Search Grants — Free, No Account Required

NHLBI - National Heart Lung and Blood Institute

Abstract In Tanzania, over 1.5 million people are living with HIV (PLH). With improvements in access to effective ART, the number of PLH surviving into older age has increased substantially. Currently, 30% of PLH in Tanzania are aged 50 years and older, with this population expected to increase by 25% by 2040. Ageing PLH face a significant burden of cardiovascular disease (CVD) due to a combination of traditional risk factors, HIV associated inflammation, and immune dysfunction. Heart failure is one of the leading causes of cardiac disease in adults in Tanzania, with hypertension accounting for about half of all cases. Cardiac echocardiography is a valuable, non-invasive tool for detecting structural and functional abnormalities associated with heart failure, including left ventricular dysfunction, valvular disease, and diastolic impairment. However, access is limited in resource constrained settings like Tanzania and as a result diagnoses are often made very late. Point-of-care cardiac ultrasound (POCUS) offers a potentially scalable solution for cardiovascular screening in ageing PLH in HIV clinics and early detection of cardiac abnormalities that could lead to heart failure. This R21 exploratory/developmental grant proposes to assess the clinical utility, feasibility and impact of implementing AI-POCUS for early detection of cardiac dysfunction in aging PLH in Tanzania. 400 PLH equal to or greater than 50 years enrolled in the Tanzania HIV ageing longitudinal cohort study (THALCS), a multisite observational cohort study of ageing outcomes and quality of life, will undergo a focused AI-POCUS assessment using the Butterfly iQ3™ portable AI-driven ultrasound system, performed by trained non-specialist providers (HCP) at THALCS study sites. Specifically, we will (1) evaluate the utility of POCUS for identifying key markers of cardiac dysfunction (e.g., left ventricular hypertrophy, systolic/diastolic dysfunction, pericardial effusion) and need for cardiology referral; and (2) assess the feasibility and acceptability of AI-POCUS among healthcare providers and participants and the clinical impact of AI-POCUS on short term (12 month) participant outcomes. The proposed work also has direct relevance to the United States, where more than half of PLH in care are now aged 50 years and older and experience disproportionately high rates of hypertension, heart failure, and other cardiovascular complications. Findings from this study may inform scalable, task-shifted approaches for integrating AI-assisted cardiac screening into HIV primary care settings in the US, including federally qualified health centers and rural clinics with limited access to cardiology and echocardiography services. This project will generate critical pilot data to inform scalable strategies for CVD screening in aging PLWH and lay the groundwork for future trials of POCUS-guided interventions. Ultimately, it seeks to reduce cardiovascular morbidity and improve quality of life in a vulnerable and growing population.

NHLBI - National Heart Lung and Blood Institute

Abstract In Tanzania, over 1.5 million people are living with HIV (PLH). With improvements in access to effective ART, the number of PLH surviving into older age has increased substantially. Currently, 30% of PLH in Tanzania are aged 50 years and older, with this population expected to increase by 25% by 2040. Ageing PLH face a significant burden of cardiovascular disease (CVD) due to a combination of traditional risk factors, HIV associated inflammation, and immune dysfunction. Heart failure is one of the leading causes of cardiac disease in adults in Tanzania, with hypertension accounting for about half of all cases. Cardiac echocardiography is a valuable, non-invasive tool for detecting structural and functional abnormalities associated with heart failure, including left ventricular dysfunction, valvular disease, and diastolic impairment. However, access is limited in resource constrained settings like Tanzania and as a result diagnoses are often made very late. Point-of-care cardiac ultrasound (POCUS) offers a potentially scalable solution for cardiovascular screening in ageing PLH in HIV clinics and early detection of cardiac abnormalities that could lead to heart failure. This R21 exploratory/developmental grant proposes to assess the clinical utility, feasibility and impact of implementing AI-POCUS for early detection of cardiac dysfunction in aging PLH in Tanzania. 400 PLH equal to or greater than 50 years enrolled in the Tanzania HIV ageing longitudinal cohort study (THALCS), a multisite observational cohort study of ageing outcomes and quality of life, will undergo a focused AI-POCUS assessment using the Butterfly iQ3™ portable AI-driven ultrasound system, performed by trained non-specialist providers (HCP) at THALCS study sites. Specifically, we will (1) evaluate the utility of POCUS for identifying key markers of cardiac dysfunction (e.g., left ventricular hypertrophy, systolic/diastolic dysfunction, pericardial effusion) and need for cardiology referral; and (2) assess the feasibility and acceptability of AI-POCUS among healthcare providers and participants and the clinical impact of AI-POCUS on short term (12 month) participant outcomes. The proposed work also has direct relevance to the United States, where more than half of PLH in care are now aged 50 years and older and experience disproportionately high rates of hypertension, heart failure, and other cardiovascular complications. Findings from this study may inform scalable, task-shifted approaches for integrating AI-assisted cardiac screening into HIV primary care settings in the US, including federally qualified health centers and rural clinics with limited access to cardiology and echocardiography services. This project will generate critical pilot data to inform scalable strategies for CVD screening in aging PLWH and lay the groundwork for future trials of POCUS-guided interventions. Ultimately, it seeks to reduce cardiovascular morbidity and improve quality of life in a vulnerable and growing population.

