Grants

The Gordian Group, Inc.

Engineering and Research and Technology Based Services

2027-11-30

technology

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THE GREAT CHAIN AND THE AUSTEN TOWNSEND LEGACY [THE ALICE AUSTEN HOUSE (AAH) WAS ONCE HOME TO TWO ORIGINAL LINKS OF THE ...

National Endowment for the Humanities

THE GREAT CHAIN AND THE AUSTEN TOWNSEND LEGACY [THE ALICE AUSTEN HOUSE (AAH) WAS ONCE HOME TO TWO ORIGINAL LINKS OF THE GREAT CHAIN?AN IRON BARRIER STRETCHED ACROSS THE HUDSON RIVER DURING THE REVOLUTIONARY. THESE HISTORIC LINKS WERE FORGED BY STERLING IRON WORKS, OWNED BY PETER TOWNSEND, THE GREAT-GRANDFATHER OF ALICE AUSTEN?S GRANDMOTHER. THE AUSTEN FAMILY PROUDLY DISPLAYED THE LINKS ABOVE THE FIREPLACE IN WHAT IS NOW THE MUSEUM?S EDUCATIONAL HISTORIC EXHIBIT SPACE, REFLECTING THEIR DEEP PATRIOTIC HERITAGE. TRAGICALLY, ALICE AUSTEN LOST HER FORTUNE IN THE STOCK MARKET CRASH OF 1929 AND WAS FORCED TO SELL MANY OF HER BELOVED POSSESSIONS, INCLUDING THE GREAT CHAIN LINK. FOR DECADES, THE LINK WAS BELIEVED LOST TO HISTORY?UNTIL IT WAS RECENTLY REDISCOVERED IN THE COLLECTIONS OF BOSCOBEL HOUSE IN UPSTATE NEW YORK. AS PART OF THE UPCOMING 250TH ANNIVERSARY OF AMERICAN INDEPENDENCE, THE ALICE AUSTEN HOUSE WILL HOST A SPECIAL EXHIBITION FEATURING THE RETURN OF THIS HISTORIC ARTIFACT ON LOAN. THE EXHIBITION EDUCATION AND PUBLIC LECTURES.]

Up to $25K

2027-01-31

Education

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The Greater Cedar Rapids Community Foundation Community Grants

The Greater Cedar Rapids Community Foundation

The Greater Cedar Rapids Community Foundation ($200M in assets) supports nonprofits in IA through grants focused on education, community development, health, arts. Awards range from $1,000 to $50,000.

$1K – $50K

Educationcommunity developmentHealth+1

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The Greater New Orleans Foundation Community Grants

The Greater New Orleans Foundation

The Greater New Orleans Foundation ($400M in assets) supports nonprofits in LA through grants focused on education, community development, health, environment, arts. Awards range from $2,000 to $100,000.

$2K – $100K

Educationcommunity developmentHealth+2

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The Greater Saint Louis Community Foundation Community Grants

The Greater Saint Louis Community Foundation

The Greater Saint Louis Community Foundation ($500M in assets) supports nonprofits in MO through grants focused on education, community development, arts, health, racial equity. Awards range from $2,500 to $150,000.

$3K – $150K

Educationcommunity developmentarts+2

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The Greater Tacoma Community Foundation Community Grants

The Greater Tacoma Community Foundation

The Greater Tacoma Community Foundation ($300M in assets) supports nonprofits in WA through grants focused on education, community development, health, arts. Awards range from $2,000 to $75,000.

$2K – $75K

Educationcommunity developmentHealth+1

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The growth factor meteorin-like and its receptor KIT in heart failure

NHLBI - National Heart Lung and Blood Institute

DESCRIPTION (provided by applicant): Heart failure (HF) is a prevalent healthcare concern associated with unacceptably high mortality rates and significant decreases in quality of life. Chronic inflammation contributes to HF pathogenesis; however, the precise role of the immune response during disease is not fully understood. Acute pressure overload, imposed in the mouse by transverse aortic constriction surgery (TAC), evokes a strong local inflammatory response. Signals emitted from stressed cardiomyocytes trigger the inflammatory cascade and cardiac expression of proinflammatory cytokines and chemokines increases. While most immune-targeting therapies have shown attenuating effects on HF after TAC, depletion of macrophages promoted functional decline, suggesting there may also be beneficial effects from the inflammatory response. One macrophage-derived cytokine that might have favorable effects during HF is meteorin-like (METRNL). METRNL is secreted by myeloid cells and was shown by our group to have a proangiogenic effect after myocardial infarction by binding to the KIT receptor on endothelial cells (ECs). The interaction between METRNL-producing inflammatory cells and KIT+ ECs is a prime example of the importance of paracrine communication in tissue repair after heart injury and opens up a new therapeutic approach. Considering that myeloid cells swiftly accumulate in the pressure-overloaded myocardium and may release protective factors, and that myocardial angiogenesis helps preserve heart function during persistent afterload stress, we hypothesize myeloid cell-derived METRNL may play an important, adaptive role in this context. This proposal aims to investigate the beneficial aspects of inflammation in HF by defining, specifically, the role of METRNL and its receptor, KIT, after pressure-overload. We want to determine if METRNL is involved in the pathogenesis of HF and assess its use as a therapy for disease amelioration. Our preliminary work supports that METRNL attenuates pressure overload-induced HF. Metrnl and Kit transcriptional expression increase significantly following TAC, and Metrnl-deficient mice have reduced survival and heart function after TAC. Our preliminary data show that patients with severe aortic stenosis have elevated METRNL plasma concentrations, indicating pressure overload also triggers METRNL release in humans. We will use genetic gain- and loss-of-function approaches to study the role of myeloid cell-derived METRNL and its receptor KIT in the pressure-overloaded heart. Our goal is to elucidate the role of METRNL in regulating HF progression (Aim 1), to define the major cell types producing and targeted by METRNL (Aim 2), and to assess METRNL’s therapeutic potential in HF (Aim 3). Successful completion of these aims will shed light on the role of crosstalk between the immune system and heart tissue during HF, and evaluate potential protein and gene transfer-based therapeutic approaches for attenuating disease progression. Our work plan and the state-of-the-art research environment emphasize technical and nontechnical training in skills that are highly relevant in contemporary cardiovascular research. The envisioned training will efficiently prepare me for a career as an independent scientist.

