foundation for future pharmacologic and genetic interventions in obese mouse models to further clarify the role of astrocyte T and NK3R signaling in hypogonadism-associated metabolic diseases.

After traumatic brain injury (TBI), astrocytes can undergo distinct changes in function and morphology, termed astrogliosis. Astrocytes are important glial cells with roles in maintaining neural circuits. This astrogliosis can lead to maladaptive changes, inhibiting proper support of circuitry that might lead to hyperexcitability.  TBI is a risk factor for the development of epilepsy, and we wondered whether increased astrogliosis is present in cases that develop epilepsy compared to TBI without epilepsy. To assess this question, we examined astrogliosis in male brain donors with a remote history of TBI with and without post-traumatic epilepsy, as well as controls in a similar age range. Immunohistochemical staining for glial fibrillary acidic protein (GFAP), an astrocytic cytoskeleton protein, was used to visualize and quantify astrogliosis. The percentage area of staining was determined in both the orbitofrontal cortex (OFC), a region commonly vulnerable to TBI, as well as the thalamus, a region important in seizure spreading in the brain. Morphologic changes in astrocytes were analyzed with immunofluorescence staining for GFAP, using Sholl analysis to determine changes in astrocytic branching patterns in the OFC and the thalamus. Our results demonstrate increased astrogliosis in the thalamus and OFC in the post traumatic epilepsy group but not the TBI without epilepsy group compared controls. This supports our hypothesis that there is an association between post traumatic epilepsy and astrogliosis. Further research is needed to understand how astrogliosis might modify neural circuits to initiate or spread hyperexcitable activity associated with epilepsy.

Self-splicing domains, called inteins, are part of a class of selfish genetic elements that are present in highly conserved regions of unicellular eukaryotes and prokaryotes. Our research investigates the self-splicing behavior of two different algal inteins in Saccharomyces cerevisiae and the competitive advantages they may confer. We have found that inteins can affect cell viability and plasmid retention in their yeast host over time, and the intein with an enzymatic domain causes different effects than the one without. To identify whether these inteins undergo cleavage, we will construct Leu2 proteins with a 3’ 6xHis tag to be assessed by Western blots. Our set of plasmids contain the LEU2 gene, with or without an intein, and the URA3 gene for double selection. Using PCR and cloning, we are adding the 6xHis tag to the 3’ end of the LEU2 gene in these plasmids. Future research will provide deeper insights into the evolution of inteins as selfish genetic elements and their impacts on protein biology.

Quantum computing has the potential to revolutionize technology by solving complex problems beyond the reach of classical computers. Atom trapping, one of the many approaches of implementing a quantum computer, performs operations on atoms (physical qubits) confined in a matrix. Current trapped atom computers use a two-dimensional matrix of qubits, resulting in significant limitations with scalability, coherence, and error rates. We aim to extend the trap array into three dimensions, where we can increase qubit counts while maintaining spatial separation, improving efficiency and fidelity of gate operations. To enable precise control in a 3D array, this project utilizes a Spatial Light Modulator (SLM) to generate and manipulate optical traps that confine atoms in controllable lattices. However, inherent imperfections in the SLM and other components introduce a high degree of optical aberration which can affect the stability of the qubit array. To mitigate this, I am incorporating a camera-in-the-loop feedback system which continuously monitors atomic trap positions, comparing the experimental results with the intended trap distribution and adjusting the hologram accordingly. I anticipate this approach to yield improved-accuracy hologram generation, proving feasibility of scalable neutral-atom quantum processors. Ultimately, this will provide a pathway toward higher qubit counts and improved computational performance.

The purpose of this research is to examine myoregeneration and tissue effects on the tongue base following surgical injury and adipose tissue accumulation in minipigs. Twenty, 8-9 months old Yucatan minipigs were studied. Eight minipigs were assigned as the control group, and other 6 same-sex pairs were used as intervention groups. In each pair, one was intentionally fed to obesity (BMI>50) and the other one with normal weight (BMI < 35) received surgical ablation of the tongue base. BrdU was administered intravenously to track muscular cell proliferation and myofiber formation, with injections given 15 days and 2 days before the termination, respectively. Tongue base samples were paraffin-embedded and cut into 7µ sections for routine H&E, Trichrome, and immunohistochemical staining. Quantitative cell counts and semi-quantitative analysis of labeled cell density and differentiation were performed using the grid system and coding approach to examine muscular responses to the injury and adipose tissue infiltration. The anticipated result will be: 1) fewer muscle satellite cells in the control group; 2) increased adipose cells occupying the spaces between myofiber; 3) significantly more active myoregeneration, with a higher presence of satellite cells in the surgical group. The outcome of this study will elucidate the potential capacity of the tongue base to respond to wound injury and adipose tissue infiltration.

The p50/RelA dimer is an essential part of the NF-ĸB signaling pathway, which is responsible for regulating inflammation and immune responses. Most prior biochemical research focused on the mouse version of the p50/RelA dimer. While the findings are useful, its implication to human health remains unclear. This raises the question, how effective do experiments involving mouse proteins reflect those involving humans? We used protocols to express and purify human and mouse p50/RelA dimers, aiming to generate proteins for structural and functional analysis. In the first stage, recombinant protein expression and affinity chromatography techniques were used for purification of both proteins, followed by an SDS-PAGE to assess molecular weight and stability. We found that mouse proteins showed higher intensity bands compared to human proteins, indicating a higher yield. This suggests stability factors as well as potential differences in degradation rates between species. In the second stage, ion exchange and size exclusion chromatography were used to further purify the proteins. During ion exchange chromatography, neither protein bounded as effectively as expected, highlighting the need for protocol optimization. Improving the chromatography conditions will help increase stability and yield of both proteins allowing for more accurate comparisons between the mouse and human p50/RelA dimers. These optimizations are important because it will improve our ability to compare NF-ĸB pathway functionality between species and ultimately make it easier to translate findings from mouse models to human health.

Alcohol consumption is known to influence individuals' perceptions and engagement in various activities, often altering how they experience different social, recreational, and everyday tasks. Understanding the effects of alcohol on enjoyment is crucial for identifying potential risks associated with alcohol use, particularly among college students. This research study aims to explore how college students perceive their enjoyment of activities like household chores, social interactions, and leisure when alcohol is consumed, compared to when alcohol is not consumed. Given the prevalent drinking habits among university students, particularly in social settings, it is important to examine how alcohol may shape their experiences in everyday life. Participants are fraternity and sorority-affiliated college students at a large public university who are enrolled in a larger study focused on increasing the availability of and engagement in substance-free social activities. The study is currently collecting data and anticipates a sample size of N = 300.  Participants will complete an online survey of self-report questionnaires. The Substance-Free Reinforcement Survey (SFRS; Correia et al, 2002) will be used to assess participants’ enjoyment of a variety of activities with and without alcohol use. Participants were asked to rate their enjoyment on a scale from 0 (unpleasant or neutral) to 4 (extremely pleasant). Activities included social and individual activities, such as group gatherings, personal leisure activities, and household chores. We will conduct t-test to evaluate whether there are differences in enjoyment between activities experienced while use alcohol versus activities experienced without alcohol. The study’s results will provide valuable insights into the relationship between alcohol use and student engagement in everyday activities. These findings could ultimately inform interventions aimed at reducing harmful alcohol consumption while promoting healthier and more fulfilling social and recreational behaviors. Understanding these dynamics can lead to more effective strategies for addressing alcohol-related risks on college campuses. 

Stigma related to substance use disorders (SUDs) has profound and far-reaching consequences on individuals’ physical and mental health, as well as their socioeconomic well-being. This can lead to social isolation and can hinder access to treatment. While most stigma reduction interventions target structural stigma (such as educating medical students or professionals who work with individuals with SUDs), our study targets social and self-stigma experienced by individuals ages 21-35 with risky alcohol and/or cannabis use. Our objective is to develop a digital intervention to support individuals who experience substance use related stigma, enabling them to cope with stigma more effectively. Its digital nature allows for increased accessibility, convenience, and consistent support to individuals who might otherwise face barriers in accessing traditional healthcare services. We employ a user-centered design approach, utilizing peer mentoring to reduce self-stigma. Over 3 Zoom sessions, we collaborate with participants to first brainstorm topics that should be included in the intervention, receive feedback on different activities participants might engage in, and finally gather feedback on a prototype of the intervention which includes completing the System Usability Scale. My role involves collaboratively drafting the focus group scripts and facilitating sessions, including engaging participants in activities. From the focus groups, we anticipate that we will better understand important factors that influence the effectiveness of the intervention such as what features are most engaging, what format of content is most effective, and what topics are most relevant to the population. Findings from this project will allow us to design an effective digital intervention that can reach more people and provide an alternative for those who may not be willing or able to access the healthcare system. 

Enteric neurons regulate intestinal immunity, motility, and other functions. However, they are not in direct contact with the intestinal lumen. This creates the question of how they can sense microbes in the intestine. Intestinal epithelial cells are in direct contact with the lumen and have also been described to regulate immune responses to pathogens. We hypothesize that enteric neurons that regulate intestinal immunity are activated by intestinal epithelial cells. To test this hypothesis, my goal was to identify if there are physical interactions between specialized types of intestinal epithelial cells and enteric neurons. To achieve this, I utilized whole-mount preparations of the intestine of mice, imaged by 2-photon microscopy, where sensory epithelial cells and enteric neurons were labeled by immunofluorescence. I further applied advanced computational analysis of the obtained 3D images of the intestine to quantify cellular proximity. By integrating these approaches and performing precise spatial mapping and statistical evaluation, I identified interaction patterns between specialized sensory epithelial cells and enteric neurons. This research provides the spatial fundaments of interactions between intestinal epithelial cells and enteric neurons, which provides the basis for neuronal sensing of luminal signals and control of intestinal immunity, with broader implications for gut health.

Humans have limited regenerative capabilities, providing incentive to study other natural models of regeneration to make advances in the field of regenerative medicine. In response to injury, species including Xenopus tropicalis employ cellular mechanisms to replenish lost tissue, a process that has high metabolic demands. Depending on their developmental stage, X. tropicalis tadpoles exhibit different regenerative capabilities after tail amputation, posing them as a unique model system. Three-day-old tadpoles (NF stage 41) are able to regenerate their tails completely after injury, but transiently lose this ability during what is known as the refractory period. However, they soon regain regenerative capabilities in the tail and in the developing hind limb before permanently losing them during metamorphosis. Previous work by the Wills lab has determined that the pentose phosphate pathway (PPP) is required for successful tail regeneration in stage 41 tadpoles, but leaves open the question of whether the PPP remains significant at subsequent regenerative stages and structures. Here I test the hypothesis that the PPP continues to facilitate appendage regeneration in post-refractory tadpoles. To functionally test the requirement of the PPP in post-refractory tail regeneration, I performed pharmacological inhibition of g6pd, a key enzyme in the PPP, during tail regeneration. To assess regeneration quality, I developed a pipeline using FIJI ImageJ and R to quantify metrics of regenerative success such as tail area and length. Using this framework, I found that post-refractory tadpoles had diminished regenerative success under PPP inhibition similar to stage 41 tadpoles. These results suggest that the PPP is required at all stages of tadpole tail regeneration and will provide a more comprehensive understanding of metabolism during regeneration, a potentially beneficial insight for research in wound-healing initiatives in mammals. 

Innate immunity is the body’s first line of defense against pathogens, with macrophages and microglia playing key roles in combating infections in the olfactory epithelium (OE) and olfactory bulb (OB)/brain, respectively. Previous experiments in our lab showed that Influenza A virus (IAV) infection is limited to olfactory sensory neurons (OSNs) in the OE. However, how the virus interacts with the immune system in the OB—the region responsible for processing smells—and the rest of the brain remains unclear. Since the OE connects directly to the OB, which leads to deeper brain regions, this suggests a protective mechanism along this pathway that prevents the virus from spreading from the OE to the OB and further into the brain. In this project, we investigated the roles of microglia and macrophages in IAV infection using three mouse models: wild-type (C57), microglia-depleted (PLX5622-treated), and RAG1KO mice, which lack T and B cells and therefore adaptive immunity, the secondary defense of the immune system. We found that viral infection in the OE triggered significant macrophage activation, particularly when microglia were depleted. When microglia were absent in the brain, macrophages in the OE became overactive to prevent viral spread into the OB and brain, suggesting that microglia are crucial for immune activation in the brain. Analysis of Iba1+ cells (a marker for both microglia and macrophages) showed increased activation in response to IAV, with the PLX5622 and RAG1KO groups showing the strongest macrophage response. These findings highlight the role of macrophages in defending against IAV in the OE and suggest a complex interaction between immune cells in preventing viral spread along the OE-OB-brain pathway. Future analyses will explore responses of specific immune cells in the OB and brain, particularly in immunodeficient models, to better understand how the immune system combats viral infections.

Understanding how blood flow can be influenced by the use of drag-reducing polymers (DRPs) is crucial for addressing secondary injury mechanisms in spinal cord injuries (SCI). SCI disrupts spinal blood flow due to increased intraspinal pressure, altered vascular topology and increased resistance, exacerbating hypoperfusion resulting in hypoxia additional cell death. Thus, mitigating the impact of these secondary mechanisms is critical for better outcomes. We hypothesize that DRPs may reduce vascular resistance by reducing turbulent flow in injured spinal cords; specifically, by reducing the effect of flow separation in larger vessels. The major experiments of this study are to (1) test multiple DRP concentrations to find optimal restoration of hemodynamics after injury and (2) to design 3D models of in-vivo vasculature structures based on ultrasound scans. We have currently tested 2 different DRP concentrations and determined an ideal injection volume in a non-injured rat to increase blood flow—we hope to further these experiments via an injury model and analyzing effects of DRP. Hemodynamic analyses will be conducted from contrast-enhanced ultrasound (CEUS) scans at baseline, post-DRP injection at 30, 60, 90 minutes where a microbubble bolus injection will be delivered. Specifically, we will examine arrival time delay (ATD) which represents relative vascular resistance and area under the curve (AUC) which represents total blood flow volume. Preliminary results showed improvement of flow attributed to the DRP injection (~ 15-20% decrease and increase in ATD and AUC respectively). I will also design 3D models of intraspinal vessels informed by imaging and bioinks to explore blood flow behavior in controlled in vitro settings. Combined, these studies will serve to understand how DRPs can be effective as mitigating secondary injury mechanisms of SCI and improve recovery

The sensation of acute pain is fundamental to survival, indicating tissue damage that motivates an animal to engage in adaptive protective behaviors. Chronic pain, however, is persistent pain beyond typical recovery window and serves little adaptive function. The negative emotional component inherent in chronic pain contributes to the development of comorbid psychiatric disorders such as depression, social aggression, and social withdrawal. Our research aims to understand the bidirectional relationship between pain and social behavior, by evaluating mechanical sensitivity and changes in social motivation, reward, and interaction following a neuropathic injury. Using social self-administration (SSA), pair-housed mice were placed in operant chambers and underwent voluntary lever press trials for the reward of social interaction with their cage mate. Mice also underwent mechanical hypersensitivity response assays called von Frey where increasing weights of plastic filament were applied to the hind paw. Following baseline von Frey testing and the acquisition of the SSA task, mice then received a spared nerve injury (SNI) to induce neuropathic pain. After surgery recovery, mice were returned to the lever press and von Frey trials at different post-operative windows. Pain sensitivity was determined by the filament weight in which the animal withdrew their paw during von Frey. Changes in social behavior were measured via changes in lever press frequency and interactions during trials. Behavior changes were quantified using Simple Behavior Analysis (SimBA) machine learning to classify interactions during social trials. Once the trials were completed, brain tissue from regions associated with reward and social neural circuitry was collected and investigated using transcriptomic methods. Our data found sexually divergent social adaptations and gene expression following chronic pain. Future experiments will further delineate these sex-specific adaptations following a traumatic injury. This research can inform social intervention as an adjunct or alternative treatment to pharmacological pain intervention and its comorbidities.

The cerebellar ventricular zone (VZ) is the primary source of progenitor cells that give rise to all cerebellar GABAergic neurons, including Purkinje cells (PCs) and interneurons (INs). While the VZ has been well studied in mice, much less is known about its role in human brain development. In this study, we investigated how progenitors and neurons form in the human cerebellar VZ, using in situ hybridization, immunohistochemistry, and single-cell RNAseq analysis. Our findings reveal several key differences from the mouse model. We found that Purkinje cells are generated during a brief two-week period, even before the cerebral cortex begins to develop. Interneurons, on the other hand, start differentiating a few weeks later and mature on a timescale of months to years. A unique feature of human cerebellar development is the presence of specialized inner and outer subventricular zones (SVZ), which are absent in mice. Most differentiation occurs in these regions, with the first wave taking place in the outer SVZ. Additionally, we observed variations in Purkinje cell arrangement and number, including a subset of Purkinje cells that continue expressing cell cycle genes, suggesting a more complex and prolonged developmental profile compared to mice. By characterizing these developmental processes, our study provides new insights into human cerebellar development, highlighting important structural and temporal differences from animal models. These findings may have implications for understanding neurodevelopmental disorders.

Freezing rain events in the Pacific Northwest are rare but can be highly disruptive. Proximity to the warm northeast Pacific Ocean typically keeps low elevation temperatures above freezing, while the Olympic and Cascade mountain ranges receive large amounts of snowfall. However, certain synoptic setups can create a “perfect storm” that leads to widespread precipitation transition events. When upper-level troughs pass over the region, arctic air masses at the surface can follow close behind. This often results in a deep cold pool becoming entrenched east of the Cascade mountains. Cyclogenesis associated with troughing and cold air outbreaks creates strong pressure gradients that drive this cold pool through mountain gaps. In metropolitan areas like Seattle, this cold air can undercut warm air aloft by continuously replenishing cold air at the surface, setting the stage for impactful mixed precipitation, including freezing rain. In this analysis, we document two high-impact freezing rain events across the Pacific Northwest through detailed synoptic analyses, using the High Resolution Rapid Refresh (HRRR) model to characterize atmospheric conditions behind these events at high spatial and temporal resolution. Model algorithms often struggle with predicting these transitions accurately, as they rely on simplified methodologies that fail to capture the nuances of lower-level temperature profiles and critical dynamical processes. To diagnose these model shortcomings, we developed innovative diagnostic maps visualizing the interplay between warm nose strength aloft and cold air at the surface, derived from HRRR analysis data. These maps provide forecasters with a cutting-edge tool to pinpoint areas prone to precipitation-type transitions with unprecedented clarity, enhancing forecast capabilities in anticipating mixed precipitation across the Pacific Northwest.

Eelgrass is a foundational biome that provides critical habitat for numerous species, making its conservation vital. Specifically, sunflower stars (Pycnopodia helianthoides) use eelgrass as a nursery. In 2013, the sunflower star population crashed due to an unprecedented disease event creating a need to determine where the stars were historically to inform efforts in both eelgrass and sunflower star recovery. The Washington State Department of Natural Resources (WDNR) monitors eelgrass trends in the Salish Sea through the Submerged Vegetation Monitoring Project (SVMP). The SVMP video archive is roughly 6000 hours of footage spanning the Salish Sea in Washington state and dates back to 2000, providing a resource to observe the correlations between the stars and eelgrass. I created this research project centered around this connection to gain insight into the abundance of sunflower stars before and after the disease outbreak. To identify stars within the video archive, I sorted the footage into high-quality clips for sunflower star detection and discarded lower-quality ones due to the difficulty of confirming sightings. A computer vision model using hierarchical criteria was developed to assist in my annotations of video clips based on quality. In the high-quality clips, I also identified and annotated various organisms to understand if there are any further correlations with the sunflower star abundance. When sunflower stars were detected, I recorded their location and timestamp, creating a historical dataset. Once the annotations were completed, I made a comprehensive map of the detected sunflower star abundance and location over the SVMP video archive's time span. This project showcases the value of cross-year pattern analysis and camera quality normalization techniques. My annotations will eventually support the development of an automated video-cleaning system and a sunflower star detection model, enhancing the SVMP archive’s effectiveness in future conservation efforts.