NIDCR - National Institute of Dental and Craniofacial Research

PROJECT SUMMARY The Portland Oral Health Research Training (PORT) Program at the Oregon Health & Science University (OHSU) School of Dentistry develops the next generation of oral health researchers. PORT leverages OHSU’s strong record of mentoring and training, rigorous scientific research, and newly renovated state-of-the-art laboratory and education facilities. The program builds on the School’s strengths in microbial sciences, biomaterials/tissue engineering, regenerative medicine, and clinical and translational research, supported by major NIH funding, including two R35 awards to mid-career faculty. PORT is closely integrated with OHSU’s campus-wide research ecosystem, which includes multiple NIH training programs and partnerships with Portland State University and Oregon State University, providing access to a robust pool of research-experienced students. PORT is facilitated by an institutionally supported prematriculation summer research program for incoming D.M.D. students that creates an early research exposure and provides continuity into advanced predoctoral and postdoctoral T32 training after matriculation/eligibility. The program’s four complementary tracks include: (I) D.M.D. summer research with post-matriculation continuation; (II) D.M.D./Ph.D.; (III) Ph.D. predoctoral training; and (IV) postdoctoral training, including a sub-track with a Master of Science in Clinical & Translational Research. We are requesting five (5) slots for Track I each summer; one (1) slot in Year 1 and two (2) slots in Years 2-5 for the Track II DMD/PhD training program; three (3) slots for the Track III predoctoral training, and four (4) slots for Track IV postdoctoral training. We anticipate that trainees will participate in Track I for eight (8) weeks, Track II for up to five (5) years, or Tracks III or IV for approximately 2-3 years. The goal is that each trainee in Tracks II-IV will apply for and receive individual funding toward the end of their tenure. Training experience emphasizes rigorous scientific reasoning and reproducibility, Responsible Conduct of Research, quantitative and computational methods, and effective scientific communication. Structured activities include seminars, workshops in grant writing, leadership, team science, and presentation skills, and formal mentor training for faculty. Trainees engage in institutional scholarly events such as the Dean’s Seminar Series and OHSU Research Week, develop Individual Development Plans with near-peer and alumni mentoring, and may pursue short, mentored externships to explore research careers across academia, industry, and government/regulatory enterprise. Program evaluation tracks skills acquisition, research outputs, time to degree or next stage, and career destinations, with aggregate training and career outcomes publicly posted on an OHSU webpage. By providing a rigorous, interdisciplinary, and professionally structured training environment, PORT will accelerate the transition of motivated dental, dual-degree, predoctoral, and postdoctoral trainees into productive research and related careers and advance the NIH mission to improve health through discovery.

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY/ABSTRACT Chronic obstructive pulmonary disease (COPD) accounts for 6% of all deaths worldwide and is potentially preventable, with well-described but poorly elucidated childhood origins. Improved understanding of early life origins of COPD could lead to interventions to substantially reduce morbidity and mortality from COPD, particularly in high-risk populations. Dysanapsis refers to a mismatch between airway tree caliber and lung volume that arises early in life. Our research team recently identified that dysanapsis is: 1) prevalent among older adults, 2) is a major predictor of COPD risk – exceeding tobacco smoke and other established risk factors, and 3) is not fully explained by genetics. We also know that there are heterogenous structural presentations of dysanapsis. However, the early life origins of dysanapsis are poorly understood. This R01 study will leverage 8 longitudinal birth cohorts of children to examine the relationship between early- life exposures and events and both structural (imaging-confirmed) and functional (spirometry-assessed) dysanapsis throughout childhood and adolescence to identify modifiable risk factors and help reduce risk of COPD in future generations at risk. Building on our preliminary data showing that magnetic resonance imaging (MRI) is as accurate as computed tomography (CT) at identifying dysanapsis, we will integrate state-of-the-art lung MRI data with extensive early-life exposure and lung function data. Aim 1 will establish relationships between early life dysanapsis and childhood lung function trajectories, and their relationship to structural dysanapsis at late adolescence. Aim 2 will determine if individual-level factors, specifically obesity and viral infections, contribute to functional dysanapsis (spirometry-assessed) and distinct structural subtypes of dysanapsis (imaging-confirmed). Aim 3 will examine community-level factors and associations with functional dysanapsis (spirometry-assessed). This study aligns with NHLBI’s strategic objective to investigate factors accounting for health differences among populations. We will establish the early-life risk factors that contribute to airway-to-lung phenotypes and enhance our understanding of the utility of both imaging- and spirometry-based measures of dysanapsis. Moreover, our findings will inform targeted interventions in high-risk groups of children to reduce their subsequent risk of COPD.

