University Of Washington

NSF Awards · FY 2025 · 2025-09

Stratospheric water vapor plays an important role in regulating Earth’s surface temperature and the concentration of stratospheric ozone, which protects life from harmful ultraviolet radiation. In the tropics, the coldest point in the atmosphere — the tropical cold point tropopause (CPT) — acts as a critical gateway that controls how much water vapor enters the stratosphere. Even small changes in CPT temperature can lead to significant impacts on climate, weather, and stratospheric ozone levels. This project aims to improve scientific understanding of the processes that shape the temperature of the CPT. Because changes in CPT temperature can influence tropical rainfall, cyclones, and convection, the results of this study are also relevant to understanding regional weather extremes. In addition, the project will support the Ph.D. research of two graduate students, providing valuable training for the next generation of atmospheric scientists. The goal of this project is to better understand the physical and dynamical processes that govern year-to-year changes in tropical CPT temperature. The investigators hypothesize that tropical CPT temperature responds to warming in the tropical troposphere through two competing mechanisms: radiative heating and dynamic cooling. These effects largely cancel out on interannual time scales, though not necessarily on seasonal or decadal scales. A second hypothesis addresses an unexplained relationship between tropical CPT and stratospheric temperatures, which may be related to the Brewer-Dobson Circulation (BDC), the deep overturning motion of the stratosphere. To test these hypotheses, the research team will analyze satellite observations, including high-vertical-resolution GPS radio occultation (GPS-RO) temperature data, modern atmospheric reanalyses, and simulations from chemistry-Earth System and radiative transfer models. This integrated approach will improve understanding of tropical CPT variability and help to resolve conflicting evidence in current Earth system research regarding its drivers. 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 · 2025-09

The overall goal of this project is to expand and enable the preclinical-to-clinical research pathway for  polycystic kidney disease (PKD) by generating products, services, and education focusing on human PKD organoids and related cellular systems, via a PKD In Vitro Center (PKD-InVent) dedicated to this area.  PKD is commonly inherited as a loss-of-function mutation in PC1 (polycystin-1) or PC2, which form a membrane complex. Thirty years after its discovery, the function of this complex remains enigmatic. A major roadblock has been the lack of assays that re-create PKD in vitro. Mice are highly complex, low-throughput, and non-human, whereas simple cells lack a PKD-specific phenotype.  Ten years ago, we reported a breakthrough - a human organoid model of PKD that expresses the pathognomonic phenotype of cyst formation. PKD1-/- and PKD2-/- organoids, derived from human stem cells, recapitulated the pathognomonic cystic phenotype in a PKD-specific manner. This revealed that PKD, previously believed to require factors found exclusively in vivo, is actually a cell intrinsic process.  PKD organoids have revealed surprising mechanisms, new candidate drugs, and public attention. We have helped other labs reproduce our discoveries, including current members of the PKD RRC. But the potential of organoids is not yet realized. The complexity and cost of organoid disease modeling remain significant barriers to entry, and there remain clear challenges for PKD organoids that require dedicated technology development. PKD-InVent will create a new center within the PKD RRC, drawing in new investigators and increasing innovation. It will make available the world’s largest collection of PKD and ciliopathy iPS cells, with protocols for organoid differentiation, phenotyping, and analysis. The experts in the field will devote time and effort to providing products, services, and training experiences, for which there is already strong demand. Focusing on organoids will bequeath this technology the attention it needs, and save the RRC time re-inventing the wheel. This will enable the technology to flourish and scale, so that it can reach its potential.  The University of Washington is extremely well-positioned to accomplish this vision. Our world-renowned team will connect the PKD RRC with other NIH Consortia, including an FDA partnership to qualify PKD organoids as clinically relevant biomarkers. Our team has a strong track record of providing high-quality reagents and data, expertise in PKD and cell biology, and knowledge of pain points. Our Center will equip and train the field for PKD organoid research, even as it further improves the technology to address unmet needs. We will accomplish this via four Specific Aims: (1) Create and organize an integrated Center for modeling PKD in vitro. (2) Maximize potential of existing organoid technology by equipping and educating the research community. (3) Expand and improve PKD in vitro models through multidisciplinary innovation.

NSF Awards · FY 2025 · 2025-09

To survive, animals must access food efficiently and, in some cases, they must fight for it. Adaptations that enhance food consumption or allow species to specialize on different resources—and therefore coexist—have been well-studied, improving our understanding of evolutionary and diversification processes. In comparison, there has been much less research regarding adaptations to defend food, especially in feeding structures. For instance, beak shape in birds has been linked to the demands of exploiting resources; hummingbirds, with their long, thin beaks suited for unique flowers, are a textbook example. Both across species, and even when comparing male to female beaks, the consensus is that the different beak shapes have evolved to better match the shapes of the flowers that the birds visit. Yet hummingbirds also fight over these resources, utilizing their beaks to stab or pluck feathers from opponents. This study investigates aggressive interactions (a previously underexplored evolutionary force shaping hummingbird beaks) and biomechanical performance in puncture, gripping, and fluid transfer, testing the hypothesis that beak shape is not only linked to matching flowers, but also determined by the use of beaks as weapons. In tandem, this project will foster new tools for public engagement and literacy in evolutionary topics of adaptive tradeoffs (e.g., a beak better fit for fighting might be worse at feeding), through a museum exhibit and development of curriculum for middle schoolers, centered around a game wherein students play as different hummingbirds and experience life with their adaptations. This research program provides lasting, transformative mentorship and interdisciplinary training to undergraduates, graduates, and postdoctoral professionals. Linking biomechanics to the ecological determinants of performance and species interactions is vital to grasp the processes shaping organismal evolution. This project challenges the status quo regarding bill-flower coevolution being the sole driver of hummingbird bill variation, to more fully consider the use of bills as weapons as a selective force shaping bill morphology and behavior. In opposition to the existing consensus that resource partitioning is the cause of dimorphism between male and female hummingbird bills, this study tests the hypothesis that differences in bill traits result from tradeoffs between nectar-feeding efficiency and performance in battles among males competing for territories and mates. This project leverages advances in high-speed videography, 3D reconstructions, geometric morphometrics, finite element modeling, and radio-based identification and tracking to assess multiple metrics of performance across organismal scales in both natural and laboratory settings. Finally, this research establishes a novel system to study the evolution of animal weaponry on feeding structures, with directly measurable tradeoffs, and constrained by extreme specialization. Detecting tradeoffs in hummingbird bill form and function will help reshape paradigms regarding hummingbird energetics, and guide research on other selective pressures involved in the evolution of these traits. Failing to detect tradeoffs would be equally compelling: if bill weaponization does not hinder nectar extraction, it would suggest alternative evolutionary workarounds and associated costs. This mechanistic approach to understanding the links between morphology, performance, behavior, and ecology, plus their evolutionary implications, will advance the emerging and interdisciplinary fields of ecophysics and mechanoethology. 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 · 2025-09