Childhood liver transplants have several risks, including rejection, homeostatic complications, and lifelong immunosuppression. Precisely controlling cell identity would enable the generation of transplantable tissue from a patient's cells through cell reprogramming, minimizing these risks and expanding transplant access. Cell identity is partly maintained by heterochromatin states that block transcription factor binding and restrict gene activation. Work from the McCarthy Lab has shown that diverse heterochromatin-associated proteins repress lineage-specific genes, and depleting these proteins can de-repress heterochromatin domains, enabling transcription factor binding, gene activation, and cell reprogramming. However, which proteins regulate distinct heterochromatin domains is poorly understood. My goal is to understand the connection between chromatin state and gene activation permissibility and investigate the roles of specific proteins in maintaining specific chromatin states. We hypothesize that we could utilize an enzymatically dead Cas9 (dCas9) fused with a transcriptional activation domain (VP64) as a programmable transcription factor proxy to investigate specific heterochromatin domains and the function of proteins that maintain them. I identified target genes in H3K27me3, H3K9me3, and unmarked heterochromatin domains in human fibroblasts, focusing on genes only expressed or elevated in the liver. I designed guide RNAs to target dCas9-VP64 to sites 75 to 150 base pairs upstream of gene transcription start sites. I transfected guide RNA plasmids for 14 genes into dCas9-VP64 expressing human fibroblasts and assayed gene activation and transfection efficiency by RT-qPCR. Like transcription factors, dCas9-VP64 could activate unmarked genes and weakly activate genes in H3K27me3 but failed to activate genes in H3K9me3. Knocking down heterochromatin protein ERH using siRNA enabled dCas9-VP64 to activate H3K9me3-marked genes. Future work will investigate connections between additional heterochromatin domains and regulatory proteins. Understanding distinct protein roles in maintaining heterochromatin and repressing genes will improve our ability to control cell identity to reprogram patient cells.

Clathrin mediated endocytosis (CME) is a cellular process that is critical for internalizing nutrients, molecules, and involved in drug delivery and viral infection. During CME, individual actin proteins assemble into filaments that produce force to help internalize clathrin coated pits against membrane tension. It has previously been shown that in vivo actin networks assemble non-uniformly around an endocytic vesicle. However, there is little understanding of how the cell leverages this non-uniformity and the variables that influence the degree of non-uniformity. Due to the small scale of the molecules involved in endocytosis, we used a stochastic, agent-based simulation to test what conditions impact actin network formation at a high resolution. We studied how varying the distribution of the actin branch nucleator Arp2/3 complex affects CME progression. We hypothesized that non-uniform localization of the Arp2/3 complex around sites of CME would drive the formation of a non-uniform actin network. To test this idea, we analyzed data from simulations with varied distributions of Arp2/3 around the endocytic vesicle (n=50 runs for each condition). We utilized the Wasserstein Distance between distributions as a quantitative metric of the non-uniformity in actin networks, studied the change in uniformity over time, and correlated this property with internalization amount. We found that median internalization was robust to varying the distribution of Arp2/3, but that with smaller regions of Arp2/3, non-uniform networks were able to internalize more. While our findings provide a deeper understanding of the conditions under which non-uniform networks assemble in CME, they also prompt further exploration of the underlying mechanisms of non-uniform networks.

Visual Perspective-taking (VPT) is the ability to recognize another’s viewpoint, and can play a role in communication and empathy. Previous research supports that VPT in Autism Spectrum Disorder (ASD) populations is altered compared to neurotypicals (NT), but the traits within both populations that contribute to VPT differences remain unknown. This study investigates how VPT differs in ASD compared to NT adults using both animate and inanimate target objects. We also explore how these differences might be associated with ASD traits, measured by the Social Responsiveness Scale-2 (SRS-2). Participants complete computerized tasks that evaluate how stimuli appear from a different perspective. Psychophysical tests determine participants' ability to identify the position of an object from the perspective of an animate object (an avatar in the image) and an inanimate object (a chair), measuring accuracy and reaction time. We expect to replicate past findings of increased reaction time with greater angular disparity between the participants’ viewpoint and the viewpoint of the target object, for both ASD and NT subjects. We hypothesize this interaction between reaction time and angular perspective for both populations may interact with the type of reference object (animate vs. inanimate) and SRS-2 scores. We believe that NT participants will demonstrate greater accuracy and faster reaction times than ASD participants in both animate and inanimate conditions, with the difference being evident in the animate condition for ASD participants, possibly due to challenges in processing social cues reflected by higher scores on the SRS-2. This research can increase the understanding of the psychological disparities in individuals with ASD compared to NT contributing to diagnostic tools and targeted interventions for improving social cognition in ASD populations and potentially other neurodivergent populations with VPT differences.

The root cause of neurodegenerative diseases such as Alzheimer’s, Parkinson's and dementia is protein misfolding which leads to toxic aggregations in the brain, causing neuron death. At the molecular level, these diseases are offset by chaperone proteins, which have the task of stopping toxic aggregation events which directly causes onset of many neurodegenerative diseases. Understanding interactions between small heat shock proteins (sHSP), which are a class of chaperone proteins, and their client proteins, such as those involved in neurodegeneration is key for preventing these diseases. The sHSPs are a class of chaperone proteins which have the purpose of preventing other proteins from misfolding. The formation of toxic aggregates plays a factor in the first steps to pathology. Prevention of these aggregates and thus the toxic events that follow means understanding the protective mechanism that exists to stop aggregation. The challenge of these mechanisms is their immense complexity and there are not many methods in which small changes in the proteins can be detected. One possible technique that allows these small changes to be detected is Fluorescence Resonance Energy Transfer (FRET), which is a highly sensitive distance-dependent physical process. Fundamentally, energy is transferred non-radiatively via an excited molecular fluorophore (the donor) to another fluorophore (the acceptor). The goal of my work is to incorporate the FRET pairs into sHSP oligomers to probe changes in these oligomers. These changes could be the binding of another protein, such as a client protein, or another sHSP. These changes in the FRET signal will be indicative of how the probes are orientated relative to each other, allowing us to gauge what interactions are happening. My work validates the use of FRET to gauge how sHSP are interacting on a molecular level.

Eukaryotic cells contain many membrane-bound organelles and rely on precise vesicle trafficking to transport cargo between them and maintain organelle function and identity. Functional defects in Adaptor Protein complex 3 (AP-3) disrupt vesicle trafficking, leading to disorders such as albinism, seizures, and neutropenia. In Saccharomyces cerevisiae, AP-3 carries cargo from the late Golgi to the lysosomal vacuole, but how it dissociates from the carrier vesicle is not clear. Adenosine diphosphate (ADP)-ribosylation factor 1 (ARF1) regulates AP-3 recruitment and shedding, relying on GTPase-activating proteins (GAPs) for proper function. AGE2, an ARF1 GAP, functions redundantly with GCS1 to regulate ARF1 (Schoppe, 2020), thus AP-3 trafficking. This study aims to identify the interaction site between AP-3 and AGE2 to better understand AP-3 shedding molecularly. Using AlphaFold3, the Merz lab predicted a conserved alpha-helix region in the AP-3 subunit Apl5 C-terminal domain (CTD) as a potential interaction site. To test this hypothesis, I introduced substitution mutations in Apl5 CTD and conducted spinning disc confocal microscope experiments to assess AP-3 pathway defects with a GNSI reporter, which enables to quantify AP-3 function via fluorescence distribution. My results show no statistically significant difference in trafficking defects between wild-type and mutant strains, suggesting that the predicted site is either not a binding site, or not necessary for AP-3 and AGE2 function. Although this study yielded a negative result, it refines our understanding of AP-3 shedding. Future studies will explore alternative regions on Apl5 subunit of AP-3 to identify the true interaction site and uncover the molecular mechanism of AP-3 shedding.

Hydrogels with tunable stiffnesses are a versatile method to study the interactions of human cells in vitro. These systems recreate human extracellular matrix (ECM) and capture the stiffness changes associated with a variety of biological processes and diseases, like cancer and cirrhosis. Photoresponsive chemistries allow light to be used to modulate the stiffness in these materials with high resolution. However, when creating more complex patterned gels with photomasks, bulk property analysis cannot capture the variation. To circumvent this and measure the stiffness of these complex gels, I performed rheology and fluorescence recovery after photobleaching (FRAP) to establish a correlation between diffusivity and stiffness in flood-illuminated gels. By finding and using the correlation, I am able to calculate the stiffness of the more complex patterned gels based off of their FRAP-derived diffusivity measurements. This method allows for better fine tuning of gels for use as a platform to study human cell growth through a range of stiffening events in multiple different parts of the body.

The triturating surface of a beaked animal is the part of the beak that contacts food. Previous work has been conducted on determining a value for the complexity of beaked turtles’ triturating surface by creating a 3D mesh of it. We analyzed these meshes using  the R package molaR which then determined an OPCr (orientation patch count rotated) number that could be compared to the known diet of the turtle. My role in this study is  to examine the effect that manipulation of thresholding the skull has on the OPCr output using five different skulls from the species Malaclemys terrapin, which are known to be durophagous. Thresholding is conducted in the first half of mesh construction, when the CT scan is run through Slicer. At this step, we input both a higher and lower threshold value, as well as a standard value. A higher threshold value will lead to higher density material being excluded from the data set. The skull that is constructed in Slicer is then put into MeshLab to be further trimmed into only the triturating surface, and then it is run through molaR. We suspect that a higher threshold value will lead to a higher OPCr value than a lower thresholding value would. The implication of these results will determine what effect thresholding has on the scan, and estimate what value will be most optimal for preserving the integrity of the scan. 

Pregnancy represents a state of "immunological paradox," where the maternal immune system supports a genetically and immunologically distinct fetus. This process requires precise and distinct immune regulation that changes throughout the different trimesters of pregnancy. Placental immune cells such as T-cells, macrophages, and natural killer cells play a crucial role in supporting fetal development as well as promoting maternal tolerance. However, while the immune functions of immune cells are well studied, the metabolic pathways that drive their activity during pregnancy remain unknown. Given that function is tightly linked to metabolism, understanding how placental immune cells produce energy throughout pregnancy is essential for uncovering key mechanisms of maternal-fetal immunology. This project aims to investigate the immunometabolic profiles of placental immune cells across trimesters using SCENITH (Single-cell Metabolism by Profiling Translation Inhibition), a method to study metabolic profiles in single cells paired with flow cytometry. By analyzing placental immune cells from first, second, and third-trimester placental samples, we will assess their reliance on glycolysis, oxidative phosphorylation, and other metabolic pathways. We hypothesize that placental immune cells undergo trimester-specific metabolic adaptions. By mapping these metabolic profiles, our research seeks to provide insights into immune function in normal pregnancy, as well as pregnancy disorders such as pre-eclampsia, preterm birth, or fetal growth restriction. By deepening our understanding of immune cells and their metabolic requirements during pregnancy, we could identify potential new therapies that can prevent these complications and pave a way for novel treatments to improve pregnancy outcomes and maternal health. 

Estrogen plays a key role in metabolic regulation including fat distribution and glucose homeostasis. Less understood are the differences of estrogen metabolism in different fat depots, and the conversion mechanisms that underlie the effects we see between two prominent isoforms of estrogen, Estradiol (E2) and Estrone (E1). E2 dominates during reproductive years, shifting to an increase in E1 post-menopause. These hormonal changes contribute to a switch in fat storage from subcutaneous to visceral depots, elevating the risk of metabolic diseases. My research investigates how differences in estrogen metabolism, mediated by cytochrome P450 aromatase (CYP19A1) and 17β-hydroxysteroid dehydrogenase (HSD17B1), influence glucose uptake in inguinal (IWAT) and epididymal (EWAT) white adipose tissue. Using ex vivo explants from C57BL6/J male and female mice, I treated IWAT and EWAT with E1, E2, an agonist of CYP19A1, and an HSD17B1 inhibitor. Glucose uptake was measured at baseline, after 24 hours, following insulin stimulation. Additionally, I performed RT-qPCR to quantify depot-specific expression of CYP19A1, HSD17B1, and related metabolic genes. Preliminary results show that IWAT exhibits higher baseline expression of CYP19A1 than EWAT correlating with IWAT also demonstrating greater insulin-stimulated glucose consumption. E1 treatment decreased glucose uptake in both depots, while E2 had minimal effect in IWAT. Most interestingly, E1 and the forskolin + HSD17B1 inhibitor combination significantly decreased glucose consumption. This suggests depot-specific metabolic adaptations driven by differences in estrogen metabolism. The differences between IWAT and EWAT in estrogen-mediated glucose regulation offers new opportunities to better understand the metabolic impact of E1 and E2 in estrogen metabolism and glucose uptake. Understanding these mechanisms could inform strategies for targeting adipose tissue to mitigate impacts of insulin resistance and obesity, especially for postmenopausal women. My contributions include conducting tissue treatments, measuring glucose uptake, and analyzing gene expression data.

Retinal cell degeneration is one of the leading causes of blindness and vision loss caused by retinal diseases and is irreversible in humans. However, regeneration of retinal cells occurs after injury in some non-mammalian vertebrates and mimicking these strategies in humans could evolve treatment options for the visually impaired. Previous research in the Reh lab discovered a way to generate new neurons by reprogramming Müller glia (MG), a support cell of the retina, through overexpression of the proneural Ascl1 transcription factor in the mouse retina. To stimulate reprogramming, we used a lentiviral construct with a glial specific promoter (HES1) to drive the expression of ASCL1. However, HES1 represses its own expression by binding specific DNA sequences called N boxes which regulate gene transcription and expression, thus creating a negative feedback loop. In order to limit the negative feedback loop, we designed two new constructs using the HES1 promoter with modifications to the N box sequences. While the current construct has a reprogramming efficiency of approximately 25 percent, the aim of my project is to use constructs with modified N boxes to increase the ratio of MG reprogramming into neurons and verify specificity of the new constructs to MG cells. My research with mouse MG has shown that constructs with N box modifications significantly increase Ascl1 expression as compared to the construct with no modifications. These results seem promising and if reproducible, I will proceed with applying this strategy to human MG by using an in vitro culture system of retinal organoids.

Sarcopenic obesity (SO) is characterized by muscle weakness, atrophy, and an increase in body fat with age. While there is currently no FDA-approved treatment for this condition due to its complex pathogenesis involving chronic low-grade inflammation, impaired mitochondrial function, and a significant shift in muscle fiber quantity, function, and composition. However, previous studies have demonstrated an association between AMPK, an enzymatic mediator of cellular energy homeostasis, and aging. Thus, we aim to evaluate AMPK's viability as a therapeutic target by investigating its role in muscle mass maintenance, body composition, and mitochondrial function in aged mice. We used muscle-specific AMPKα2i transgenic (α2 D157A mutant, TG) mice and compared them to wild-type (WT) mice. Young (4-6 month) and old (20-24) female and male TG and WT mice were evaluated for body composition, grip strength, endurance, and muscle mass. We then used immunohistochemical and histochemical techniques on the collected muscle samples to analyze muscle fiber composition and mitochondrial activity, respectively. As shown in our previous studies, when compared their WT counterparts, young TG mice only demonstrated a decrease in endurance; old TG mice also had decreased muscle mass, greater body weight and fat mass, and more fatigable muscles. We expect to see consistent results when investigating mitochondria in AMPKα2i mice, namely a decrease in mitochondrial activity and density. AMPK is crucial for maintaining endurance in young mice, as well as retaining muscle mass and strength while attenuating obesity in old mice. Therefore, AMPK serves as a promising therapeutic target for prevention and treatment of SO.

Spinal cord injury (SCI) is a destructive neurological and pathological state that causes major motor, sensory and autonomic dysfunctions with an estimated global rate between 250,000 and 500,000 individuals every year. Many therapeutic strategies have been proposed to overcome neurodegenerative events and reduce secondary neuronal damage. Available treatments are limited and only provide supportive relief to patients with lifetime disability. The severity of impairment is related to the function of the remaining viable neural resources since the central neurons cannot yet be repaired or replaced, only reorganized.   Use-dependent movement therapies have been proven to increase neuronal plasticity. In addition, electrical stimulation can directly induce neuronal plasticity, enhancing therapeutic efficacy. Using a well-known rat model of Acute Spinal Cord Injury (ASCI) available in our laboratory, we hypothesized that targeted, activity-dependent spinal stimulation (TADSS) with physical retraining enhances motor recovery after SCI by facilitating and directing intrinsic synaptic plasticity in specific spared motor circuits below SCI. Long-Evans rats will undergo training and testing for pellet reaching four-legged assessment test, and CatWalkXL test for 4 weeks followed by a moderate to severe unilateral dorsal spinal contusion at the C4/C5 border ipsilateral to the dominant forelimb, resulting in a marked and persistent inability to extend the elbow, wrist, and digits for injured group. Following injury, a neurochip is implanted which delivers closed-loop electrical stimulation below the lesion point throughout the weekdays of training (for 6-8 hours per day). All groups will resume training for another 40 weeks and data will be collected and analyzed. Based on our initial data, we expect to prove that electrical stimulation combined with physical training improves the functional recovery of limb use after acute unilateral spinal cord injury.  

DNA computing utilizes the unique properties of DNA molecules to process information while still in molecular form and enable the programmable control of matter at the nanoscale. However, a major limitation is the low reading bandwidth of DNA circuit outputs with fluorescent-based reporters, which hinders scalability and practical applications. Nanopore sequencing is an advanced DNA sequencing technology capable of rapidly detecting single molecules of DNA as they pass through a nanoscale pore, unlike traditional sequencing methods that require amplification. My research seeks to overcome this barrier by integrating DNA computing architectures with nanopore sequencing technology to achieve high-throughput readout and real-time monitoring of circuit kinetics. I am designing DNA-based reporters that encode DNA circuit outputs in a format compatible with nanopore sequencing. These reporters have distinct sequence signatures that can be efficiently read by Oxford nanopore sequencing devices, enabling high-throughput, real-time parallel sequencing. My work involves designing and engineering these reporters, validating their function through experimental assays, and optimizing their compatibility with nanopore platforms. By bridging DNA computing with nanopore sequencing, this research has the potential to expand the capabilities of molecular computing, making it more practical for real-world applications. Beyond computing, this approach could enhance biosensing and diagnostic technologies by enabling rapid and precise detection of molecular signals. For example, DNA circuits could detect specific disease biomarkers, with nanopore sequencing providing an immediate readout. Since nanopore sequencing is a more accessible and portable technology, it could be better deployed in low-resource settings, broadening DNA computing's impact on global healthcare and research. Ultimately, this work not only advances DNA computing but also has implications for broader fields such as DNA nanotechnology and personalized medicine.