NIEHS - National Institute of Environmental Health Sciences

Project Summary/Abstract: Autism spectrum disorder (ASD) is a growing public health concern, with rising prevalence and substantial economic and societal costs. Epidemiologic evidence links abnormal maternal thyroid function during pregnancy to increased risk of child ASD and other neurodevelopmental disorders. Lithium, widely used as a psychiatric medication for bipolar disorder and depression due to its mood-stabilizing effects, also presents concerns as an environmental exposure during pregnancy. Lithium inhibits thyroidal iodine uptake, is concentrated in the thyroid, and has known neurotoxic effects. Additionally, more than 56% of U.S. groundwater samples exceed the EPA’s health advisory level for lithium, and conventional water treatment processes do not remove it. Findings from prior case-control studies on the relationship between prenatal lithium exposure and ASD risk are limited by retrospective exposure assessment, emphasizing the need for direct measures of lithium exposure during pregnancy. Our central hypothesis is that higher prenatal lithium exposure increases the risk of maternal thyroid dysfunction, which in turn elevates the risk of child ASD. To our knowledge, no prior study has explored a pathway linking prenatal lithium exposure to ASD through thyroid dysfunction as a potential mechanism. To test our hypothesis, we plan to take advantage of two established ASD studies: (1) MARBLES (Markers of Autism Risk in Babies – Learning Early Signs), a prospective cohort of over 550 pregnant women who have a child with ASD and CHARGE (CHildhood Autism Risk from Genetics and Environment), a population-based, case-control study with over 2000 children and families enrolled. In this project, after selecting MARBLES pregnant women who provided urine samples during pregnancy and subsequently delivered a child with a final diagnosis, we will analyze their urine samples for lithium. Then, we will examine whether prenatal exposure to lithium is associated with child ASD. We will also examine the impact of prenatal lithium exposure on thyroid dysfunction. For CHARGE, we will reconstruct prenatal residential lithium exposure for 500 cases and 500 controls by integrating lithium levels of national databases with geocoded residential histories and drinking water source data, applying the same hypothesis tests as MARBLES. To explore the broader impact of exposure mixtures, we will apply state-of-the-art modeling strategies, and mediation analyses will be conducted to evaluate thyroid dysfunction as a potential mediator in the pathway from lithium exposure to ASD. This study is expected to (1) provide robust evidence of a causal pathway linking prenatal lithium exposure, thyroid dysfunction, and ASD etiology; (2) identify critical windows of exposure to lithium that contribute to thyroid dysfunction and/or ASD; and (3) elucidate the impact of exposure mixtures on thyroid dysfunction and ASD risk. By focusing on modifiable environmental factors, this research will inform intervention and prevention strategies to reduce lithium exposure and mitigate ASD risk, offering actionable insights for public health.

OD - NIH Office of the Director

ABSTRACT Protein aggregation is a shared pathology of Alzheimer’s disease and related dementias known as tauopathies. Because each disorder develops a unique combination of protein aggregate polymorphisms that may influence the course and severity of disease, elucidating the relationship between tau aggregate structure and biological activity has become a high priority in the field. Advances to date have been limited, however, by the lack of rigorously standardized aggregate preparations from tissues and cells which is the focus of many researchers at our university and beyond. Acquiring the proposed state-of-the-art high-performance liquid chromatography (HPLC) system is key component of our efforts to provide high quality protein aggregates associated with Alzheimer's Disease (AD) and Alzheimer's Disease Related Dementias (ADRD e.g. Tau to researchers at Mitchell Center for Neurodegenerative Diseases (MCND), the University of Texas and nationwide. These protein preparations will support research into the molecular basis of disease pathogenesis and catalyze efforts toward creating novel diagnostic and therapeutic strategies specifically tailored against protein aggregate polymorphs.

National Park Service

A. Project Goals 1. To advance and promote to use of research, science, and technology for conserving our nation s cultural heritage. B. Project Objectives 1. Create two videos for art conservators to expose the public to art conservation methods for recovering collections after a disaster. 2. Disseminate preservation technology information.