PROJECT SUMMARY/ABSTRACT Latino adults face a higher risk of Alzheimer’s disease and related dementias (ADRD) than non-Latino White adults. The number of cases is expected to rise sharply in the coming decades, with Latinos facing the largest increase among all racial and ethnic groups. This growth will intensify caregiving demands on Latino families, who already face challenges managing behavioral and psychological symptoms of dementia (BPSD) and often lack culturally appropriate professional support. STAR-C is an evidence-based behavioral intervention that equips caregivers with strategies for managing BPSD. It was originally delivered in-person by a coach but was later adapted to a virtual format with e-learning modules and phone check-ins with a coach. However, STAR-C was not developed with consideration of Latino cultural values, beliefs, and practices. As a result, the content lacks cultural and linguistic relevance for Latino caregivers. Latino caregivers’ engagement with the STAR-C virtual intervention also remains underexplored since prior testing included mostly non-Latino White participants. To enhance access for Latino caregivers, it is crucial to address cultural and linguistic relevance, time constraints, and the need for personalized support. Artificial intelligence (AI) offers a promising solution by providing culturally and linguistically tailored on-demand support. We propose to integrate an AI-driven virtual assistant with chatbot functionality into STAR-C. This virtual assistant will provide real-time support between coach check-ins and reminders to engage with e-learning modules that have been culturally adapted. This Stage I study has three specific aims. Aim 1 is to develop and integrate an AI-driven virtual assistant in the STAR-C intervention. We will follow our recent approach for creating a Large Language Model (LLM)-based chatbot. We will refine the model with input from STAR-C coaches, selecting the best-performing version. We will conduct usability testing with Latino caregivers to further optimize the virtual assistant based on their feedback. Aim 2 is to evaluate fidelity and caregiver acceptance of the AI-enhanced STAR-C intervention. Fifty Latino caregivers will participate in a 6-month intervention involving e-learning modules, phone check-ins with a human STAR-C coach, and on-demand support from the virtual assistant. The study will assess fidelity of intervention delivery and caregivers’ perceived usefulness, ease of use, behavioral intention, and actual use of the intervention. Aim 3 is to assess Latino caregivers’ attitudes toward using the AI-enhanced STAR-C intervention. Qualitative interviews with the 50 participants will assess their perceived benefits, challenges, and emotional responses to the AI-enhanced STAR-C intervention. These qualitative findings will be integrated with quantitative data from Aim 2 to provide a comprehensive understanding of Latino caregiver acceptability of the AI-enhanced and culturally adapted STAR-C intervention. The findings of this Stage I study will lay the groundwork for advancing along the NIH Stage Model to develop a scalable and effective intervention that improves health outcomes for Latino caregivers and their family members with ADRD.

NSF Awards · FY 2025 · 2025-09

How can we interpret results from complex machine learning algorithms? How can we mitigate the risks associated with using such models for policy decisions? This project addresses fundamental challenges in deriving valid, reliable, and interpretable causal conclusions from complex data using modern machine learning tools. As machine learning becomes increasingly integral to disciplines such as medicine, economics, education, and the social sciences, the demand for causal insight --- beyond predictive accuracy --- has become more pressing. Yet many machine learning algorithms function as “black boxes”, offering limited transparency and lacking rigorous frameworks for replicability and uncertainty quantification. This project aims to establish a theoretical foundation for causal learning that makes outputs from machine learning explainable, statistically sound, and actionable in real-world decision-making. The work is complemented by educational and outreach activities that promote understanding of causal reasoning among students and the broader public. Planned efforts include public lectures, collaborations with K–12 educators, and integration of research findings into university curricula. Collaborative partnerships with institutions such as Microsoft, Eli Lilly, and the Fred Hutchinson Cancer Center will help translate methodological advances into impactful scientific and societal applications. Technically, the project advances causal learning through three interrelated aims. (1) It develops methods for imputing unobserved counterfactual outcomes --- the hypothetical “what if” scenarios that form the core of causal reasoning --- by integrating flexible machine learning models with statistical principles to preserve both interpretability and rigor. (2) It promotes design-based approaches for quantifying uncertainty, particularly in settings where treatments are assigned randomly or pseudo-randomly via permutations. These methods isolate uncertainty from treatment allocation mechanisms, complementing model-based inference. (3) The project builds a statistical framework for finite-population inference, extending traditional inference techniques beyond super-population assumptions. By drawing on tools from empirical process theory and random matrix theory, the framework provides robust inferential guarantees in realistic data settings where independence and large-sample assumptions fail. Together, these contributions will advance the theory and practice of causal learning, bridging machine learning and statistics to improve both scientific understanding and data-informed decision-making. 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 · 2025-09

PROJECT SUMMARY Each year, more than 250,000 older adults in the United States are transferred from the emergency department (ED) to another hospital for care, yet more than a quarter do not require specialized resources or procedures once transferred. It is unknown whether these potentially avoidable transfers positively impact patients or simply expose them to the risks of transfer without clear benefit as data on outcomes after interfacility transfer of older adults is lacking. Acutely ill or injured elderly patients may be particularly vulnerable to separation from their social support systems and are at increased risk for adverse events such as delirium and falls. Even justifiable transfers may not be concordant with patient preferences. This knowledge gap, combined with a lack of understanding of the experiences and specific challenges faced by older adults during transfer, limits physicians’ ability to provide fully informed, patient-centered care when considering whether to transfer an elderly patient. The overall objective of this proposal is to quantitatively and qualitatively advance our understanding of interfacility transfers of older adults and lay the groundwork for development of an intervention to optimize transfer decisions. This project proposes the following specific aims: 1) To characterize outcomes of older adults who experience interfacility transfer; 2) To explore older adult and care partner experiences with transfer; and 3) To identify factors influencing transfer decisions among key decision-makers. To accomplish Aim 1, we will quantify hospital outcomes and adverse events among transferred older adults, including clinically relevant subgroups of older adults, using statewide administrative claims data. For Aims 2 and 3, we will conduct interviews with patients, care partners, and other key individuals involved in the transfer process. This proposal is closely aligned with the “National Institute on Aging: Strategic Directions for Research, 2020-2025;” this investigation will be used to develop strategies to improve the interaction of older adults with the health system. Specifically, this work will translate to improvements in patient-centered care delivery for older adults potentially needing transfer. This GEMSSTAR project, professional development plan, and mentorship by accomplished clinician- researchers with complementary skill sets will help the PI acquire relevant skills to become a physician- scientist with expertise intersecting aging, emergency medicine, and patient-centered outcomes research. The findings will also serve as preliminary evidence to support a future Beeson career development award application to develop interventions to help older adults and their providers successfully navigate interfacility transfer decisions.

