University Of Washington

NIH Research Projects · FY 2026 · 2025-08

Project Summary Age-related vocal atrophy (ARVA) affects a substantial portion of the population. ARVA impairs voice, swallowing, and communication, and is associated with social isolation, depression, and reduced quality of life. Vocal fold muscles are thin, bowed, with an incomplete closure during voicing. The underlying reason individuals experience ARVA is not well understood, and current treatments are often ineffective. Moreover, the diagnosis of ARVA is largely subjective and shows overlap with Alzheimer’s disease-related vocal atrophy. Motor evoked response studies are considered the gold-standard test to diagnose many neuromuscular disorders. This electrophysiologic study produces a compound motor action potential (CMAP), which is a summation of muscle fiber action potentials upon electrical stimulation of the motor nerve. The CMAP assesses the integrity of the nerve, neuromuscular junction, and muscle. The candidate has previously used the CMAP to quantify the degree of injury to the recurrent laryngeal nerve (RLN), which is the primary motor nerve to the larynx, in an animal model. The CMAP has been shown to detect acute changes in laryngeal innervation, measure conduction time changes, and quantify the degree of recovery after injury. The candidate has developed a reliable method to perform laryngeal evoked response studies in an aging rat model and human subjects. Pilot data have led to the central hypothesis that there is progressive desynchronization of efferent nerve-muscle signal in the aging larynx. The overall goal of this proposal is to quantify the neuromuscular changes in the aging larynx. The laryngeal evoked response study is the primary outcome measure and will be performed in a rat model (Aim 1) and in human subjects (Aim 2). The rationale for this proposal is that measuring neuromuscular changes in the aging larynx can lead to targeted treatments for this condition. This proposal combines an animal model and human subjects. While the two aims are not dependent on the other, the animal and human studies help to inform one another. The candidate’s primary mentor is David Marcinek, PhD, and he investigates aging muscle physiology and mitochondrial energetics. Jay Rubinstein, MD, PhD and Randal Paniello, MD, PhD are both co-mentors for this proposal. Both Dr. Rubinstein and Dr. Paniello are surgeon-scientists with expertise in computational neurophysiology and laryngeal injury and recovery, respectively. All three mentors have successfully mentored post-doctoral researchers and physician-scientists in career development programs. Local coursework and training programs in neuroscience, cellular biology of aging, instrumental measures of voice production, and biostatistics will allow for the candidate’s ongoing career development. This proposal will provide a strong foundation for independent investigations testing treatments for ARVA.

NIH Research Projects · FY 2026 · 2025-08

ABSTRACT Providing access to medications for persons with active substance use and housing insecurity is a remaining challenge to achieving the national goal of HCV elimination by 2030. Our pharmacist-led collaborative care model is designed to offer low-barrier syndemic care, including direct-acting antivirals (DAAs) for hepatitis C to people who use drugs (PWUD) in the community. Through our prior NIDA grant (1R34DA047660), we developed and pilot-tested the “Pharmacist, Physician, Patient Navigator Collaborative Care Model” (PPP- CCM) approach for expanding access to DAAs. Guided by the RE-AIM framework, we will conduct a pragmatic implementation trial using a parallel-group, cluster randomized design to evaluate PPP-CCM’s ability to improve access to DAAs for HCV within a network of supportive housing units in Seattle and King County. We will enroll 16 units, each housing 40-190 individuals, and randomize half of the units to receive point-of-care (POC) HCV screening plus PPP-CCM versus POC HCV screening alone (control) for 12 months, after which we will implement the intervention in control arm units as well. We will evaluate the implementation measures based on RE-AIM (Reach, Adoption, Effectiveness and Maintenance) as well as other clinical outcomes and substance use/HIV behaviors among the two arms. Additionally, we will conduct qualitative research to better understand barriers and facilitators to implementation and maintenance which will inform the development of a toolkit for dissemination to other supportive housing units throughout the state and country.

NIH Research Projects · FY 2025 · 2025-08

ABSTRACT Motor vehicle injuries (MVI) have been a leading cause of death in the United States since the 1930s. Fatalities had trended downwards from the 1970s until 2019; however, these trends appear to have reversed recently. Forty percent of crash decedents were alive when emergency medical services (EMS) providers arrived at the crash scene. Improved post-crash care may prevent MVI fatalities. The National EMS Information System (NEMSIS) contains EMS information from over 14,000 EMS agencies nationally. NEMSIS includes case definitions for EMS scenarios including crashes. However, NEMSIS lacks the level of detail available in EMS data systems and does not include information from other data sources such as crash records. Linking EMS to crash records and health outcomes can provide better alignment of MVI classification across all data sources. Washington State has linked the Washington EMS Information System (WEMSIS), which includes 95% of state EMS calls between 2020 and 2024, to crash reports records as part of the Traffic Records Integration Program (TRIP) program. In this project, we will complete TRIP’s integration of Washington’s Rapid Health Integration NetwOrk (RHINO), a syndromic surveillance system containing ED, urgent care and primary care medical encounter data, and Washington Comprehensive Hospital Abstract Reporting System (CHARS), which collects hospital discharge data. We will then develop a technical report explaining the processes of building TRIP, including both a quantification of linkage failure rate and potential for selection biases and a qualitative guide to data governance discussions. We will also explore the governance steps necessary to submit a de-identified limited data set of the TRIP repository to an NIH data repository. Next, we will conduct several data science-driven analyses. We will use the TRIP to identify crashes, then compute sensitivity and positive predictive value of the current NEMSIS case definition. We will use data science, including machine learning variable importance metrics, to identify elements that can improve NEMSIS crash case definitions. We will also use the same linked data and data science approaches to explore predictors of 30-day mortality to improve NEMSIS’s injury severity scoring algorithm. Finally, we will leverage outcome information from linked ED and vital statistics data to explore associations between time to care, transport time, care facility, and crash victim mortality. Specifically, carefully considering Washington’s trauma triage protocol, we will estimate the impact of EMS response time (scene response time, scene time, and transport time) and ED facility trauma designation status (trauma level I through V or non-trauma center), on 30-day post-crash mortality.