NIMH - National Institute of Mental Health

Project Summary The majority of Americans will experience a traumatic event during their lifetimes, but only a subset experience chronic negative psychiatric outcomes such as post-traumatic stress disorder (PTSD) and depression. Several cohort studies over the past 10 years have identified brain-based risk mechanisms early after trauma, which predict risk for chronic symptoms such as hyper-arousal, intrusive memories of the trauma, and negative affect. One of the most widely-replicated and theoretically-grounded such mechanisms involves early high amygdala responses to threat cues. Given the strength of current evidence, we propose that this is an actionable target for intervention early post-trauma, to prevent chronic impairing and distressing symptoms. Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that can induce functional brain changes as potential intervention for neuropsychiatric disorders. Emerging findings along with our preliminary data suggest that the amygdala can be reached and dampened via stimulation of a functionally connected cortical prefrontal area. Here we propose that using TMS to dampen amygdala hyperreactivity will prevent a cascade of symptoms that could develop following trauma exposure. We propose to identify Emergency Department patients who have experienced a recent traumatic event (meets DSM-5 Criterion A), and who have high initial PTSD symptoms at 1 week post-trauma. In the R61 phase we will deliver a staged single-blind TMS intervention with a lead-in sham, followed by active treatments with increasing doses, measuring amygdala reactivity at each phase. R61 milestones involve: 1: Target engagement: Determination that active TMS versus sham decreases within-subject amygdala threat reactivity (decrease in reactivity to fearful faces). 2: Dose response: Determination that 4 vs 1 session of TMS decreases these same targets. 3: Safety and feasibility: Demonstrating feasibility of recruitment and retention (75% of participants are able to complete 75% of sessions), and no Serious Adverse Events (SAE) deemed related to the TMS intervention. If these are met, the R33 phase will involve a randomized double-blind sham-controlled trial, providing a double- blind replication of the immediate effects on the amygdala target and 1-month later, as well as longitudinal assessments of TMS effects on both PTSD and depression symptoms over 3 months post-trauma. The research environment at Emory University School of Medicine will provide excellent support for the successful completion of the proposed research, particularly with state-of-the-art neuroimaging facilities, a well-developed infrastructure for identifying participants at risk for chronic trauma-related symptoms through the Grady Trauma Project and Grady Healthcare System, and a strong community of experts in trauma and neuromodulation. If the hypotheses are confirmed, this study will lay the groundwork for future early intervention trials using non- invasive dampening of amygdala reactivity to prevent chronic trauma-related symptoms.

NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development

Project Summary While antiretroviral therapy (ART) has drastically reduced mother-to-child HIV transmission, increasing evidence suggests that in utero ART exposure can disrupt fetal immune development and placental function—even in the absence of vertical infection. HIV-exposed uninfected (HEU) infants experience higher rates of preterm birth, growth restriction, and immune dysregulation, yet the mechanisms remain poorly understood. Addressing these gaps is critical for reducing long-term immune-mediated morbidity in this growing population. Our central hypothesis is that ART exposure reprograms immune signaling at the maternal-fetal interface (MFI), creating a pro-inflammatory environment that impairs immune tolerance and fetal immune maturation. In response to PAR- 25-362, we propose a multi-pronged investigation into how ART influences immune cell development, antigen presentation, and extracellular vesicle (EV)-mediated communication at the MFI. Our study will use cutting-edge immunopeptidomics, transcriptomics, and functional co-culture assays to define how ART disrupts key regulatory mechanisms at the placenta. This work will generate mechanistic insights into immune dysregulation in HEU infants and inform safer therapeutic strategies during pregnancy.

NINDS - National Institute of Neurological Disorders and Stroke

Project Summary / Abstract Nociception is the process whereby a subset of somatosensory nerve fibers (called nociceptors) detects noxious stimuli and transmits this information to the central nervous system, ultimately producing a percept of discomfort or pain. Nociceptors are faced with the complex task of recognizing disparate environmental and endogenous signals of both a physical and chemical nature; these include temperature, pressure, irritants, pruritogens, and inflammatory agents. Consequently, nociceptor activation elicits acute pain as well as injury-evoked pain hypersensitivity and can contribute to so-called ‘maladaptive’ processes underlying persistent pain syndromes. Our goal is to understand how nociceptors detect, integrate, and transmit these signals under numerous environmental and physiological conditions. This proposal is aimed at identifying and characterizing molecules, cells, and mechanisms that contribute to nociception in the context of acute (protective) or pathological (chronic) pain states. Our approach is multifaceted and ranges from structural biology to integrative physiology. At the most reductionist level, we will use biophysical, biochemical, and pharmacological tools to elucidate structural mechanisms underlying ion channel function, with an emphasis on identifying proteins and other cellular elements that physically and functionally engage with members of the TRP ion channel family that play key roles in nociception. We will also leverage cutting edge approaches in electron cryo-microscopy and tomography to visualize these channels and signaling complexes in cellular membranes and, ultimately, in their native environment of the primary afferent nociceptor. At a more integrative level, we shall probe mechanisms of intero-nociception by asking how primary afferent nociceptors interact with tissues to detect noxious signals and transmit this information to the spinal cord. We will focus on the intestine and joints, using mice as genetically tractable models for understanding mechanisms underlying chronic visceral or osteoarthritic (OA) pain. We will employ state-of-the-art techniques, such as genetically encoded neurotransmitter sensors and single cell sequencing, to characterize interactions between nociceptors and sensory epithelial cells in the gut or subchondral bone in joints. Because visceral and OA pain are more prevalent in women, we will ask if these interactions or other properties of resident nociceptors differ with sex or with age, which is also a significant factor contributing to OA. Models of OA or visceral hypersensitivity will be used to ask if genetic, functional, or anatomical characteristics of nociceptors change under maladaptive states. Visceral and OA pain remain poorly managed, reflecting our current lack of mechanistic insight into these common debilitating disorders. Together, these studies will help bridge this knowledge gap and facilitate the development of novel analgesic therapies.

