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

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

Older adults recovering after hospitalization in an intensive care unit (ICU) are at high risk of functional decline. Older adult ICU survivors often report symptoms of cognitive impairment, sleep disturbances, and pain, which can complicate functional recovery. In addition, certain social determinants of health (SDoH) are associated with worse cognitive and physical outcomes that lead to functional decline in older adult ICU survivors. Little is known about the relationships between patient-reported symptoms (e.g., cognitive function, sleep quality, and pain intensity), selected SDoH, and functional recovery for older ICU survivors during hospitalization. This project has two overall aims: 1) explore associations between patient-reported symptoms of cognitive function, sleep quality, pain, and SDoH; and 2) explore associations between these variables and successful participation in physical therapy and/or occupational therapy (PT/OT). We collected and utilized data from two ongoing randomized controlled trials. Older ICU survivors hospitalized at University of Washington Medical Center or Harborview Medical Center were recruited and enrolled. Participants answered the PROMIS Cognitive Function Abilities, Sleep Disturbances, Sleep Related Impairment, and Pain Intensity questionnaires to evaluate self-reported cognitive function, sleep quality, and pain intensity. We did chart review of electronic health records to gather relevant information regarding SDoH, and length of PT/OT participation in minutes. We examined the differences using t-tests, Chi-squared tests, and ANOVA for binary, categorical, and/or continuous variables, respectively. We used descriptive analysis to explore trends between self-reported pain, sleep quality, and selected SDoH on self-reported cognitive function and participation in PT/OT. Results from this project will inform the design of subsequent clinical trials, which could aid in the development of personalized interventions aimed at reducing functional decline in older ICU survivors. 

Extensive research has established that certain social determinants of health (SDoH) can significantly influence health outcomes for older adults. Older adults from socioeconomically disadvantaged backgrounds often lack access to a tertiary or quaternary care hospital for complex care for severe chronic illness. Such healthcare disparities have the potential to negatively impact cognitive and mental health for older adults with chronic illnesses, particularly after intensive care unit (ICU) hospitalization. There is limited research examining the associations between SDoH, cognitive function, and mental health in older adult ICU survivors during the early post-ICU inpatient transition period. We aim to gain insight on how to best tailor inpatient interventions to suit older adult ICU survivors from disadvantaged or vulnerable backgrounds. Our project has two overall goals: 1) explore associations between SDoH, self-reported depression and anxiety, and severity of illness; and 2) explore associations between SDoH, selected objective measures of cognitive function, and severity of illness. Data from two ongoing randomized controlled trials of older adult ICU survivors enrolled from the University of Washington Medical Center or Harborview Medical Center are utilized. Participants answer the PROMIS Depression and Anxiety questionnaires to evaluate self-reported depression and anxiety symptoms. Chart review of participants’ inpatient electronic health records provides relevant information regarding SDoH, including home addresses, which provide information on census tracts towards index calculations. Other relevant clinical variables documented by inpatient healthcare providers, particularly severity of critical illness, are used for descriptive analyses. Ultimately, we anticipate that the results from this study will guide the development of future clinical trials. Possible next steps involve creating personalized interventions that integrate insights on SDoH to promote cognitive and mental health in older adult ICU survivors at high risk for cognitive decline.