NSF Awards · FY 2025 · 2025-08

Weather forecasts are believed to be inherently limited by the growth of small errors present at the initial time, with all skill lost by about two weeks. This long-held belief derives from experiments with traditional models that represent the laws of physics for the atmosphere. Recently, forecast models based on machine learning (ML) have emerged with skill comparable to the physics-based models. Since the ML models do not solve to solve physical equations but only learn from data, they provide a new way to explore the limit of weather forecast skill. In this research, the two-week limit of forecast skill is tested by making small changes to the initial state using ML tools that reduce forecast errors far in the future. The main hypothesis is that the long-lead limit of weather forecast skill is much longer than currently believed, perhaps 3-4 weeks or longer. Current estimates of the limit of atmospheric predictability, absent influences from slowly-varying boundary conditions, is about two weeks. The relative contribution of nonlinear upscale error growth from the mesoscale relative to error growth within synoptic to planetary scales is unclear, in part because it is estimated from physics-based models which parameterize small-scale processes that strongly influence predictability. Machine learning (ML) enables a transformative new approach to predictability research that warrants reconsideration of the two-week limit. ML models have forecast skill comparable to physics-based models at a fraction of the computational cost, and they are built using tools that can take derivatives of all components of the forecast. These tools are used with a nonlinear gradient-descent approach to find initial conditions that minimize long-lead forecasts errors. Two models, GraphCast and NeuralGCM, and two reanalysis products, ERA5 and MERRA2, are used to test the hypothesis that the deterministic atmospheric predictability limit is greater than 3 weeks. A second hypothesis is that errors are dominated by synoptic and planetary scales rather than the smaller mesoscale. In that case skillful weather forecasts with lead times longer than two weeks could be achievable in practice. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-08

Project Summary for Equitable Primary Care for Pain Care (EquiP PC) Introduction: Based on data showing that 25% of the U.S. population suffers from chronic pain (CP) and that ~1/2 the CP population seek relief in primary care (PC), there is consensus that multidisciplinary coordinated care within PC is critical for treating CP. Integrating behavioral health (IBH) within PC has been shown to improve patient outcomes for mental and chronic physical health conditions but has not been applied to CP management. With PCORI funding, we have developed and tested an IBH Primary Care (IBH-PC) toolkit, which provides a multi-faceted implementation strategy to improve IBH. Given use of the IBH-PC Toolkit has demonstrated improved behavioral health integration, we propose to adapt this toolkit to improve equitable access to CP care, train BHPs in CP care, and augment it with implementation of digital therapeutic app tools for home use, to improve quality of care and ensure sustainability. Approach: We will conduct a large multi-site pragmatic 3-arm cluster randomized control trial comparing the IBH-PC toolkit + apps vs. IBC-PC toolkit only vs. treatment as usual, and use the PRISM RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework to evaluate implementation outcomes. To address Reach, we will recruit 2,025 patients with CP and randomize PC practices from partnered practice based research networks and healthcare system (HCS) partners that treat underserved communities including BIPOC (Black, Indigenous and people of color), Hispanic, and people with low socioeconomic status (SES). In the UG3 phase, we will convene a Community Advisory Board (CAB) to develop the infrastructure to ensure UH3 RCT success: AIM 1: Finalize outcome measures, practice and patient recruitment process, and establish a centralized data coordinating infrastructure. We will incorporate the HEAL Common Data Elements and develop a strategy for participation in the NIH Pragmatic Trials Collaboratory Resource Coordinating Center working groups.. AIM 2: Recruit 27 PC practices and create a Community Advisory Board (CAB) from the practices. The CAB will be comprised of patients, primary care providers, BHPs, HCS administrators, and practice facilitation experts. AIM 3: Refine the IBH-PC Toolkit for CP care, choose DTx apps for homecare use, and adapt the BHP training materials. In the UH3 phase, we will execute a 3-arm cluster-randomized pragmatic randomized control trial across 27 PC clinics: AIM 1: To determine effectiveness of the adapted (1) IBH-PC Toolkit + apps vs. (2) IBC-PC Toolkit only vs. (3) treatment as usual for improving pain interference and level of integration of IBH. AIM 2: Evaluate Implementation of the interventions: IBH-PC Toolkit + apps and IBH Toolkit only. AIM 3: Evaluate equity in access and outcomes of CP care in PC. This proposal is innovative as it equitably expands access within existing PC practices through IBH multidisciplinary coordinated care teams, integrates evidence-based apps and is expected to have a positive impact on transforming PC to equitably treat over half of all patients suffering from CP.