NIGMS - National Institute of General Medical Sciences

PROJECT SUMMARY We propose to establish an interdisciplinary training grant called the Program for Advancing Training in Cell Biology Research (PACeR) at the University of Utah. With unique resources including a cryo-electron microscopy core, state-of-the-art cell imaging facilities, and a vibrant cell biology research community with 37 faculty members across 11 departments, the University of Utah offers an exceptional training environment in cell biology research. This training grant will provide infrastructure and support to an already strong cell biology research community, uniting cell biology researchers across campus and accelerating training of future scientists in this area. The goals of PACeR are to provide intentional and individualized mentorship and training for talented students to create the next leaders in cell biology and to create an environment/culture where trainees feel accepted and recognized as valuable members of the scientific community. These goals are achieved through coursework in cell biology, biostatistics, ethics, and responsible conduct of research, as well as trainee-specific activities, including: bimonthly PACeR group discussions, where trainees will work on presentations skills and receive individualized feedback on their project and presentation; a grant writing and reviewing program, in which trainees will review NIH grant applications in mock study section format as they prepare their own fellowship applications; mentorship training and opportunities to mentor undergraduate students; industry internships; and annual individualized development plan meetings designed to align research objectives with career goals. Most of PACeR’s programming will be intentionally limited to small groups to foster community and cohesiveness among trainees; however, we propose joint annual symposia with other training groups on campus for synergy, collaboration, and networking. Trainees will also interact and engage with scientists of all backgrounds as part of the Rising Stars Symposia and the award-winning University of Utah SACNAS Chapter. Trainees will enter PACeR from four distinct PhD programs, which matriculate an average of 52 training grant eligible students each year. The mentor pool comprises faculty with proven track records of research excellence and mentorship. Mentors have trained 262 PhD students over the past 10 years, and 96% of those trainees are currently pursuing research-related careers. The program will be overseen by a 6-member advisory committee (that includes the co-directors), and program evaluation will be conducted in a collaborative fashion between the advisory board and a centralized office that oversees all T32 training programs at our institution, using an evidence-based evaluation system. We are requesting support for eight predoctoral trainee positions (four in the first year). With its interdisciplinary approach, outstanding mentorship, and focus on cutting-edge research, the PACeR program is poised to produce world-class leaders in cell biology research, driving innovation and advancing scientific discovery at the University of Utah and beyond.

NCI - National Cancer Institute

Summary The Epstein Barr virus is a DNA tumor virus that is associated with human pathologies including Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, stomach cancer, nasopharyngeal carcinoma and autoimmune diseases. EBV is particularly problematic in the HIV/AIDS population where EBV associated lymphomas are especially prevalent. While more than 90% of the world’s population carries EBV, the virus typically exists in a “latent” state with little impact on the host. In response to certain stimuli or local microenvironmental cues, however, EBV enters the viral lytic replication program, leading to viral spread both within and between hosts. Despite the known role of viral latency proteins in EBV associated cancers, there are well-established links between elevated lytic replication and the onset of EBV associated cancers. Further, general elevation of EBV lytic replication is observed in the context of HIV co-infection (+ or – ART), likely contributing to the increased susceptibility of HIV infected individuals to EBV associated lymphomas and autoimmune diseases. With minimal genetic content, viruses are highly dependent on host cell resources for their replication and they elicit extensive alterations of host cell metabolic processes to facilitate efficient virus replication. One of the most conserved and well studied virus-host interactions in herpesvirus replication is “host shut off” where virus encoded factors degrade host cell RNAs destined for translation, freeing up translation resources for dedicated production of high amounts of viral structural proteins. Recently, the Glaunsinger lab showed that despite inducing global Pol III activation of host B2 SINE elements, the murine γ-herpesvirus, MHV68, inhibits host Pol II transcription as a second arm of host shut off, further promoting preferential viral protein synthesis. Using EBV reactivation models that facilitate interrogation of transcriptome changes in pure reactivating cell populations, we have gained insights into remarkable and unexpected interactions between EBV and the host cell transcriptome. Unlike MHV68, we found that EBV sustains cell Pol II gene expression at canonical promoters during lytic replication and strikingly, causes transcription at >10,000 new Pol II initiation sites across the cell genome. While the reason for the broad induction of predominantly non-coding Pol II (EBV) or Pol III (MHV68) transcription across host genomes is unclear, it could relate to some role in remodeling nuclear structure or redistribution of nuclear resources. Our studies also revealed that EBV reactivation induces widespread, noncanonical exon skipping, the extent of which surpasses the degree of exon skipping observed upon severe depletion of most spliceosome components. Preliminary analysis of KSHV reactivation similarly revealed widespread induction of exon skipping indicating that splicing disruption is not unique to EBV. Previous studies have shown that exon skipping can cause either nuclear retention or cytoplasmic nucleolytic degradation by the cellular nonsense mediated RNA decay (NMD) pathway; and we show that nearly 50% of exon skipping events observed during reactivation are NMD candidates. We hypothesize that EBV (and KSHV) lytic replication induces extensive non-canonical exon skipping of cell transcripts resulting in either nuclear retention or degradation through the cytoplasmic NMD pathway as a second, new arm of host shut off. While classic host shut off has been studied for many years, how specificity for cell transcripts is achieved has been largely enigmatic. Notably, herpesviral lytic genes exhibit a remarkably consistent feature of being primarily mono-exonic (i.e. unspliced). We hypothesize that splicing derangement is a new arm of host shut off that facilitates selective targeting of spliced cell transcripts to free up resources for high-level production of viral proteins. In this proposal, we will test this hypothesis, we will begin to address the mechanisms through which EBV induces splicing derangement and we will begin to address the consequences of splicing derangement on host and viral gene expression.