Up to $5K

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The Gus Schumacher Nutrition Incentive Program Produce Prescription Program

Agriculturerural development

National Institute of Food and Agriculture

The GusNIP-PPR, Assistance Listing 10.331, presents the opportunity to bring together stakeholders from distinct parts of the food and healthcare systems and to foster understanding of how prescribing fresh (ONLY) fruits and vegetables might improve the nutrition and health status of participating households. The primary goals of the GusNIP-PPR are to demonstrate and evaluate the impact of projects on:1. The improvement of dietary health through increased consumption of fruits and vegetables; 2. The reduction of individual and household food insecurity; and 3. The reduction in healthcare use and associated costs.

$500K

2026-07-16

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THE HAMILTON SCHOOL CELEBRATES AMERICA'S 250TH ANNIVERSARY [THE HAMILTON SCHOOL FOR CLASSICAL AND CIVIL EDUCATION AT THE...

National Endowment for the Humanities

THE HAMILTON SCHOOL CELEBRATES AMERICA'S 250TH ANNIVERSARY [THE HAMILTON SCHOOL FOR CLASSICAL AND CIVIL EDUCATION AT THE UNIVERSITY OF FLORIDA SEEKS A $25,000 MATCHING GRANT FROM THE NATIONAL ENDOWMENT FOR THE HUMANITIES THROUGH THE CELEBRATE AMERICA! CHAIRMAN?S GRANT PROGRAM TO SUPPORT THE HAMILTON SCHOOL CELEBRATES AMERICA 250?A YEAR-LONG SERIES OF PUBLIC LECTURES, ROUNDTABLES, AND STUDENT EVENTS COMMEMORATING THE 250TH ANNIVERSARY OF THE UNITED STATES. THE PROJECT WILL ENGAGE SCHOLARS, STUDENTS, AND THE PUBLIC IN EXPLORING THE NATION?S FOUNDING IDEAS, CONSTITUTIONAL PRINCIPLES, AND CIVIC IDEALS THROUGH RIGOROUS SCHOLARSHIP AND DIALOGUE. DESIGNED TO ADVANCE THE NEH MISSION OF PROMOTING EXCELLENCE IN THE HUMANITIES AND PUBLIC UNDERSTANDING OF AMERICAN HISTORY, THE INITIATIVE WILL GENERATE BOTH IMMEDIATE AND LASTING IMPACT THROUGH LIVE AND RECORDED PROGRAMMING, STUDENT PARTICIPATION, AND FREELY ACCESSIBLE ONLINE RESOURCES.]

Up to $25K

2027-01-31

Education

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The Hazardous Waste Electronic Manifest System (“e-Manifest”) Advisory Board: Request for Nominations

Environmental Protection Agency

The U.S. Environmental Protection Agency (EPA) invites the public to nominate experts in Information Technology (IT) to be considered for a three-year membership appointment to the Hazardous Waste Electronic Manifest System ("e-Manifest") Advisory Board (the "Board"). Pursuant to the Hazardous Waste Electronic Manifest Establishment Act (the "e-Manifest Act" or the "Act"), EPA has established the Board to provide practical and independent advice, consultation, and recommendations to the EPA Administrator on the activities, functions, policies, and regulations associated with the Hazardous Waste Electronic Manifest (e-Manifest) System. In accordance with the e-Manifest Act, the EPA Administrator or designee will serve as Chair of the Board. This document solicits nominations for possible consideration of candidates to potentially fill a vacancy on the Board to serve as an IT expert for a three-year appointment. EPA may also consider nominations received through this solicitation to fill any unanticipated future vacancies on the Board for the following positions including an industry representative member with experience in using or representing users of the manifest system; and a state representative member responsible for processing manifests.