NIH Research Projects · FY 2025 · 2025-08

ABSTRACT The spirochete Treponema pallidum subspecies pallidum (TP) causes syphilis, a multi-stage sexually transmitted infection. Cases of TP are rapidly increasing in high income countries and remain persistently high worldwide, with a total of 8 million incident cases globally each year. TP can disseminate to nearly any tissue, leading to significant morbidity in advanced stages of disease, and can be vertically transmitted, causing congenital syphilis. Despite its protean manifestations, TP has a minimalist genome with limited genetic diversity and accumulates single nucleotide changes slowly. In contrast, TP readily undergoes inter-strain or intra-chromosomal homologous recombination (HR) to generate novel variants. For example, intra- chromosomal HR between 53 defined donor sites and seven extracellular loops of the Treponema pallidum repeat protein K (TprK) generates novel epitopes and underlies immune escape. Additionally, we recently examined samples from a patient with uncontrolled HIV and co-infected with two strains of TP, with HR observed between the strains in a penicillin-binding protein and a fatty acid transporter, with unknown fitness effects. In spite of considerable evidence that TP uses genetic recombination as a survival strategy, little is known about mechanisms of HR in TP. Building on our published and unpublished findings, here we will identify the TP genes involved in HR and the response to DNA damage and examine TP genomic changes following the induction of recombination. This will be achieved via two complementary Specific Aims: In Aim 1, we will induce DNA damage and HR directly by treatment with genotoxic agents or indirectly with sublethal penicillin treatment. Then, we will examine longitudinal transcriptional responses to identify gene networks, such as homologs of the SOS Response pathway, involved in HR. We will also identify putative transcription factor binding sites among differentially expressed TP genes. In Aim 2, we will use whole genome sequencing and targeted amplicon long-read sequencing to observe the genomic alterations caused by HR between Nichols and SS14 strains during longitudinal co-infection in vitro and in vivo (Aim 2.1) and between TP and HR donor plasmids following DNA damage or sublethal penicillin treatment (Aim 2.2). We will determine the TP genes that undergo HR most frequently when supplied with donor template, focusing particularly on penicillin binding proteins and extracellular loops of outer membrane proteins being considered for inclusion in an eventual syphilis vaccine. This proposal makes use of simple and elegant experiments using our established protocols for in vitro culture, rabbit infection, TP RNAseq, and whole genome and long-read amplicon sequencing. Insights gained from these experiments will have implications for antibiotic stewardship and help inform selection of antigens for syphilis vaccine development. Together, these studies provide crucial insight into a previously unexplored mechanism of TP pathogenesis.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY Generating cells with different fates, functions and behaviors is critically important for the development and maintenance of tissues, organs, and multicellular organisms. Cellular diversity can be generated through Asymmetric Cell Division (ACD), a process used by stem cells to create differentiating sibling cells while self- renewing the stem cell in the process. Such binary cell fate decisions could be induced through asymmetric partitioning of RNA molecules, but only a few cell fate determining RNAs have been isolated so far and very little is known about the mechanisms through which they function. Here, I propose to use asymmetrically dividing Drosophila neuroblasts, the neural stem cells of the developing fly central nervous system, to identify and characterize asymmetrically segregating RNAs in vivo. Previous studies identified a few RNAs with polarized localization in neuroblasts but their function is mostly unknown. We will use an unbiased and innovative in situ biotinylation approach to identify RNAs that localize and segregate in a highly polarized fashion in fly neural stem cells. Such sequencing-based proximity-labeling methods have not been used in whole organisms so far but will provide us with a ‘parts-list’ of potential new cell fate determinants. We will validate the most promising candidates with follow-up approaches such as Fluorescent In-situ Hybridization (FISH) and traditional fly genetics. We will also implement live cell imaging approaches to characterize and quantify the localization dynamics of identified RNAs. Live cell imaging will allow us to determine whether and how RNAs segregate asymmetrically, and whether RNAs will be locally translated. Methods to visualize RNA localization dynamics will be combined with nanobody and optogenetic approaches to perturb the segregation of RNAs with high spatiotemporal precision, thereby testing the requirement of biased RNA localization and segregation. This research program will benefit from several novel and innovative tools, consisting of in situ biotinylation, live cell imaging, RNA sequencing and acute RNA mislocalization and perturbation systems (nanobody, optogenetics). Polarized localization and biased segregation of RNA species occurs in different cell types and in diverse developmental contexts. Thus, we anticipate that this project will reveal new principles underlying cell polarization and asymmetric cell division, which may be universal to other animals and humans. ACD is an evolutionary conserved mechanism, and the proposed research program is medically significant because defects in ACD can cause neurodevelopmental disorders or cancer.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY/ABSTRACT Vector mosquitoes, such as Aedes aegypti, drink human blood to nourish their developing eggs, transmitting devastating human diseases that result in over half a million annual deaths in the process. A comprehensive understanding of the cellular and molecular mechanisms that underlie mosquito blood-feeding behaviors is critical for identifying new strategies to control mosquito populations and mitigate disease transmission. To drink blood, a mosquito inserts a flexible needle-like structure called the labrum into the host’s skin to probe for blood vessels. Although it is clear that different groups of sensory neurons in the tip of the labrum respond to phagostimulant compounds like ATP and other blood components, the molecular receptors mosquitoes use to detect blood are unknown. The sensory processing and behavioral impact of individual classes of labral sensory neurons are also unclear. Gene editing technologies like CRIPSR/Cas9 are powerful tools for probing gene function. However, these techniques remain time consuming and laborious to implement in non-standard genetic model systems, making it a high-risk endeavor to study neofunctionalized or potentially species- specific genes involved in blood detection and other specialized mosquito abilities and behaviors. This project seeks to combine emerging technologies for single-nuclei RNA sequencing with my recently-developed high- throughput genetic analysis approaches to perform a deep mechanistic analysis of the mosquito blood- detection system. We will characterize the diversity of sensory neurons present in the labrum, gaining genetic access to each cell type in order to characterize the anatomical location, functional sensitivity, and behavioral impact of each class. Our high-resolution transcriptomics data will be merged with our new higher-throughput screening approaches to facilitate rapid, unbiased testing of candidate molecular receptors that control blood feeding. Though the gustatory system represents one of the most poorly understood mosquito sensory systems, cutting-edge techniques and recent discoveries in mosquitoes have set the stage for a research program on contact chemosensation that is exciting and feasible. This project is poised to open the labral chemosensory system to molecular study and transform it into an accessible model of mosquito taste. This award will be the first to fully map the inputs to the neural circuits for blood feeding in Ae. aegypti while examining the functional significance of each cell type and their underlying molecular mechanisms. Finally, the approach developed here will provide a blueprint and genetic tools that can be readily ported to facilitate future molecular discovery efforts aimed at addressing other pressing questions in mosquito biology.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY/ABSTRACT Background: Tuberculosis (TB) remains one of the leading infectious causes of death globally, yet an estimated 3-4 million people who develop TB are not diagnosed each year. This case-detection gap critically impedes global efforts to end the TB epidemic. Identification of individuals with suspected TB through active case finding (ACF) and linking them to care can help to achieve earlier diagnosis and treatment and prevent onward transmission. ACF aims to diagnose TB by screening people in the community and among persons at risk as opposed to passive case finding which requires affected individuals with symptoms to seek care at health facilities and then be evaluated for TB. Project: In this study, we will use spatial approaches to optimize active case finding strategies, through three research aims: (1) employ multiple sources of human mobility and activity space data, collected via a combination of surveys, individual geo-tracking, and aggregated cell phone locations to pinpoint precise geographic locations within Nairobi, Kenya, with the highest potential yield for TB screening; (2) develop a geospatial statistical model to estimate neighborhood-level local TB burden in Nairobi utilizing serial TB prevalence survey data alongside case notifications and spatial covariates; and (3) produce an individual-based TB transmission model to simulate the impact of spatially-targeted ACF strategies in Nairobi. Candidate: I am an infectious diseases physician-scientist and epidemiologist with a background in global health policy, TB and HIV epidemiology, and geospatial analysis as well as experience conducting research in South Africa, Uganda, and Kenya. My long-term career goal is to become an independent investigator working to develop data-driven, targeted public health strategies for controlling the TB and HIV epidemics in high-burden settings. Career development plan: I am pursuing a K01 Career Development Award to establish my research niche at the intersection of geospatial analysis, human mobility, and infectious diseases epidemiology, with specific applications to TB and HIV. I seek advanced training and further research mentorship to develop additional skills in (i) geospatial modeling, (ii) agent-based modeling, (iii) human mobility data, and (iv) responsible conduct of research in international settings. Mentors and Environment: Dr. Jennifer Ross, an expert in infectious disease epidemiology and geospatial modeling, will oversee my overall career development and serve as my primary mentor. Co-mentors are Dr. David Horne, an expert on TB aerobiology and transmission; Dr. Videlis Nduba, senior scientist at the Kenya Medical Research Institute (KEMRI); and Dr. Abraham Flaxman, lead modeler at the Institute for Health Metrics and Evaluation (IHME). Scientific advisers consist of Dr. Thomas Hawn (TB immunology), Dr. Jane Ong’ang’o (population-based surveys in Kenya), and Dr. Adrian Dobra (data science & mobility data). This study will build upon an ongoing collaboration between the University of Washington and KEMRI Centre for Respiratory Diseases Research.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY Chronic pain affects over 20% of the U.S. adult population and frequently has debilitating effects on quality of life and physical and mental functioning. Individuals living in rural communities experience higher rates of chronic pain as well as poorer health outcomes because of pain. The 46 million Americans who live in rural areas frequently lack access to evidence-based, non-pharmacologic treatments for chronic pain. As such, a critical need exists to implement effective, comprehensive programs for pain management that include non- pharmacologic treatment options. Nurse care management (NCM) has been successfully used to enhance care for individuals with other chronic conditions or at high risk of complications. Using a type 2 hybrid effectiveness-implementation design, we propose to adapt, pilot, and implement a NCM model that includes care coordination, cognitive behavioral therapy (CBT), and referrals to a remotely delivered exercise program for rural patients with chronic pain. Each health system will identify appropriate health care professionals to be trained as care managers. For the CBT component, care managers will be trained to engage patients in a remotely delivered CBT program. For exercise, we will offer remotely delivered Enhance Fitness, which is an evidence-based, 16-week program that includes aerobic and strength training exercise. In the UG3 phase, we will engage patients, clinicians, and care managers from 2 health systems serving rural patients in a learning collaborative to pilot the NCM model. In addition, we will adapt infrastructure and workflows to implement the intervention program and engage the partnering health systems in developing relationships with community partners and identifying care managers. In the UH3 phase, we will conduct a randomized controlled trial of the adapted NCM model versus usual care in rural dwelling patients with chronic pain. We have recruited 6 health systems from 2 practice-based research networks, the WWAMI (Washington, Wyoming, Alaska, Montana, and Idaho) region Practice and Research Network and the Mecklenburg Area Partnership for Primary Care Research in rural North Carolina. Our primary outcome is pain interference as measured by the Pain, Enjoyment of Life and General Activity (PEG) scale. Our secondary outcomes include physical function, sleep, pain catastrophizing, depression, anxiety, treatment satisfaction, substance use disorder, pain medication use/dosage including opioids, and health care utilization. We will explore if disparities exist by examining heterogeneity in treatment effects via subgroup analyses by age, gender, race/ethnicity, and health insurance. We will use the RE-AIM framework to assess implementation outcomes and qualitative interviews conducted with a subset of patients to evaluate experiences with the intervention. If successful, this study will have a transformative effect on chronic pain management in rural areas by expanding access to evidence-based, non-pharmacologic treatments through an innovative NCM model.