The 4-letter genetic alphabet found in Nature is the fundamental basis of biological information storage. As synthetic biologists continue to manipulate the genetic alphabet, they have begun to push against the boundaries of nature itself. Unnatural base-pairing xenonucleic acids (XNAs) are synthetic nucleotides that can pair orthogonally with the standard bases. By increasing chemical and structural diversity, XNAs are poised to enable a plethora of next-generation biotechnologies, including XNA-containing nucleic acid therapeutics (XNAptamers), catalytic nucleic acids (XNAzymes), and an expanded genetic code through a larger codon table. Although the potential of XNAs is near-limitless, the infrastructure required to study XNAs, notably sequencing, is antiquated. Previously, the Marchand Group leveraged commercial nanopore sequencing devices from Oxford Nanopore Technologies to sequence XNAs. This process outputs characteristic current signals that need to be decoded or “basecalled.” The first XNA basecallers used statistical k-mer models to decode XNA containing current signals, yet, their basecalling accuracy is a far cry from commercial basecallers (k-mer: 60-80%, commercial: >95%). Modeling our approach after commercial DNA basecallers, we have built a binary classification training pipeline that leverages long short-term memory (LSTM) neural networks and commercial nanopore sequencing to achieve more precise sequencing of XNAs. Thus far,  we have built models to effectively basecall three XNA base pairs with varying motivations: B≡Sⁿ for studying XNA replication fidelity in PCR due to high error rates, and P≡Z/Ds:Px for their unnatural functional groups (e.g. nitro groups and hydrophobicity) making them useful for applications such as XNAptamers. Currently, our binary classification models have testing accuracies as high as around 95% and we look to further improve our training methods through new model architectures such as transformers. Moving forward, we look to expand our basecaller to perform multi classification, allowing for generalized, de novo basecalling similar to commercial basecallers.

The merits of undergraduate research are well-established at four year institutions, but little is known about the impact it has at the community college level. In this work, we examined a Pacific Northwest two-year college physics education research program to identify possible impacts of undergraduate research on the academic journey of community college students. We designed an interview protocol for current and past students from the program using open-ended questions. Students shared how their undergraduate research experiences affected them personally and educationally, and using a qualitative analysis, we coded for keywords and ideas that aligned with: increasing sense of belonging, boosting self-confidence, building a stronger community, and fostering student-instructor relationships. With all the advantages shared by these students, it is not far-fetched to posit that undergraduate research experiences can lead to better retention, completion, and transfer of community college students. In this presentation, we hope to highlight exemplary work already occurring at the community college level and recommend that a stronger focus be placed on increasing opportunities for these students to engage in research in the future.

Transcription factors (TFs) capable of binding specific DNA sequences are integral to targeted genetic regulation in both natural and synthetic contexts. However, the design of de novo TFs has proven challenging despite major advancements in computational tools for protein design. Preliminary efforts to design de novo TFs yielded a small library of dimers composed of two protein subunits in complex with one another, mimicking a common structural conformation of native TFs. Although these de novo TFs induced genetic repression, the magnitude of repression was relatively modest compared to natural repressors. Furthermore, the design characteristics indicative of the highest performing de novo TFs were unclear, suggesting that TF-induced repression was more complex than just allosteric inhibition of the RNA polymerase. To create TFs capable of higher levels of repression, machine learning tools including RFdiffusion, ProteinMPNN, AlphaFold3, and RoseTTAFoldNA were used to design de novo homodimeric TFs able to bend the DNA upon binding. In doing so, designed TFs could further inhibit the function of the cellular machinery involved in transcription by altering the structure of the DNA promoter region. The top designs were selected, synthesized, and tested for efficacy as genetic inhibitors in Escherichia coli, with preliminary results suggesting that these DNA-bending TFs successfully magnified repression of the target gene. These TFs represent a major advancement in engineering protein-DNA interactions and could have a variety of applications across synthetic biology and genetic engineering. In particular, successful designs could have applications in synthetic gene circuits, as biosensors for various cellular processes, and even therapeutics for a wide range of genetic diseases.

The chemical compositions of rocks that go into subduction zones influence how these rocks break or deform at depth; thus it is crucial to understand the degree to which subducted rocks have been altered by fluid-rock interactions prior to subduction. When oceanic crustal rocks are changed by heat and pressure through a process called metamorphism, we refer to these rocks as metabasalts. Metabasalts often experience seafloor alteration via fluid-rock interactions before being subducted, which changes the chemical composition of the rock through the exchange of isotopes and other chemical constituents. Therefore, seafloor alteration plays a vital role in metamorphism and deformation within subduction zones due to how composition affects the reactions that occur as the rock undergoes different pressure and temperature conditions. In this study, we investigate the degree of seafloor alteration in the Catalina Schist metabasalts, which are ancient and understudied rocks resulting from the subduction of oceanic crust under the North American plate around 120 million years ago. Here, we use strontium isotope ratio analysis of 87Sr/86Sr of a representative sample size of metabasalts obtained in the field and observe how these ratios are shifted towards a value indicative of seawater and away from a value indicative of unaltered basalt, as well as quantify the degree of alteration and percent seawater. Mineral assemblages, i.e., glaucophane and epidote, and bulk-rock major-element compositions of the metabasalts which show deviations from normal mid-ocean ridge basalt compositions, indicate water-rock interactions. We anticipate the strontium isotope ratio analysis to corroborate these findings. Quantifying the degree of seafloor alteration allows us to constrain the initial hydration and alteration state of the metabasalts. Determining how the inputs of subduction affect metamorphism and deformation of rocks allows us to more fully understand subduction zone behavior, having major impacts on earthquake hazard preparedness and mitigation. 

Phosphorus is often used in agriculture as a fertilizer because it is a critical nutrient for crop growth that is required for biomolecules such as DNA, RNA, and ATP. However, phosphorus is often a limiting nutrient during primary ecological succession because it only becomes biologically available after it has been weathered from phosphorus rich rocks. Generally, this means that phosphorus is poorly available in rocky soils; however, some plants such as the O’hia Lehua (Metrosideros polymorpha) and ‘Ae fern (Polypodium pellucidum) are able to thrive in rocky, nutrient poor conditions such as Hawaiian lava flows. We hypothesize that these plants associate with phosphate-solubilizing endophytes that aid in plant-phosphorus acquisition. Primary colonizing plants growing on the 2018 Pahoa Lava Flow on Hawaii’s Big Island were collected in July of 2024. The plants were ground to create extracts that were plated on media containing only the mineral phosphate, meaning that the bacteria would need to dissolve the phosphate in order to grow. Endophyte strains isolated from the extracts were tested for their ability to dissolve different mineral phosphates. The strains that are successful in dissolving phosphates will be able to have broad applications in agricultural practices by allowing a greater uptake of phosphorus for plants, and potentially decreasing the need for expensive and environmentally damaging fertilizers. These endophytes also have application in space biology, where they may help plants uptake mineral nutrients from Martian and Lunar regolith.

The relationship between morphology and behavior reflects evolutionary pressures leading to adaptation and anatomical diversity. We investigated how locomotive behavior influences scapular morphology in Old World monkeys and Great Apes, and how these adaptations may be mediated by body mass, to better understand the morphological evolution of Primates. To do so, we compared scapular length-to-width ratios (LWR), scapular spine depths (SSD), and scapular shapes across 67 specimens (18 species) grouped by locomotion strategy and body mass. We determined scapular shape using landmark-based geometric morphometrics and traditional linear measurements. Seven anatomical landmarks were digitized and analyzed via Generalized Procrustes Analysis (GPA) and Principal Component Analysis to examine shape differences. Maximum LWR was measured using ImageJ, while SSD was measured with calipers. Statistical tests, including Procrustes-based Linear Models (PLM), Analysis of Variance (ANOVA), and phylogenetic ANOVA were used to assess the influence of locomotion strategy and body mass on scapular morphology. We specifically tested the hypothesis that scapular morphology is primarily shaped by locomotion strategy (H1), body mass (H2), or neither (null hypothesis). We found that: (1) scapular shape variation is influenced by factors beyond species and size, with body mass showing a small effect, indicating an allometric relationship; (2) there were significant differences in scapular LWRs and SSDs across locomotion categories, with arboreal species having narrower scapulae and deeper spines compared to terrestrial species; and (3) SSD did not vary significantly between body mass groups while LWR did. The amount of morphological variation was greater in smaller primates than in larger ones, contradicting H2. These results suggest that locomotor habits play a dominant role in shaping scapular morphology, with limited influence from body mass. Our study highlights the interplay between ecological pressures, body size, and skeletal adaptations, offering insights into the evolutionary mechanisms driving morphological variation in primates across diverse habitats.

In the past decades, there has been a noticeable and disproportionate decline in the native eelgrass populations at sites in the San Juan Islands, reaching as high as a 75% decline. Despite knowing that there is decline, the prominent factors are not well known. One of those factors however, may be recreational boating which is known to harm seagrasses in other parts of the world. Beginning from 2018, we conducted a preliminary analysis utilizing the Automatic Identification System (AIS) and aerial views across bays in the San Juan Islands which revealed a significant increase in boating activity during the height of the COVID-19 pandemic. With the given data, we will construct heatmaps at selected spots such as Echo Bay, Sucia Islands and Blind Bay, Shaw Island to identify spots of high density recreational boat presence. These analyses will then be compared to maps of eelgrass populations at these sites, which are monitored by the Submerged Vegetation Monitoring Program administered by Washington State Department of Natural Resources. Our heatmaps will make it possible to direct research towards possible impacts from attributes associated with boating presence such as shading, anchor scarring, gray and black water discharge, and fuel and oil leakage.

Sulfate aerosols cause pollution and affect climate by influencing cloud properties and incoming solar radiation. Emissions and abundances of sulfur-containing aerosols are one of the largest sources of uncertainties in global climate modeling. The largest biogenic and most uncertain emission source of sulfur aerosols is from phytoplankton in the form of dimethyl sulfide (DMS). In the atmosphere, DMS is oxidized to methanesulfonic acid (MSA) and other compounds that can form sulfate. Historical emissions of DMS are studied by measuring MSA concentrations in ice cores as a proxy for DMS oxidation. Declining levels of MSA have been found in ice core records, implying that production of DMS has also been decreasing; however, anthropogenically driven changes in atmospheric chemistry have altered the ratio of MSA to sulfate produced from DMS over time. To better understand DMS oxidation mechanisms and its relationship to the production of MSA and sulfate aerosols, we need more recent ice core records of MSA and sulfur isotopes of sulfate (δ³⁴S(SO₄^2–)) at higher temporal resolution. To measure δ³⁴S(SO₄^2–) at seasonal resolution in an ice core, rather than an annual resolution, the measurement size is smaller than previously measured by an order of magnitude, at about 1 µg S per sample. We will develop a new method to isolate samples containing less than 1 µg of sulfur from an ice core sample by separating SO₄^2– from other major ions in the sample using an ion chromatograph. We will quantify the isotopic ratio of sulfur in our samples by using an Orbitrap mass spectrometer. Quantifying sulfur isotopes at this resolution will provide information about the seasonality and change in phytoplankton sulfate production.

Asthma is a chronic respiratory disease characterized by airway inflammation and remodeling. One key feature of airway remodeling is the thickening of the subepithelial basement membrane zone (BMZ) beneath the airway epithelium, which has been identified in severe asthma relative to milder severity asthma and other airway diseases. We aim to characterize the relationship between BMZ thickness, airway physiology, and airway immune cell populations. I am utilizing design-based stereology to precisely measure BMZ thickness in endobronchial biopsies obtained from 30 individuals with asthma and 10 healthy individuals. These individuals underwent extensive characterization for asthma airway physiology, profiling of airway immune cell populations, and airway inflammatory gene expression. Stereology provides unbiased thickness estimates that have greater reproducibility and overcome the limitations of two-dimensional measurements. I am measuring BMZ thickness using the orthogonal intercept method, which involves averaging the lengths of lines extended perpendicularly from the epithelial surface across the thickness of the BMZ at systematically sampled points. I am correlating BMZ thickness with clinical characteristics (allergic sensitization), airway physiology (baseline lung function, measurements of airway hyperresponsiveness), densities of both mast cells and eosinophils in the airway wall, and gene expression profiles obtained from airway epithelial brushings. I hypothesize that individuals with asthma patients will have more BMZ thickening in comparison to healthy controls. I also anticipate that there will be a positive correlation between the thickness of the BMZ and the expression of type-2 (T2) inflammatory genes (IL4, IL5, IL13). Finally, I hypothesize that there will be a positive correlation between BMZ thickness and the density of mast cells in the airway epithelial compartment. This research study provides new insights into the potential mechanisms responsible for airway remodeling in individuals with asthma and how they connect with airway inflammatory endotypes, which may guide further development of targeted therapeutics. 

Sequencing of deoxyribonucleic acid (DNA) is important for a variety of biological and medical research. Nanopore sequencing is a fast and effective way to sequence DNA, and can be used for DNA with genetic alphabets that go beyond the four naturally occurring nucleobases (adenine, guanine, cytosine, thymine). Our group has used nanopore sequencing on synthesized eight-letter “hachimoji” DNA, which contains four artificial nucleotides (called P, Z, S, and B) in addition to the four nucleotides of natural DNA. Expanding sequencing efforts is critical in furthering biotechnological applications of such artificial DNA. Nanopore sequencing requires a motor enzyme to control the translocation of the DNA through the pore. Here, I analyzed the interactions between the Hel308 helicase and hachimoji DNA, specifically the time that Hel308 spends at a step along the DNA (known as the dwell time) and the tendency for Hel308 to step backwards (known as the back step probability). I compared my results to previous work done by our group using natural DNA, and found sequence-dependent behavior at similar sites in the enzyme for both the natural and artificial nucleotides. Studying the kinetics of Hel308 offers deeper insight into its mechanisms and role in genetic processes, as well as its use for other bioengineering applications.

HCoV-OC43 is a member of the viral family Coronaviridae, commonly known as coronavirus, and is known to cause respiratory infections in humans. HCoV-OC43 is therefore categorized as a human coronavirus, which includes the virus SARS-CoV-2, known to cause COVID-19. Previous studies showed that human coronavirus infections, specifically HCoV-OC43 and SARS-CoV-2, activate the IRE1α component of the unfolded protein response, leading to a splicing of XBP1 mRNA, which then encodes for a transcription factor. Additionally, the IRE1α and XBP1 host factors were found to be necessary for ideal viral replication. However, the specific genes upregulated by XBP1 that contribute to viral replication remain unknown. Given data suggesting XBP1 regulates genes involved in lipid metabolism, our research aims to explore whether Acetyl-CoA Carboxylase (ACC), an enzyme involved in fatty acid synthesis, is upregulated by IRE1α and involved in human coronavirus replication. We used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to measure relative gene expression of ACC after HCoV-OC43 infection, and in the presence of the IRE1α inhibitor, 4μ8c. We found that activation of IRE1α during HCoV-OC43 infection caused increased expression of the gene encoding ACC, which was blocked by 4μ8c. We then tested the hypothesis that ACC supports viral infection using small molecule inhibitors and found that viral RNA was decreased after inhibition of ACC. Next, we bypassed ACC by adding the downstream product, palmitate, and found restoration of viral RNA. Our results indicate that IRE1α induced splicing of XBP1 mRNA increases ACC transcription, which then promotes optimal viral replication. A greater understanding of the mechanisms behind human coronavirus replication allows for the development of potential therapies targeting these viruses. In our continuation of this research, we plan to expand our knowledge of human coronaviruses by investigating the role of IREα and ACC expression in SARS-CoV-2 infections. 

Down syndrome (DS) is one of the most common genetic conditions and is due to chromosomal anomaly, associated with heightened skin autoimmunity disorders like psoriasis. DS individuals have a significantly altered immune system, often indicated by a higher frequency and severity of infections. A hallmark of this altered immunity is a heightened pro-inflammatory state, characterized by increased signaling by cytokines such as interferon-gamma (IFN-γ). The goal of our project is to investigate the relationship between elevated cytokine signaling and epithelial cell biology, particularly how this dysregulation contributes to inflammation-induced immune responses and dermatological conditions. We hypothesize that elevated signaling of pro-inflammatory cytokines in the serum of individuals with DS alter the biology of epithelial cell function, predisposing them to skin disorders such as psoriasis and vitiligo. To explore this, we are first treating skin samples with serum from individuals with DS to assess its effects on epithelial cells. The serum alone induces a weak transcriptional response, so additional factors may be required to drive significant epithelial cell changes. To better define the impact of IFN-γ, we are treating skin samples with high-dose IFN-γ and comparing the resulting gene expression patterns to known cytokine-induced signatures. This approach will help elucidate the molecular mechanisms underlying epithelial dysfunction in DS. This research may provide insights into targeted anti-inflammatory interventions to preserve normal epithelial function and mitigate skin-related complications like inflammatory skin conditions, barrier dysfunction, slow tissue healing, abnormal cell turnover, and even cancer. Future experimental investigations could  focus on the epithelial microenvironment itself, rather than serum exposure alone, to capture localized skin-specific changes that may provide further mechanistic insights. 

Caffeine is one of the most widely consumed stimulants globally, yet its effects on explicit memory remain an area of active research. This literature review examines how caffeine influences explicit memory, particularly in short-term recall and recognition memory in young adults ages 18-22. By synthesizing findings from recent peer-reviewed studies, we explore the neurochemical mechanisms, focusing on caffeine’s role in modulating adenosine receptors, enhancing neuronal activity, and affecting hippocampal-dependent memory functions. Some studies indicate that caffeine improves attention and alertness, which can indirectly support memory formation. However, other studies suggest that excessive intake or habitual use may lead to adverse effects, particularly if it disrupts sleep patterns or increases anxiety—both of which are known to impair memory. These conflicting findings highlight the complexity of caffeine’s effects and the challenge of drawing definitive conclusions. Beyond individual consumption patterns, methodological differences across studies like varying dosage intake and testing periods also contribute to conflicting findings. Variations in participant characteristics, experimental designs, and memory assessment methods make direct comparisons across studies challenging. Some studies focus on immediate recall, while others examine delayed retrieval or recognition memory, further adding to the variability in reported outcomes. By critically evaluating existing research, we aim to clarify the relationship between caffeine and explicit memory while identifying research gaps that future studies should address. Given the widespread use of caffeine among young adults, particularly for academic performance, a deeper understanding of its cognitive effects is essential. Investigating how caffeine influences memory under different conditions—such as varying levels of stress or sleep deprivation—could provide valuable insights. Future research should also refine methodologies to isolate caffeine’s specific effects on explicit memory in young adults.

The auditory brainstem response (ABR) tests are used to objectively evaluate the clinical hearing threshold of infants and young patients. However, the ABR testing process can be time and resource-consuming, as audiologists have to test multiple frequencies. For each frequency, an ABR threshold (the lowest level at which a discernable ABR response is detected) must be determined by repeating the test for a multitude of levels. The efficiency of these tests depends on clinical expertise. Audiologists can expedite this process by utilizing their experience to quickly analyze the ABR waveform and jump to the next test, skipping redundant intermediary steps. Clinicians with this expertise might not be widely available. To address this issue, the long-term goal of this study is to create an automated system that can mimic the efficient testing procedure of experienced audiologists using machine learning. A set of clinical ABR data was leveraged for model development. Our baseline models operate by analyzing one waveform at a time and predicting the next stimulus a clinician would choose based on individual waveforms. We hypothesize that a neural network that treats ABR waveforms collected in a single session as a time series would outperform baseline models. We are comparing these baseline models with neural networks that hold memory, meaning they treat ABR waveforms collected in a single session as a sequence. Multiple models were built and evaluated, including multiple time series neural networks (e.g., Long-Short Term Memory model). Initial testing indicates that including sequential data ordered as time series results in better performance. The outcome of this research is likely to improve the efficiency of ABR testing without requiring real-time supervision of expert clinicians.