See notice

environmental cleanup

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The Health Outcomes of Psychedelics Use Survey (POCUS): a Nationally Representative Survey Study

NIDA - National Institute on Drug Abuse

Abstract The use of psychedelics such as psilocybin-containing mushrooms has increased dramatically in recent years, due to rapidly changing scientific evidence, public opinion, and regional policies. Although psychedelics remain Schedule I substances at the federal level, they are unevenly regulated by a patchwork of state and municipal policies. In addition to decriminalized naturalistic use, a growing number of states are creating legal frameworks for the provision of psychedelic services for adults, for any purpose. These environments differ greatly from rigorous clinical trials, where participants are highly screened and known doses of psychedelics are paired with extensive preparation and psychotherapy. Although clinical trial results for psychiatric conditions are promising, research on the use, safety, and health effects of psychedelics in community settings—where most psychedelic use occurs—remains scant. Understanding real-world trends in psychedelic use is of great public health importance given that the rapid speed at which these policies are changing far outpaces the research, with some analyses projecting over half of US states legalizing psychedelics by 2037. Drawing on our substantial expertise in conducting research focused on how and why people use psychedelics as well as associated health outcomes, our objective is to characterize national perceptions of risks and safety, use patterns, and safety outcomes associated with psychedelics. Our overarching hypotheses are: 1) interest in and use of psychedelics is rising–especially in jurisdictions with active psychedelic decriminalization policies, 2) policy changes will impact use patterns (e.g., at licensed centers vs. home) and substance sourcing (i.e., illicit vs. licit), and 3) psychedelic use impacts other drug use, either in polypharmacy or substitution contexts. To test these hypotheses, we propose two aims: 1) Conduct four annual waves of a nationally-representative, probability weighted survey (n=5,000 individuals per wave) via the National Opinion Research Center's Amerispeak Panel to characterize perceptions of harm and safety of psychedelics compared to other drugs, as well as psychedelic use prevalence, and; 2) Among individuals reporting past-year psychedelic use in Aim 1, we will further assess intention for use, use characteristics (e.g., substance used, use with or without a therapist), health outcomes (e.g., mood disorder symptoms), side effects, and impacts of psychedelic use on other substances. In both aims, we will assess relationships between existing psychedelic policies (e.g., decriminalization) and our findings. In the face of rapidly changing policies and public perception, our study will effectively monitor national trends detailing psychedelic safety in real-world contexts, how these substances are used, and their associated health outcomes, including on mood and substance use. We will directly disseminate our results to patient advocacy groups, clinicians, and policymakers, providing critical evidence to inform appropriate public health outreach and education efforts in the era of psychedelic policy reform.

Up to $727K

2031-03-31

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The Hillman City Restorative Justice Project

Hillman City Restorative Justice Committee

The Hillman City Restorative Justice Project will build community capacity by organizing twelve free monthly workshops about Restorative Justice. They will be held at the Hillman City Collaboratory located at 5623 Rainier Ave S. Neighbors, businesses, youth and others will learn Restorative Justice practices that will help them resolve conflict and strengthen community relationships. The project will transform the current tensions in our community to a spirit and practice of unity.

Up to $25K

justiceworkforce

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The impact of a personalized video-based stroke educational platform onpatient-centered and health system-centered outcomes

NINDS - National Institute of Neurological Disorders and Stroke

PROJECT SUMMARY Stroke education represents a unique opportunity to empower stroke survivors (and caregivers) to promote self- management, augment adherence, and reduce post-stroke healthcare utilization. Despite being a key quality metric for stroke centers, most patient and caregiver education is poorly retained and a common source of dissatisfaction. In fact, most survivors are unaware of the cause of their stroke, their modifiable risk factors, and how to properly respond to future stroke symptoms. Although there is no gold standard, most centers rely on a combination of bedside verbal communication and standardized printed materials. Prior work has clarified that effective and durable educational interventions benefit from engaging content, personalization, accessibility, and low cost/burden. Retention is very poor during the stroke hospitalization, but this can be overcome by promoting ongoing engagement after discharge. To that end, our group developed a web-based educational platform (MyStroke) that leverages the electronic health record to personalize video-based educational content for each stroke survivor. Simple but engaging videos are curated to address each patient's stroke etiology, individualized risk factors, prescribed stroke prevention medications, and post-stroke lifestyle issues. This approach transforms point-of-care stroke education, and integrated nudges reveal opportunities for re-education and re-engagement after hospital discharge to achieve a durable impact. In a recent single-center pilot trial, MyStroke improved patient and caregiver satisfaction and improved key elements of stroke knowledge. The objective of this proposal is to build upon our encouraging preliminary experience and conduct a multicenter randomized trial to evaluate the impact of MyStroke on both patient-centered (stroke knowledge, self-efficacy, satisfaction, quality of life) and health system-centered outcomes (medication adherence and health system utilization). Electronic nudges will leverage principles of behavioral economics (i.e. enhanced nudges) to promote ongoing engagement. Our preliminary data indicate that even bland nudges promote engagement, but here we propose to use both bland nudges and enhanced nudges, such that platform analytics will compare the influence of different nudge types. Use of technology in this context stands to bridge geographic distances, connect stakeholders, and increase access to information, but it important to recognize the potential to exacerbate inequities for elderly patients and those with limited access to technology. Issues of digital engagement will be evaluated to reveal opportunities for platform improvement. The MyStroke platform offers a scalable solution stroke education which imposes no burden on the clinical team due to its reliance on a limited number of input fields which can be harvested from the electronic health record to individualized content for each patient.