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

People living with HIV/AIDS (PLWH) are at increased risk for type 2 diabetes due to age-related metabolic changes and risk factors such as poor dietary quality, HIV infection and ART use. Diabetes is commonly reported among PLWH as people live longer, with estimates varying from 12-30%. Novel cost-effective non pharmaceutical approaches to prevent diabetes for aging PLWH are needed but require multilevel interventions that address the structural factors affecting dietary change and medical adherence. Food insecurity is 2-3 times higher in PLWH than the general population. Food insecurity is associated with poorer dietary quality due to consumption of cheaper, less nutritious foods, stress, and poor health outcomes, such as diabetes, lower ART adherence, lower CD4+ counts, and unsuppressed viral load. Few dietary interventions, however, have targeted prevention or management of diabetes in PLWH, and those that have, are small, provide pre-packaged meals, and/or lack a control group. While pre-made meals designed for specific diseases can improve health outcomes, they do not address nutrition knowledge and cooking efficacy, which are important for developing long term dietary behavior change. Studies using meal kits (high quality ingredients and simple recipes) have been shown to improve dietary quality, food insecurity, and psychosocial health, but studies have been limited by a lack of nutrition education needed for long-term use of meal kits. Dietary recommendations for prevention of diabetes in PLWH, who are food insecure, have been hindered by a glaring gap in a lack of well-designed interventions and rigorously collected data. To address this gap, Project GLOW (Glucose Levels for Optimizing Wellness for People Living with HIV) aims to improve diet, glycemic and HIV outcomes for aging PLWH with prediabetes through implementation of a food security intervention at a clinic in the Boston/Suffolk County EMA, a priority jurisdiction for ending the HIV Epidemic. Guided by the Exploration, Preparation, Implementation and Sustainment (EPIS) framework, we will engage patients and health care providers to identify barriers and facilitators to study processes and change in health outcomes to implement and refine the intervention. Our hypothesis is that tailored education with complementary food provision will reduce food insecurity and improve dietary behaviors and glycemic and HIV outcomes. This pilot and feasibility trial will randomize 100 PLWH aged >40 years to intervention (n=50) or usual care (n=50) with measures at baseline and 16-weeks and post 12 months for sustainment. This study contributes to NIDDK’s scientific goal of advancing research to disseminate and implement evidence based prevention strategies and treatments in clinics and community settings, to improve the health of all people, more rapidly and more effectively.

Renaissance 21

Project L.I.T. by Star Tech Global Academy will engage youth in multimedia art projects that uplift community spaces and connect with community leaders. This free project will be in hybrid format with both virtual and in-person participation in 3 Teen Centers across Seattle: Garfield, Rainier Beach, and Southwest Teen Life Center. Community members will be recruited as project staff to guide teens through workshops that teach leadership, community building, and multimedia design skills. Hands-on workshops will connect youth with role models and spotlight their work to improve community spaces and motivate to Lead, Inspire, and Transform (L.I.T.).

National Park Service

Through this agreement, the NPS and NCTA will work together on a variety of programs and activities, including: organizing crafts and museum exhibits; developing traditional music presentations and programs; training park personnel in cultural presentation techniques; assisting local non-profit groups with organizing cultural events in national parks; and strategically linking artist and art organizations with parks to create a sense of place, broaden the scope of experience for American artists (especially youth), while improving quality of life.

NIGMS - National Institute of General Medical Sciences

PROJECT SUMMARY / ABSTRACT Proteins are often used for drug targets. Understanding the structure, function, and reaction mechanisms of proteins is crucial. Over the last three decades, inductively detected Electron Paramagnetic Resonance (EPR) has been utilized to elucidate the structure, function, and reaction mechanisms of enzymes and membrane proteins, as well as to quantify reactive oxygen and nitrogen species. The EPR is useful because it is a highly sensitive, powerful, and versatile technique. Proteins such as metalloproteins, membrane proteins, and G-proteins are challenging to purify in sufficient quantities to obtain measurable signals using standard EPR methods. These proteins, Metalloproteins, membrane proteins, and G-proteins constitute almost 30% of all drug targets. However, due to the scarcity of sufficient samples, understanding the structure-function relation using EPR is challenging and thus poorly understood. This proposal focuses on developing a novel micro-resonator to increase the sensitivity of the current state-of-the-art X-band EPR spectrometer by an order of magnitude. If successful, the unprecedented sensitivity for EPR spectroscopy would broaden its applicability to low- yield biomacromolecular samples whose structures are currently poorly understood due to a lack of sensitivity. The resonator is at the heart of any EPR spectrometer, which interfaces with the samples and enhances the signal-to-noise ratio. The ultimate goal of the proposed project is to design, simulate, build, and demonstrate the proposed novel micro-resonator. The proposed project also focuses on a resonator design that is easy to manufacture using a standard commercial PCB substrate and integrates seamlessly with the existing X-band EPR spectrometer. The preliminary simulated result indicates that the proposed resonator would exhibit ultra-high sensitivity due to its high quality factor (Q ~ 9000), nanoliter fill factor, and highly efficient magnetic field concentration for Electron Paramagnetic Resonance.