NIH Research Projects · FY 2026 · 2025-08

SUMMARY/ABSTRACT Exposures to pollen and other ambient aeroallergens are well-established drivers of allergic rhinitis and asthma, but their role in Chronic Obstructive Pulmonary Disease (COPD) is largely unknown. A lack of aeroallergen monitoring data has contributed to limited research in this area, despite expanding aeroallergen levels associated with climate change. Monitoring technology for aeroallergens is advancing rapidly based on image analysis using artificial intelligence (AI), providing an opportunity to measure aeroallergen concentrations in near-real time and at multiple-locations. Our overall objective is to determine the impact of short- and long-term aeroallergen exposure on COPD outcomes and to ascertain whether allergic phenotypes among those with COPD—including blood eosinophil count, aeroallergen sensitization, sputum characteristics and airway transcriptomics—alter susceptibility to adverse health effects of aeroallergens. We leverage the SPIROMICS and SOURCE cohorts that comprise uniquely phenotyped, prospectively characterized participants with COPD or at high risk for developing COPD. We will develop taxa-specific estimates of daily and seasonal aeroallergen concentrations at individual home addresses using existing data from the nearest National Allergy Bureau (NAB) aeroallergen counting station (between-city measures) and sophisticated fine- scale, spatiotemporal models of aeroallergen concentrations (within-city measures) using advanced geospatial exposure models that incorporate not only the historical NAB monitoring data but also high resolution monitoring data from new aeroallergen monitors with AI-based image analysis. We will assess whether both short- and long-term ambient aeroallergen exposures are associated with respiratory symptoms, frequency and timing of exacerbations, lung function decline by spirometry, CT-based quantitative emphysema and small airway abnormalities, and disease prognosis in the well-characterized SPIROMICS and SOURCE participants. These results will provide historic and real-time pollen counts to inform risk communication, develop personalized treatment approaches and exposure mitigation strategies for patients with COPD, and forecast new risks due to the changing environment.

NIH Research Projects · FY 2026 · 2025-08

PROJECT SUMMARY ABSTRACT The genetic basis of obesity is well documented through classical twin studies and modern sequencing methods that generate genome-wide polygenic risk scores. The strong influences of socioeconomic, environmental, and health-behavior risk factors for obesity have also been identified. However, neither genetic nor environmental factors alone can explain the rapid rise in obesity prevalence over the past forty years. It is likely that the underlying biological drivers of the obesity epidemic lie at the intersection of genetics and the modern environment. The overall goals of the proposed research are to fill gaps in our understanding of the neurobiological underpinnings of genetic risk factors for common obesity, and to probe mechanisms whereby genetic factors may magnify the risk of environmental exposures through effects on the brain. Specifically, rodent models indicate that dietary exposures cause cellular inflammation – known as gliosis – in the mediobasal hypothalamus, which contains the arcuate nucleus, leading to dysfunction of local neurons that regulate body weight, increases in adiposity, and obesity. The cumulative literature from translational studies supports a role for hypothalamic inflammation and gliosis in the pathogenesis of obesity in humans. However, genetic susceptibilities that modify the extent to which obesogenic diets stimulate hypothalamic inflammation and gliosis remain largely uninvestigated. It is also possible that potent environmental stimuli promote hypothalamic gliosis regardless of genetic makeup which could have broad implications for population health. The proposed research therefore uses epidemiologic and twin study approaches to 1) test genetic risk factors for hypothalamic gliosis and 2) test environmental risk factors for obesity and hypothalamic gliosis and determine, through twin study methods, if environmental factors act independently of genetic background to promote obesity and/or hypothalamic gliosis. The proposed studies will utilize genetically informative samples from the Framingham Heart Study, the Adolescent Brain Cognitive Development Study, a brain tissue repository, and the Washington State Twin Registry. Hypothalamic gliosis will be measured both in vivo using magnetic resonance imaging and post-mortem using histopathology performed on hypothalamic tissue. Genotype-phenotype association study designs include both candidate gene and genome-wide approaches. Twin studies are used to disambiguate inherited, environmental, and health behavior risk factors for obesity and hypothalamic gliosis. In sum, the proposed research could significantly impact the field by uncovering molecular and neurobiological pathways involved in obesity pathogenesis, advancing our understanding of the influence of genetic factors on hypothalamic inflammation and gliosis, and opening avenues for novel mechanistic studies or precision health interventions.

