Grants

NCI - National Cancer Institute

Abstract Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is projected to be the third leading cause of cancer-related death by 2035. HCC surveillance, defined as screening high risk individuals with abdominal ultrasound every 6 months, is associated with earlier detection, increased curative treatment receipt, and improved overall survival. National data demonstrate that only 25% of patients with cirrhosis receive adequate HCC surveillance and little progress to increase uptake has been made over the past decade. While the current clinical practice paradigm for HCC surveillance focuses on high risk patients with cirrhosis, the rapid increase in the prevalence of metabolic dysfunction associated steatotic liver disease (MASLD) will lead to a larger population at risk for HCC for whom the net benefits of further risk stratification and HCC surveillance are unknown. Given changes in chronic liver disease etiology and HCC epidemiology, emerging novel risk-stratification and surveillance tools, and the initiation of the first multisite trial of HCC surveillance in the United States, there is a need for research to better understand HCC surveillance practices to determine optimal care among patients at risk for HCC development. The long-term goal is to improve healthcare delivery and outcomes for patients at risk for HCC by creating a population-based surveillance registry that will facilitate the implementation of targeted interventions to improve risk-stratification and appropriate healthcare delivery of HCC surveillance. The objective of this application is to establish the feasibility of developing a population-based HCC surveillance registry and assessing our ability to identify at risk patients with MASLD. These objectives will be accomplished through the following specific aims: 1) Develop and implement the tools required to establish a population-based HCC surveillance registry; and 2) Determine the prevalence of MASLD and the performance of ICD codes, lab results, and radiology imaging reports to identify MASLD. The study is conceptually innovative as it is centered on the paradigm shift driven by changes in liver disease etiology that will significantly impact the risk of developing HCC and thus the benefits and harms of HCC surveillance. The proposed research is significant because it will lay the foundation for future research to identify gaps in HCC surveillance and opportunities for improvement. Novel frameworks and approaches are needed to evaluate the impact of the rapid changes in the epidemiology of liver disease etiologies on HCC risk, surveillance, and outcomes.

Up to $400K

2028-04-30

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

Early Detection of Prodromal Brain Network Activity in Alzheimer’s Disease

NIA - National Institute on Aging

Project Summary / Abstract Prodromal symptoms of AD occur years or even decades before the onset of cognitive symptoms in Alzheimer’s disease and may serve as an early diagnostic tool in identifying individuals at risk for dementia. However, since these symptoms are non-specific, they are often missed or attributed to other health-related issues, and even when they are noticed it can be difficult to make a clear determination of AD risk. The goal of the present application is to identify a neural signature that can clearly distinguish between early AD and normal aging. In Aim 1, we will record from 10 brain regions that have been implicated in behavioral process that are disrupted in prodromal AD in mouse model of human tauopathy (htau mice) and wild-type controls (C57BL/6J) across the lifespan. Htau mice display behavioral deficits reminiscent of prodromal AD as well as reductions in 5-HT expression and neural activity starting at 4 months of age, so we expect network-level disruptions at that timepoint or earlier. Here in Aim 1 we will compute new electrical oscillatory features (Electome factors) that distinguish htau and C57BL/6J mice at different ages. As a converging approach, we will also assess predetermined Electome factors in these mice that were previously defined in mouse models of stress vulnerability. The translational potential of the model will be enhanced by leveraging Electome factor activity to identify specific network features in resting state fMRI that define prodromal AD across the aging spectrum. Once we have defined a neural signature of early AD, Aim 2 will assess the role of brainstem monoaminergic neurons in driving these network-level changes in the brain. Serotonergic and noradrenergic neurons in the DRN and LC accumulate tau pathology prior to the entorhinal cortex, leading to neurodegeneration. These neurons also have well-delineated roles in sleep, mood and arousal which are disrupted in prodromal AD. In Aim 2, we will use 3D imaging as well as genetic and chemogenetic manipulations in Sert-cre x htau and Dbh-cre x htau mice to determine whether monoaminergic depletion or reduced neuronal activity drives network activity in early AD.

Up to $2.8M

2030-06-30

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Early Detection of Respiratory Impairments in ALS: A Novel Diagnostic Approach

NINDS - National Institute of Neurological Disorders and Stroke

ABSTRACT Title: Early Detection of Respiratory Impairments in ALS: A Novel Diagnostic Approach Early detection of respiratory impairments in amyotrophic lateral sclerosis (ALS) is crucial for improving survival and quality of life. Current clinical tests, focusing on volitional forced breathing, fail to adequately challenge the respiratory neural drive, leading to undetected and therefore unmitigated loss of respiratory function in the early phases of the disease. Unlike limb muscles, respiratory muscles are controlled by both involuntary (ponto-medullary-spinal) and voluntary (cortico-spinal) pathways. This study proposes a novel diagnostic test to detect automatic breathing impairments in ALS, combining airway occlusion pressure (P0.1) and Chemosensitivity (Δ minute ventilation per Δ%SpO2). Preliminary data from asymptomatic genetic ALS carriers indicate deficits in automatic breathing, despite normal functional vital capacity (FVC) and maximum inspiratory pressure (MIP). We hypothesize that a composite score of P0.1 and Chemosensitivity can identify early respiratory impairments in ALS. The study aims to develop a linear prediction risk score and ROC cutoff to distinguish healthy controls from symptomatic ALS patients, and to identify subclinical impairments in asymptomatic/pre-symptomatic carriers. Microstructural changes in the brainstem-spinal cord and elevated blood neurofilament light chain (Nf-L) levels will be assessed to confirm the diagnostic test’s effectiveness. This innovative approach aims to fill a critical gap in ALS care by enabling earlier intervention and providing crucial markers for future clinical trials.