NSF Awards · FY 2025 · 2025-09

Ensuring the reliable and economical production and delivery of electric power is a critical national objective with broad economic and national security implications. Power system modeling plays a key role in enabling these objectives by allowing operators and regulators to accurately simulate how a power grid behaves under different conditions, to design and test control strategies for various grid components, and to predict the impact of changes to the power grid structure, among other tasks. Within this context, data assimilation (DA) and model calibration (MC) tasks, which involve the combination of observations and numerical models, are critical to ensure that predictions from power system models are accurate and useful. This project will have a direct impact on a wide range of fields where “computer models” are used, including atmospheric sciences, oceanography, ecology, astronomy and engineering, among many others. This project aims to develop machine learning tools for data assimilation and model calibration aimed to situations in which the behavior of the underlying system can be described through physical laws encoded in (systems of) ordinary differential equations (ODE), differential algebraic equations (DAE) or partial differential equations (PDE). The techniques are based on Bayesian non-parametric regression methods, where the structure of prior is derived from the system of differential equations describing the underlying system. The main expected outcome of this project is a novel set of tools for DA and MC tasks that: (1) are applicable across a broad spectrum of ODE/DAE/PDE-based systems; (2) allow for proper uncertainty quantification; (3) are endowed with rigorous theoretical guarantees, (4) can be efficiently implemented in practical settings. Hence, the project will expand the toolbox available to scientists and engineers that operate and regulate the U.S. power grid, enhancing the reliability of critical national infrastructure. 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 2026 · 2025-09

PROJECT SUMMARY/ ABSTRACT The AMANI (Accelerating Maternal And Newborn survIval) study aims to address persistently high rates of maternal and neonatal mortality in Kenya by improving maternal and infant death auditing and response. Maternal and Perinatal Death Surveillance and Response (MPDSR) is a structured quality improvement (QI) process for health workers to identify, report, review, and respond to maternal and/or perinatal deaths at a facility level. The WHO developed MPDSR global technical guidelines and they were adopted by the Kenyan government as national policy nearly a decade ago. However, MPDSR is rarely conducted with fidelity, in part due to lack of health worker clarity about MPDSR steps, lack of familiarity with QI including how to identify concrete response actions, and cultures of blame surrounding maternal or perinatal deaths. The AMANI study builds on our team’s prior research identifying critical issues contributing to neonatal deaths during facility delivery and identifying factors influencing guideline adherence. Through structured interrogation of these findings with Kenyan policy makers and health workers, we co-developed a multi-component practice facilitation package that includes audit and feedback (AF) and enhanced mentorship (EM). We will conduct a cluster randomized trial across 20 health facilities to test the practice facilitation package using the RE-AIM framework. In Aim 1, we assess participation in practice facilitation components in intervention facilities (Reach) and evaluate the effectiveness of the AMANI intervention on maternal and perinatal mortality, adoption of MPDSR following a maternal or perinatal death, and implementation of MPDSR with partial or full fidelity (primary outcome). We will also identify determinants of implementation fidelity and track adaptations to MPDSR implementation. A 24-month implementation phase will be followed by a 12-month maintenance phase, during which no external practice facilitation will take place. We will evaluate if the strategy has an enduring impact on fidelity during the maintenance phase. We will also track if AF and EM activities continue to be implemented in intervention facilities. In Aim 2 we will investigate the primary mechanisms through which the practice facilitation package influences MPDSR implementation fidelity. Leveraging the Information-Motivation-Behavioral skills (IMB) model, the study team will conduct mediation analyses to determine if the strategy activates hypothesized mechanisms of provider knowledge, social support, attitudes, and self-efficacy. Other mechanisms investigated include psychological safety and provider burnout. By leveraging routine data sources and political support, this study has the potential to dramatically influence progress towards achieving Sustainable Development Goals 3.1 and 3.2 by improving the implementation of the WHO-endorsed MPDSR tool. Moreover, it contributes to the collaborative testing of a pragmatic strategy to enhance the adoption, integration, and sustainability of an evidence-based intervention, potentially reducing preventable deaths in high mortality settings.

NIH Research Projects · FY 2025 · 2025-09

Project Summary Chromosomal instability (CIN), characterized by changes in chromosome number and structure, leads to aneuploidy (abnormal chromosome numbers) and copy number variations (CNVs), where specific genomic regions are duplicated or deleted. Although often considered a hallmark of tumor transformation and cancer, CIN is also surprisingly prevalent in human embryos from the first cleavage event. These initial divisions are directed by maternal machinery pre-loaded into oocytes before genome activation, making early embryogenesis particularly prone to errors, resulting in a high prevalence of mosaicism. Some embryos with both normal and aneuploid cells develop to term by selectively eliminating abnormal cells, suggesting robust elimination mechanisms that favor euploid cells through differentiation and selective apoptosis of aneuploid cells. While CIN in cancer has been intensively studied, the mechanisms of CIN progression and tolerance in tumor cells remain poorly understood. This gap is even more pronounced in early development due to ethical and technical challenges in studying human embryos and fetuses, and the lack of suitable model systems to examine chromosomal and cellular phenotypes. The remarkable resilience of embryos to chaotic chromosomal events highlights embryogenesis as a unique platform for understanding cell-type specific and context-dependent cellular fitness. Leveraging stem cell and organoid techniques with state-of-the-art genomic and imaging tools, the proposed study aims to establish a unique, controllable, and easily modulated in vitro model system using the embryonic and extraembryonic stem cell lines we have developed to capture embryogenesis traits and reflect CIN status. The study will address three main questions: 1. Cell type-dependent intrinsic mechanisms of CIN tolerance and suppression reflected in stage-specific stem cell lines will be uncovered through CNV-revealing single-cell multi- omics and modulated through high-throughput genomic tools. 2. Context-dependent cell competition will be dissected to explore modulation strategies targeting specific pathways, including p53, Myc, and Hippo, as well as identified non-canonical cell competition pathways. 3. Non-cell-autonomous environmental cues in the uterus that affect and constrain CIN will be investigated through a unique co-culture system with endometrial organoids. This research opens new avenues for studying cellular fitness in the context of CIN. The information gained will pave the way for therapeutic innovations that harness the body’s own mechanisms to correct chromosomal imbalances, potentially leading to advancements in enhancing embryo viability. Additionally, through these innovative strategies, I aim to develop comprehensive and powerful new methodologies that could be applicable to studying other CIN-affected disease or condition prognosis.