Up to $644K

2030-12-31

Free to search & build · $99 one-time to unlock the application pack · No subscription

The Impact of Acid Ceramidase in Myeloid Cells on Intestinal Inflammation

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

Abstract Sphingolipids play significant roles in mediating inflammation in disease. Patients with inflammatory bowel disease (IBD) and colitis associated cancer (CAC) demonstrate elevated expression of various sphingolipid metabolism enzymes. Acid ceramidase (AC) is highly expressed in disease and deacylates ceramide generating the product for the generation of the bioactive lipid sphingosine 1-phosphate (S1P). Samples from patients with IBD and colorectal cancer, and animal models of colitis, have identified tissue infiltrating macrophages to be a likely source of elevated AC expression; however, the role of AC and immune cell sphingolipid metabolism in IBD remains understudied. The goal of this proposal aims to elucidate the role of myeloid cell derived AC in the progression of IBD and determine the role of AC in immune cell recruitment in IBD. Several studies have implicated sphingolipid metabolism in IBD and CAC using genetic manipulation or pharmacologic inhibitors in mouse models. Many of these studies have examined total body knockouts; however, the contribution of immune cell specific sphingolipid metabolism has not been thoroughly investigated. Our lab has demonstrated that loss of AC in myeloid cells protected mice from acute colitis using dextran sulfate sodium (DSS). The preliminary data presented in this proposal have extended these studies assessing myeloid specific loss of AC in a model of chronic colitis utilizing IL-10 deficient mice. The loss of AC protected from colonic inflammation, increased ceramide content, and reduced innate immune cell infiltrate. Furthermore, loss of AC in myeloid cells altered adaptive immune cell populations in the colon and peripheral tissues, potentially indicating a role for AC in cell- to-cell communication. Our findings have led us to hypothesize that loss of AC in myeloid cells impairs inflammatory signaling, and immune cell recruitment or maturation to alleviate chronic colitis. We therefore propose the following specific aims: Specific Aim 1: Determine the mechanism by which loss of AC protects from chronic colitis. Specific Aim 2: Determine the role of AC in T cell maturation and immune cell recruitment in colitis.

Up to $50K

2028-05-14

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The Impact of Bile Salt Hydrolase on Intestinal T Cells in Colitis

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

PROJECT SUMMARY/ABSTRACT Inflammatory bowel disease (IBD) affects up to 3.1 million adults in the U.S. Bile acids are recognized as key signaling molecules in microbe-immune communication and may therefore be new therapeutic targets for IBD. Microbes deconjugate bile acids with bile salt hydrolases (BSHs), which can produce a variety of bacterial bile acid amidates (BBAAs). However, whether the microbiome affects the immune system through BBAAs remains a gap in knowledge. To investigate this, there is a critical need for a research tool that allows us to overexpress specific BSHs in the gut microbiota to manipulate the BBAA pool. The innovation of this proposal is the use of engineered native bacteria, which allow the stable overexpression of single BSH enzymes in the lumen without disrupting the native microbiota. Preliminary data show that an engineered native bacteria expressing BSH is protective against colitis. The overall goal of this study is to determine how BSH has this effect. The candidate will colonize mice with BSH-expressing engineered native bacteria to test the central hypothesis that BSH protects against colitis through the production of specific BBAAs. In the next three years, the candidate will pursue this hypothesis with two specific aims. The first aim will determine if BBAA production is necessary for BSH to protect against colitis. The candidate will administer engineered native bacteria that produce different BSHs to mice in the dextran sodium sulfate colitis model and determine whether only BSHs that produce BBAAs reduce colitis severity. The second aim will determine if BBAAs are sufficient to recapitulate the effects of BSH. The candidate will administer synthesized BBAAs to mice in the dextran sodium sulfate colitis model and determine if BBAAs alone are protective against colitis. The expected outcome of this study is a mechanistic understanding of how BSH activity ameliorates colitis, and clarity as to whether the production of certain BBAAs mediates this effect. These findings will have a positive translational impact, since characterizing microbial metabolites that ameliorate colitis could provide new therapeutic targets for the development of IBD treatments. The candidate is an outstanding scientist with a clear goal of establishing herself as an independent researcher specializing in the host-microbiome interface in inflammatory disease. Her training objectives include: designing experiments with engineered native bacteria, conducting microbiome and metabolomics studies, gaining expertise in animal models of inflammatory bowel disease, acquiring the skills necessary for independent research, and expanding her professional network. To achieve these objectives, she has developed a comprehensive plan that integrates hands-on bench research, targeted coursework, seminars, participation in national meetings, and other career development activities. This plan will be carried out under the guidance of a mentorship committee led by Drs. Amir Zarrinpar and Pieter Dorrestein.

Up to $43K

2029-03-25

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The Impact of Changes in Primary Care Clinicians' Work Effort on the Health of Older Adults