NSF Awards · FY 2025 · 2025-08

The UW Bothell Engineering and Technology Scholars project will contribute to the national need for well-educated scientists, mathematicians, engineers, and technicians by supporting the retention and graduation of high-achieving, low-income students with demonstrated financial need at the University of Washington Bothell. UW Bothell is a Minority Serving Institution, and its student body is one of the most diverse in the state where 38% of incoming first-year students are first generation and 28% are eligible for federal Pell Grants. Over its six-year duration, this Track 2 S-STEM project will fund scholarships to 60 unique full-time students who are pursuing bachelor's degrees in Engineering and Technology (E&T), including computer and software systems, computer engineering, mechanical engineering, electrical engineering, data visualization, mathematics, and physics. Project activities include dedicated math and science courses and cohort-based programming that provides academic success workshops, networking and career development opportunities, and faculty mentoring. Faculty mentors will learn about proven best practices and support each other through a faculty learning community. This project investigates which of several evidence-based strategies are the most effective in supporting and training low-income students specifically interested in E&T degrees through their journey from first year through graduation. In addition to measuring traditional elements of student success such as pass, persistence, and graduation rates, the project tracks students' sense of purpose, academic and social belonging, career readiness, and overall well-being. Faculty will deepen their understanding of the complex student experiences and use this knowledge to help address institutional barriers for all students entering UW Bothell in the post-pandemic era. The overall goal of this project is to increase STEM degree completion of academically talented, low-income undergraduates with demonstrated financial need. This project seeks to increase the percentage of students who complete an E&T major by providing coaching, dedicated academic support, and re-designed prerequisite courses; increase the number of students obtaining an E&T major by providing faculty mentoring, networking, and career development opportunities that promote a sense of belonging and a sense of purpose; and enhance faculty and staff ability to best support student populations by creating an ongoing faculty learning community. Currently, only 30% of incoming students who want to pursue E&T degrees graduate with an E&T degree, and the diversity of the incoming class is starkly different from the graduating class. National and institutional research indicates that the loss of UW Bothell students in E&T fields can be attributed to four primary barriers: financial burdens, early academic struggles, a lack of sense of belonging and purpose, and complex institutional systems. Research has shown that providing financial support, academic support through dedicated coursework and academic seminars, mentoring, cohort experiences, and/or career development opportunities can help bridge these barriers. The project will provide additional support to faculty mentors to help students overcome these barriers and provide faculty opportunities to learn about and address institutional barriers. Most research studies only examine one or two of these components. This project seeks to understand which combination of programing, academic support, pedagogical approaches, and faculty mentoring have the greatest impact for low-income students by implementing an extensive assessment plan. The assessment plan utilizes both formative and summative evaluation methods that include student and faculty mentor surveys, student focus groups, and monitoring of institutional data to explore our research questions: (1) How are academic supports affecting students' academic skills and metrics of success? (2) How are mentorship and professional development activities affecting students' sense of belonging, purpose, and commitment to pursuing a STEM degree? (3) What is the relative importance of various program elements for retaining students in STEM? (4) How is the faculty mentor learning community affecting faculty perceptions of student experience and assets? (5) To what extent is the program providing responsive program supports and how can the program supports be improved? Results of the project will be published in journal articles and presented at conferences. Project information will also be available on a public website. This project is funded by NSF's Scholarships in Science, Technology, Engineering, and Mathematics program, which seeks to increase the number of low-income academically talented students with demonstrated financial need who earn degrees in STEM fields. It also aims to improve the education of future STEM workers, and to generate knowledge about academic success, retention, transfer, graduation, and academic/career pathways of low-income students. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-08

With support from the Chemical Structure and Dynamics (CSD) program in the Division of Chemistry, Professor Anne B. McCoy of the University of Washington is developing versatile computational approaches to gain new insights into proton transport in aqueous environments, and more specifically solvation of hydroxide and hydronium ions in complexes with water molecules. The origins of the similar frequencies of the ionic hydrogen bonds in complexes of hydronium and hydroxide ions with water molecules as well as spectral signatures of proton migration in these complexes remain poorly understood. Despite considerable work in studying the solvation of hydronium ions, much less is known about the interactions between hydroxide ions and water. In this work, Professor McCoy and her students will develop potential surfaces that will enable these studies. They will also develop strategies for evaluating energies and wave functions for vibrationally excited OH stretching states of these ions. Their studies could lead to the development of general models to provide insights into the coupling of high and low frequency vibrations in protonated water clusters, obtain the vibrational spectrum of polycyclic aromatic hydrocarbon molecules, and study rotation-vibration coupling in molecules that undergo large amplitude vibrational motions. Through this work, students working with Dr. McCoy and her collaborators will gain valuable experience in computation science and in coding more broadly, and modules based on this work will be developed for use by other researchers and for classroom instruction. Dr. McCoy also seeks out opportunities to provide venues to showcase the work of early-career scientists. The supported work focuses on the development of theoretical and computational tools for studying couplings among molecular vibrations and how they are manifested in vibrational spectra. The two primary approaches that will be employed are vibrational perturbation theory and diffusion Monte Carlo approaches. The diffusion Monte Carlo work will focus on developing potential energy surfaces for complexes of hydroxide ions with water, with the goal of understanding the similarity of the spectra for size selected water clusters containing a hydroxide or hydronium ion, and the insights into proton transport in aqueous systems that can be gleaned from these spectra. The work on perturbation theory will focus on systems, where couplings among the vibrations have a significant impact on the spectra. This work will focus both on how to identify the most important couplings and the development of general models that can be applied to broader classes of molecular systems. The tools that are developed will be incorporated into the PyVibDMC and PyVibPTn program packages that have been developed by Dr. McCoy and her students. In addition, they will continue to develop tutorials for students who wish to learn more about computational studies involving molecular vibrations. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-08

ABSTRACT CAR-T cell therapy has revolutionized the treatment of hematological cancers but has yet to achieve durable efficacy in more common solid tumors, such as non-small cell lung cancer (NSCLC). In a phase I trial evaluating CAR-Ts targeting the tumor-associated antigen ROR1, we observed limited efficacy due to CAR-T exhaustion and heterogeneous ROR1 expression on tumors, which led to the escape of antigenlow/null tumors even in transient responders. To address these challenges, we developed an autochthonous model of ROR1+ NSCLC (KPROR1), which recapitulates the suppressive tumor microenvironment (TME), heterogeneous ROR1 expression, and CAR-T exhaustion observed in patients. We found that enhancing T cell function by overexpressing the AP-1 transcription factor c-Jun improved response to PD-L1 blockade but failed to prevent escape of ROR1low/null tumors, emphasizing the need for strategies that both preserve CAR-T function and control escape of antigenlow/null tumors. To enhance CAR-T sensitivity, we engineered chimeric TCRs (ChTCRs), which fuse a CAR single-chain variable fragment (scFv) to a TCR constant chain. ChTCRs show superior sensitivity to antigenlow tumors and outperform CAR-Ts in vivo in models of B cell malignancies. Moreover, bi-specific ChTCRs targeting two antigens outperform optimized bi-specific CAR-Ts, suggesting they may be more effective than CAR-Ts at controlling heterogeneous solid tumors. However, while ChTCRs do not require synthetic costimulation for efficacy in B cell malignancies, their activity in solid tumors may be limited by insufficient co-stimulation in the suppressive TME. To overcome this barrier, we designed novel co-stimulatory receptors that convert inhibitory PVR-TIGIT signals into activating signals and enhance ChTCR-T function in vitro. Since co-stimulation partially relies on AP-1 activation, overexpression of c-Jun could further amplify the favorable effects of co-stimulation. I hypothesize that ChTCR-Ts will be more sensitive to ROR1low tumors in vivo than CAR-Ts, and that co-expression of co-stimulatory receptors targeting the PVR/TIGIT axis will synergize with c-Jun overexpression to enhance ChTCR-T activity, enabling more effective control of tumors with heterogeneous ROR1 expression. In this proposal, I will: 1) assess ChTCR-T activity against ROR1low tumors in the KPROR1 model relative to CAR-Ts and identify barriers to efficacy, and 2) determine whether the co-stimulatory receptors I designed synergize with c-Jun to enhance ChTCR-T function and response to PD-L1 blockade. These studies will reveal the barriers to ChTCR-T efficacy in vivo and potentially identify strategies to control escape of heterogeneous lung tumors. Through this fellowship, I will gain expertise in tumor immunology, computational biology, and preclinical mouse models, equipping me to advance immunotherapies by integrating fundamental research with clinical practice.