NIH Research Projects · FY 2025 · 2025-09

Preterm birth (PTB) is the leading cause of under-5-year-old mortality and neurodevelopmental impairment worldwide and affects between 5-29% of pregnancies. Periodontal disease (PD), including either gingivitis or periodontitis, is a risk factor for PTB. Unfortunately, PTB and PD disproportionately occur in many low- and middle-income countries where access to physicians and dentists is limited. Using a novel inexpensive and non- invasive treatment approach, we recently completed a cluster-randomized trial in Malawi entitled the Prevention of Prematurity and Xylitol (PPaX) Trial in which we demonstrated that use of xylitol-containing chewing gum significantly reduced clinical metrics of maternal periodontal disease (p=0.03) and the occurrence of PTB (xylitol 12.6% vs control 16.5%, aRR 0.76, 95% CI 0.59-0.99). Xylitol is a naturally occurring sugar alcohol found in several chewing gum products and is a prebiotic, known to prevent the growth of periodontopathic bacteria and dampen the pro-inflammatory cascade. As infection and inflammation are risk factors for PTB, xylitol may be a novel, inexpensive innovation that improves maternal and offspring outcomes. While the results of the PPaX trial are promising, we propose to conduct a double-blinded, 3-arm, placebo- controlled trial to address the PPaX trial’s limitations and prove the results are reproducible. PPaX trial limitations included: (a) lack of blinding, (b) lack of placebo control, (c) lack of optimized xylitol dosing based on recent evidence that 5-10 grams of xylitol/day is best for oral health benefit, (d) and lack of individual randomization (PPaX was cluster randomized with only 8 clusters). These limitations inflate the risk of spurious findings. The proposed individually randomized trial will enroll n=6000 Malawian pregnant individuals at <20 weeks’ gestation. The 3 study arms (n=2000 each) will be (a) an optimized dose of xylitol-containing chewing gum (6.4 grams/day), (b) the PPaX trial xylitol dose (2.1 grams/day), or (c) flavored sorbitol gum base (placebo control). The Specific Aims of the research are to determine whether optimized-dose xylitol vs placebo or PPaX-trial-dose xylitol vs placebo impacts: (1) the incidence of PTB or low birthweight offspring (co-primary outcomes), (2) clinical metrics of PD, and (3) adverse offspring outcomes including neonatal mortality, infant mortality and 12-month neurodevelopmental outcomes. We anticipate xylitol-containing chewing gum will prevent PTB and low birthweight offspring and improve overall maternal and offspring outcomes, with most benefit seen with the optimized xylitol daily dose. The findings from this work will definitively prove and confirm whether xylitol has such preventive benefit in a Malawian population, confirm an optimal daily dose, lead to definitive action in Malawi and lay the foundation for a future multi-country, multi-institution clinical trial confirming generalizable benefit worldwide. This trial has the potential to lead to a momentous breakthrough in medicine that could ultimately prevent death and/or disability for millions worldwide.

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY/ABSTRACT Sexual assault remains an all too prevalent public health problem, particularly among young adults. Posttraumatic stress and alcohol misuse are common and co-occurring negative health outcomes associated with sexual assault, which can either resolve or become chronic in the first year after the assault. Social support has been indicated as a key factor that may influence recovery trajectories in the early aftermath of an assault. However, research has been limited by a focus on retrospective designs, sparse recognition of the social structures within survivors’ social networks, and limited integration of alcohol-related social factors on trauma recovery. To fill these gaps, the current study leverages a longitudinal social network design to examine how social resources both shape and are shaped by a recent experience of sexual assault. Three forms of social support resources will be engaged: structural social support (the quantity of support available in survivors’ social networks), sexual assault-specific social support (the quality of responses to disclosures), and alcohol-specific social support (social network drinking). To follow the recovery process in the first 12 months post-SA and draw rigorous conclusions about directionality and mechanisms, the research aims of this study are to: (1) clarify the direction of association between structural social support and posttraumatic stress in the year after a sexual assault, (2) examine how sexual assault-specific social resources are related to posttraumatic stress and alcohol misuse, and (3) characterize the co-evolution of social network drinking and survivor alcohol misuse after sexual assault. To achieve these aims, a national sample of 500 young adults aged 18 to 30 who have experienced a sexual assault in the past 12 weeks will be recruited. Participants will complete a baseline social network interview, then six weekly surveys about social interactions during the early recovery period (spanning 2-20 weeks post-assault). Finally, participants will complete nine monthly surveys, timed in reference to the date the assault occurred (4-12 months post-assault). By studying sexual assault as a critical antecedent process that influences and disrupts trajectories of social connectedness in young adulthood, this research is consistent with the NIAAA mission to reveal the sociocultural origins of alcohol misuse and understand its health impacts. Beyond the direct utility of this information for survivors and their peers, findings will identify modifiable peer- and network-level characteristics that can be targeted through interventions designed to improve support for sexual assault survivors.

NIH Research Projects · FY 2025 · 2025-09

Project Abstract One of the most comprehensive and beneficial interventions for newborn-child health is early and exclusive human milk feeding. Exclusive human milk diet, compared to formula or mixed feeding, improves breastfeeding rates, reduces mortality, and improves long-term outcomes, including neurodevelopment, especially among premature infants. Thus, it is standard practice for premature infants to receive parent’s own milk (POM) and/or donor human milk (DHM) if POM is insufficient or unavailable. Access to DHM is limited in low-resource settings (LRS) despite these regions experiencing >60% of the global burden of preterm birth and high rates of infant mortality. Only 7 of 54 (13%) African countries have human milk banks (HMBs), which are facilities that screen human milk donors, collect donated milk, store and process DHM, and re-distribute DHM to be used among infants without POM access. The contributors to these HMB deserts are multifaceted and linked to well-known challenges in infrastructure, resources and cultural beliefs. Parent perspectives from countries such as Ghana, Kenya, Uganda, and Ethiopia demonstrate feasibility of DHM with many parents willing to donate milk and accepting of DHM in the absence of their own milk. Nonetheless, infrastructure and resources required for the screening, collection, storage, pasteurization and redistribution of milk to support “typical”, stand-alone HMB are limited. Novel strategies are needed to achieve sustainable, culturally and contextually appropriate HMBs in LRS. Through systematic evaluation of best implementation strategies for a facility-specific HMB in a single neonatal intensive care unit (NICU) in Saint Paul’s Hospital Millenium Medical College (SPHMMC), our proposal aims to build and evaluate a sustainable and contextually adaptable approach to HMB in Ethiopia. The newly developed platform will create a proof-of-concept HMB that can be adapted for other LRS context(s). The specific aims of the current proposal are to (1) determine key factors that influence the integration of a facility- specific HMB into existing routine NICU facility operations through the identification of multi-level facilitators and barriers of HMB integration, and (2) co-develop and pilot standard implementation and operational procedures for launching a facility-specific HMB program through simulation. The proposed research will provide the evidence-base for implementation of strategies to improve access to human milk and thereby improve outcomes of premature newborns cared for at SPHMMC NICU. Ultimately, our proposal provides the proof-of-concept for the successful implementation of a facility-specific HMB, which can promote newborn-child health in Ethiopia and beyond. Subsequent studies beyond this proposal include: 1) adaptation and integration of facility-specific HMBs in other LRS, 2) randomization to DHM or standard care and impact on neonatal outcomes and mortality in LRS, and 2) DHM nutritional profile and effect on growth in LRS.