NIA - National Institute on Aging

Project Summary There are demonstrated benefits of comprehensive, continuous, and coordinated primary care for older adults, ranging from higher rates of appropriate preventive care receipt to lower rates of hospitalization and mortality. However, the benefits of strong primary care are threatened by an impending primary care workforce crisis, exacerbated by prevalent trends of primary care physician (PCP) workforce attrition and clinical effort reduction. Partly in response to these trends, there is increasing representation of NPs and PAs, collectively referred to as advanced practice clinicians (APCs), in the primary care workforce. However, burnout, intent to leave, and intent to reduce clinical effort are also prevalent among primary care APCs. These trends across primary care clinicians (PCCs; comprising physicians, NPs, and PAs) may significantly threaten quality of and access to care for older adults. At present, there is limited evidence to inform healthcare leaders and policy makers about how primary care workforce disruptions impact access to and quality of primary care received by older adults. There is additionally insufficient information on the actionable factors associated with PCC turnover and PCC reductions in clinical effort. In this grant, we will leverage data from Medicare fee-for-service and Medicare Advantage, which together provide coverage for 93% of older adults, in order to: 1) quantify the number of Medicare patients impacted by PCC turnover and sustained reductions in billed clinical effort and identify factors associated with these work effort changes; 2) assess the impact of PCC turnover and PCCs’ sustained reductions in billed clinical effort on patterns of primary care receipt and non-primary care utilization, including emergency department visits and hospitalizations; and 3) assess the impact of PCC turnover and sustained reductions in billed clinical effort on quality of care for older adults. All analyses will be conducted for the overall population of older adults as well as for subgroups of more vulnerable older adults, including those with dementia, multiple chronic conditions, and from underserved groups (e.g., dually eligible for Medicaid). Additionally, analyses will be conducted for physicians and APCs separately, and for the overall study period and comparing the pre- and post-COVID periods. The results from this study will elucidate how changes in PCCs’ work patterns influence the care of the growing US population of older adults. They will provide actionable insights for leaders seeking to design clinical systems and policies that enhance primary care for older adults. Overall, this proposal will enhance the ability of clinical, operational, and policy leaders to maintain the effort of the primary care workforce and optimize care for older adults.

Up to $680K

2031-01-31

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The impact of chronic low dose cadmium exposure on skeletal growth and maintenance in mice models

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

PROJECT SUMMARY/ABSTRACT Osteoporosis is a debilitating skeletal disease affecting over 50% of women and 25% of men over the age of 50, often resulting in painful and disabling fractures that significantly reduce quality of life and increase mortality. Achieving optimal peak bone mass and strength during early life is one of the most critical factors in reducing lifetime fracture risk. Cadmium (Cd) is a toxic heavy metal increasingly present in the environment due to industrial uses as a metal lubricant, in battery production, pigments, and plastics. Critically, Cd bioaccumulates in the body with a biological half-life of approximately 30 years, raising serious concerns about its effects during key developmental windows such as skeletal modeling in early life. This proposal aims to investigate the long- term skeletal consequences of Cd bioaccumulation during early skeletal growth and attainment of peak bone density, at doses that have previously been considered safe. We will assess effects of Cd on lumbar spine and femur during early skeletal development in mice up to time of peak bone density using advanced high resolution micro-computed tomography imaging, histomorphometry, evaluate biochemical markers of bone turnover and perform assays of bone strength and fracture resistance. This study will provide critical data on how environmentally relevant, chronic Cd exposures during development may compromise skeletal health. This work will inform public health policy and environmental safety standards, particularly as Cd exposure continues to rise globally. Moreover, it will highlight the vulnerability of developing skeletal systems to toxic environmental insults.

Up to $157K

2028-05-31

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The impact of demography and selection on the genetic architecture of human traits

NIGMS - National Institute of General Medical Sciences

Project summary The human population has complex genetic structure because of past and ongoing patterns of migration and admixture, because of nonrandom mating based on heritable traits, and because of selection on disease and non-disease traits. These processes have profound consequences not only for our understanding of human genetic variation, but also for our understanding of the genetic architecture of human traits, including those relevant to human health and flourishing. The genetic architecture of a trait can be summarized as: (i) the loci that underlie variation in the trait; (ii) the effects and frequencies of the alleles at these loci; and (iii) the correlations between alleles across these loci. My work seeks to understand how these features of genetic architecture interact with one another, and how they—and our ability to learn about them from genomic data— are impacted by the processes that determine the genetic structure of human populations. In the first part of my proposed research, I will develop a novel genomic test for stabilizing selection (selection against extreme values of traits) and assortative mating, based on the different effects of recombination on the allelic correlations across loci—long-range linkage disequilibria (LD)—that stabilizing selection and assortative mating generate. I will use this LD–recombination signature to jointly estimate the strengths of stabilizing selection and assortative mating in genome-wide association study (GWAS) data for human traits. I will furthermore characterize how the long- range LD generated by stabilizing selection slows down the allele-frequency dynamics expected under stabilizing selection. I will interrogate the consequences of this slowdown for the equilibrium distribution of allele frequencies and effect sizes, and for the portability of genomic studies across populations. Second, I will seek to understand how demographic processes and selection impact the GWASs that we often use to learn about genetic architecture. Traditional methods to control for the biases that population structure can generate in GWASs have recently been shown to be inadequate in important test cases. I will use coalescent-based approaches to reframe these methods in terms of their ability to capture long-range LD structure in the genome. I will then use this theoretical framing to understand the shortcomings of these methods by studying the consequences of various demographic and selective forces on long-range LD. Then, I will develop and analyze a GWAS design that uses chromosome-specific polygenic scores to control for non-random mating and selection—which traditional methods struggle to control for—in population-based GWAS. Third, I will show that stabilizing selection on complex traits generates selection against the minor-parent ancestry in admixed populations. Using comprehensive simulations of demographic and selective scenarios relevant to Neanderthal–human introgression, I will explore whether this novel mechanism of selection against introgression can explain the extent and pattern of Neanderthal ancestry in the human genome. Finally, I will characterize the genomic signals of introgression unique to this mechanism of selection, and test for them in biobank-scale data.