Seattle Repertory Theatre

Through Public Works Seattle, Seattle Rep will use the art of theatre to connect people with one another and with the city as a whole. Working collaboratively with five non-profits, the project will engage over 150 people to participate in free weekly workshops and attend monthly performances at the Seattle Repertory Theater. The project culminates in an ambitious work of participatory theater featuring a large community ensemble, with four free performances for 3,000 attendees.

Seattle Repertory Theatre

Seattle Repertory Theater will partner with local organizations to share theater experiences and the arts with audiences across Seattle, with an emphasis on engaging populations that face barriers to arts access. A twelve-week series of free workshops, rehearsals, performances and acting intensives will be offered during Fall 2019 to Spring 2020 at 7 different locations. The first workshop will be held at the Ballard Senior Center(5429 32nd Ave NW) and other locations.

Puerto Rico Council on the Arts

Arts and cultural grants for organizations in Puerto Rico, supported by NEA federal funding.

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY/ABSTRACT With an emphasis on the integration of basic, translational and clinical approaches, the 68th annual Aspen Lung Conference (June 9th – 12th, 2026) will focus on answering a central question: Are current advancements in understanding the mechanisms of lung vascular cell dysfunction and lung vascular remodeling sufficient to develop effective strategies for the treatment of pulmonary vascular disease in conditions like pulmonary hypertension (PH), chronic lung disease, sepsis, and acute lung injury. To explore this central question, we structured the program into a series of six thematic sessions, each beginning with an opening keynote address: (1) Novel insights into PH phenotypes and vascular remodeling in the pulmonary circulation; (2) The vascular niche in the pulmonary circulation: Modifying resident cell function to treat pulmonary vascular disease (PVD); (3) The vascular niche in the pulmonary circulation: Modifying circulating and recruited cell function to treat PVD; (4) Understanding cellular interactions in the pulmonary circulation in chronic lung disease: Towards a cure for Group 3 PH; (5) Mechanisms of cardiac adaptation and maladaptation and their effects on heart-lung interactions in PVD; (6) Current and emerging diagnostic and treatment strategies for pulmonary hypertension and PVD. By addressing these topics, we seek to accomplish the following: 1) Provide a forum for leading basic, translational, and clinical researchers to exchange ideas regarding the current state of the field; 2) Stimulate interactions between scientific fields to identify emerging and shared interests leading to more efficient and productive research; 3) Enhance the likelihood of success in translation of preclinical scientific advances into direct patient benefit; and 4) Challenge and stimulate the scientific interests of trainees and attract a new generation of early career investigators into the fields of PVD and right heart failure. We identified outstanding thought leaders to present 12 State-of-the-Art lectures (35 min) on these topics. Lectures will be followed by 25 minutes of moderated discussion, a hallmark of the Conference. The program continues the Conference’s dedication to trainees and early-stage investigators, which will be supported by three Travel Awards (given to top scoring submitted abstracts). Travel Awardees give a 15-minute presentation in sessions that follow each State-of-the-Art speaker (24 total). Two evening poster sessions will provide additional presentation opportunities for trainees, early and established investigators (40 total posters). The final presentation is provided by the Conference Summarizer, who reviews the impact and common themes of the Conference. The Conference Summary is published annually in the Am. J. of Resp. Cell and Mol. Biol. as a “state of the field” review and includes key challenges and future directions for basic, translational, and clinical research. To encourage participation by trainees and early-stage investigators, registration is free for all students, trainees, fellows, Instructors, and Assistant Professors. The Conference is live-streamed and recorded to allow real time participation and/or viewing by investigators unable to attend in person.

Quad Cities Community Foundation

Quad Cities Community Foundation ($150M in assets) supports nonprofits in IL through grants focused on education, community development, arts, health. Awards range from $1,000 to $50,000.