The effects of ongoing climate change on river systems present an ever-growing cause for concern, with flooding and other potential hazards threatening millions of people who live near rivers. To investigate how river systems react to climate change, we must turn to analogous events in Earth’s sedimentary rock record. The Paleocene-Eocene Thermal Maximum (PETM) is one such analog, during which global temperatures and precipitation seasonality rose significantly. Rivers record their response to these environmental shifts through the sedimentary structures they create. For example, we can measure cross-sets, which form as rivers preserve sections of sand dunes and ripples on the riverbed, to determine whether a river was in a state of equilibrium, with a year-round stable flow, or in disequilibrium, with increased flash flooding and river channel migration. Here, I test the hypothesis that river systems shift towards disequilibrium during periods of climate change by measuring cross-sets in PETM-aged rocks of the Bighorn Basin, Wyoming. To generate a large number of accurate measurements, I use three-dimensional (3D) digital reconstructions of rock outcroppings. This study will equip river-adjacent communities with insights on how rivers evolve during climate change, and allow them to make adequate preparations for potential hazards. 

Protein Kinase Inhibitors (PKIs) are a family of heat stable, high-affinity inhibitors of the catalytic subunit of Protein Kinase A (PKAc). In the presence of Mg-ATP, the three isoforms—PKIα, PKIβ, and PKIγ—bind to PKAc with very low dissociation constants: 0.758nm, 1.875nm, and 0.4142nm respectively. In vitro studies have shown that PKIs can translocate PKAc from the nucleus to the cytoplasm, suggesting a role for PKIs in terminating nuclear cAMP-driven PKA activity. Previous research, including studies from our lab, has found that dysregulated PKAc mutants play a significant role in Cushing’s syndrome, a rare and potentially fatal metabolic disorder caused by excessive cortisol production. Building on these findings, we hypothesized that increasing PKI expression could counteract the hyperactivity of PKAc mutants and reduce cortisol production. To test this, we expressed each PKI isoform in adrenal cell lines and assessed their steroidogenic capacity using biochemical assays such as western blots, RNA-seq, qPCR, and ELISA-based cortisol assays. We observed that PKIα and PKIγ led to a general suppression of steroidogenic associated proteins such as StAR, Cyp11a1 and SF1. This altered proteome was accompanied by significantly suppressed cortisol synthesis only in the PKIα and PKIγ expressing cells. The difference between PKIα/γ and PKIβ was surprising given that all PKI isoforms are postulated to potently inhibit PKAc. Thus, we questioned whether PKIα/γ effects are mediated through PKAc. To answer this, we have cloned mutant PKI isoforms that do not bind PKAc, and confirmed the mutant PKIs do not inhibit PKAc through kinase assays. Our next step is to express the mutant PKI isoforms in adrenal cells and assess their effect on steroidogenic capacity of the cells. Our findings suggest that PKIα and PKIγ play key roles in cortisol regulation and may have broader implications for gene regulation in adrenal cells.

Past research has shown that microorganisms can dissolve insoluble metal phosphates found in soil, such as tricalcium phosphate. Because plants struggle to use these forms of phosphate, microbial communities are invaluable to their survival. However, iron phosphate, found primarily in weathered soils, resists common mechanisms of dissolution such as soil acidification. Therefore, identifying other solubilization mechanisms is crucial to understanding plant nutrient uptake in such highly weathered soils. To identify potential phosphate solubilizers, we isolated endophytic microbes from plant hosts such as ferns and mosses collected from plants growing in the Bogacheil Rainforest, and plated them on mineral phosphate plates. One strain isolated from Isothecium moss (cat tail moss) produced red halos on iron phosphate plates, indicating possible iron sequestration and phosphate solubilization. Subsequent ITS sequencing identified it as a yeast of the species Metschnikowia pulcherrima. Members of this genus are known for their production of the red pigment and chelator pulcherrimin. Pulcherrimin has been shown to confer antimicrobial properties through iron precipitation and sequestration and we hypothesized that it could dissolve iron phosphate. To evaluate our strain’s ability to solubilize iron phosphate, we inoculated phosphate-free media supplemented with iron phosphate and allowed cells to grow for 48 hours. We then measured the change in free phosphate concentration using a molybdenum blue colorimetric assay. On average, we found that inoculated cultures achieved an average change in concentration 34 times greater than background dissolution (p < 0.05). This finding suggests that endophytic M. pulcherrima may improve phosphate availability and uptake by plants in highly weathered soils.

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with poor long-term survival rates. Cytarabine (Ara-C) is a standard chemotherapy used to treat AML patients. However, many patients relapse due to refractory disease, highlighting the need for new therapeutic strategies. Heparan sulfate proteoglycans (HSPGs) are glycoproteins that regulate key signaling pathways by interacting with growth factors and receptors. HSPG glycan chains are modified by the addition of negatively charged sulfate groups. HS2ST1 and HS6ST1 catalyze sulfate addition at the 2-O and 6-O positions of heparan sulfate chains, respectively. In AML, increased HS6ST1 expression correlates with worse patient survival, while low HS2ST1 expression is linked to adverse outcomes in certain AML subtypes, suggesting distinct roles in disease progression. To investigate the contribution of HS modifications to chemotherapy response, we generated CRISPR-edited (sgHS2ST1, sgHS6ST1, or sgControl) MOLM-13 AML cells. Compared to sgControl cells, sgHS6ST1 cells displayed increased sensitivity to Ara-C, suggesting that 6-O heparan sulfation may contribute to chemoresistance. To test whether MOLM-13 AML cells alter the expression of HS-modifying enzymes in response to chemotherapy, I performed RT-qPCR analysis at 24 and 72 hours after Ara-C treatment. Upon Ara-C treatment, HS2ST1 expression increased by 1.5-fold and HS6ST1 transcript increased by 4-fold at 24- and 72-hours post-treatment. In contrast, sulfatase 2 (SULF2) removes 6-O sulfate modifications at the cell membrane. Strikingly, compared to vehicle treatment, SULF2 expression was increased by sixfold at both time points. Our results highlight HS sulfation as a dynamic regulator of AML chemoresistance and suggest that targeting HS-modifying enzymes could enhance chemotherapy efficacy. In the future, I will create an sgSULF2 cell line to characterize the functional role of SULF2 in AML disease progression and chemotherapy resistance.

In nature, Per-Arnt-Sim (PAS) domains comprise a sensor that undergoes conformational changes upon signal recognition which either activates or deactivates an effector domain. Natural PAS domains detect environmental cues, such as oxygen, light, and small ligands; however, they do not sense phosphorylation, a key post-translational modification. Here, we present a designed de novo phosphorylation-inducible heterodimer that serves as a sensor domain. This system toggles between association and dissociation states in response to phosphorylation and dephosphorylation events. To engineer reversible association and dissociation, we designed phosphorylated peptides and their corresponding binders. Starting from a library of previously designed peptide-binder complexes, mutations were introduced into the peptide sidechains, replacing selected residues with phosphorylated tyrosine, serine, or threonine. Next, we ran iterative cycles of LigandMPNN-FastRelax to generate binder sequence candidates. Finally, we used AlphaFold2 and Chai1 to predict the folded structures of our input sequences and selected those that were predicted with high confidence. For experimental validation, the designed proteins will be overexpressed in Escherichia coli and purified using affinity and size exclusion chromatography. Phosphorylation-dependent binding specificity and affinity will be assessed through enzyme-linked immunosorbent assays (ELISA), surface plasmon resonance (SPR), and fluorescence polarization (FP). Subsequently, we will fuse these sensor domain designs to a collection of previously designed hinge proteins—which can bind/release an effector protein—to produce de novo PAS domains, thereby linking the sensing event to downstream functional responses. This adaptable system offers broad applications in biomaterials and synthetic biology, including the development of responsive scaffolds for biosensors and synthetic protein motors with controlled conformational cycles. 

Latines are the largest minority group in the United States but only represent 8% of clinical trial participants. This underrepresentation is due to significant barriers the Latine population faces including, but is not limited to language differences, limited access to insurance coverage, socioeconomic, urban-rural divide, immigration status concerns, and mistrust of research. Increasing Latine participation in clinical trials is an essential step in reducing health disparities. This study aims to explore the impact these barriers have on Latine participation in clinical trials and determine ways to address them. We are utilizing a mixed-method approach to conduct research - we are analyzing existing literature data, conducting qualitative interviews, and gathering survey data. Initial findings have suggested that language barriers are a main contributing factor to lack of representation, as many Latine participants report difficulties with reading and understanding consent forms in addition to other legal documents and speaking with healthcare professionals. Insurance coverage presented another significant barrier, as individuals without insurance are less likely to participate in clinical research due to the burden of out-of-pocket expenses. Additionally, there is also hesitancy with sharing personal information, as immigration status was a major concern, with individuals fearing deportation or detention. In order to address the challenges that impact Latine participation in cancer research it is important to set up culturally competent outreach programs, provide language and community health resources, and advance policy changes to ensure equitable participation. This study emphasizes the urgency for inclusive clinical research methods in order to reduce health inequalities and improve healthcare outcomes for Latine populations.

Organs-on-a-chip (OOAC) are biomimetic systems that replicate the physiological environments of human organs at a micro-scale. They are gaining industry acceptance due to their ability to control critical parameters including shear stress, concentration gradients, and cell-biofluid interactions. By mimicking the behavior of human organs, OOACs are transforming how pharmacokinetics, physiological, and toxicological studies are performed, offering a more relevant model than animal-based studies. Our studies focus on how drugs and toxins affect the human kidney, a crucial organ for processing medications and filtering out harmful compounds. A key component of kidney OOACs is a hydrogel, which provides a structural scaffold and a biological substrate for cells. The hydrogel consists of rat tail Collagen I (Col-I) and specialized cell culture media (PTEC and 199 (10x)). The media mimics the extracellular fluids that surround kidney cells in the body, providing a more realistic environment for cell growth/interaction. Collagen IV (Col-IV) is the most abundant protein in kidney tissue but lacks structural rigidity. A combination of these materials is crucial for achieving a more accurate representation of kidney structure and function. While adding more matrix to the hydrogel improves the model’s ability to replicate the native environment, it is challenging to maintain structural stability, hence the need for a stabilizing agent. The aim of this project is to determine the proximal tubule epithelial cell (PTEC) viability of a mixed collagen I and IV matrix. At this stage, we have shifted from determining optimal collagen ratios to evaluating cell viability. By refining these models with optimized kidney extracellular matrices, the Kelly-Yeung lab aims to develop OOAC systems that better predict how drugs, toxins, and diseases impact human kidneys. This progress will lead to more effective and personalized treatments, as well as a reduction in reliance on animal testing. 

The strong tides along the San Juan Channel (Salish Sea) draw water from the Strait of Juan de Fuca and the Strait of Georgia, causing significant mixing that influences various water parameters. Among these variables are two that are linked to primary productivity: dissolved oxygen (DO) and light irradiance (LI) – light energy that penetrates the surface per square meter. This study evaluates how tidal conditions (ebb, flood, and slack) affect DO and LI across the San Juan Channel, between Friday Harbor Marine Preserve and Shaw Island Marine Preserve. Ebb and flood tides are outgoing and incoming tides, respectively, while slack tides are periods in between where the water stays stagnant. A CTD was deployed between both locations along a transect at five equally distributed stations, with repeated sampling three times per day (two days total), each capturing one tidal condition. Six contour plots were produced to visualize changes in DO with depth along the transect – these showed that slack tides had the highest surface DO concentration and minimal variation with depth, while ebb and flood tides exhibited extreme variation with depth. Two linear regression models were also produced that examined the relationship between DO and LI under each tidal condition – these revealed a strong correlation between DO and LI as indicated by large R² values (0.6-0.9). The study suggests that slack tides promote stratification and stabilizing DO, while ebb and flood tides cause mixing and dynamic fluctuations in DO. These results provide valuable advancements to our understanding of tidal variation and DO fluctuation.

Cannabis is the most commonly used drug in America, with 52.2 million individuals (19% of Americans) reporting use in 2021. The primary psychoactive compound, Delta-9-tetrahydrocannabinol (THC), binds to cannabinoid receptors, among the most abundant in the brain. This interaction causes mental and locomotor impairment, contributing to increased motor vehicle crashes in states with legalization. However, a comprehensive baseline for THC’s biophysical effects on behavior and motor function remains lacking. This research aims to establish such a baseline using advanced AI-driven behavioral analysis in mice. Mice received intraperitoneal injections of THC (0.1–30 mg/kg) or a vehicle solution (control). One hour post-injection, each mouse was recorded for 15 minutes in a custom Linear Track designed for dual-view (side and bottom-up) behavioral assessment. Video recordings were analyzed using an AI computer vision model tracking 29 points of interest at 100 fps. The collected data trained a THC behavioral regression AI algorithm to predict doses based on behavioral patterns. Analysis of novel videos revealed a model accuracy with a mean squared error of 0.50, successfully identifying THC-induced impairment. This approach also enabled investigations into specific brain regions mediating THC behaviors through local drug infusion. This study marks the first successful attempt to predict THC dose relative to impairment levels using AI modeling. The research aims to computerize behavioral analysis, developing a preclinical AI model capable of recognizing and predicting THC’s effects with minimal human bias and error. This technology provides a data-driven approach to characterizing subtle behavioral differences, offering potential applications in both research and clinical settings.

Cellulose nanofibres (CNFs), produced from sustainable plant resources, are an emerging class of renewable structural biopolymers. Through surface modification via carboxylation and control of fiber length and aspect ratio, CNFs are open to wider usage through further modification of the carboxylated site. However, an understanding of the foundational specific thermodynamics and kinetics of cellulose defibrillation and surface charge modification has not been developed and generalized, hindering widespread adoption of this biopolymer in applications. Additionally, the current fabrication methods for carboxylated cellulose nanofibers (C-CNFs) require harsh solvents and limit reusability. Thus, this study utilizes a deep eutectic solvent treatment (DES) containing citric acid, oxalic acid, and iron(III) chloride to guide the defibrillation of bacterial cellulose (BC) fibers and their carboxylation. We controlled the ratio of the DES components, normalized by the weight of the BC, and determined the reaction rate of bacterial cellulose carboxylation. Through electron microscopy (EM) and zeta potential analysis of titration results, we determined the morphology and composition of the carboxylated BC and surface charge. This work provides insights into the kinetic and thermodynamic interplay that governs the surface charge modification and defibrillation of bacterial cellulose, offering a foundation for further application.

The Aedes aegypti mosquito is the primary transmission vector for dangerous diseases, such as yellow fever and dengue viruses. Emerging vector control efforts use strategies based on mass release of sterile and transgenic male mosquitoes to suppress local populations. These strategies rely on modified males outcompeting wild-type males in securing mates. However, our knowledge of mosquito mating remains limited. Male mosquitoes locate mates by identifying the distinct flight tone (WBF) females produce by beating their wings, which ranges from 450-600 Hz. But auditory neurons in male antennae are tuned to lower frequencies (200-400 Hz). It is hypothesized that as males fly and encounter a female, nonlinear interactions between male and female WBFs occur in the antennae, producing additional tones called distortion products. These distortion products are what male auditory neurons believed to be tuned to. Distortion-based hearing predicts that only flying males can detect a female flight tone. We tested this prediction by conducting behavioral phono-taxis experiments to compare the acoustically-mediated behaviors of flying and walking wild-type Ae. aegypti. Fifteen to twenty male mosquitoes that were either free to fly or had their wings removed were placed in a cage that had a speaker on either side. Pure tones, ranging from 100-1000 Hz, were played randomly from one of the speakers. Positive phono-taxis responses were quantified by recording the number of male mosquitoes that moved towards the speaker while a sound played. In contrast to the prediction of distortion-based hearing in mosquitoes, we found that non-flying, walking mosquitoes responded to similar female-specific WBFs that free-flying mosquitoes did. This challenges current theories on distortion products being the main way male mosquitoes hear and locate mates and suggests there are more complexities to the mosquito hearing process than initially believed. Future work will focus on further characterization of mosquito hearing processes.

TikTok has transformed how health information, including sensitive topics like eating behaviors, is shared and consumed by predominately young and female audiences. A growing trend on TikTok, "What I Eat in a Day" videos showcase users' daily intake to highlight dietary habits, preferences, or fitness goals. This study aimed to understand popular eating behaviors on TikTok, how content creators discuss body image and health, and the extent to which content is evidence-based. We conducted a qualitative thematic analysis of the most popular TikToks under the hashtags, or keywords: #WhatIEatinADay, #WIEAD, and #WhatIEat. Thematic analysis was conducted using a qualitative descriptive methodology, and videos were selected and prioritized based on popularity. A deductive codebook was developed to abstract the analytics from each TikTok and code video content for meal components, health perceptions, body image, language related to food, visual descriptions, and the evidence behind supporting claims made. The ten most popular videos were analyzed to understand prevalent messages about food, health, and fitness goals. Common themes included: 1) Fixation on strict calorie counting, reflecting creators' emphasis on weight loss; 2) Supplementation to meet nutritional goals, suggesting a perceived necessity for dietary aids and 3) Guilt related to perceived unhealthy decisions. Among the dietary claims made, less than half were evidence-based. Together, the three themes emphasized a relationship between food and weight loss. Themes from TikToks were derived from popular videos which often trend to impressionable audiences, while content on health perceptions and nutritional goals can impact personal perceptions of body image and eating behaviors which are not evidence-based. By evaluating the messages underlying trending "What I eat in a Day" TikToks, this research provides insights to inform audiences to be critical of the media that we digest and be mindful of content that may promote stigmatizing themes.

Bacterial cellulose (BC) nanoparticles (BCNPs) are a promising sustainable nanomedicine platform for drug delivery and provides a scalable, eco-friendly alternative to synthetic counterparts. We aim to develop a small library of BCNPs with different chemical moieties to incorporate a broad range of active agents for drug delivery use. To produce BCNPs, a BC pellicle is grown in a kombucha media of tea, sugar, vinegar, and bacterial co-cultures. The pellicle is isolated and chemically and manually broken down using dimethylacetamide, lithium chloride, and an ultrasonicator probe to produce an organic BC dissolution. The BC dissolution is precipitated into an aqueous Pluronic F-127 (F127) surfactant solution under 650 rpm stirring conditions and incubated for 2 h to form nanoparticles ~100 nm, near neutral charge, and low polydispersity index (<0.3). In this study, we optimize the dissolution and nanoprecipitation processes using acetylated and methylated BC pellicles to form acetyl- and methyl-functionalized BCNPs. The functionalized BCNPs were characterized using Fourier transform infrared spectroscopy, nanoparticle tracking analysis, electron microscopy, and light scattering to assess physicochemical properties. Our results demonstrate that functionalized BCNPs can be formulated using similar formulation parameters to unmodified BCNPs. Ongoing work evaluates drug loading and encapsulation efficiencies in the functionalized BCNPs using curcumin as a model drug. Engineering BCNPs with different chemical moieties enables incorporation of a wider array of drugs, which can improve the utility of BCNPs as a sustainable alternative to current synthetic nanomedicines.