NIH Research Projects · FY 2026 · 2025-09

ABSTRACT There are over 16 million children exposed to HIV (CHEU), the majority of whom reside in East and Southern Africa (ESA). This population is expected to grow as more women living with HIV access services to prevent vertical transmission of HIV. Evidence points to poorer neurodevelopment outcomes among CHEU compared to HIV unexposed children (CHU). Exposure to neurotoxic metals and pesticides also play a role in pathogenesis and may synergistically affect neurocognitive outcomes among CHEU. Studies that determine the combined impact of HIV and environmental exposures on child outcomes are lacking, despite the high prevalence of these exposures in ESA. Understanding whether HIV exposure impacts school-age outcomes has been challenged by changing ART regimens as the epidemic has evolved, and lack of assessment of multiple risk factors including environmental exposures. We propose to extend follow-up for a well characterized large cohort (n=2,000) of CHEU/CHU, enrolled at age 6 weeks and followed up to 3 years, to study neurodevelopmental outcomes at school age (age 5-8) and the impact of HIV and environmental exposures on neurodevelopmental outcomes. We will use exposure, biological samples, and neurodevelopmental data available from the first 3 years of life. The majority of CHEU were exposed to maternal dolutegravir-based ART (77%) and 85% started ART pre-conception. In Aim 1, using stored samples and neurodevelopmental data collected in the first 3 years of life, we will test for Pb levels and determine the association between early Pb exposure and neurodevelopment and determine whether HIV modified the impact of Pb exposure. In Aim 2, we will re-enroll 1,000 children and follow them up to age 8 years to determine the longer-term impact of HIV and Pb exposure on neurocognition and motor function. In Aim 3, we will assess concentrations of neurotoxic heavy metal exposures and pesticides using novel biological samples (nails and hair). Pb and heavy metal assays will be conducted using x-ray fluorescence (XRF) and we will assess associations between these exposures, HIV exposure, and neurocognition. This proposal leverages a large unique longitudinal mother-child cohort of CHEU and CHU, with comprehensive neurodevelopmental assessments and analysis at scale, to comprehensively understand burden, mechanism and neurodevelopmental outcomes in CHEU. We will utilize novel biological samples and efficient technology to assess environmental exposures contributing evidence on inform use of these methods to assess environmental exposures in ESA and globally. We will work with national and global health leaders, community members, and policymakers to discuss study findings, implications, and next steps.

NIH Research Projects · FY 2025 · 2025-09

Recent advances in functional genomics and computational modeling and hardware have ushered in a new era of sequence-to-function (S2F) deep learning models, allowing the direct prediction of functional outcomes from DNA sequences. We are poised to build comprehensive models of gene regulation and precisely predict gene expression consequences of arbitrary genotypes. However, two significant challenges limit the potential of current models. Firstly, current models are not able to correctly predict the subtle gene expression consequences that arise from natural genetic variation. Secondly, current models can only make accurate predictions for the cellular contexts with abundant functional genomic training data and are not applicable to contexts important for many diseases such as early developmental time points and difficult to isolate cell types. Our proposal aims to address these challenges and advance the field. Aim 1 develops S2F models that are performant on the full spectrum of natural genetic variations. Current S2F models generalize across genomic regions, but struggle to generalize across diverse genotypes represented in personal genomes, due to the subtleties in gene expression changes. We propose a novel and general learning framework that integrates allele-resolved functional genomic data, enhancing the model's ability to predict variant effects. This framework employs custom loss functions and learning algorithms for efficient utilization of personal genomes and allele-resolved datasets. Aim 2 introduces modularized model architectures that improve generalization and adaptability, particularly in scenarios with limited data. Gene expression regulation involves complex processes, each with a distinct relationship to DNA sequence. We propose factorized models that utilize biological prior knowledge to constrain the model and decouple its parameters to correspond to distinct biological processes. Regularizing the model with known biological principles enhances generalization, yields interpretable predictions, and enables context-specific fine-tuning in data-limited settings. Aim 3 applies these enhanced models to study regulatory mechanisms underlying neurodevelopmental disease. Collaborating with domain experts, we will investigate how sequence variations affect gene expression in autism spectrum disorder (ASD) and schizophrenia (SCZ). ASD and SCZ involve abnormalities in brain development that may occur even before birth. Hence, functional data from the relevant cell-types and developmental time points is limited. Here, we will apply our models to Whole-Genome Sequencing data collected from SCZ and ASD patients to predict gene expression values across genome and brain cell types across early developmental time points. By associating the resulting imputed gene expression values with disease outcome, our approach will drastically reduce the multiple testing burden that is currently hampering rare non-coding variant investigation in complex disease. In summary, our methods will offer powerful computational tools to study and interpret personal genomes, enabling mechanistic investigation of the full spectrum of genetic variation in complex disease.

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY/ABSTRACT Infants born preterm do not grow as well as their term counterparts. Poor growth during the neonatal intensive care unit admission is associated with worse neurobehavioral outcomes. Furthermore, poor infant growth and neurodevelopment have been linked with gut microbial changes. One protective driver of the infant gut microbiome is the consumption of parent’s own milk (POM). POM contains its own microbiome and human milk oligosaccharides (HMOs) unique to each parent-infant dyad. HMOs and the milk microbiome contribute to the infant gut microbiome. However, many preterm-delivering lactating parents do not have sufficient POM, requiring supplementation with donor human milk (DHM). DHM is pasteurized and pooled from multiple, mostly term donors, which likely alters HMO composition and decreases live bacteria. We hypothesize that these differences between POM and DHM likely alter the preterm infant gut microbiome and reduce the infant’s growth from birth to 36 weeks corrected gestational age. To test this hypothesis, we will leverage ongoing sampling from a funded cohort of parent-infant dyads born between 24 to 32 weeks gestation of age to examine milk microbiome (live and nonviable), HMO composition, and how these relate to infant gut microbiome and infant growth. The Specific Aims are to: 1) determine the milk microbial and HMO composition of preterm POM collected at weeks 1, 4, and 8 postpartum compared to DHM; 2) evaluate which HMO and milk microbiota (live and nonviable) are associated with infant gut microbial diversity and composition at weeks 1, 4, and 8 of age; and 3) evaluate which HMO, milk microbiota, and stool microbiota are associated with anthropometric z-score changes from birth to 36 weeks corrected gestational age. We will utilize high performance liquid chromatography for HMO analysis, metagenomic sequencing to characterize milk and stool microbiome, and propidium monoazide to distinguish live versus nonviable bacteria in milk. Growth will be measured by changes in weight, length, and head circumference z-scores from birth to 36 weeks corrected gestational age. Career Development Objectives are to 1) acquire essential knowledge in milk as a bioactive system by gaining advanced skills in systems biology and experimental design, 2) develop core competencies in multi-omic clinical- translational trial design and bioinformatic analysis, and 3) attain sophisticated skills in ethical and equitable study management, scientific writing, presentation, and grant preparation. After completion of the career development objectives and the research specific aims, the applicant will be well-positioned to obtain external funding and conduct clinical-translational studies on nutrition and growth in vulnerable parent-infant dyads. Study Impact: This study will identify critical differences between POM and DHM and their impact on the preterm infant gut microbiome and growth. The data will inform potential pre-biotic and pro-biotic supplementation for DHM in future randomized, placebo-controlled trials.