Up to $451K

2031-01-31

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The Impact of Dynamic Fluctuations in Caregiver Stress on Children's Language Environments, LanguageDevelopment, and School Readiness

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

PROJECT SUMMARY Children’s language development and school readiness are deeply influenced by their early social interactions with caregivers. As a child’s main interaction partners, caregiver stress can also have profound influences on child development. The PI’s prior work, as well as the broader literature investigating associations between caregiver stress, caregiver–child interactions, and child development, have mainly used static, laboratory-based measures of stress and caregiver–child interactions. This foundational work fails to capture the inherently dynamic nature of variations in caregiver stress and caregiver–child interactions. Understanding how stress influences the caregiver–child relationship early in childhood is particularly important, as this is a critical window for development and preparation for entering formal schooling. The proposed work will test an innovative developmental model whereby the PI will investigate how caregiver stress and children’s language environments co-vary in real time, with cascading effects on children’s cognitive development. The use of innovative, real-world measurement tools, such as ecological momentary assessment and daylong language recordings, will allow for a nuanced investigation of the daily factors that are key for promoting child development. Results will critically advance our understanding of how time-varying measures of children’s and caregivers’ experiences influence children’s language development and school readiness, while also advancing the PI’s training and progression toward an independent research career. Aim 1 will characterize the variation in caregiver stress across time and daily contexts using ecological momentary assessment. Aim 2 will determine how time-varying fluctuations in caregiver stress relate to fluctuations in caregiver–child language interactions measured via daylong audio recordings. Aim 3 will examine how the variability of caregiver stress and associated language interactions relate to measures of children’s language development and school readiness. It is hypothesized that caregivers will display variation over time in ecological assessment of stress, and that this variation will be associated with time-locked differences in caregiver–child language interactions. Further, it is hypothesized that higher levels of caregiver–child interactions will positively predict child developmental outcomes and may serve as a “protective factor” against higher levels of dynamic stressors. The training aims will advance the PI’s skills in the use of ecological momentary assessment tools, application of intensive longitudinal design and analytic approaches, and the skills needed to independently run a productive laboratory focused on how caregiver factors influence child development. Ultimately, this work has the potential to pinpoint targets for intervention to support developmental outcomes for children and their caregivers who experience increased levels of stress. Improved understanding of the predictors and mechanisms by which children learn language may guide efforts in working with families to mitigate the long-term impacts of language learning difficulties.

Up to $79K

2029-02-28

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The Impact of Environmental factors on Lewy Body Dementia: Combining Claims Data and Mechanistic Studies

NINDS - National Institute of Neurological Disorders and Stroke

Project Summary/Abstract Lewy body dementia (LBD) is a neurodegenerative disorder affecting over one million Americans, second only to Alzheimer’s disease as a cause of neurodegenerative dementia. LBD is associated with abnormal deposits of α-synuclein (αSyn) in the brain. These deposits, called Lewy bodies, affect brain cell populations whose impairments, in turn, lead to problems with cognition, movement, and behavior. Older age and genetics are possible risk factors. Harmful environmental exposures may also increase the risk of LBD, yet their effects on LBD have generally been understudied. This proposal responds to PAR-24-249 and seeks to understand the interaction between environmental factors and LBD and its mechanisms. Our goal is to leverage massive nationwide claims datasets, coupled with advanced causal inference statistical methods reinforced by causal mechanistic studies in an in vitro LBD model system, to identify rigorously the modifiable environmental factors that contribute to LBD exacerbation and identify vulnerable subpopulations who may be at higher risk. We address this goal using Medicare claims where LBD is well identified through ICD codes. We have access to 100% Medicare Part A (inpatient hospitalizations) claims (>550k LBD hospitalizations over the study period) with longitudinally linked individual-level age, sex, race, cause-specific hospitalizations, and date of death for 2000- 2020, as well as 20% Part B (outpatient) and Part D (prescriptions) for a subset of years (2016-2018). We will link these data to daily (PM2.5, NO2, ozone) and annual (PM2.5, NO2, ozone, PM2.5 components (e.g. lead, iron, zinc), county level annual pesticides, daily weather variables, and area level factors (greenness, urban/rural, region, smoking). To mechanistically evaluate LBD susceptibility to environmental factors, we employ an SH- SY5Y model of LBD seeded with αSyn fibrils amplified from LBD patient-derived Lewy bodies that recapitulates phospho-S129-αSyn aggregates characteristic of LBD. Specifically, in Aim 1 we will quantify the association between individual and joint exposure to air pollution, metals, and pesticides and LBD exacerbation, evaluating both short-term (acute) and long-term (chronic) effects as well as identify vulnerable subpopulations. In Aim 2 we will evaluate toxicity and molecular mechanisms of PM2.5, metals, and pesticides in in vitro LBD models. And in Aim 3 we will quantify the association between temperature and temperature variability and LBD exacerbation as well as identify vulnerable subpopulations. In summary findings of this study will provide evidence on the causal link between environmental exposures and LBD exacerbation with the highest possible scientific rigor and will identify multiple modifiable risk and protective factors that lead to increased vulnerability in LBD. Completion of this project will provide the foundation to inform actionable policy (e.g., ensure stringent air pollution standards for PM2.5, implement heat prevention strategies, regulate use of certain pesticides) to help slow the LBD disease burden and improve the quality of life for millions of Americans.