Magnetoencephalography (MEG) is a powerful, noninvasive type of brain imaging that uses magnetic field readings from outside the skull to reconstruct the neuronal current sources that produce them in accordance with Maxwell’s equations. However, as these magnetic fields do not have unique current sources, algorithms are structured with constraints to guarantee the correct solution. In this project, we design a novel algorithm to reconstruct neural current sources. Using a cone-shaped beam with its vertex at the origin and a spherical-head model, we show we can reproduce any signal produced from within the cone using a current distribution on the cone’s surface, effectively allowing us to spatially localize the current source responsible for a given dataset of MEG measurements. I have employed this algorithm on an artificially produced dataset using MATLAB and assessed its effectiveness through reconstruction error analyses and visual techniques like heat maps. Future work will include testing the method on phantom-head data. We anticipate this algorithm is adaptable to non-spherical head geometries and cases involving multiple significant current sources, and we are working towards these advancements. Unlike other inverse methods, we expect our approach to assume minimal a priori knowledge about the brain’s conductivity profile, making it easier to implement in cases where detailed information about the subject's neural anatomy is limited.

Common drug delivery materials, like poly(lactic-co-glycolic) acid, are sourced from non-renewable resources and involve multi-step processing with harsh organic solvents that require proper waste disposal. A more sustainable material derived from biological sources and abundant in nature is bacterial cellulose (BC). BC requires mild growth conditions, is commercially scalable, and has current drug delivery applications in antimicrobial wound dressings. The aim of this project is to establish a sustainable approach to targeted drug delivery using bacterial cellulose nanoparticles (BCNPs). BCNPs are nano- scale, allowing for sufficient tissue penetration, and have easily modifiable hydroxyl end groups that make them susceptible to incorporation of different drugs among other beneficial interactions. The BCNP modifications to the end group are achieved through substitution with methyl-, acetyl-, or amino- functional groups because these groups allow the use of more hydrophobic or hydrophilic materials due to their molecular interactions. To formulate the modified BCNPs, a BC pellicle was grown in black tea media, isolated and washed. The pellicle undergoes methylation, acetylation, and amination reactions and is characterized through Fourier Transform infrared spectroscopy and contact angle measurements. The unmodified and modified pellicles were chemically and mechanically dissolved, and then nanoprecipitated into surfactant solution to form the BCNPs. After dialysis and size filtering the BCNPs were applied in vitro to BV-2 cells, a microglial cell model, to assess cell death through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tetrazolium reduction assay. These preliminary cytotoxicity results support the translation of unmodified and modified BCNPs into ex vivo models to certify a wider range of biocompatibility for BCNPs in targeted drug delivery. 

The primary objective of this study is to evaluate the safety and effectiveness of the study drug Mevidalen, in alleviating symptoms in individuals with mild to moderate Alzheimer's disease dementia. Mevidalen is a selective positive allosteric modulator of the dopamine D1 receptor. The efficacy of this drug is being assessed by examining the patient's cognitive function, daily activities, sleep patterns, Alzheimer disease progression, physical activity levels, and overall stress. I am conducting patient appointments to collect relevant data for the statistical analysis of the study drugs efficacy and safety. Patients are between the ages of 60-80 years old, and are experiencing mild to moderate memory loss. Cognitive function tests including MMSE to gauge the patients working memory, and C-SSRS to monitor mental health throughout the course of this trial. Vital signs and ECG's are measured multiple times during each appointment to track the patient's overall health. Patients are either assigned and titrated to a placebo, low dose study drug, or moderate dose study drug. This is a double blind study, so both the researchers and the patients are blinded to the drug assignment. Over the course of 14 weeks, the patient is monitored by a neurologist at periodic visits, and via an Ax6 wristwatch device that measures sleep patterns. The hope is that this drug is effective, and will soon become a FDA approved therapy for Alzheimer disease dementia, to alleviate memory loss symptoms from patients around the world.

Antibiotic treatment is commonly used to manage bacterial infections in very preterm infants (defined as born before 32 weeks of gestation) admitted to the neonatal intensive care unit (NICU). Because immediate treatment is crucial to treat life-threatening sepsis, antibiotics are often administered empirically before microbiology test results confirm infection. As a result, it is common practice that some infants without confirmed infection receive multiple days of antibiotics, which can disrupt the newborn’s developing microbiota. Research suggests that empiric antibiotic therapy is associated with adverse long-term outcomes, including retinopathy of prematurity (ROP), a disease of the eyes, and bronchopulmonary dysplasia (BPD), a chronic disease of the lungs. Understanding the implications of empiric antibiotic use is essential for developing evidence-based guidelines for preterm infection management. We hypothesized that empiric antibiotic exposure is associated with higher rates of ROP,  BPD, and mortality after adjusting for confounding variables. To investigate this, we are conducting a retrospective study of very preterm newborns admitted to a level III NICU in Washington state (N = 55). We statistically modeled the association between the number of days exposed to antibiotics within the first 14 days after birth and the incidence of ROP, BPD, and all-cause mortality after 2 weeks from birth. Preliminary findings indicate a non-significant trend toward higher rates of ROP, BPD, and all-cause mortality (after 2 weeks) with longer duration of empiric antibiotic therapy within the first two weeks. We are conducting an ongoing study to expand the sample size and refine statistical models to account for additional confounding variables. Research on the effects of empiric antibiotic use can improve clinical practice guidelines for treating unconfirmed infection and reduce potential harms associated with early antibiotic exposure.

Organ slice cultures present a promising alternative to cell culture to study biological processes in-vitro by maintaining the integrity of interactions between different cell types. A need for a model that can be used to investigate cell interactions becomes apparent when studying the impact of stress, due to its effect on many pathways. Resilience, which decreases with aging, is defined as the ability to respond to stress. This project aims to investigate the impact of a chemical stressor to study resilience in aging C57BL/6 mice. Organ slice cultures were prepared from thin slices of the brain and the chemotherapy drug, cyclophosphamide (Cyp), was added to represent an immune response. After 2 weeks, tissues were fixed and embedded in wax blocks to make tissue slides. Immunohistochemistry (IHC) assays were performed to evaluate the impact of Cyp on microglia, astrocytes, and chronic inflammation. These particular markers were chosen for IHC analysis for their role in the immune response. It is anticipated that Cyp will induce a stress response in the brain slice cultures and increase chronic inflammation, and activated microglia and astrocyte counts compared to the control group. The results from this study will provide information about the ability to recover from a chemical stressor while improving the protocol for culturing brain organ slices to reduce the number of animals used in research. Developing stress tests is important to be able to identify at-risk individuals that may require early intervention to reduce the likelihood of cognitive decline with aging.

In the Puget Sound region, some lowland lake ecosystems have been contaminated with metals from the former ASARCO copper smelter located in Ruston, WA. Arsenic, a toxic metalloid, has accumulated in various parts of lake environments from this contamination. Chinese Mystery Snails (CMS) are a ubiquitous freshwater snail species that feed on periphyton, an environmental compartment found to hyperaccumulate arsenic (Hull et al., 2023). This feeding could be a key entry point of arsenic into our food chain. Our research has utilized CMS to test the hypothesis that trophic transfer of arsenic occurs through consuming periphyton and their gut microbiome is altered as a result. To test this hypothesis, our lab conducted a feeding-based arsenic exposure with lab acclimated reference lake CMS. These CMS were either fed algae wafers (control) or periphyton obtained from a high arsenic concentration lake. Trophic transfer of arsenic and gut microbiome alterations were not observed in the food-based arsenic exposure. This led us to hypothesize that waterborne arsenic exposure is an important route for bioaccumulation in CMS, with arsenic concentration correlating to gut microbiome changes. To test this, we conducted a comparative waterborne experiment, exposing CMS to arsenic concentrations of 0, 20ppb and 200ppb. At the end of the exposure, 16S amplicon sequencing was performed on CMS gut contents to assess how the varying arsenic concentrations affect microbiome composition. Whole-body arsenic quantification was conducted using ICP-MS to determine the degree of arsenic bioaccumulation that occurs at different concentrations. 

The NF-KB family of transcription factors regulates genes involved in immunity, inflammation, and other biological processes. Members of the NF-KB family can form homo- or heterodimers, which contribute to specific responses to various stimuli. The p50/c Rel heterodimer, an important player in adaptive immunity, regulates gene expression, but its DNA-binding specificity and regulatory mechanisms remain incompletely understood. This study investigates the expression and purification of recombinant p50/c Rel heterodimers. I expressed recombinant c Rel and p50 in Escherichia coli and purified the proteins using Ni²⁺ affinity chromatography. SDS-PAGE analysis confirmed the successful isolation of both proteins at the expected molecular weights. This work lays the foundation for further biochemical characterization, including the investigation of their DNA-binding properties and role in immune signaling. These findings contribute to the understanding of the p50/c Rel heterodimer's function in NF-KB mediated gene regulation. Future studies are needed to explore its DNA-binding specificity and how these interactions impact immune responses and diseases such as cancer and inflammatory disorders. 

Fat, oil, and grease (FOG) in residential wastewater presents significant environmental challenges, contributing to the formation of fatbergs that disrupt wastewater systems, increase treatment costs, and heighten public health risks. Traditional methods, like commercial enzymes, are only temporarily effective and require constant maintenance. The goal of this research is to develop Engineered Living Materials (ELMs) comprising a yeast strain, Yarrowia lipolytica, within polymeric matrices for sustained FOG degradation. Y. lipolytica is known for its ability to efficiently degrade hydrophobic FOG components due to its diverse lipase enzyme expression. I encapsulated engineered Y. lipolytica strains in UV-cured poly(ethylene glycol) diacrylate (PEGDA) hydrogels. The findings showed sustained lipase activity and robust cell growth, confirmed by enzyme assays and confocal microscopy. However, over 28 days, significant degradation of the PEGDA-based ELMs occurred, likely due to the breakdown of ester bonds by lipolytic enzymes. To address this, I switched to a thiol-ene polymer network composed of tetra-PEG-allyl and PEG-dithiol, which is expected to resist degradation more effectively. I confirmed the viability and lipase production in these thiol-ene ELMs using the same methods. Varying polymer chain lengths in the thiol-ene network influenced Y. lipolytica growth patterns and morphology, including a shift toward hyphal growth—a filamentous form typical of its dimorphic nature. These changes were influenced by the polymer network’s architecture and material stiffness. Moving forward, I will investigate how hyphal growth impacts FOG degradation and assess the long-term mechanical properties of these thiol-ene ELMs. I expect these ELMs to remain stable over time and reduce FOG concentrations in simulated wastewater. Ultimately, this research aims to provide a sustainable solution for wastewater treatment, addressing the environmental, economic, and infrastructural impacts of fatbergs.

Radio Detection and Ranging (RADAR) uses radio waves for object detection in applications such as air traffic control, radio astronomy, and defense systems. This project explores the feasibility of performing RADAR using Modulated Johnson Noise (MJN), which leverages the thermal noise inherent in electrical conductors to transmit information without the use of a conventional radio frequency (RF) carrier. Unlike traditional RADAR, MJN enables stealthier, low-interference operation and ability to function in areas with no ambient radio frequency. In this project we test the hypothesis that RADAR can be performed with MJN by transmitting a square wave signal made with two different noise levels and timing its reflection. To establish a proof of concept, the project follows a multi-phase approach. First, prior MJN research is reproduced by implementing a noise-modulated transmitting system using a Raspberry Pi, an RF switch board, and a Software Defined Radio (SDR) in an anechoic chamber. Next, signal control (transmit) and processing (receive) are integrated into a single microcontroller unit for synchronized operation. The electrical components for the receiving system are validated for amplification and filtering of the reflected signal. The antennas for transmitting and receiving the signal are selected based on their radiation pattern and optimal placement for the RADAR application. Once the transmit and receive systems are finalized, a microcontroller (ie. STM32 Nucleo board)  is used to synchronously transmit and receive reflected signals. Then, indirect time of flight methods are used for distance measurement by analyzing the phase shift between the transmitted and the received signal. The findings will contribute to the development of a RADAR system suitable for resource-constrained environments such as remote locations on Earth or in space and is beneficial for stealth operations where the object emitting the signal must be unidentifiable.

In the U.S., Colorectal Cancer (CRC) is the third most common cancer in both men and women and the second leading cause of cancer-related death among individuals over 60. In the past year alone, 53,010 deaths were caused by CRC. While several post-diagnoses treatments exist, preventative treatments are notably limited. A significant contributor to CRC development is enterotoxigenic Bacteroides fragilis (ETBF), a mutant gut bacterium that secretes B. fragilis toxin (BFT). BFT alters signaling pathways in the intestine, producing reactive oxygen species, DNA damage, and carcinogenesis. Patients with Ulcerative Colitis and Inflammatory Bowel Disease exhibit higher quantities of ETBF in their intestine, placing them at higher risk for CRC. There is an urgent need to develop an effective and low cost therapeutic that eliminates the carcinogenic effects of BFT protein and mitigates CRC development in at-risk populations. In my research, I am using deep learning (DL) methods to design cyclic peptide inhibitors targeting BFT. Preliminary data from our lab has identified a promising BFT binding site that has informed my design process. Using RFpeptides, a DL based protein design software, I generated thousands of cyclic peptide backbones for this site. Next, I used ProteinMPNN, a DL sequence design tool to generate 10 optimized sequence variations per backbone resulting in ~10,000 potential binders. Finally, I filtered these design models using AlphaFold, a machine learning based structure prediction tool which assessed the efficacy of proteins to fold and bind as designed. I am chemically synthesizing the top selected binders and characterizing their binding affinity and kinetics towards BFT. If the designed binders inhibit BFT, they will serve as a basis for an effective and low cost preventative therapy for CRC in at-risk populations, reducing incidence and potentially saving thousands of lives.

Invasive Red lionfish (Pterois volitans) are responsible for the heavy destruction of reefs, resulting in a decline in biodiversity and negative impacts on commercial fishing. Their success in their non-native range is attributed to their lack of predators in their invasive range. Parasites are often overlooked as predators, but low parasitic loads make for a more biologically fit individual, allowing for higher invasion success. For this reason, it is hypothesized that lionfish carry a lower parasitic load in their invasive range. This project aims to assess the parasite abundance in lionfish collected from along the entire reef slope in Curaçao in 2019 and 2022 by the Tornabene Lab. Using these fish I am conducting dissections examining various parts of the fish under a dissection microscope and carefully looking for parasites. The parts that are examined are the skin, body cavity, buccal cavity, fins, gonad, liver, spleen, eye, heart, intestine, filet, and gills. Using data collected from dissections, I am performing descriptive analyses to summarize parasite presence and quantity by species and body site where they were found. It is most likely that there is a low abundance of parasites within these lionfish, suggesting that parasites could play a major role in regulating populations. Understanding the role that predation plays in invasive species can help us develop strategies to control their spread and prevent ecological damage.

Hyperphosphorylation and aggregation of the microtubule protein tau is a notable feature of diseases such as Alzheimer’s Disease, Frontotemporal Dementia and Chronic Traumatic Encephalopathy. However, the mechanism by which this causes diseases is still unclear. One avenue of interest is sphingolipid metabolism because various genes in sphingolipid metabolic pathways have been implicated in both tau toxicity and disease development. Sphingolipids are critical for cell membrane structure and stability, and play major roles in cell signaling pathways. This project will investigate the effects of mutations in gba-3, sphk-1, asah-1 (corresponding to GBA, SPHK1 and ASAH1 in humans), and various genes implicated in similar pathways, on a C. elegans model of tau toxicity. Forward mutagenesis screening identified a mutation of unknown function in gba-3. Previous investigation of loss of function gba-3 mutants showed no suppression of tau toxicity, so I intend to generate the identified mutation again using CRISPR. sphk-1 and asah-1 are known to be critical for the proper catabolism of sphingosine-1-phosphate (S1P), which plays a role in calcium regulation and neural differentiation and health. Improper catabolism of S1P has been implicated in the aggregation of hyperphosphorylated tau in neurons. This project will analyze the role of these key genes using various approaches, including locomotive assays, protein and lipid quantification, and the measurement of resistance to oxidative stress. Results from these three initial genes will help guide the subsequent investigation of specific metabolites implicated in disease development and may even highlight potential therapeutic targets.

Sleep deprivation (SD) is a pervasive issue linked to significant cognitive and neurological impairments, affecting billions of people. SD accelerates markers of aging, but some individuals exhibit resilience to its effects. SD response is indicative of resilience. Identifying factors that promote SD resilience may inform interventions to enhance resilience. Studies have shown that SD alters gene expression in rodents, yet it remains uncertain which changes are specific to homeostasis. Previous rodent studies examined the effects of single day SD. Our study increases the duration to five days and separates mice into high and low responders, providing a novel insight into SD responses. This establishes a valuable evaluation of resilience for aging interventions. Female mice in the treatment group were sleep deprived through continuously stirring them during sleep periods. Control and treated mice were then subjected to the box-maze assay to evaluate relative learning rates and cognitive impairment. High performance in the box maze was designated as a high responder, and vice versa. Mice were then euthanized, and the hippocampus was isolated. The transcriptomes of control and treated mice were analyzed via mRNA sequencing. Analyzing transcriptomes of control, high, and low responder mice showed distinct changes in expression of key physiological and biochemical phenotypes. Genes known to be associated with SD were isolated and examined separately regardless of difference. Overall, high degrees of similarity were observed in control and high responders to SD, while low responders had the greatest changes in comparison to the latter groups. These experiments provide an efficient, robust platform to study the biochemical effects of SD, offering attractive insights for frameworks to quickly evaluate therapeutic strategies aimed at enhancing resilience to aging,

Mast cells are key contributors to allergic disease including asthma, food allergies, rhinitis and atopic dermatitis. Therefore, understanding mast cell biology more deeply is critical for the discovery of new targets to modulate mast cell function in health and disease. The research question being addressed in the Piliponsky Lab is what proteins play a role in mast cell activation and release of mediators that contribute to allergic disease. DOCK8 deficiency is a rare, combined immunodeficiency (CID) associated with allergic diseases which led our lab to investigate the impact of DOCK8 on mast cell function. We took microscopic images of mast cells and enumerated mast cell numbers in mucosal and connective tissues using mice with mast cells deficient in DOCK8, DOCK8 mutant mice, and littermate controls. We used western blots to confirm the absence of DOCK8 protein in the mutant mice and genotyped mice with DOCK8 deficiencies. Our findings suggest that mast cell intrinsic DOCK8 deficiency can cause increased mast cell degranulation in skin and mast cell mediator release at baseline. Learning more about mast cells can help increase understanding of the mechanisms of allergic disease and inflammation, leading to more treatment options. 

Climate change and anthropogenic pollution have led to a rise in coral bleaching events. These bleaching events cause the loss of corals’ symbiotic algae cells, depleting coral colonies’ energy and leaving them vulnerable to starvation and death. This study aimed to understand whether the sex of gonochoric corals (in which colonies are either male or female) has any correlation to corals’ growth and development, with implications for corals’ response to bleaching events. For the gonochoric species Porites compressa, preliminary results indicate that female colonies develop their gametes earlier in the year compared to males. Energy conserved to produce these lipid-rich eggs may limit the overall growth of female colonies. However, unlike male colonies, females might be able to resorb their eggs to better recover from bleaching events. In summer 2023, twenty-four P. compressa colonies from Kāne‘ohe Bay, HI were stained with an alizarin dye, sexed as male or female based on sperm/egg histology, and returned to the reef to measure one year of skeletal growth. Following their collection in the summer of 2024, eighteen surviving colonies were scanned using an Artec Spyder to produce 3D models revealing colony surface areas and volumes. We then cut cross-sections of each colony to reveal their alizarin growth bands from 2023, allowing us to determine the amount of growth from 2023-24. We anticipate that differences in growth rates will show that female colonies are saving energy by limiting their growth, leaving them less susceptible to bleaching compared to male colonies. 