NIH Research Projects · FY 2025 · 2025-09

Fathers play a pivotal role in early child health and development with impact on mental, social, and financial wellbeing throughout a child’s lifespan. One in ten fathers experience severe mental health challenges due to the stressors of parenting. Fathers’ poor mental health adversely impacts their relationships with partners, parenting behaviors and families’ health and safety, yet mental health services for fathers are scarce. The adverse effects of low paternal involvement disproportionately affects low- and middle-income countries (LMICs) of Africa where a quarter of ≤5 year-olds are developmentally delayed. WHO’s “Nurturing Care Framework” prioritizes fathers’ parenting role and calls for strategies to improve dyadic father-child mental health. Parenting interventions that support effective parenting knowledge, skills, and behaviors improve parent-child mental health outcomes, including in LMICs. Involving fathers strengthens and extends positive outcomes. Yet, most parenting programs solely engage mothers and prioritize mothers’ roles. Improving fathers’ mental health and parenting skills requires interventions tailored to fathers’ unique roles, needs, and preferences. Stigma and logistical challenges are reported by men in LMICs as barriers to in-person counseling. Mobile health (mHealth) interventions increase confidentiality and convenience to address these barriers. mHealth parenting interventions are acceptable and feasible in LMICs with benefits similar to in-person programs. To date, no mHealth tools tailored to fathers’ mental health are developed for LMICs. We propose using the IDEAS framework to develop “BABAText”—a father-facing mHealth parenting intervention to improve father-child mental health tailored to the needs and preferences of Kenyan fathers. The proposed project leverages our team’s ongoing study (R01HD100201, PrIMA-X) and extends novel data collection to adapt an existing mHealth platform (Mobile WACh) which sends automated theory-based SMS messages and enables 2-way communication with a remote nurse-counselor. In Aim 1, we will identify mental health needs, parenting challenges, and preferences for mHealth approaches among Kenyan fathers in a mixed methods needs assessment. In Aim 2, we will collaboratively develop “BABAText”, an mHealth parenting intervention for fathers, using a user-centered approach by incorporating fathers’ needs and preferences, feedback from iterative codesign workshops, and effective elements from evidence-based parenting and mental health interventions. In Aim 3, we will evaluate the acceptability, preliminary efficacy, and implementation barriers and facilitators of BABAText. This program of research will be conducted in partnership with fathers in Kenya to maximize impact. Overall, I anticipate a mHealth parenting intervention co-developed with fathers will improve father-child mental health and family wellbeing. This proposal addresses the high mental health burden among men in settings of Africa and is designed to provide an acceptable, effective mHealth parenting support intervention for fathers.

NIH Research Projects · FY 2025 · 2025-09

Children exposed to HIV in utero but who are not infected (HEU) have been shown to have compromised growth, neurodevelopmental delays, and increased morbidity and mortality. It is critical to define mechanisms for these differences. This P01 proposes to conduct 3 Projects to examine the influence of maternal dolutegravir (DTG) and viral load (Project 1), microbiome and breastmilk human milk oligosaccharides (HMOs) (Project 2) and maternal/infant immune activation and CMV (Project 3) on outcomes in HEU children and children who are not HIV-exposed (HUU). The three Projects will use a shared Measurement and Analysis Core (MA Core) to ensure standardized child neurodevelopmental evaluations and aligned analytic approaches. The three Projects address domains of translational and mechanistic importance. DTG use is currently expanding in PMTCT programs and there are no data on child neurodevelopmental outcomes. Gut-brain connections and the role of the microbiome in neuroimmune outcomes are topics of increased interest with limited data from birth cohorts. Studies have demonstrated early differences in gut microbiome of HEU and HUU infants. Finally, marked differences in maternal immune activation and infant CMV timing occur in HEU infants which could influence growth and neurodevelopment. The three Projects will involve 3 distinct birth cohorts that will leverage 3 ongoing R01 studies led by early-stage investigators: Projects 2 and 3 will extend ongoing R01-funded HEU/HUU birth cohorts (not originally designed to assess neurodevelopment) to incorporate neurodevelopmental assessment while Project 1 will enroll a new HEU cohort and compare this cohort to a comparator R01-funded HUU birth cohort. With or without detection of differences between HEU and HUU infants, the 3 birth cohorts will provide novel insights on the influence of biologic factors on birth and neurodevelopmental outcomes. Overall P01 Aims: 1. To build a P01 structure that involves 3 Projects and 2 Cores to synergistically evaluate the influence of distinct biologic factors on birth and neurodevelopmental outcomes in HEU/HUU birth cohorts. 2. To implement a shared Measurement and Analysis Core that provides standardized training on neurodevelopmental assessments, technical input, and aligned analytic approaches between Projects. 3. To implement a shared Administrative Core to oversee shared project coordination, administration, and dissemination, convene annual meetings and to facilitate communication between the 3 Projects. The proposed P01 will cohere a group of early and established Kenyan and US investigators focused on optimizing HEU and HUU child outcomes and advance a synergistic scientific agenda that probes biologic mechanisms influencing child outcomes. The P01 will yield mechanistic and translational insights and impact and provide opportunities for collaborative development of next-generation US and Kenyan trainees.

NSF Awards · FY 2025 · 2025-09

Mammals display remarkable variation in the form and function of their skulls, related to what and how they eat. However, the skulls of individuals within a species can vary. If we ignore these differences, we risk missing important clues about how animals behave and adapt to their environments. This project will investigate which carnivoran mammals (i.e., bears, cats, dogs, and their relatives) show differences between males and females and why. The researchers will measure traits such as size and shape, biting ability, bone structure, and bone strength of skulls using computer models based on 3D scans of samples from local and national museum collections. The researchers will then test for differences in skull form between the sexes and whether they translate to differences in skull function. Finally, the researchers will test whether differences can be explained by diet or other aspects of their biology. The project will produce large datasets of 3D skull models. These will be saved in an online database that experts, educators, and the public alike can use to explore and learn. The project will also support training of undergraduate students and outreach and educational programs at a museum that reaches thousands of visitors a year. Understanding how ecological variation influences phenotypic diversification is a central goal of evolutionary biology. However, variation in ecology and phenotypes is not always uniform among different species, and the functional implications of morphological dimorphism remain largely unknown despite well documentation of this phenomenon (i.e., morphological dimorphism) in many mammals. In this project, the researchers will investigate the underlying evolutionary processes of sexual dimorphism and its influence on the evolution and ecomorphological diversification of the carnivoran skull. The researchers will use micro-Computed Tomography, lever mechanical modeling, and finite element analyses to quantify the degree of sexual dimorphism in the size, shape, and functional traits of the skull and test if these sexually dimorphic morphologies translate to intersexual differences in the structural mechanics, performances, and biomechanics of the skull. The researchers will then use phylogenetic comparative methods to (1) determine how sexual selection, niche divergence, and other evolutionary processes influence the evolution of these sexual dimorphic traits; (2) test how sexual dimorphism influences skull ecomorphological diversity and its tempo and mode of evolution; and (3) investigate how sex-specific static allometry contributes to the evolutionary allometry of sexual dimorphism. Overall, this work will demonstrate how intraspecific variation within the sexes affects the adaptive diversification of phenotypic traits, contrary to most other macroevolutionary studies that typically examine only one sex or species means. This work will also identify the multiple underlying processes that influence and facilitate the evolution of sexual dimorphism, thus moving the focus from sexual selection to other potential ecological factors. Lastly, the researchers will also develop a Course-based Undergraduate Research (CURE) program to train and mentor undergraduate students in research and partner with a large natural history museum to disseminate results to public audiences through outreach events. 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 2026 · 2025-09