Up to $1.8M

2029-04-30

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The impact of exogenous polyamines on cervicovaginal T cell immunity

NIAID - National Institute of Allergy and Infectious Diseases

Project Summary/Abstract The cervicovaginal mucosa is a critical immunological interface balancing protection against pathogens with tolerance to commensal microbes and semen. Cervicovaginal T cells are essential for viral defense, such as against herpes simplex virus type 2 (HSV-2), which infects half a billion people worldwide and persists at the vaginal mucosa. However, the metabolic factors shaping cervicovaginal T cell function remain poorly understood, creating a critical need to define how local metabolites influence mucosal immunity and infection susceptibility. In the gut mucosa, microbial and diet-derived polyamines exert strongly immunosuppressive effects by promoting the expansion of regulatory T cells (Tregs) and inhibiting the activation of pro-inflammatory immune cells. Similarly, in the tumor microenvironment, polyamines produced by tumor cells inhibit the function of effector T cells. It is unknown how exogenous polyamines modulate cervicovaginal mucosal immunity and susceptibility to infection. Notably, the cervicovaginal mucosa is exposed to much higher levels of exogenous polyamines compared to gut, primarily through seminal fluid, which is rich in spermine and spermidine, and bacteria associated with bacterial vaginosis, which produce putrescine. Recent evidence suggests that the catabolism of high levels of exogenous polyamines induces oxidative stress and mitochondrial damage, which may contribute to polyamine-mediated immunosuppression. We have recently found that exogenous polyamines at physiologically relevant concentrations are taken up by circulating T cells, suppress T cell activation and proliferation, and decrease mitochondrial membrane potential. Thus, we hypothesize that exogenous polyamines suppress cervicovaginal T cell activation and function by inducing metabolic dysfunction, thereby creating an immune-tolerant environment that increases HSV-2 infection susceptibility. To test this, Aim 1 will determine how exogenous polyamines influence cervicovaginal T cell activation, proliferation, cytokine production, and metabolism in vitro. Aim 2 will examine the effects of exogenous polyamines on cervicovaginal immunity and HSV-2 infection susceptibility in vivo. By defining how microbial and seminal metabolites regulate cervicovaginal mucosal immunity, this work will provide novel insights into immune- metabolic interactions in the female genital tract and may reveal new therapeutic targets for STI prevention, improving reproductive health outcomes, and optimizing mucosal vaccine efficacy. To carry out these aims, the PI has assembled a team at Harvard Medical School and the Ragon Institute with combined expertise on mucosal immunology, immunometabolism, and infectious disease who will collaborate and support the PI’s development as an aspiring physician scientist and leader in mucosal immunology.

Up to $43K

2029-04-30

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The impact of low-abundance commensals on gut colonization resistance

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY Clostridioides difficile infection (CDI) poses a significant public health burden, with approximately half a million cases annually in the United States and recurrence rates of up to 25%. CDI is primarily driven by disruptions to the gut microbiome, often due to antibiotic treatment, which creates an environment conducive to C. difficile (Cd) colonization. Current microbiome-based therapeutic strategies, such as fecal microbiota transplants (FMTs), have shown promise in restoring colonization resistance; however, their safety, reproducibility, and regulatory challenges limit widespread clinical application. While defined microbial consortia represent a promising alternative, their efficacy remains suboptimal. We hypothesize that these failures stem at least in part from an over-reliance on high-abundance (HA) species and an incomplete understanding of how low- abundance (LA) species contribute to microbiome stability and pathogen resistance. This project seeks to systematically evaluate the role of LA species in microbiome assembly and in conferring colonization resistance using a combination of synthetic microbial communities, metabolomics, and gnotobiotic mouse models. We hypothesize that LA species play crucial metabolic and ecological roles, through direct competition with Cd and by reinforcing community resilience under antibiotic-induced perturbations. To test this hypothesis, we will employ a defined yet complex synthetic community, mhCom, that encompasses both HA and LA species and assembles reproducibly in vitro and in vivo. Leveraging high-resolution metabolomics, we will (i) characterize the metabolic niches and functional redundancies of LA species and (ii) determine their role in resistance to Cd colonization and microbiome recovery and Cd suppression following antibiotic-induced CDI. In Aim 1, we will map the metabolic functions of LA species within mhCom in vitro, identifying privileged metabolic niches and cross-feeding interactions that contribute to community stability. We will use untargeted metabolomics and species dropouts to establish whether LA species and/or Cd fill metabolic voids when HA species are lost. In Aim 2, we will use gnotobiotic mice to assess the impact of LA species on C. difficile colonization resistance, determining whether the inclusion of LA species enhances pathogen exclusion both before and after antibiotic-induced microbiome disruption. By addressing a critical knowledge gap in microbiome ecology, this study has the potential to redefine microbiome-based therapeutics, either by demonstrating that LA species are not merely passive members of the gut community but essential contributors to microbiome resilience or by affirming strategies focused on HA species. The outcomes of this research will inform the rational design of next-generation microbial therapeutics with enhanced robustness against CDI and will have direct impact for other microbiome-related diseases, providing a foundation for safer, more effective, and precision-targeted microbiome interventions.