NIH Research Projects · FY 2025 · 2025-08

ABSTRACT Effectiveness of pre-exposure prophylaxis (PrEP) for HIV prevention methods currently available to cisgender women hinges on daily medication adherence, yet >50% of women discontinue within the first month of use. Digital technologies to improve adherence to HIV treatment and prevention interventions are rapidly expanding in the WHO African Region, despite mixed effectiveness findings. Systematic reviews note the near absence of articulated mechanisms of action (MoA) for HIV digital health strategies which limits translation into practice and thus population-level impact. Tools from behavioral health research and implementation science are useful to elucidate, articulate, and test MoA for digital strategies. There is substantial pragmatic value in understanding MoAs and moderators for how digital strategies work, including adapting intervention message content balance to emphasize the most potent mechanisms and tailoring content to specific populations. We propose an R21 to utilize data from the mWACh PrEP study (R01NR019220), a hybrid effectiveness-implementation trial that tests the impact of a two-way, interactive, SMS-based platform on PrEP adherence and maintenance (continuing PrEP refills and use) during pregnancy and postpartum in Kenya. The parent study includes 5 study sites based at public sector antenatal clinics in a setting with high HIV prevalence. To date N=600 (100% of planned enrollment) women are enrolled (1:1 randomization) to be followed until 9 months postpartum. The trial utilizes the Information-Motivation-Behavior (IMB) model, which specifies 1) knowledge acquisition, 2) motivation, and 3) behavioral skills as potential MoA. Within this R21, we propose to test hypothesized MoA for the mWACh PrEP digital strategy, assess specific context variables as moderators, and characterize experiences of MoA activation. In Aim 1, we will test whether knowledge acquisition, motivation, and behavior skills are MoA through which mWACh PrEP influences PrEP adherence and maintenance. We will consider both self-reported adherence, hair concentrations of PrEP, and PrEP continuation. We will employ deductive analysis using structural equation modeling and inductive analysis using coincidence analysis. In Aim 2, we will elucidate whether MoA are moderated by mental health, relationship climate, sexual behavior, access to care, and medical history, using structural equation modeling. Finally, in Aim 3, we will characterize how and why MoA are activated by assessing the experiences of women, SMS content, and health provider insights. We will conduct in-depth interviews with women, analyze two-way messages between women and providers, and engage facility and study staff through a workshop to understand activation of MoA. Our study is designed to move the field from theoretical to empirical knowledge of how and why women maintain and sustain PrEP use behaviors. Our findings will have pragmatic utility beyond HIV prevention in pregnancy for adapting digital message content to emphasize potent mechanisms and tailor message content to diverse populations.

NSF Awards · FY 2025 · 2025-08

The University of Washington (UW) requests funds for oceanographic instrumentation that are needed to carry out NSF-supported scientific research on board the R/V Thomas G. Thompson and R/V Rachel Carson, two vessels operating as part of the U.S. Academic Research Fleet (ARF). The specific suite of instrumentation requested includes upgraded computer workstations for the R/V Thompson and R/V Carson’s mapping systems; and an upgraded broadband transducer to replace an aging and decaying system aboard R/V Carson. These instruments will help ensure the vessels maintains their high-level capabilities to support NSF-funded research. The principal impact of the present proposal is under Merit Review Criterion 2 of the Proposal Guidelines (NSF 23-525). It provides infrastructure support for scientists to use the vessel and its shared-use instrumentation in support of their NSF-funded oceanographic research projects (which individually undergo separate review by the relevant research program of NSF). The acquisition, maintenance, and operation of shared-use instrumentation allows NSF-funded researchers from any US university or other organization access to well-maintained, high-quality, calibrated instruments for their research. It ensures the collection of high-quality oceanographic data in support of science, reduces the cost of that research, and expands the base of potential researchers. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-08

Project Summary/Abstract Periodontitis is one of the most chronic oral inflammatory disease in humans and affects more than 10% of the global population, while gingivitis is estimated to affect more than 46% of all adults aged 30 years or older in the United States alone1, 2. While advances in periodontal research over the past 50 years in both humans and animal models has vastly improved our understanding of the etiology and pathophysiology across the spectrum of this disease3-11, most studies have focused on investigating the severe, chronic, and irreversible form of periodontal disease, periodontitis, often in comparison to other healthy individuals. Critical knowledge gaps remain in our understanding of how inflammation is triggered and maintained during the reversible, intermediary, and most prevalent form of periodontal disease – gingivitis1, 2, 12, 13, and importantly what cell types, functions, and signaling is disrupted leading to further chronic inflammation progression and ultimately periodontitis. To date, several single cell transcriptome (scRNA-seq) studies aimed at resolving active cell types within gingival tissues in health and disease (experimental gingivitis, periodontitis) have been published. However, at the time of this application, no scRNA-seq studies characterizing gingivitis have been published or made available to the broader scientific community – representing a significant knowledge gap. Furthermore, no existing scRNA-seq datasets have aimed to resolve the relationship of active periodontal disease associated bacteria within subgingival plaque to observed active cell expression in adjacent gingival tissues. In this study we seek to employ recent advances in scRNA-seq14 to increase cell recovery and capture underrepresented cell types in current periodontal scRNA-seq datasets (gingivitis and periodontitis), while robustly characterizing the dental plaque microbiota and target chemokines/cytokines in GCF in parallel. This will uniquely allow us to resolve key differential signaling pathways between healthy sites and gingivitis and between gingivitis and periodontitis. In particular, the activity of key cell types (neutrophils, macrophage, mast, natural killer, conventional dendritic, and various T-cells) involved in the activation of enzymatic degradation of periodontal tissues and osteoclast differentiation effecting alveolar bone resorption during periodontitis. Overall, a major thrust of NIH/NIDCR in general is to provide single cell resolution of active inflammatory cell types across tissues. The success of this project and deposition of resulting data will significantly contribute to existing public resources15, 16 and greatly expand current knowledge. Resolving transcriptionally active cell types within gingival tissues, soluble host immunomodulatory signals, and the active bacteria within sites of active inflammation compared to distant clinically healthy tooth sites in the same individual may identify key signaling pathways and regulatory mechanisms for future therapeutic, diagnostic, and mechanistic studies that aim to maintain healthy homeostasis, resolve periodontal inflammation, and prevent periodontal disease progression.