Abstract. This HEAL project will employ computational, machine learning (ML) and Artificial Intelligence (AI) tools to accelerate the discovery of vaccines and antibodies against highly toxic ultrapotent synthetic opioids (UPSO). United States, Canada, and Europe have registered dramatic increases in fatal drug poisoning due to the widespread availability of fentanyl, fentanyl analogs, emerging compounds of the nitazene class, and their mixtures. Because of their potency, ease of illicit synthesis, and widespread availability, UPSO are fueling the ongoing overdose crisis. Beyond their impact on individuals with Opioid Use Disorder (OUD), these compounds could be involved in mass casualty incidents (MCI) or deliberately deployed in chemical attacks. Current FDA- approved countermeasures consist of opioid receptor antagonists, which may not always be sufficient to reverse overdoses involving UPSO or drug mixtures containing UPSO. To address this public health threat, our team has developed vaccines and monoclonal antibodies (mAb) against a series of UPSO. Vaccine-elicited antibodies and mAbs selectively bind the target drug in serum, reduce distribution of the unbound (free) drug to the brain, and prevent or reverse drug-induced effects. Based on their pre-clinical profile, anti-UPSO vaccines and mAbs have the potential to counteract overdose toxicity and poisoning in both civilian and defense scenarios. Due to their selectivity, vaccines and mAbs could be combined with existing treatments to increase survival. Because of the speed with which new and emerging UPSO can enter the drug supply, new tools to optimize and streamline the process of vaccine and antibody discovery are needed to rapidly address these threats by accelerating their translation into the product development space. To address this challenge, this project will employ state-of-the- art structure- and computational-guided platforms and AI/ML tools to accelerate discovery of vaccines and mAb against emerging UPSOs such as nitazenes. Specifically, AIM1 will focus on discovery of novel conjugate vaccines against nitazenes paired with computational methods to identify correlates of vaccine efficacy, AIM2 will focus on isolation of mAb against nitazenes and other UPSO accelerated by structure-informed design, and AIM3 will focus on evaluation of vaccines and mAb in vivo in rats challenged with nitazenes, fentanyl analogs, and their mixtures. Completion of this research proposal will lead to development and validation of computational methods to rapidly isolate vaccines and mAb against novel and rising UPSO, and other chemicals of concern.

NSF Awards · FY 2025 · 2025-09

Polymer foams are essential in industries like packaging, electronics, and healthcare due to their low cost, lightweight nature, insulating properties, and energy absorption. However, current foaming methods offer limited flexibility for material customization, rarely introduce new functions to meet specific application needs, and often lack environmental sustainability. This Faculty Early Career Development (CAREER) grant supports fundamental research to establish an innovative manufacturing method for on-demand foaming of polymers and composites. The project aims to advance scientific understanding of selective foaming, which could enable applications such as miniaturized sensors and wearable electronics, benefiting US industries ranging from aerospace to medical devices. The project also looks to lay the groundwork for a sustainable manufacturing approach, promoting the use of recyclable materials in advanced technologies like flexible electronics. By improving material performance and advancing sustainable production methods, the research can contribute to national prosperity and environmental sustainability. Additionally, the project integrates research and education to cultivate a skilled US workforce. Targeted outreach efforts leverage the multidisciplinary nature of this research to inspire students and encourage them to pursue studies and careers in advanced materials and manufacturing, building a more innovative workforce for the future. This CAREER project looks to build understanding of solid-state foaming and microstructure engineering in thermoplastic composites through laser-induced foaming. This direct-foam-writing technique enables selective surface engineering and controlled microstructure modification within polymer composites to create locally tailored structural, thermal, and electrical properties. The mechanisms of cell nucleation and growth and the effects of filler properties will be systematically studied to establish relationships between composite properties, process parameters, and cell microstructures. Mechanical, thermal, and electrical properties of the microcellular composites will be experimentally characterized, while physics-based models will be developed to predict the effective properties of the foamed regions. These findings look to elucidate process-structure-performance relationships, resulting in an efficient, scalable, high-resolution fabrication process for devices with spatially tuned properties. This program also integrates research and education to train new workforce members in manufacturing practices that emphasize recyclable materials. A new course will be developed to equip students with expertise in sustainable electronics, multifunctional polymer composites, advanced image processing, and laser-matter interactions. Outreach activities will engage K-12 students in communities across Washington state, sparking early interest in STEM and demonstrating feasible pathways to the University of Washington, empowering them to become future leaders in manufacturing innovation. 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 · 2025-09

This proposal for an NIDDK Research Education Program has an overarching goal to further the development of individuals into future surgeon-scientists engaged in urology research careers. The planned Program reflects the commitment of the University of Washington Department of Urology to the current and future research workforce needs in Urology. This Program will capitalize on unparalleled resources including a committed Department, a robust research environment, dedicated and experienced faculty, data and research support resources, and a structured curriculum. These resources include research mentors who are practicing urologists, near-peer mentors who are current residents and fellows to act as career development mentors, and a biostatistician to facilitate maintaining the timeline for the Program by working with the participants on research study analyses. This Program leverages the success of the Department’s past mentored research experiences to refine and expand the scope and breadth of research opportunities in areas of urologic disease from earliest prenatal development to the commonest aging associated problems. The objective of this application is to train medical students in benign clinical and health services research, seek out residency positions with dedicated research experiences, all with the long-term goal to support the career development of individuals into urology research careers and to create novel research solutions to benign urological conditions with high public health impact. To achieve this objective, program participants will pursue the following Specific Aims: 1) To gain exposure to methodologies for conducting contemporary clinical and health services research in benign urologic diseases; 2) To conduct a hypothesis-driven research project through which they will develop sophisticated skills in applying clinical and health services research methods; 3) To gain skills in analysis of study data and presentation of research results through manuscripts, scientific presentations, and patient-centered research dissemination strategies; and 4) To prepare trainees for careers in academic urology through dedicated mentorship that includes career and leadership development. Supported by the mentoring and resources of this program, the overarching goal of this NIDDK Research Education Program is to ignite these participants to initiate and retain an excitement for urological research and carry it with them throughout their entire careers.