Up to $434K

2028-03-31

Free to search & build · $99 one-time to unlock the application pack · No subscription

The Impact of Problematic Smartphone Use on Behavioral and Neural Functioning

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

Project Summary Presently, approximately 95% of U.S. teens now own smartphones giving rise to growing concerns about excessive and compulsive use patterns of use. Although smartphones offer unprecedented opportunities for learning and connection, problematic smartphone use (PSU), which affects roughly one in four adolescents, manifests as compulsive behavior that interferes with daily functioning and well-being. During this sensitive period of heightened neuroplasticity, PSU's behavioral patterns mirror other compulsive disorders, raising critical questions about its impact on adolescent development. The timing of PSU emergence coincides with a crucial period of neural and social development. During adolescence, smartphone-related disruptions can strain family relationships and weaken peer bonds, potentially compromising essential support systems. Physical health may also suffer as increased screen time increases sedentary behavior. These behavioral changes occur against the backdrop of significant brain maturation, particularly the asynchronous development of social-emotional systems and cognitive control networks. The constant stream of notifications and engaging apps may be especially disruptive to the frontoparietal network, which plays a vital role in attention regulation and inhibitory control. Although existing research has identified correlations between PSU and various negative outcomes, understanding the temporal dynamics and bidirectional influences of these relationships on adolescent development remains crucial. This study will address these gaps using complementary longitudinal approaches with a multimodal framework. The first project will follow adolescents (N=100) with mild to severe PSU (ages 13–18) over six months, using weekly experience sampling to examine fluctuations in PSU, social support, and physical activity. A cross-lagged panel model will assess bidirectional relationships and explore moderating factors, such as family and peer dynamics. The second project will leverage three waves of data from the Adolescent Brain Cognitive Development (ABCD) Study (N=4,754) to investigate how PSU influences changes in frontoparietal network connectivity over time, or conversely, whether neural connectivity patterns influence PSU. By exploring the interplay between PSU, social behavior, physical activity, and brain development, this research aims to delineate the temporal dynamics of PSU's developmental consequences and provide actionable insights for mitigating the negative impact. The findings will inform scalable interventions and evidence-based guidelines to support adolescent well-being. This work addresses a critical public health priority by advancing understanding of how digital behaviors shape development during this pivotal period of growth. Moreover, by identifying key periods of vulnerability and resilience, this research will establish a foundation for targeted interventions that promote healthy technology use while fostering crucial developmental milestones.

Up to $132K

2031-04-30

Free to search & build · $99 one-time to unlock the application pack · No subscription

The Impact of Short Chain Fatty Acids on Calcium Regulatory Pathways in Kidney Stone Formers

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

Project Summary/Abstract Urolithiasis (urinary stone disease) is a rapidly escalating public health crisis worldwide. The prevalence of kidney stones has more than doubled over the past 40 years, yet minimal new strategies for disease prevention have become available for decades. Calcium oxalate (CaOx) is one of the most common types of urolith, but this mineral composition requires expensive methods of physical removal. Following stone removal procedures, recurrence rates are as high as 50% in 5 years, highlighting an urgent need for novel, effective, and accessible stone prevention strategies. Disturbances in calcium balance constitute the most common metabolic abnormality underlying CaOx stone formation, yet the causes of these imbalances are often not identified. Recent discoveries suggest that the microbiome and microbial metabolites may influence stone formation. For instance, patients with CaOx urolithiasis exhibit deficiencies in short chain fatty acids (SCFAs), a class of metabolites produced in the gut following microbial fermentation of dietary and prebiotic fibers. In rodent models of urolithiasis, SCFA supplementation markedly reduces CaOx renal crystallization, potentially by lowering urinary oxalate and exerting anti-inflammatory effects in the kidneys. However, the relationship between SCFAs and calcium homeostasis in the context of CaOx urolithiasis remains poorly understood. This gap in knowledge is especially important given the high prevalence of idiopathic calcium disturbances in CaOx stone formers. In this study, we will use a multi-omics approach to delineate the interplay between the microbiome, SCFAs, calcium regulation, and stone risk in a natural canine model of CaOx urolithiasis. Dogs are a particularly powerful translational model for studying CaOx stone formation, as dogs form CaOx stones commonly and share several risk factors and features of disease pathology with humans. This includes parallels in calcium disturbances, microbiome abnormalities, and lower abundances of SCFA-producing bacteria. First, we will perform a prospective, case-control study to define interactions between SCFAs and individual calcium regulatory pathways in dogs with and without CaOx urolithiasis. This will bridge major gaps in our understanding of the microbiome and its role in stone pathogenesis. Second, we will examine how these pathways can be manipulated using prebiotic fibers to enrich SCFA production. This will provide practical insight into an inexpensive and accessible dietary supplement as a potential new stone prevention strategy. Third, we will determine how specific microbial and metabolic features predict stone recurrence. This will help us identify potential risk factors for stone recurrence that can be used to guide patient monitoring. We have assembled a powerful multidisciplinary mentoring team that is uniquely suited to guide this project. Data from this work will also lay the foundation for a future R01 funding application. With the resources and protected time provided through this award, I will advance my professional training and create a clear path towards independence as a translational microbiome and urological researcher.

Up to $161K

2030-05-31