NSF Awards · FY 2025 · 2025-08

Radiocarbon, a naturally-occurring but unstable isotope of carbon that decays away over time, is a powerful tracer supporting insights into the global carbon cycle. Radiocarbon is also an essential tool for independent dating of carbon-bearing biological and geological materials over the past 50,000 years. This isotope is produced by cosmic rays interacting with nitrogen in the atmosphere, and dissolves slowly into the ocean as carbon dioxide. As a result, the ocean is always depleted in radiocarbon relative to the contemporaneous atmosphere, meaning that organisms that grow in the ocean (such as corals, bivalves, zooplankton and phytoplankton) have a lower starting ratio of radio to stable carbon in their bodies. This makes organisms that create their bodies or shells from sea water appear 'old' relative to the ratio of radio to stable carbon expected for an organism exchanging carbon dioxide directly with the atmosphere (for example, a land animal or plant), limiting the precision with which we can interpret marine radiocarbon dates of environmental events. The correction would be simple if the offset of the radiocarbon content or 'reservoir age' of the ocean relative to the atmosphere was constant, however it varies through space and time in complex ways, largely associated with changes in ocean circulation. While researchers know these changes occur, they are constrained by limited data in only a few locations, and there is little consensus on the radiocarbon ventilation history of the Pacific Ocean, which comprises the largest reservoir of carbon actively exchanging with the atmosphere on the planet. To address this knowledge gap, investigators will reconstruct ocean ventilation variability from marine sediment cores in the Northeast Pacific that contain both marine microfossils and terrestrial organic debris during the past 23,000 years. This reconstruction will advance the understanding of the marine carbon cycle, as well as provide an improved tool for dating marine sedimentary records of environmental and geohazard variability. Broader impacts activities include training undergraduate students, a graduate student, and a postdoctoral researcher, redesigning an undergraduate and a graduate class around research themes using new, project-derived cores/samples, and producing training products (Navigating the Academic Research Fleet) for the University-National Oceanographic Laboratory System (UNOLS) to improve participation in seagoing research. This study will leverage sites on the Pacific Northwest margin with confirmed undisturbed sedimentary sequences and demonstrated preservation of coeval benthic and planktic marine foraminifera as well as terrestrial plant debris. Investigators will apply genomic sample identification techniques to confirm genus-level identification of fragmented vascular plant material that are well established in the field of molecular ecology – yet novel in the field of marine radiocarbon dating. The resulting reconstruction, pinned to the atmospheric radiocarbon calibration curve, will offer insights into reorganization of Pacific Ocean circulation and ventilation from the surface to a depth of 2,500 m (modern Pacific Deep Water) during several events of abrupt climate change through the Pleistocene-Holocene transition, allowing for the evaluation of hypotheses surrounding the phase relationship between climate variability in the Pacific and Atlantic. Research outcomes will increase understanding of the marine reservoir age effect in the Northeast Pacific, refining the utility of radiocarbon as a chronostratigraphic tool for applications ranging from understanding changes in regional paleohydrology during past warm periods to the recurrence intervals and rupture lengths of great earthquakes, supporting research themes identified as priorities in the National Academy of Sciences Engineering and Medicine 2015-2025 Decadal Survey of Ocean Sciences. Outcomes will form an essential component of cohort-based undergraduate research experiences, and data will be incorporated into the adaptation of an undergraduate and development of a graduate level course to meet inquiry-based learning objectives. Investigators will also develop an annual webinar series, “Navigating the Academic Research Fleet” to help lower barriers to participation in seagoing research on vessels within the Academic Research Fleet and effectively utilizing NSF/UNOLS Facilities. The webinar series will also address cruise planning tools, logistical best practices, and how to best access these resources. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-08

Polynomial equations are among the simplest types of mathematical expressions. Examples include x^2+y^2 = 0 and x-y=0. At a basic level, these equations involve only addition and multiplication. Despite their simplicity, they are ubiquitous across the sciences, appearing in fields ranging from computer science and physics to chemistry and biology. When one tries to solve these equations, one often finds not just one answer, but an infinite number of them. To make sense of this, mathematicians look at the shape formed by all the solutions together. These shapes are called an algebraic variety. Major conjectures in modern Algebraic Geometry suggest that all algebraic varieties can be built, at least roughly, from just three basic types: Fano varieties, Calabi-Yau varieties, and varieties of general type. This project will describe how these three building blocks fit together. The project also includes research training opportunities for students. In more detail, the PI will (1) construct and investigate specific moduli spaces of fibered varieties, (2) explore the birational geometry of algebraic stacks, and (3) study both the local and global geometry of certain moduli spaces of varieties of general type and polarized Calabi-Yau varieties. Regarding (1), the PI will generalize existing frameworks for constructing moduli spaces of maps from families of curves to Deligne-Mumford stacks, and study specific examples of these moduli spaces. A key technique in this work involves the study of weighted blow-ups, a type of birational transformation for algebraic stacks that parallels classical blow-ups in the theory of projective varieties. Regarding (2), the PI plans to adapt and extend current methods in birational geometry to the more general setting of algebraic stacks. Finally, regarding (3), the PI will study the local and global geometric properties of moduli spaces of varieties of log-general type and Calabi-Yau varieties, contributing to a deeper understanding of their structure and classification. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY/ABSTRACT Sarah Holton, MD, PhD plans for a career as a physician-scientist in the fields of human immunology and fibrotic interstitial lung disease. Support from this K23 Career Development Award will provide necessary training in development of patient cohorts, statistical approaches, and methods for the analysis of single cell and spatial transcriptomic datasets. The training plan described will complement Dr. Holton’s basic science and engineering background and facilitate her transition to independent research. The proposal leverages Dr. Holton’s unique access to both the Benaroya Research Institute’s expertise in Immunology and Bioinformatics and the University of Washington’s expertise in lung biology and Interstitial Lung Disease as well as access to clinical samples and mentorship at both sites. The proposal focuses on the role of alveolar/interstitial macrophages and peripheral blood monocytes in the development of Progressive Pulmonary Fibrosis. These patients have limited therapeutic options that do not improve lifespan, and their 5 year survival is only 50%. It is critical to identify the mechanisms that lead to development of fibrosis in order to develop therapies targeted to intervene at early disease stages. We leverage our expertise in isolating and characterizing human alveolar macrophages and peripheral blood monocytes, an existing pulmonary diseases biorepository that contains paired alveolar, blood, and lung tissue samples, and recruiting a prospective cohort of patients from the UW Center for Interstitial Lung Disease. In this patient-oriented research plan, Dr. Holton will use these resources to address her hypothesis that CD163+ alveolar macrophages and peripheral blood monocytes are associated with the development of Progressive Pulmonary Fibrosis and have pro-fibrotic transcriptional programs. Dr. Holton will address these hypotheses through the following three aims: 1) Test for associations between CD163+ alveolar macrophages and progressive pulmonary fibrosis in patients with fibrotic ILD in existing samples using flow cytometry, 2) Establish the spatial and transcriptional relationship between CD163+ macrophages and regions of fibrosis in biopsy samples isolated from patients with early fibrotic ILD using spatial transcriptomics, and 3) Identify how the peripheral blood CD163+ monocyte population changes over time and how that is associated with PPF in a prospectively recruited cohort. Dr. Holton will also uncover the potential mechanism in which these cells contribute to fibrosis using in vitro models. The findings of these studies will have direct patient impact and will provide Dr. Holton with the infrastructure and skills necessary to submit an R01 proposal by Year 4 of her proposed K23 funding period. The research outlined in this proposal will serve as the foundation to growing a rich clinical biobank of samples from patients with ILD so that Dr. Holton can continue her research in defining the contribution of macrophage and other immune cell populations to fibrotic lung disease.