NIDA - National Institute on Drug Abuse

PROJECT SUMMARY/ABSTRACT Shifting cannabis policy and access to high potency cannabis products creates an urgent need to evaluate and disseminate data on cannabis exposure and risks among aging people living with HIV (PWH). Higher potency products confer heightened risk of cannabis use disorder (CUD), cognitive impairment, and falls. Because PWH are more frail than people without HIV (PWoH), they may be more susceptible cannabis-associated harms (e.g., geriatric syndromes including falls/fractures, delirium/dementia) and ART failure or non-adherence. Our proposal responds to RFA-DA-26-055 (Accelerating the Pace of Drug Abuse Research Using Existing Data) and NIDA priorities of understanding the role of substance use in HIV pathogenesis. Electronic health record (EHR) data can advance cannabis research; innovative approaches are needed to maximize its utility. We will use longitudinal nested Veterans Aging Cohort Study (VACS) cohorts and our expertise in informatics, cannabis epidemiology/policy research, HIV, and causal inference to estimate causal effects of cannabis use on geriatric syndromes and ART failure/adherence. Specific Aims: Aim 1. Determine the association of CUD and incident geriatric syndromes and ART failure/adherence. In VACS-HIV (N~180,000), we will estimate the association of CUD and incident falls and fractures (Aim 1Ai) and delirium and dementia (Aim 1Aii). Among PWH, we will determine the association of CUD and HIV viral suppression and ART adherence (Aim 1B). We will assess how associations (Aim 1A-1B) generalize to a non-veteran population (Mt. Sinai HIV cohort, N~850,000, Aim 1C-D). We will explore how cannabis legalization alters these associations (Aim 1E). Aim 2. Estimate causal effect of cannabis use (self-reported) on incident geriatric syndromes. In VACS-Survey (N~9000), we will use target trial emulation to determine the effect of past-year cannabis use on incident falls and fractures (Aim 2Ai) and delirium and dementia (Aim 2Aii). Aim 3. Build and validate a novel EHR-based cannabis use ascertainment algorithm (NLPWH) by extending an existing natural language processing algorithm (NLPREOP) and validating NLPWH. We will create NLPWH by retraining NLPREOP on multiple EHR clinical note types (e.g., primary care) from VACS-HIV in 9 U.S. states (Aim 3A); internally validate NLPWH using cannabis biomarker and self-report (Aim 3B); externally validate NLPWH by chart review in the Mt. Sinai HIV cohort (Aim 3C); and assess impact of cannabis legalization on algorithm performance (Aim 3D). Using the target trial approach from Aim 2, we will evaluate the causal association of NLPWH-derived cannabis use with geriatric syndromes, ART failure, and ART adherence. IMPACT: Using data from two healthcare systems we will provide early and increasingly complete evidence identifying and quantifying medical harms from cannabis use among PWH and PWoH. The new NLP tool we validate may help health systems rapidly estimate cannabis exposure in their patients and guide urgently needed policies for CUD screening, diagnosis, and treatment.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY Dolutegravir is widely used for HIV treatment globally, yet glaringly little data on integrase resistance after dolutegravir failure among children are available. While dolutegravir is associated with improved efficacy and decreased resistance compared to other antiretroviral therapy (ART) regimens, a recent study from Malawi found that integrase resistance was present in 30% of select adults failing dolutegravir. While this may be an overestimate, children have multiple risk factors that increase the risk of developing integrase resistance including greater reuse and resistance to companion antiretroviral drugs, lower rates of viral suppression, higher viral load at failure, and more severe immunocompromise. To address this knowledge gap we will quantify integrase resistance in a population of children failing dolutegravir in Nigeria and utilize this resistance data to develop and validate a rapid diagnostic in collaboration with colleagues there. The 2021 World Health Organization HIV Drug Resistance Report specifically calls for surveys of integrase resistance in order to provide early signals of emerging dolutegravir resistance. Our population of highly treatment-experienced children who were rapidly transitioned to dolutegravir ART, of which 12% have detectable viremia, represents such a clinical population at increased risk of developing integrase resistance, and will inform nationally representative surveys of drug resistance. Nigeria is home to more children living with HIV than any other country in the world. A national survey of pre- treatment drug resistance among ART-naïve infants ≤18 months of age (2016) shows high rates of resistance, including to the most widely used companion drugs among children: abacavir and lamivudine. Such resistance may predispose children to develop integrase resistance. Since 2004, APIN Public Health Initiatives has provided HIV care and treatment to over 22,000 children in Nigeria, and thus is uniquely positioned to provide critical drug resistance data from multiple pediatric sites/regions across Nigeria. We propose to evaluate integrase resistance among 500 children in Nigeria failing dolutegravir-ART at two different time points to provide critical data on the evolution of integrase resistance. We will further utilize these data to develop rapid diagnostics to detect specific integrase resistance mutations with the goal of making dolutegravir resistance testing accessible globally via rapid, low-cost assays. These studies address a critical gap in knowledge regarding integrase resistance among children failing dolutegravir ART, will inform future surveys of drug resistance, and will support the development and validation of a rapid integrase resistance assay in this setting. This has the potential to impact international guidance on dolutegravir use and resistance testing for this vulnerable population of children.

It Takes a Village

The Queens Healing and Liberation project will be a hub for transformative work, committed to the thriving of Black, indigenous and people of color community members and the liberation of everyone. This project will offer space, resources, and nourishment for changemakers grappling with the challenges of our world. Our organization focuses on 3 core fields- health and healing, art and education, and environment and justice. This project will be completed by February 28th, 2023.