NSF Awards · FY 2025 · 2025-09

This project will support the development of the first global emissions inventory for volcanic hydrogen sulfide (H2S). By improving estimates of natural sulfur emissions to the atmosphere, the uncertainty in the estimates of the global radiative forcing of anthropogenic sulfate aerosols will be reduced. The investigators of the project plan to: (1) make an initial inventory of global volcanic H2S emissions based on current carbon dioxide and sulfur dioxide emissions measured during passive degassing; (2) measure H2S emissions from select volcanoes; (3) use these observations along with previous work to construct a global emissions inventory of H2S from passive volcanic degassing; (4) implement the new volcanic H2S emissions inventory into the GEOS-Chem global chemical-transport model; and (5) examine the global chemical and radiative implications of the volcanic source of H2S. This work will partially support two graduate students, one each at the University of New Mexico and the University of Washington. 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 · 2025-09

All languages have syntax, which allows smaller units, like words, to be combined into larger units, like sentences. Syntax is a primary method of communicating between speakers. Languages differ syntactically in restricted ways, and the dividing line between sentence and word is an important area of research. The formation of words in some languages is complex and, despite decades of research, is still not completely understood. Part of the reason why is that there are incomplete tools and data for answering these questions, including a lack of detailed syntactic descriptions. Such descriptions are important not only for linguistic typology and theory, but also for other benefits including educational opportunities and refinement of artificial intelligence (AI) and other language technologies. This project investigates syntax in a language for which a detailed description of lexical structure exists. This project approaches the study of syntax in two ways, through the study of sentences in recordings of natural speech, supplemented with questions to speakers about possible and impossible sentences and their meanings. The project transcribes and translates narratives, then posts them with their audio or video on a website so that the widest possible audience can read, understand and enjoy the language. The entire corpus of data collected during the project is archived in a publicly accessible archive, which may help future investigators find answers to questions not imagined in the current project. New words from the recordings are incorporated into an already-substantial dictionary draft. The project yields a syntactic description and a dictionary, and a website of texts. The results from this project have broad applicability in linguistics, history, anthropology, and other disciplines and provide innovative educational opportunities that build capacity for linguistic research in a non-academic setting. 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 · 2025-09

PROJECT SUMMARY / ABSTRACT Tuberculosis (TB) is an ancient disease that continues to be a leading cause of infectious morbidity and mortality, with approximately 1.5 million deaths per year. Efforts toward development of effective TB vaccines and host-directed therapies have been hampered by an insufficient understanding of immunity to Mycobacterium tuberculosis (Mtb). For decades, the central mechanism by which the immune system has been understood to control Mtb is through activation of direct Mtb-restricting mechanisms in infected lung monocyte-derived macrophages (MDMs) by the cytokine interferon gamma (IFNγ). However, data from humans and animal models has often been challenging to reconcile with this model. Meanwhile, increasing attention has been paid to the role of the lung inflammatory environment, cellular milieu, and immunometabolism in controlling Mtb and preventing TB disease. Here, we propose and test the novel hypothesis that IFNγ-activated MDMs regulate immunity to Mtb largely by modulating the cellular and inflammatory state of the lung, thereby limiting immunopathology and promoting phagocyte bacterial restriction in trans. Furthermore, we posit that the enzyme aconitate decarboxylase 1 (ACOD1, also known as immune-responsive gene 1 (IRG1)) is a primary mediator of this host-protective activity. The rationale supporting this proposal includes 1) our observations that absence of T cell-derived IFNγ leads to a profound susceptibility to Mtb burden and disease pathology associated with inflammation, type 2 cytokines, granulocyte infiltration to TB lesions, and inhibition of Irg1; 2) our re-analysis of published flow cytometry data revealing results supporting a cell-extrinsic mechanism of Mtb restriction by IFNγ-activated MDMs, 3) published evidence that myeloid cell expression of Irg1 is protective against Mtb in trans, 4) mounting evidence to support a critical role for IRG1 and its enzymatic product, itaconate, in suppressing inflammation, alternative macrophage activation, and granulocyte responses. In Aim 1, we will assess the link between IFNγ and IRG1-mediated immunity to Mtb, using bone marrow chimeric mice and itaconate administration to determine whether and how deficiency in Irg1 phenocopies Ifngr deficiency in terms of effects on cell-intrinsic and extrinsic MDM immune mechanisms in TB. In Aim 2, we determine the relative contribution of neutrophils vs eosinophils to TB lesion and disease severity in mice deficient in either IFNγ or IRG1. The proposal is innovative because it investigates an unexpected mode of action for IFNγ-activated MDMs in Mtb, as well as a potential pathogenic role for eosinophils in Mtb, which has not previously been documented. The Research Strategy and Career Development Plans described here will support Dr. Maciag to launch her independent research career as a physician-scientist investigating immunity to TB.

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY/ABSTRACT K99 training: The goal of the proposed K99/R00 Pathway to Independence Award is to provide Dr. Jonas Dora with training needed to launch his career as an independent scientist. Following his PhD in cognitive psychology, Dr. Dora has already started to make important contributions to the field of alcohol use research as a postdoctoral research fellow in the Department of Psychology at the University of Washington. The proposed K99 training period builds on Dr. Dora’s PhD background and his current training in the study of alcohol use in natural environments. The K99 phase will provide a period of intensive training in the combined study of alcohol use with experimental, ecological momentary assessment, and computational approaches, and will position Dr. Dora to make substantial contributions to the field of alcohol research over the course of his career. Dr. Dora will learn from the proposed mentor (Dr. Kevin King), local collaborators (Drs. William George, Mary Larimer) and external collaborators (Drs. Matt Field, James Murphy, Katie Witkiewitz), who are leading experts in the field of alcohol use research using both experimental and ecologically valid approaches, as well as the advanced computational modeling of behavioral and subjective data. In addition, Dr. Dora will attend courses, scientific conferences, and workshops to meet his training objectives. The University of Washington is a world-class research institution that provides an optimal environment, the necessary resources, and a stimulating intellectual space to facilitate successful completion of this project. K99 research: Together with his mentor and collaborators, Dr. Dora will conduct controlled experiments in a simulated bar environment as well as studies in people’s natural drinking environment to test the idea that negative and positive reinforcement of alcohol can be observed when heavy drinkers with and without symptoms of alcohol use disorder (AUD) make decisions between alcohol and substance-free reinforcers. R00 research: Dr. Dora will translate the K99 research using a task involving hypothetical choices between alcohol and substance-free reinforcers into an ecologically valid test of the hypothesis that positive and negative affect differentially motivate real-world value-based decisions to consume alcohol (vs regulate affect via alternative emotion regulation strategies) in heavy drinkers with/without symptoms of AUD in everyday life. Significance: By combining methods from cognitive psychology and alcohol use research, this research will provide a novel test of the idea that alcohol use is reinforcing in the face of positive and negative emotions, and in that way will advance NIAAA’s strategic aim to identify mechanisms that contribute to AUD. By studying alcohol use as a form of value-based decision-making, the insights from this project will suggest new possibilities to target people’s emotions in the prevention and treatment of alcohol use disorder.