Approximately 18% of older adult intensive care unit (ICU) survivors with delirium are diagnosed with Alzheimer’s disease or related dementia (ADRD) within three years of hospitalization. The constant, 24-hour ICU care can cause disruptions to sleep quality and the biological circadian rhythm. These disturbances, which affect up to 80% of ICU patients, can decrease the efficacy and benefits of interventions to manage delirium and improve cognitive function. We aim to explore the roles of individual chronotypes (morning, afternoon, or evening preference) and self-reported cognitive function on acceptability and adherence to a computerized cognitive training (CCT) intervention for older adult ICU survivors.  Data from two ongoing randomized controlled trials (the SLEEP-COG Study and OPTIMIZE Study) are utilized for this project. Older adult ICU survivors hospitalized at University of Washington Medical Center or Harborview Medical Center are enrolled based on the following eligibility criteria: ages 60 and older, functionally independent prior to hospitalization, and within 48 hours after transfer from intensive care to acute care. Participants who are randomized to CCT complete 30-minute daily sessions for up to 7 days or until discharge. Participants answer the Composite Scale of Morningness questionnaire to determine their individual chronotype and complete the PROMIS Cognitive Function & Cognitive Function Abilities instruments to examine self-reported cognitive function. Upon completion of the CCT intervention, participants answer Likert-type surveys and open-ended questions about feasibility, acceptability, and usability.  Analyses will explore trends between chronotype, self-reported cognitive function, and acceptability.  Differences will be described using t-tests, Chi-squared tests, and ANOVA for binary, categorical, and/or continuous variables, respectively. Potential future directions may include the development of personalized interventions that integrate individual chronotype and perceived cognitive ability to minimize delirium and cognitive decline associated with ADRD in older adult ICU survivors. 

Superatoms are (often inorganic) clusters of several to several hundred atoms in size, that mimic the chemistry of elemental atoms by exhibiting a high degree of valence electron delocalization, effectively creating a unified valence shell over the entire superatom. Our lab works with M₃(solv)_xCo₆Se₈L₆ (M = Cr, Mn, Co, Zn; solv = thf, py; L = PPh₂NTol)  clusters, leveraging the molecular nature of the Co₆Se₈ core to attach three metal “edge sites” held in place by phosphine ligands, arranged such that they serve as an interface between the exterior chemical environment and the inner superatomic core. By swapping the edge metal, we are able to modify properties of the overall metalated cluster, imparting a degree of chemical and electronic tuneability. While investigations into these compounds have shed light on their electronic structure and reactivity, applying these properties in a practical sense has been an elusive and ongoing area of study. In 2021, however, the Nuckolls lab demonstrated a mixture of Co₆Se₈(PEt₃)₆, Cr₆Te₈(PEt₃)₆, and C₆₀ that formed an isotropic crystal structure capable of up to 100-fold increased conductivity compared to crystals of Cr₆Te₈(PEt₃)₆ or Co₆Se₈(PEt₃)₆ mixed with C₆₀ alone. In this work, I am investigating the conductivity of mixtures of various M₃(solv)_xCo₆Se₈L₆ clusters via a 2-probe method. In previous work, our lab has demonstrated the occurrence of charge transfer in the solution phase between clusters metalated with Co and Cu; building off of this, I intend to determine whether such a phenomenon can be observed in the solid state, and to a degree of reversibility that facilitates improved conductivity through the mixture. The observation or lack thereof of such behavior could hold implications for the applicability of metalated clusters in future semiconductor or materials technologies.

This research explores the effects of water deficit treatments on the leaf structure and efficiency of photosynthesis of Miscanthus sinensis 'Bandwidth,' a grass popular in landscaping and known for its variegated leaves, an alternating green and yellow banding pattern found along each leaf blade. Previous research on Miscanthus suggests that leaf variegation can influence the efficiency of photosynthesis, however, the impacts of variegation in Miscanthus under water stress remains underexplored. By measuring chlorophyll concentrations, leaf areas, and photosynthetic efficiency in both the green and yellow regions of the leaves, this research evaluates how water stress affects the plant’s overall performance. Measurements are compared between the green and yellow portions of the leaves across high and low water treatment groups to better understand the impact of water deficit on the plant's overall performance. The preliminary results indicate that water availability affects total leaf area, the ratio of green to yellow area, chlorophyll content in both yellow and green sections, and photosynthetic performance, as measured by stomatal conductance of gas exchange and the performance of photosynthetic components in the leaves under both high and low water treatments. This research is part of the University of Washington’s Climate Ready Landscape Plants project, which aims to promote sustainable landscaping practices and urban resilience strategies in response to climate change. The results from Miscanthus can continue to encourage sustainable landscaping, urban resilience, and maintaining biodiversity by examining plant adaptability under drought-like conditions.