Fishes are the most species-rich and ecologically diverse group of vertebrates, and display a broad array of sensory adaptations that are essential for survival. Included in this evolutionary toolkit are appendages on or around their heads that may act as additional sensory organs. Such attachments, which are often referred to as cirri, occur in dozens of lineages across the fish phylogeny, and are present in species such as decorated warbonnets (Chirolophis decoratus) in the Stichaeidae family, roughhead blennies (Acanthemblemaaria aspera), in the Chaenopsidae family, and kelp greenlings (Hexagrammos decagrammus), in the Hexagrammidae family. While there is limited research on the purpose of cirri, I hypothesize that they serve a role in chemoreception or some other sensory behavior, due to their location on the body, their structure, and their appearance. With the use of electron microscopy, clearing and staining, and histological sectioning to observe cirri morphology, I analyze the types of cells, physical support systems, and signals cirri may receive from the surrounding environment. These methods help determine possible roles of cirri in chemoreception, mechanoreception, camouflage, or mating, although predicted results lean towards chemoreception for gustation or olfaction. These result can help fill gaps in the fish phylogeny, shed light on fish morphology, and indicate possible signs of convergent evolution across diverse lineages of fishes. 

Visuospatial attention is a complex, dynamic process critical to our conscious perception of the world. The N2pc event-related potential (ERP) is a time-locked EEG waveform implicated in the modulation of visuospatial attention and observed in Posner task paradigms. The N2pc ERP functionally represents attention mechanisms, with hypotheses suggesting it could represent target enhancement or distractor suppression. Further, perceptual differences have been found in autism spectrum disorder (ASD) populations, suggesting that these differences could be discriminated in N2pc properties. Visuospatial cueing differences are observed in autistic individuals, yet the neural mechanisms underlying these differences remain unclear. This study investigates possible differences in the N2pc component reflecting distinct patterns of attentional modulation in autism. We conducted 32-electrode EEG recordings of neurotypical and autistic adults engaged in a Posner paradigm visual detection task, detecting grayscale circles embedded in a checkerboard stimulus. Using MatLab and EEGLAB, we expect to localize N2pc ERPs in parietal regions in epochs post-cue and post-stimulus presentation. We hypothesize that we will see different amplitude and latency N2pc ERPs in autistic individuals compared to neurotypical controls, reflecting differences in attention modulation. Results may provide insight into how attentional mechanisms differ in autistic individuals, allowing for a greater understanding of neurotypical and neurodivergent approaches to visuospatial attention.

Rapid-growth wildfires disproportionately contribute to loss of life and destruction of property. Further improving our understanding of longer-term signals of impending fire-associated weather is crucial if we are to mitigate future destruction. Recent work compared local conditions, including surface wind and 100-hour dead fuel moisture (FM100) to fire growth (Murphy and Mass 2025). We investigate the evolution of larger scale weather patterns prior to rapid wildfire growth. Using two individual-fire-growth datasets, Fire Events Data Suite (FEDS) and Fire Events Delineation (FIRED), we separate fires by season, growth rate, and region. We conduct analyses of several meteorological variables for periods preceding maximum growth in rapid-growth wildfires. Using the European Centre for Medium-Range Weather Forecasts Reanalysis v5 (ERA5) dataset, we compare weather patterns at different heights in the atmosphere prior to maximum growth for fires of different growth rates and in different seasons, to identify any signals comporting to eventual fire extremity. We also consider how the patterns affect FM100 and near fire winds and the impacts of region of wildfire within California.

Brain-computer interfaces (BCIs) decode neural signals from the motor cortex to enable direct control of external devices. While existing BCI designs often combine signals from the premotor (PMd) and primary motor (M1) cortices, these regions have distinct functional roles and anatomical organizations. Prior research demonstrates that PMd and M1 play distinct roles in movement preparation and execution, with information generally flowing from PMd to M1 (Cisek & Kalaska, 2005). Additionally, cortical processing is known to occur in a layer-dependent manner (Bastos et al., 2012), suggesting that different depths within these motor areas may encode distinct aspects of task-related information, highlighting the need for depth-specific analyses. My hypothesis is that task-related information flows directionally from deeper layers of PMd to superficial layers of M1 as behavior transitions from movement preparation to execution. To investigate this, I used Neuropixel probes, which provide high-resolution sampling of neural activity across cortical depths, and performed simultaneous PMd and M1 recordings in two male rhesus macaques as they performed an arm reaching (center-out) task. Preliminary analyses provide evidence that (1) different cortical depths in PMd and M1 encode distinct movement-related and planning information, (2) neural activity in deep PMd exhibits stronger coherence with superficial M1 compared to other depth pairings within and across regions, particularly during movement-related periods, and (3) information flow between PMd and M1 is depth and directionally organized, with information flowing from deep layers of PMd to superficial layers of M1. These findings suggest that the spatial and temporal dynamics of task-related information across cortical depths are important for motor control. Revealing how task-related signals are organized and transmitted across motor cortical layers can inform the development of BCIs that target recordings to leverage these functional dynamics.

Cardiovascular diseases are the leading cause of morbidity and mortality in the United States. Among the many contributing factors, mishandling of intracellular calcium (Ca2+) dynamics plays a crucial role in the etiology of cardiac diseases including heart failure, and arrhythmogenic disorders. Cardiac ryanodine receptor 2 (RyR2) channels play a central role in excitation-contraction coupling by regulating Ca2+ release from the sarcoplasmic reticulum (SR). Abnormal activity of the RyR2 by impairing Ca2+ release from the SR results in sudden death in many cardiac disorders. Thus, regulators of RyR2 could provide a novel therapeutic target in several heart diseases. Our initial studies implicate the role of the chloride intracellular channel, CLIC4 in modulating the activity of RyR2. We identified CLIC4 as a mitochondrial-associated endoplasmic reticulum membrane protein. The absence of CLIC4 induced faster Ca2+ release from SR, indicating abnormal RyR2 activity. Further, co-immunoprecipitation studies indicated an interaction between RyR2 and CLIC4. Moreover, we found that the absence of CLIC4 increased myocardial infarction upon ischemia-reperfusion (IR) injury in mice. Thus, based on our findings we hypothesize that CLIC4 by either stabilizing RyR2 in a closed state or by regulating the anionic gradient across SR modulates the  RyR2 activity. In this study, we will map the domain in CLIC4 specific to interaction with RyR2 and modulate its activity. We will systematically clone and express various N- and C-terminal truncated CLIC4 constructs to investigate their interaction with RyR2. Further, we will determine the effects of these constructs in modulating calcium release from RyR2. Our studies could aid in the development of a peptide-based therapeutic approach to modulate RyR2 activity in cardiac diseases.

During neonatal inter-facility transport there is a critical need to accurately measure heart rate. The electrocardiogram (ECG)  signals are particularly noisy during transport due to factors such as road noise and infant movement. This inaccuracy leads to false alarms from patient monitors when the measured heart rate values fall out of range. The Pan-Tompkins algorithm is commonly used to measure heart rate from ECG signals but frequently fails under these conditions. This project introduces a novel variation of the Pan-Tompkins algorithm, using the derivative of the ECG signal with additional filters specifically designed to target transport-related noise in neonatal ECGs. We test this modified Pan-Tompkins against the traditional Pan-Tompkins on neonatal transport data to determine if it is more effective for neonatal transport. Each algorithm is applied to a common set of ECG signal patterns taken from a real neonatal transport. The different patterns are classified as clean, somewhat noisy, or very noisy. Each algorithm will be evaluated on Sensitivity and Positive Predictability for each pattern. This research will help save the lives of neonates by reducing false alarms, which will in turn reduce alarm fatigue for providers and draw their attention only when it is truly necessary.

The bacterium Pseudomonas aeruginosa (PA) is an opportunistic pathogen that regulates certain virulence traits via quorum sensing (QS). In PA the QS signaling molecules are acyl-homoserine lactones (AHL). In the well-studied laboratory strain PAO1, there are two complete QS systems: Las and Rhl. Here we study the Rhl system, which has two QS genes that have coevolved and regulate QS activity— rhlI, which codes for an enzyme that produces the signaling molecule N-butyryl-L-homoserine lactone (C4-HSL) and rhlR, which codes for the C4-HSL receptor. In clinical isolates of PA, there are variant rhlR genes, which we hypothesize are important for receptor specificity to C4-HSL and therefore QS activity. We created rhlR genes coding for single amino acid variants of PAO1 RhlR to replicate genotypes found in the clinical isolates. To measure how each variant affects QS activity, we we will use rhlA-gfp as a reporter. The rhlA gene is directly activated by RhlR, and we will compare GFP fluorescence of variants to wild type PAO1 rhlR. QS is a tightly regulated system in PA, and receptor specificity is vital for ensuring this metabolically taxing system is turned on at the right time and properly regulates subsequent protein activity.

In the face of global climate change, there is growing interest in growing seaweed and sinking it to depths to remove carbon dioxide. However, quantifying the carbon sequestration potential of such ventures is challenging. One key consideration is that rising seawater temperatures may increase the rate of kelp decomposition, thereby reducing the export of carbon-containing tissue to the seafloor. To assess whether blades of the bull kelp Nereocystis luetkeana decompose more rapidly in warmer water, twelve 35 mm-diameter tissue disks were allowed to decay at 10-12 °C (ambient temperature treatment) and another 12 tissue disks were allowed to decay at 17-19 °C (elevated temperature treatment). After 7 days, the mean change in disk mass for the ambient temperature treatment was compared to the mean change in mass for the elevated temperature treatment. Samples at elevated temperatures were visibly flimsier and more diaphanous, which was correlated with a significantly greater decrease in weight. In tandem with other studies, this finding suggests that brown algae may decompose more rapidly at elevated temperatures, which has important implications for how to maximize future macroalgal carbon sequestration as ocean temperatures rise.

Extracellular vesicles (EVs) play a crucial role in cell communication and may provide insights into improving care and outcomes for patients with pulmonary diseases. EVs have been studied as potential disease biomarkers to improve diagnosis of lung diseases. This study investigates medium (150-500 nm) and large (500-1000 nm) EVs in patients with Idiopathic Pulmonary Fibrosis (IPF) and Cystic Fibrosis (CF) to determine antibody presence and variation between these two patient groups and between larger sized extracellular vesicles. The characterization of macrophage populations, macrophage subsets, and T Cell phenotypes in IPF and CF patients is done through the analysis of immunophenotypic markers. The experimental findings contribute to understanding immune cell dynamics in IPF and CF patients, potentially informing targeted therapeutic strategies. 

The aorta is the largest blood vessel in the body and is responsible for transporting blood to our organs and extremities. A type A aortic dissection (TAAD) is a tear in the inner and middle layers of the ascending aorta. Given the significant and traumatic nature of such an event, the mortality rate is a major concern as some literature cites up to a 2% increase in mortality rate per hour of an individual suffering from TAAD. Genetic aortopathy, which is an umbrella of genetic diseases, significantly increases the risk of catastrophic aortic events such as TAAD. Patients with genetic aortopathy have been found to have an increased risk of aortic dissections which has already proven to be deadly. However, there is very little research that has been done to show the effect of genetic aortopathy on the short-term outcomes of patients who have undergone surgical repair of TAAD. Our goal is to identify whether differences in outcomes between patients with and without genetic aortopathy truly exist. The dataset we are using is localized to treatment at the UW Medical Center, and contains genetic testing on TAAD patients – something very few centers have previously done. To date, we have completed the database entry of the patients relevant to the study and are beginning the statistical analysis phase which is executed with R programming. The results of this study concern both patients and physicians interested in postoperative outcomes. But, to the patient, this is perhaps the most pressing question moving forward. What is the risk of needing a repeat surgery? What effect does this have on my life expectancy? These are all common yet largely unanswered questions which we provide clarity on.

The circumgalactic medium (CGM) consists of diffuse gas surrounding galaxies out to distances of roughly 300 kpc, forming an interface between a galaxy's interstellar medium (ISM) and the intergalactic medium. Researching the CGM's properties, including its metallicity and dynamics, provides crucial information about galaxy evolution and the fuel available for star formation. In this work, we study Complex C, a well-studied high-velocity cloud in the Milky Way's halo, to understand how its metal content varies on small spatial scales. Using 21-cm HI emission data in an Aitoff projection of the all-sky survey H14PI, we identify the spatial extent of Complex C. Assuming a distance of 3 kpc to the cloud, we then identify blue horizontal branch (BHB) stars from the Sloan Digital Sky Survey (SDSS) that lie behind it. These stars serve as bright background sources, allowing us to probe absorption from ionized calcium in Complex C along different sightlines. The cloud's distinct velocity offset from the Milky Way's ISM allows us to separate absorption features associated with Complex C from those arising in the ISM. By stacking spectra of multiple BHB stars, we can better isolate the absorption signature of Complex C in Ca-II and study how its calcium content varies across different regions of the cloud.

The aim of this study was to examine deformational changes of the tongue base during chewing in normal and obese minipigs. Six same-sex sibling pairs of 8-9-month-old Yucatan minipigs were studied (half each sex). Of each pair, one was a normal weight (BMI< 35) and the other was fed  to obesity (>50). Eight ultrasound-emitting crystals were surgically implanted within the tongue base in a cubic-shaped configuration. The signals between crystal-pairs were recorded to quantify dimensional distance changes of the tongue base. Recordings were taken when the minipigs were unrestrainedly fed and synchronized with simultaneous electromyography and laterally projected videofluoroscopy. The analyses include length, width, and thickness in the dorsoventral, anteroposterior, and lateral regions. Consecutive chewing cycles were backtracked per minipig showing either increased (peak/elongation) or decreased (valley/shortening) signals. The anterior-dorsal width was set up as reference for the onsets calculation (time-zero) due to its stability and showing elongation during the jaw-opening phase of chewing. Thus, onsets, amplitudes, and durations were calculated. Chewing cycle lengths were 0.65±0.01s and 0.64±0.02s in the normal and obese groups respectively. The normal group showed dorsoventral lengthening, anteroposterior widening, and anterior thickening with posterior thinning. In the obese group, dorsal lengthening with ventral length shortening, anteroposterior widening, and posterior thickening with anterior thinning. Overall, widening in the normal group was lower than that of the obese group (p<0.05). In contrast, the posterior thinning remained higher in the normal group compared to the obese group (p<0.05). Earlier onsets of the anterior ventral width and left dorsal length, and left posterior thickness occurred in both groups. The findings of this study suggest decreased deformations mainly ventrally and anteriorly in obese minipigs. This may explain potential mechanisms in breathing and mastication disorders including dysphagia. 

Turner Syndrome (TS) is a chromosomal disorder caused by the lack of the second sex chromosome, also known as monosomy-X. Individuals with TS are phenotypically female and are likely to exhibit defects of variable severity such as short stature, neurocognitive problems, congenital heart defects, and infertility. Over 95% of TS conceptions do not survive to birth. This fetal lethality and other developmental anomalies are thought to be caused by the reduced dosage of X-linked genes or the complete lack of Y-linked genes, but the exact mechanisms are unclear. Our lab has generated isogenic X0/XY or X0/XX human induced pluripotent stem cell (hiPSC) lines from patients mosaic for TS to study the impact of the lack of a second sex chromosome on the same genetic background. My project is to investigate the effect of monosomy-X on early human development by differentiating our TS derived isogenic hiPSC line pairs into RA-Gastruloids, a stem cell-based embryo model corresponding to week 4 of human development. By performing morphological and gene expression analyses we aim to gain insight into the mechanistic causes of fetal lethality in TS. To date, I have optimized the differentiation conditions to successfully differentiate three pairs of isogenic lines and four independent lines (two X0, one XX, one XY) into RA-Gastruloids. Preliminary results showed no clear evidence of morphological differences among different genotypes. To investigate the cell composition of the gastruloids, I will use quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to measure the expression of cell type-specific markers, as well as immunohistochemistry to detect morphological differences. Due to the severity of TS developmental phenotypes, I expect X0 RA-Gastruloids to have abnormal gene expression and/or cell compositions compared to their XX or XY counterpart. This work will help understand the molecular mechanisms of abnormal development in TS.

Autism Spectrum Disorder (ASD) is a developmental disorder characterized by impairments on socialization and communication skills. Research shows that socialization for neurotypical (NT) individuals can be exhausting- depending on personality traits, desire to conform to social settings, and similarly their social skills. When compared to neurotypical individuals, autistic individuals tend to experience socialization withdrawls to a higher degree leading to irritability and lethargy in behavior. This study aims to look at the relationship between socialization, irritability and lethargy. 399 participants (ASD 280) aged 6-11 years from the NIH funded Autism Biomarkers Consortium for Clinical Trials (ABCCT) were included in the analysis. Parents of participants completed questionnaires based on behaviors they observed in their child within the past 6 months using the Social Responsiveness Scale (SRS-2) and Aberrant Behavior Checklist (ABC) measure. Within the SRS-2, the t-scores from the Social Communication, Social Cognition, and Social Motivation scores will be used. We will divide these scores into high and low socialization, cognition, and motivation based on clinical cutoff. Scores on irritability and lethargy will be derived from ABC measure. Analysis of Variance (ANOVAs) will be run to look at the differences in lethargy and irritability scores based on high/low socialization. We expect to see individuals with higher communication, motivation and socialization skills to have lower scores of lethargy and irritability. We also expect to see scores within the SRS-2 and ABC measures to be lower for autistic individuals. This study will help us gain a better understanding of the emotional and autonomic effects socialization can have on autistic individuals. 

Developing solutions to address social risk factors (SRF) in low- and middle- income countries (LMIC) can be difficult as many SRFs are a result of lacking financial support. SRFs are adverse living conditions that may impact the physical or mental well-being of an individual or community. Addressing SRFs in LMICs can increase implementation of evidence-based practices aimed at improving mental health outcomes. In this study, we focused on who is involved in proposed solutions that address SRFs and what specific roles those individuals undertake. Understanding what persons and roles are involved in a solution can help organize and facilitate action. We conducted a secondary inductive thematic analysis on qualitative data from a parent NIMH-funded study which aimed to develop strategies to address SRFs alongside a culturally adapted form of trauma-focused cognitive behavioral therapy (TF-CBT) for children who experienced parental death in Western Kenya. In the parent study, clinical supervisors conducted a workshop and training for TF-CBT lay-counselors to co-develop strategies to address SRFs. Most suggested strategies supported economic empowerment and a worksheet was designed to aid implementation of the strategies. This study uses data from worksheets filled out at 10 different schools in which lay-counselors designed economic empowerment strategies. The primary solutions included poultry rearing, vegetable gardening, and tree nurseries. Preliminary results show that most solutions tend to require school administration, teachers, children, for whom the solutions are for, and their guardians. Administrative roles tended to supply land required for solutions, teachers and guardians mostly supplied resources, while children were tasked with implementation of the solutions. Knowing who executes what roles can help inform what resources, skills, or knowledge a person can contribute to a solution, which may facilitate transferability between solutions. This can help researchers and communities individualize strategies to address SRFs where certain persons may be unavailable.

Students often face academic pressure, interpersonal issues, and employment challenges during the transition into college. While 48.9% of undergraduate students face depressive symptoms (Luo et. al, 2024) and 52% of students report anxiety significantly inhibiting their academic performance (Crosswell et al), only 15% of students with mental illness utilize college mental health resources (Jaisoorya, 2021). To overcome conflicting schedules, stigma, and limited accessibility, we investigate whether self-regulated mindfulness practices would reduce anxiety and depression symptoms in college students. Participants were instructed to practice guided meditation videos daily. Depression and anxiety were measured through Qualtrics using the Beck Depression Inventory (BDI) (Beck et al., 1996) and Generalized Anxiety Questionnaire (APA) (Spitzer, et al., 2006) before and after a 2-week meditation practice. We hypothesize that regular mindfulness meditation practices moderately reduce anxiety and depression in college students. 