NIH Research Projects · FY 2025 · 2025-08

Project Summary/Abstract This K08 award will support the training and research experience needed for me to become an independent clinician investigator in the development and evaluation of interventions to address cancer screening inequities. I am an Assistant Professor of Medicine and primary care physician at the University of Washington. The training goals set forth in this proposal will allow me to achieve my career goals to 1) develop expertise in implementation science and health equity research, 2) lead research with communities to address inequities, and 3) develop and evaluate interventions to address inequities. I have convened a mentorship team with expertise in implementation science (Dr. Bryan Weiner), community-engaged research (Dr. Geetanjali Chander and Dr. Rachel Issaka), and the design and evaluation of novel interventions (Dr. James Ralston) to help me to achieve these goals. Breast cancer mortality is significantly higher and screening rates are significantly lower among Black women compared to White women. Patient portals offer multiple features such as online mammogram scheduling, screening reminders, and secure messaging that can help lower barriers to breast cancer screening (BCS); however, Black patients access the portal less often than White patients. Inequitable use in portals that may contribute to differential BCS rates is an example of an intervention-generated inequity. In this K08 proposal, we will design, implement, and test an intervention to promote portal use among Black women to address this intervention-generated inequity and to help lower barriers to BCS. The specific aims of the research are to 1) determine facilitators and barriers for portal use to facilitate BCS among Black women, 2) co-design an adaptive (multi-phase) intervention for portal access and uptake to facilitate BCS, and 3) pilot and evaluate the adaptive (multi-phase) intervention among Black women due for BCS and not engaged in portal use. The proposed work will inform an R01-level, multi-center randomized trial to test the intervention and help me to become an independent, NIH-funded investigator focused on developing pragmatic, community co-designed interventions to address cancer screening inequities.

NSF Awards · FY 2025 · 2025-08

With the support of the Chemical Synthesis (SYN) program in the Division of Chemistry, Professor Alexandra Velian of the University of Washington is studying the development of new catalytic platforms that mimic defect sites found in inorganic heterogeneous catalysts. This research could enable more efficient and selective chemical transformations of small, abundant molecules such as carbon dioxide, nitrogen, methane, and water into useful, value-added products. If successful, the work may contribute to addressing global environmental and energy challenges. The project will also incorporate broad-based educational and outreach initiatives aimed at engaging and retaining students in STEM fields. In addition, Professor Velian’s team plans to raise public awareness of catalysis and its societal benefits through outreach to both scientific and non-scientific communities. The research will focus on designing atomically precise transition metal chalcogenide clusters that contain well-defined catalytic sites embedded in molecular structures. These platforms will be used to emulate the active sites and cooperative interactions found in heterogeneous catalysts. This project will explore how structural and electronic communication between catalytic centers and their supports influences reactivity, selectivity, and efficiency. A key goal is to understand how metal–support interactions modify metal–substrate binding throughout catalytic cycles. The project will combine synthetic chemistry, spectroscopy, and computational modeling to guide the design of next-generation catalytic systems. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-08

Project Summary/Abstract Excess weight is the greatest modifiable risk factor for the development of obstructive sleep apnea (OSA). Successful weight management improves OSA severity and symptoms but is hard to achieve. Weight management pharmacotherapy and bariatric surgery are effective adjunctive strategies, but our analyses indicate they are rarely delivered. Delivery of these health services is particularly low among patients living in rural settings, who already face a greater comorbidity burden relative to urban peers. Glucagon-like Peptide-1 receptor agonists (GLP-1RAs) are recently FDA-approved medications that dramatically increase the rates of clinically meaningful weight loss, improve comorbidities, and reduce OSA severity. Due to their favorable toxicity profile and less intensive monitoring, GLP-1RAs are a scalable treatment that may help bridge the gap to rural areas. However, early evidence suggests GLP-1RAs are underutilized. We hypothesize that rurality will be independently associated with lower usage for GLP-1RAs for chronic weight management among patients with OSA and excess weight, while accounting for other patient-, provider-, and health system factors embedded in the Access to Care Model. Informed by domains of the Health Equity Implementation Framework, we also anticipate that patient and provider perspectives will identify multi-dimensional barriers to GLP-1RA access and delivery. The specific aims of this mixed methods proposal are to: 1a) Test the association of rurality with initiation of GLP-1 RAs among patients with OSA and excess weight; 1b) Test the association of rurality with discontinuation of GLP-1 RAs among patients with OSA and excess weight; and 2) Examine perspectives of patients, sleep specialists, and primary care providers to understand the barriers and facilitators to GLP-1RA use among rural patients with OSA and excess weight. These aims will be completed using a national cohort of patients with OSA and excess weight assembled from administrative data within the Veterans Health Administration (VHA). This proposal will identify intervenable barriers to weight management care among rural patients with OSA and excess weight in order to develop strategies to overcome these barriers. Dr. Leonhard will achieve his training aims of gaining expertise in advanced biostatistical and epidemiologic methods, qualitative research methodologies, and employing health equity frameworks through the completion of this project. He will be well supported in his training environment at the University of Washington and the Veterans Affairs Health Systems Research Center of Innovation for Veteran Centered and Value Driven Care. He will be mentored by a multidisciplinary team with a strong track record of collaborative mentorship and with extensive experience in quantitative and qualitative research, health systems research, and research to reduce disparities in the delivery of care. These resources will prepare Dr. Leonhard to become an independent health systems investigator whose work improves care delivery for patients with sleep and pulmonary disorders in ways that achieve patient-centered outcomes and reduce disparities.

NIH Research Projects · FY 2025 · 2025-08

Project Summary Many animals have specialized proprioceptors that fire when a limb reaches the limit of its range. In mammals, including humans, the extremes of joint position are detected by low-threshold Ruffini endings and Pacinian corpuscles embedded within joint capsules. Like other proprioceptors, joint receptors are distributed throughout the body, which has made it challenging to understand if and how they are specialized for sensing and controlling specific movements. This project will leverage tools only available in the fruit fly, Drosophila, to provide new insight into basic neural mechanisms of limb sensorimotor control by specialized proprioceptive organs called hair plates. Hair plates are tightly- packed arrays of sensory hairs positioned close to joints in the insect cuticle. Our preliminary data suggests that hair plate proprioceptors fire at the limits of the joint range, in a manner analogous to mammalian joint receptors. In this project, we will combine experimental and computational approaches to test the hypothesis that hair plates function as proprioceptive limit detectors to stabilize limb posture and guide movement. A deeper understanding of proprioceptive limit detection and its contributions to motor control has the potential to transform the way in which we understand and treat sensorimotor disorders.