Alterations to sleep structure have been observed in healthy aging humans as well as those diagnosed with Alzheimer’s disease (AD). To gain further insight into how sleep is affected by age and neurodegenerative diseases we will analyze sleep in healthy aged rats and in a transgenic rat model of AD. We collected neural data from the hippocampus of aged  (30-32 months old) and adult rats (4-9 months old) during 30-60 minute sleep sessions before and after the performance of a spatial navigation task. We have collected similar sleep data from transgenic F344AD rats (12 months old; a model of AD) and their wildtype littermates. First, we will combine movement tracking and measures of hippocampal local field potential (LFP) activity in the hippocampus to distinguish periods of awake activity, quiet wakefulness, slow-wave sleep, and REM sleep. Specifically, we will use an established measure, the theta-delta ratio, to distinguish slow-wave sleep from REM sleep. Using this approach, we will characterize the sleep structure of the young and old rats and the AD/control rats to determine if there are any differences in, for example, the amount of time spent in a particular sleep stage or the average length of each stage. In addition, we will investigate whether there are any differences in sleep patterns between shorter (30-60 minute) sleep sessions and longer (4 hour) sleep sessions. These analyses will determine whether our rat models of aging and AD recapitulate the sleep changes seen in aged humans with and without AD.

Traumatic brain injury (TBI) can occur after experiencing an explosion or any external force to the head. TBIs are exceedingly common and frequently associated with some degree of behavioral and/or cognitive impairment. However, the underlying causes of these impairments are unknown. To bridge this gap in knowledge, our lab examines the pathology in brain regions that account for the nodes of networks important in cognitive and behavioral function, including the default mode/executive control and limbic/salience network respectively, in brain donors with a history of behavioral, cognitive, or mixed decline. Oligodendrocytes are glial cells in the brain that are important to the production of myelin. Injury to the brain can lead to their cell death. We aim to uncover whether TBI donors with cognitive, behavioral, or mixed decline have reduced amounts of oligodendrocyte in brain regions associated with such functions. To investigate this, slides of over 20 regions of the brain are stained with an antibody that marks oligodendrocytes, Olig2. The slides are then scanned with an Aperio slide scanner and imported to Halo image analysis software. Utilizing this software, I annotate the grey matter of these slides, so that the percentage of the area of staining can be determined for pixels in a specific intensity range. Preliminary results in 5 of the brain donors demonstrates no significant difference in the % staining of Olig2 across the brain regions regardless of clinical pattern of decline. Experiments will need to be conducted on controls of donor brains without TBI and on white matter, a region with higher amounts of oligodendrocytes that may function differently than oligodendrocytes in grey matter.

Microbial volatile organic compounds (mVOCs) are small molecules produced by microorganisms during biosynthetic pathways that easily diffuse through the air, interacting with other nearby organisms despite not physically touching. One method to measure this mVOC communication was the previous iteration of our co-culture device, a bottomless glass vial sealed onto a chip with two separated culture wells, where mVOCs could be released into the headspace. However, spores, a non-mVOC aerosol, also diffused through the headspace, and the device’s structure made it difficult to ensure a fully intact seal. We are developing a device that supports a co-culture that communicates through mVOCs only, uses an intact vial to improve encapsulation, and allows for solid-phase microextraction (SPME) coupled with gas chromatography-mass spectrometry. To test its efficacy, we use the sporulating fungus Aspergillus fumigatus and the bacteria Pseudomonas aeruginosa as model organisms, which are opportunistic pathogens often co-infecting cystic fibrosis patients. We assemble the device by inserting two layers of CNC milled polystyrene platforms containing wells into a vial. We add 1-octen-3-ol or isopentanol, mVOCs produced by A. fumigatus, to the first layer, and P. aeruginosa cultures to the second. The second layer contains polytetrafluoroethylene (PTFE) membranes that only mVOCs can diffuse through. We incubate the vials, plate the P. aeruginosa cultures onto agar, incubate, and observe their growth to assess mVOC communication. We anticipate higher concentrations of mVOCs to inhibit P. aeruginosa growth, demonstrating that the mVOCs interacted with microorganisms in the upper layer. In the future we will co-culture A. fumigatus and P. aeruginosa in the device to study their mVOC interaction, and explore using different biomarkers to determine their effects. This device could be used with other co-infecting pathogenic microorganisms to study their mechanisms and explore therapeutic possibilities.

Latinx individuals in rural communities face significant barriers to accessing non-pharmacological treatments for chronic pain, especially Spanish-speaking populations. Many evidence-based treatments, such as cognitive behavioral therapy (CBT) and exercise programs, have not been adapted to align with the cultural values and needs of Latinx patients.  To address this gap, a multi-pronged nurse care management model is being adapted to align with the cultural norms, values, and needs of Latinx patients with chronic pain. This model integrates culturally adapted versions of cognitive behavioral therapy (CBT), the Enhance Fitness exercise program, and care coordination. Ten primarily Spanish-speaking adult participants (18+) living with chronic pain were recruited through partnerships with a community organization and a healthcare provider. Virtual community engagement sessions will be conducted from February - July 2025 using a structured framework to ensure adequate cultural adaptation. Participants will provide feedback on recruitment strategies, study materials (such as consent forms), and overall study design. Their insights will be analyzed to identify key themes in adapting the intervention for Latinx communities. Participants are compensated for their time. Preliminary findings will be presented on making healthcare interventions more culturally relevant and accessible to Spanish-speaking populations. Emerging themes are expected to include the need for culturally appropriate language, the importance of family dynamics in healthcare decisions, and the best ways to engage Latinx communities in research. By engaging directly with Latinx patients, this project aims to ensure that chronic pain treatments are not just effective but also accessible and culturally meaningful. These insights will help improve healthcare interventions for underserved populations.

All cells have a stochastic component to their gene expression, such that even when in the same environment, there will be cell-to-cell differences in gene expression. Studies of this variability in gene expression dynamics have been limited by technological capabilities for measuring gene expression history with single-cell resolution. We have built a history-dependent integrase recorder of gene expression with single-cell resolution in the model plant Arabidopsis thaliana to study the impact of cell-to-cell gene expression variation in two contexts: development of side or lateral roots (LRD) and root regeneration (RR). The recorder uses integrases, proteins from bacteriophages that mediate permanent, heritable DNA changes based on the presence and orientation of a pair of integrase sites. Fluorescent reporter genes within the target construct allows for expression of fluorescent proteins associated with sequential expression of developmental genes. The recorder allows us to tie the switching to expression of developmental genes by expressing integrases with developmental promoters for genes that guide root differentiation. Utilizing our recorder, we are able to illuminate and evaluate variation in the recorder output among roots growing in different contexts. We hypothesize that regeneration leads to more heterogeneity in gene expression than lateral root development, as the latter has more standardized initial conditions and consistent local cues to constrain transcriptional dynamics. We aim to investigate connections between larger scale anatomical variation and underlying cell-to-cell gene expression heterogeneity. This technology will allow us to further understand the dynamics of gene expression during root development and could unlock new avenues for agricultural research and engineering.

Asthma affects approximately 25 million people in the U.S., with 3,517 deaths reported in 2021. The disease becomes more prevalent with age and remains one of the most common and costly conditions, with an economic burden of an estimated $82 billion spent annually in the U.S. alone, highlighting the significant health and financial impact of the disease. Current therapies, such as inhaled medications and various antibiotics, help manage symptoms but do not prevent disease onset. A key driver of asthma is Thymic Stromal Lymphopoietin (TSLP), an epithelial-derived cytokine that responds to allergens and irritants. TSLP activation initiates an inflammatory cascade, leading to mast cell accumulation, increased immune cell infiltration, and elevated type 2 cytokine production (IL-4), exacerbating airway inflammation and hyperresponsiveness. In this project, I am leveraging the recent advances in deep learning methods to generate cyclic peptide inhibitors targeting the interaction between TSLP receptor (TSLPR) and TSLP, which holds promise as a therapeutic strategy for asthma prevention, specifically at the interleukin-7 receptor alpha (IL-7Rα) ectodomain. Using RFpeptides, a deep-learning based design tool, I generated tens of thousands of cyclic peptide scaffolds. Next, I applied ProteinMPNN, a sequence optimization tool, to produce 50 variants per scaffold, yielding approximately 500,000 potential binders. These were further filtered using AlphaFold, a structure prediction algorithm, to assess binding affinity and folding efficiency. The most promising peptide candidates will be chemically synthesized and evaluated for binding affinity and kinetics against TSLP. If successful, these inhibitors could serve as a cost-effective preventative therapy for asthma, targeting the early stages of the inflammatory process. By reducing the incidence in high-risk populations, this approach has the potential to lower treatment costs and improve quality of life for individuals with asthma.

The efficiency and reliability of solar energy systems depend on panel orientation and energy storage performance, especially in seasonal climates. This research focuses on optimizing solar panel angles and addressing energy storage inefficiencies to enhance the University of Washington Tacoma's Giving Garden solar energy system. By adjusting panel tilt based on seasonal variations, the system can maximize solar energy capture throughout the year. Furthermore, diagnosing and resolving storage inefficiencies—such as battery faults, voltage fluctuations, and improper charging cycles—can improve overall system performance and longevity. This study also examines fault protection mechanisms within the system, identifying current leakage points and implementing solutions to maintain battery health. Through experimental analysis, real-time data collection, and practical system adjustments, this research aims to develop a comprehensive strategy for improving energy output, minimizing losses, and ensuring a more resilient off-grid power solution for sustainable agricultural applications.

Malaria is a mosquito-borne infectious disease caused by Plasmodium parasites and in 2023 caused an estimated 597,000 deaths. Although two currently approved malaria vaccines are available, they offer insufficient protection in endemic populations, which prompts the need for new vaccines. Here we tested several lipid nanoparticle (LNP) vaccines and quantified the number of surviving parasites in vaccinated mice challenged with Plasmodium yoelii sporozoites. To quantify surviving parasites, we utilized the Plasmodium 18S rRNA reverse transcription PCR assay, which is a highly sensitive assay that can quantify the amount of Plasmodium parasites in liver or blood samples. The assay works by amplifying and detecting parasite 18S rRNA in a sample through specific primers, probes and quenchers for mouse GAPDH mRNA and pan-Plasmodium 18S rRNA and can be used to quantify the burden of Plasmodium in a sample. Through the 18S assay, we identified LNP formulations that most effectively protected against rodent malaria. Notably, these LNPs required the adjuvant 7DW85 to be protective.  In the absence of the adjuvant, fewer mice vaccinated with LNPs were protected against rodent malaria. Together, we identified our leading LNP vaccines, which we continue to optimize with the goal of attaining sterile protection against rodent malaria. 

Antibiotic resistant bacteria are an issue of significant global concern and contribute to the increased health burden caused by pathogens. Ongoing research has found that a pandemic urinary tract pathogenic strain of E. coli, ST1193, acquired a high level of fluoroquinolone resistance (FQ-R ) due to two point mutations in gyrA and one in parC, which encode subunits of the topoisomerases DNA gyrase and topoisomerase IV. Rather than a drug sensitive strain acquiring these mutational changes in a sequential, stepwise process, research shows these mutations were acquired by ST1193 during a single horizontal gene transfer event via Hfr conjugational transfer of chromosomal sequences from a distantly related FQ-R commensal E. coli strain. In order to model the evolution of ST1193, we are studying the transfer of the gyrA and parC genes to drug sensitive recipients related to the drug resistant ST1193 strain. I have created a donor derived from an E. coli K12 laboratory strain that can simultaneously transfer mutated gyrA and parC genes to a FQ sensitive recipient. With this I have been able to recover diverse isolates where gyrA and/or parC genes from a FQ-R donor have recombined into the recipient cell chromosomes. Comparisons from whole genome sequencing of these recombinants show a vast diversity in lengths and chromosomal sequences recombined into the recipient chromosomes, ranging from 33kb to as much as 558.5kb. As part of my analysis, I am examining whether some fitness cost are associated in transferring one or two gyrA mutations with or without parC. My comparisons of transfer and recombination events between different branches of the E. coli evolutionary tree are illuminating diverse ways in which bacterial pathogens with high resistance to antibiotics arise.

Globally, men who have sex with men (MSM) are at disproportionate risk of contracting STIs like HIV, particularly in sub-Saharan Africa (sSA). This epidemic is further compounded due to the sexual stigma and heteronormative culture present in countries like Kenya, where male-male sex remains illegal. MSM must maintain discretion surrounding their sexual behaviors, commonly preventing them from accessing sexual health services and disclosing their sexual orientation and activity. Consequently, female partners of men who have sex with both men and women (MSMW) may be at greater risk of STI transmission not only due to physiological causes but also because of social factors, such as being unaware of the same-sex sexual activity that their partners engage in. Kenya is a resource-limited area where preventative STI screening is prohibitively expensive and inaccessible, and the standard of care is syndromic treatment – individuals only seek medical care if they experience STI symptoms, yet over 80% of STIs are untreated due to individuals being asymptomatic. Despite the significance of this issue, few studies have attempted to distinguish the psychosocial characteristics and sexual behaviors of MSMW from those of men who have sex with men exclusively (MSME). This baseline analysis of the Tatu Pamoja Study explores differences in risk factors for STI transmission between MSMW and MSME in Kenya. We hypothesize that, compared to MSME, MSMW will exhibit a higher prevalence of poor mental health and partnership-level sexual risk behaviors, including one-time partners, condomless anal sex, and group sex – all characteristics associated with STI transmission. The findings of this study aim to identify MSMW as a subpopulation of MSM at particularly high risk of STI transmission who may benefit from being offered further preventative interventions – such as doxyPEP and routine STI testing – to prevent onward transmission and reduce the incidence of STIs in sSA.

Social insects not only take care of their nestmates in life but also in death. Research has shown that ants, honey bees, and termites demonstrate a variety of corpse managing behaviors, such as corpse removal, burial, avoidance, and even cannibalism. These behaviors, collectively known as undertaking behaviors, help to maintain the fitness of the colony, keeping the nest hygienic and promoting nutrient recycling. However, how undertaking behaviors arose in the evolution of sociality is unknown. To address this gap in knowledge, we performed experiments that exposed bumblebees, Bombus impatiens, to dead adult nestmates or larvae to identify key undertaking behaviors. Unlike ants, honey bees, and termites, bumblebees are described as “annually eusocial” and lack the strict age-based division of labor seen in other highly eusocial insects. Instead, bumblebees exhibit smaller colony sizes, flexible division of labor, and annual life cycles. Their unique position on the spectrum of sociality makes investigating their corpse management behaviors impactful for understanding the evolution and diversity of behaviors that enable social living. Using deep learning methods, we identified key behaviors like corpse removal, antennation, and mandible contact, and even less frequent behaviors like aggression. Our results characterize the intricacies of this important set of social behaviors and help construct the evolutionary history of this behavioral adaptation. Our future work will explore the plasticity and specialization of bumblebee undertaking and the neural mechanisms behind the behaviors.

Sunflower stars (Pycnopodia helianthoides) are the world’s largest sea stars and critical predators for habitat health. Sunflower stars historically dominated west coast benthic ecosystems, but in the last decade lost over 90% of its global population due to an epidemic of wasting disease. The complete extirpation of Sunflower Stars in many regions of the west – notably Northern California – has exposed kelp forests to overgrazing by urchins, leading to a loss in critical habitats for many marine organisms, increased coastline erosion due to wave action, and decreased atmospheric carbon sequestration. The beginning of restoration efforts are underway to restore populations of these endangered stars, including the first-ever sunflower star captive breeding program at Friday Harbor Labs, where our work was conducted. Despite their clear ecological importance, the surprisingly complex behaviors of sunflower stars has very little documentation in literature. In this experiment, we used an emerging technique called Motion Sequencing to measure juvenile stars’ responses to basic abiotic factors of light and temperature. We found that Sunflower Stars exhibit the most movement during periods of changing light, supporting the dominant theory. We also found they move more in higher temperatures, potentially hinting at resilience to climate change. In doing so, we hope to expand our understanding of sunflower star behaviors – such as their diurnal activity levels, and how they respond to shifts in temperature and other stressors, thus informing both ongoing and future conservation efforts.

Tufas are dendritic carbonate precipitates that form in highly alkaline lakes, such as Mono Lake in California. They are used as paleoclimate archives and evidence of microbial life. One model for their growth is a process known as Diffusion Limited Aggregation (DLA). DLA occurs when there are no advective forces and diffusion is the primary means of particle transport. Branching patterns, such as those you might see in a snowflake, frost on a window, or mineral veins in a rock, are characteristic of DLA. To date, no quantitative comparisons between tufa shape (e.g., branching patterns) and DLA exist. Here, I build a computational model of DLA with the intention of comparing my outputs to real-world three-dimensional (3D) models of tufas. I aim to test whether my models are statistically similar or different to my samples. My initial efforts have successfully recreated branching morphologies with enough detail to enable this comparison. Researchers have also pointed out that fluid flow may modify the shape of tufas. Therefore, as a future step, I intend to modify my models to include an advective component and test the effects of increasing current on tufa shape.

The island of Sifnos hosts a unique outcrop of rocks displaying a transition from blueschists to eclogites that form deep within subduction zones from metamorphic reactions in the subducting oceanic crust. Subduction zones have the potential to produce megathrust earthquakes. Studying the metamorphism and deformation preserved in these exhumed subduction rocks can inform hazard assessments. The blueschist and eclogite facies samples in my study are thought to represent peak metamorphic conditions where the slab is at its highest pressure (P)-temperature (T) conditions. A previous study of Sifnos found bulk compositional differences between the eclogites and blueschist and concluded they metamorphosed from different proliths at the same P-T conditions during subduction. Re-examining the Sifnos blueschist-eclogite unit with modern petrological tools reveals blueschist samples with a similar bulk composition to the eclogites, challenging previous interpretations of the formation of Sifnos blueschist-eclogite unit. I will be investigating chemical zoning in the minerals glaucophane, mica, garnet, omphacite, and epidote within four samples from the blueschist-eclogite unit using electron probe microanalysis. Variations in chemistry within the samples, for example, from core to rim within individual grains or between the matrix and inclusions within other mineral grains reveal the metamorphic history of a sample by comparing variance across the samples. Based on preliminary results, I hypothesize the blueschists of Sifnos were instead produced by retrograde metamorphism of eclogite by fluid interactions during exhumation. This hypothesis is supported by preserved high-pressure (omphacite) grain inclusions within garnets in blueschist samples, and compositional shifts between glaucophane in the matrix and found as garnet inclusions. The blueschists also display stronger deformation fabrics than the eclogites, implying a link between the fluid-driven retrogression and deformation on Sifnos. This highlights the potential for feedback between metamorphism and deformation that may play a role in the dynamics of subduction zones and their related hazards.

Stromatolites are fossilized, centimeter-to-meter scale laminated buildups formed by microbial activity. When examined, these sedimentary structures offer insights into the emergence of early life on Earth. However, before we can use stromatolites as a tool to study early life, we must understand what their morphology (e.g., shape and spatial arrangement) tells us about their formation. To date, few studies have quantified exactly how such variables affect stromatolite morphology. Here, I produce and apply morphological metrics to two-billion-year-old stromatolites to test two hypotheses: 1) the distribution of the individual constructions is non-random and 2) the space between stromatolites varies in thickness across space. To investigate these hypotheses, I use digital three-dimensional (3D) reconstructions of ancient stromatolite bedding planes from Great Slave Lake, Canada and make measurements. I identify the organizational patterns of these stromatolites using metrics such as area, width, length, aspect ratio, and circularity distributions across space, and explore whether such patterns are indicative of life. Ultimately, this work will broaden scientific understanding of stromatolite morphogenesis and the processes that drive early Earth systems; knowledge that may help us better interpret potential signs of life found elsewhere in our solar system. 

Adenomyosis is a painful gynecological condition with a prevalence ranging from 20-35% in symptomatic patients. Current detection methods, ultrasonography and magnetic resonance imaging, are suboptimal and definitive diagnosis frequently relies on hysterectomy, prompting more research for less invasive diagnostic tests, which is the aim of this study. We enrolled 108 women undergoing hysterectomies, after post-operative histopathology diagnosed women with adenomyosis (n=46) and other benign conditions (n=62). Cervicovaginal lavage (CVL) and vaginal swab samples were collected. CVLs were used for global metabolomic data, as well as immunoproteomic profiling. We conducted 16s rRNA microbiome profiling on vaginal swabs. The integration of datasets was performed using MetaboAnalyst and MetOrigin. No significant differences were found in body mass index, menopausal status, co-occurring conditions, and parity between patient groups. Pathway enrichment analysis revealed co-metabolic pathways pyrimidine metabolism, D-amino acid metabolism, arginine and proline metabolism, and histidine metabolism as the most enriched in the adenomyosis group. Using least absolute shrinkage and selection operator (LASSO) for biomarker selection, multivariate receiver operating characteristic (ROC) analysis revealed that a model based on metabolomics dataset has an area under the curve (AUC) of 0.852, predictive accuracy (PA) of 77%, and Youden's Index (J) of 0.607. Compared to immunoproteomics and microbiome models, which had a PA of 68.8% and 66.5%, respectively, combining metabolomics with immunoproteomics resulted in an improved PA of 74.8%, while combining metabolomics with microbiome led to a PA of 74.3%, both outperforming their individual counterparts. Three-omics integration in a multivariate model resulted in an AUC of 0.859, PA of 77.4%, and J of 0.624, with metabolites being the top predictive features in the model. Our study identified that global metabolomics is the best single omics predictor of adenomyosis. Multi-omics integration increases performance metrics. Overall, this study identified key metabolic biomarkers for diagnostic development and assessment in future studies. 

Hearing loss affects approximately 40 million people in the US. It is primarily caused by the damage and loss of hair cells, which do not regenerate in humans. In the Raible lab, we use zebrafish as a model to study hair cell development, death, and regeneration. Unlike mammals, zebrafish can regenerate their hair cells after damage. I am currently using CRISPR-Cas9 gene editing technology to create mutant zebrafish to test a gene’s role in hair cell development and regeneration. We use guide RNA to target and mutate different genes that have been shown to be expressed in hair cells or support cells, which act as a new source of hair cells during regeneration. At 5 days post fertilization we quantify the number of hair cells and compare the numbers between mutant and non-mutant fish to test for developmental defects. If there are no defects, we treat these fish with the ototoxic antibiotic neomycin to kill their hair cells. After neomycin treatment, we wait 48 hours for the hair cells to regenerate and then compare the number of hair cells in non-mutant fish to mutant fish to examine whether the loss of that gene impacts hair cell regeneration. By developing an understanding of what genes are important for hair cell function and regeneration in zebrafish, we can begin to apply these findings to help with studies looking into hearing loss in humans.

Research by Najera and Jander (2011-2012) established that honey bees (Apis Mellifera) have the cognitive ability to utilize secondary decision making places when foraging among different flower patches. Furthermore, honeybees can associate and predict specific times and places to when there will be an available food source. Najera and Jander were able to come to this hive level conclusion using a novel methodology to measure departure direction and map out the movement of individual bees from food source to food source. This study is largely considered to be moderately successful. Yet many questions still remain, such as how far a honeybee’s special intelligence could be taken and how these findings could be applied commercially. Although their method is very reliable, it can be expensive and requires dedicated and trained researchers that are often not available at small institutions. Here we explore adaptations of Najera and Janders original experiments to provide greater accessibility and increase research opportunities for small institutions or private beekeepers. With greater accessibility, it will be much easier to answer any lingering questions. Adaptations include: reduction in size of both hives, number of patches, researcher training, and increased efficiency of data collection. 

Cryptic diversity, the existence of genetically distinct but morphologically similar taxa that thus were previously classified as a single entity, is a fascinating subject in evolutionary biology and alpha taxonomy, but can be challenging to assess in practice. Genetic analyses have proven successful in identifying cryptic taxa, but are often impractical to employ as a starting point. Morphology thus can play an important role in cases of possible cryptic diversity, especially in determining if further study is warranted. Here, we use statistical analyses on morphological data to assess a possible case of cryptic diversity within Allium acuminatum, a species of wild onion native to western North America. Specimens collected primarily from several counties in Washington State (Kittitas, Yakima, and Klickitat) have been noted to differ morphologically from formal descriptions of the species. Morphological data was recorded for 165 specimens from the University of Washington Herbarium, Burke Museum collection. The data was then analyzed using a Factor Analysis with Mixed Data (FAMD) algorithm, and the results of the FAMD were then analyzed with a k-means clustering algorithm. The k-means clustering results were then plotted on a geospatial map using the original locality data from the herbarium specimens, and geospatial patterns for the clusters were assessed visually. Finally, t-tests and chi-squared tests were performed for the continuous and categorical traits, respectively, between the k-means cluster groups. The k-means clustering algorithm generated 3 clusters from the FAMD data, one of which was strongly centered around the area of interest (Kittitas, Yakima, and Klickitat counties), according to the geospatial map. Further, the statistical tests showed that, for 10 of the 14 traits analyzed, there were notable differences between the k-means cluster groups with a high level of statistical significance (p ≤ 0.0001).  Most of these differences were reflected in the cluster centered around the area of interest. These results indicate there is detectable morphological variation within A. acuminatum, and this variation is centered around the geographical area of interest. Additionally, we believe these results indicate further study is warranted to determine if the morphologically different populations are worthy of taxonomic recognition using more sophisticated methods, such as molecular techniques.

Dissociation is an altered brain state caused by trauma, epilepsy, and drugs in which critical mental functions such as sensory processing and consciousness are disconnected. While its brain circuit mechanisms remain underexplored, their improved understanding would not only help treat dissociative psychiatric disorders but also help develop more precise dissociative anesthetics. Here, we used immunohistochemistry, in vivo fiber photometry, high-density electrode recordings, and machine learning behavioral analysis in a ketamine-induced dissociation model in mice to address how affective processing is disrupted in dissociation. We hypothesized that ketamine-induced dissociation alters the signaling of the locus coeruleus-norepinephrine (LC-NE) system, a brain region responsible for regulating stress and aversive responses. Previous studies have found that suspending a mouse by its tail induces escape-related behaviors, which are lost when treated with a dissociative dose of ketamine (50-100 mg/kg). We performed tail suspension experiments to further characterize these behavioral differences using a machine learning approach. Using DeepLabCut, a deep learning algorithm to track animal body parts, and Keypoint Moseq, an unsupervised machine learning algorithm for decomposing behavior into behavioral modules, we characterized differences in these behavioral modules between awake and dissociated states. We then compared changes in LC activity between ketamine- and saline-treated mice, using cFOS immunostaining as a marker for neuronal activation. We also used fiber photometry to examine downstream norepinephrine (NE) release in the medial thalamus during tail suspension, using a genetically encoded fluorescent NE sensor to measure NE activity in real-time. Our data shows increased NE activity during tail suspension, suggesting that the LC remains responsive in the dissociative state. This responsiveness may suggest that the disruption of the aversive response in dissociation is downstream of the LC-NE system. We plan to examine the medial prefrontal cortex and basolateral amygdala as possible loci of disruption using fiber photometry, Neuropixel recordings, and optogenetics.

Physical rehabilitation sensing technologies play a critical role in enhancing patients’ recovery through real-time monitoring and help doctors evaluate the effectiveness of rehabilitation treatment. However, traditional sensing devices are bulky which may not only limit the patients’ movement and reduce the accuracy of doctors’ evaluation but also add additional burden to the patients. Thus, we want to develop a unified multimodal sensing wearable, capturing multimodal data in a more compact and efficient form factor, allowing the patients to perform rehab tasks in a more natural way. While a multimodal wearables strategy does exist, their sensors usually stack on top of each other for multimodality, which sacrifices flexibility, and compactness, making patients inconvenient to wear. To address these limitations, we developed a novel multifunctional smart oversleeve, integrating a customized portable sensing circuit that can perform joint deformation monitoring and measure muscle activities through electrical impedance tomography (EIT) and electromyography (EMG). The sensors of the circuits are highly unified as well as the readout circuit. Compared with traditional bulky sensors with multiple layers, patients can easily wear them as regular sleeves, which combines the function of reading all of the signals that are mentioned above (EMG, EIT, etc.). From the perspective of the circuit, it can effectively calculate the bending angles of the elbow and track the activities of the bicep, triceps, and forearm muscles, reflecting the patients’ recovery performance. These capabilities provide valuable insights into patient recovery performance and highlight the potential of this device as a versatile tool for physical rehabilitation monitoring.

Approximately 320 million years ago, teleost fish experienced a whole-genome duplication event, which is theorized to have contributed to developmental and morphological innovations that enhanced the reproductive success of their modern descendants. However, the role of duplicated genes in the genesis of novel cell types remains unknown. Here we show that the African Turquoise Killifish (Nothobranchius furzeri) possesses a novel immune lineage specified prior to gastrulation—a far earlier stage than observed in other teleosts. Surprisingly, through single-cell RNA sequencing, we found that this lineage unexpectedly expresses nanos1b, a duplicated paralog of nanos1, a gene well known for its role in germline development across vertebrates. To verify this novel expression of nanos1b in immune cells before gastrulation, I performed RNA in situ hybridization to visualize the expression of nanos1b, eomes (a mesodermal marker), and lcp1 (a marker of mature immune cells). The results revealed co-expression of nanos1b with both eomes and lcp1, supporting the hypothesis that nanos1b expression links the myeloid lineage to the developing mesoderm. These investigations will help elucidate the pathway through which the killifish embryo fast-tracks the production of immune cells during early development.

Controlled and untethered Micro Aerial Vehicles (MAVs) near 1 gram offer transformative potential in applications like disaster response, inventory inspection, and precision agriculture, offering reduced costs and minimal hazards compared to larger drones. However, MAVs of this size face significant challenges in achieving both flight stability and maneuverability, particularly due to difficulties in generating sufficient lift and controlling multiple degrees of freedom mid-flight. While recent advancements have addressed various aspects of untethered flight, there has yet to be a MAV near 1 g that has also demonstrated stable hover and autonomous navigation. We introduce Coin-copter, a dual-rotor helicopter designed to overcome these limitations. We present three Coin-copter sizes, ranging from 0.8 g, to 1.1 g, and 1.8 g that leverage a foldable flybar-propeller mechanism for achieving passive stability and a feedback-controlled tail motor for yaw-axis control. Our prototypes achieve free-flight stabilization with payload capacities of up to 0.3 g, 2 g, and 5 g respectively, and evaluate the operational efficiency of each design to determine the optimal Coin-copter size for maximizing duty cycled flight time under practical energy harvesting scenarios.

Young adult cannabis use has become increasingly prevalent in the US, particularly among individuals attending four-year colleges. The perceived social acceptability of cannabis use plays a crucial role in shaping attitudes and behaviors towards substance consumption. While societal attitudes towards cannabis have evolved over the last two decades, there is a gap in understanding how these perceptions differ between college students and their non-college peers. My research aims to compare perceptions about the social acceptability of cannabis with the actual frequency of use among young adults who attend four-year colleges, versus same aged individuals that are not attending school. I am using a subsample of young adults using baseline data from a larger longitudinal study on health behaviors, the Washington Young Adult Health Survey (WYAHS), for the analysis. I am conducting the data preparation and analysis using SPSS. I believe that there will be a significant difference in perceived social acceptability of cannabis use between college students and those not attending school, but I also anticipate that actual consumption will not be significantly different. The results of this research could be important for improving substance use education and addressing preconceived notions of cannabis use acceptability among young adults. Previous research on the WYAHS data has shown significant changes in substance use behaviors over the last six years, especially throughout the pandemic. Future research is needed, which focuses on how my findings may change when based on data from before the COVID-19 pandemic.

Alzheimer’s disease (AD) is a neurodegenerative disorder that disrupts memory, thinking, and behavior. It is the most common type of dementia and occurs with increasing frequency with increasing age. Transgenic AD mouse models have not predicted clinical efficacy because neurodegeneration occurs rapidly at a young age, so an aging environment is not a factor. To address this, an adeno-associated viral vector model of AD (AAV-AD) containing a green fluorescent-induction marker (GFP) was created to deliver pathogenic proteins Aβ-42 and P301L tau to neurons of old mice. The AAV capsid was engineered to have an affinity for neurons. Analysis of the model demonstrated successful expression of Aβ-42 and P301L tau in neurons in the brains of old mice when the vector constructs were administered intravenously (IV). However, it has yet to be shown whether the AAV-AD vector has off-target effects in systemic organs like the liver. Characteristic AD pathology does not naturally occur outside the brain. Therefore, this project was designed to determine if the AAV-AD vector became established in hepatic cells. Paraffin-embedded tissues were obtained from 27-month-old C57BL/6 male and female mice infected with the AAV-AD or sham vector for 3 months. Immunohistochemistry (IHC) was used to examine expression of GFP, Aβ-42, P301L tau, MCP-1 inflammatory cytokine, and yH2AX DNA-damage response. Images were taken using digital microscope software, and quantified through an open-source digital image software. Age-related histopathology lesion scores from H&E-stained brain and liver were compared with IHC stains. The expectation is there will be little evidence of AAV-AD proteins but incremental increases in inflammatory and DNA-damage proteins proportional to histopathology lesion scores. These observations would help validate translational efficacy of the AAV-AD mouse model for preclinical testing of pharmaceuticals to treat or prevent AD.

Since 1950, there has been an exponential increase in the production of plastic from 2 million to 460 million metric tons produced per year. With this production also comes the exacerbated effects on climate change and health: 2.24 billion metric tons of carbon emitted annually, pollution of ecosystems, and degradation of plastics to microplastics that enter living organisms. There is a clear need to develop eco-friendly plastic alternatives. The Roumeli Research Group has previously observed the ability to form biodegradable plastics (bioplastics) from unprocessed biological matter (biomatter). More specifically, use of whole cells of microalgae spirulina can be processed using conventional plastic manufacturing techniques like hot pressing. My project focuses on understanding the changes in chemical and molecular properties of spirulina that occur during the biomatter to bioplastic transition as a function of processing conditions. I fabricated hundreds of dime-sized samples by hot pressing spirulina powder in customized molds under various temperatures, pressures, and periods of time. I also characterized these samples using Fourier Transform Infrared Spectroscopy (FTIR) to inspect the relationship between chemical bonds and spirulina morphology. I analyze these FTIR results in conjunction with creating and pressing samples of biomatter analogues to better understand spirulina’s complex structure. My efforts, along with other characterization techniques like hardness testing and Scanning Electron Microscopy (SEM), will inform modifications of the processing design to obtain desired mechanical properties of the resulting spirulina bioplastic. These findings can be integrated into a machine learning model that concurrently analyzes multiple characterization results to identify trends in the data and further contribute to our understanding of structure as it relates to pressing conditions. 

The School Breakfast Program (SBP) has been widely recognized for its positive effects on student health, academic performance, and school attendance, particularly for low-income students. However, there is limited research on the long-term economic impacts of SBPs, such as their influence on family income, employment, juvenile delinquency rates, and overall educational attainment. This study aims to fill this gap by analyzing the broader economic implications of SBPs through a state-by-state comparison. Using a Difference-in-Differences (DiD) model, this research will compare educational and economic outcomes between schools in Minnesota (control) and Wisconsin (intervention), where recent SBP expansions have been implemented. Key variables will include graduation rates, family income, employment levels, and juvenile delinquency rates. Data will be sourced from the U.S. Department of Agriculture, the National Center for Education Statistics, and the U.S. Census Bureau. By exploring the long-term effects of school breakfast programs, this study will provide insights into their role in shaping economic mobility and community well-being.

Stress resilience, the ability of cells and tissues to adapt to stimuli, declines with age. Skeletal muscle contraction is a physiological stressor when repeated through exercise training enhances stress resilience and mitigates age-related comorbidities. However, as the body's capacity to mount adaptive responses diminishes with age, the extent to which this decline affects physiological adaptation to stress remains unclear. This would guide future therapeutic strategies surrounding muscular degeneration over the lifespan. The goal of this study is to assess the magnitude of stress response activation across metabolic, oxidative, proteostatic, and heat shock stress response pathways. We use gene expression analysis to evaluate the transcriptional response to controlled in vivo muscle stimulation, providing insight into age-related differences in stress resilience. Young (6mo) and old (23-24mo) male and female mice (C57Bl/6JNia) underwent an in vivo fatiguing muscle stimulation (Stim) or served as an unstimulated control (Unstim). Three hours following the stimulation both right and left limb muscles were collected and processed for gene expression analysis. Following stimulation and collection, I performed tissue processing, RNA extractions, and RT-qPCR assays on muscle tissue. There was a significant increase in PGC1a, HMOX1, TRIM63, and HSPa1a genes in response to muscle stimulation when compared to the unstimulated limb within the same animal. The magnitude of these changes in response to stimulation were not different across age or sex. Analysis of basal changes in unstimulated groups across age and sex is planned for next month. These preliminary results suggest no significant age or sex differences across multiple pathways of stress resilience in skeletal muscle. A strength of this study design is that we use a combined within- and between-animal analysis of both stimulated and unstimulated conditions to control for any potential variations associated with each age, sex, and stimulation condition, increasing confidence in our results.

Infants and adults process fundamental sound attributes such as pitch, timbre, and loudness differently, but the underlying neural mechanisms that drive these differences remain unclear. Pitch is the perceptual attribute of sound that can be arranged from low to high as in a musical scale, while timbre differentiates sounds of the same pitch and loudness, such as different musical instruments. Timbre, related to the spectral distribution of frequencies, is perceived as brighter when high-frequency energy increases. In natural sounds, pitch and timbre often covary; for example, a flute’s sound is both high in pitch and bright in timbre. Our prior research showed that infants outperform adults without musical training in pitch discrimination in the presence of random brightness variations. One possible interpretation is that adults have learned the statistical covariation between pitch and brightness, leading to efficient coding but poorer performance when these expectations are violated. To investigate further, we recorded mismatch negativity (MMN)—a brain response to unexpected sound changes—using electroencephalography (EEG) in both 7-month-olds and adults. We measured responses to pitch changes in two conditions: 1) with random brightness variations and 2) without brightness variations. The results are consistent with our prior behavioral findings: infant MMN amplitudes were comparable in both conditions, whereas adult MMNs were larger without brightness variation. These results are consistent with our past behavioral findings and the interpretation that infants have not learned the statistical covariation between pitch and brightness, thus experiencing less interference when discriminating pitch in the presence of random brightness variation. This research offers insight into the differences between how the infant and adult brains process fundamental attributes of sound that are important for speech and music perception. My role in this project involved the acquisition of EEG data, data management, and dissemination of research findings.