Up to $196K

2028-03-31

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Early Elementary School Start Time: Impact on Sleep, Health, and Learning

NHLBI - National Heart Lung and Blood Institute

ABSTRACT Many U.S. schools are shifting start times earlier for elementary students to accommodate a national shift toward evidence-based later start times for middle and high schoolers. This shift, however, is occurring despite the absence of data showing whether early start times are harmful to young learners, including kindergartners. Up to 30% of the population, including young children, are considered “night owls”, meaning that they are inclined to sleep and awaken later. Uniformly imposing early start times in elementary schools, under an assumption of no harm, may pose unanticipated risks for circadian misalignment, sleep deprivation, learning and attention challenges, and obesity for many young night owls. Supported by our preliminary findings of a negative effect of early school start times for young night owls, the overarching goal of this proposal is to determine the impact of early school start times on sleep health, learning and attention, and obesity in 200 kindergartners and to follow them through second grade to examine cumulative effects on outcomes. We will enroll 50 kindergartner night owls and 50 kindergartner “morning larks” who attend early-start schools (by 8:00 a.m.), and 50 kindergartner night owls and 50 kindergartner morning larks who attend late-start schools (after 8:00 a.m.). Baseline circadian phase will be measured through salivary melatonin (dim light melatonin onset) for a subset of participating 50 kindergartners during their first study year to evaluate the concordance of chronotypes established by behavioral measures. For all study participants, sleep/wake behavior will be measured via wrist actigraphy and validated sleep health and chronotype questionnaires annually. Participants will also complete reading, math, and attention measures annually. Parents will complete child-sleep quality questionnaires annually. Teacher-report of learning and attention will be collected annually, each winter or spring, based on enrollment date. Obesity will be assessed via calculated body mass index (BMI)-for-age percentile and obesity-promoting routines through parent-report annually. These study outcomes will allow us to examine the following Specific Aims to achieve our goal: Aim 1. Determine whether sleep health outcomes (school day sleep duration, weekend midpoint, weekend oversleep, social jetlag, and daytime sleepiness) differ between night owls and morning larks in early and late start elementary schools. Aim 2. Determine whether learning (reading and math scores) and attention differ between night owls and morning larks in early and late start elementary schools. Aim 3. Determine whether night owls exhibit greater risk for obesity (BMI-for-age percentile) and obesity-promoting routines compared with morning larks in early and late start elementary schools. Results of our study may inform educational policy to better support healthy start times for all students.

Up to $784K

2031-06-30

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Early Epigenetic Drivers of Revival Stem Cell Emergence in Intestinal Injury

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

PROJECT SUMMARY/ABSTRACT Radiation-induced intestinal injury is a frequent and debilitating complication of abdomino-pelvic cancer therapy, often resulting in malabsorption, infection, and chronic gastrointestinal dysfunction. The intestinal epithelium regenerates through dedifferentiation events that give rise to revival stem cells (RevSCs), which replenish lost LGR5⁺ intestinal stem cells (ISCs) following injury. While the identity and regenerative potential of RevSCs are increasingly well understood, the earliest chromatin remodeling events and mechanisms that initiate their formation are not. Preliminary scRNA-seq data from our lab show that Bmi1-YFP⁺ epithelial cells, derived from Bmi1-CreERT2; Rosa26eYFP mice, form a distinct RevSC cluster as early as 24 hours post-irradiation, a timepoint significantly earlier than previous reports of RevSCs emerging from 48-96h. Thus, employing this mouse model provides a unique mechanistic window for studying the early emergence and regulation of RevSCs. We observed widespread chromatin accessibility changes at RevSC loci within 3 hours following injury from ATAC-seq data on intestinal epithelial cells (IECs), indicating promoter and enhancer remodeling as a key early event. Given the role of CBP/p300 histone acetyltransferases in maintaining enhancer activity, I hypothesize that injury-induced chromatin remodeling and a transient reduction in CBP/p300-dependent acetylation following injury, direct IECs toward a “pre-RevSC” state, which can be investigated through the lens of the Bmi1-lineage, enabling subsequent RevSC formation. I will test my hypothesis with two SPECIFIC AIMS. Aim 1 will define the transcriptional and chromatin dynamics that drive RevSC emergence by combining single-nucleus multi-ome (snRNA+snATAC-seq) and CUT&RUN profiling in both whole intestinal tissues, capturing broad, lineage- independent changes, and Bmi1-YFP⁺ IECs to investigate drivers of RevSC emergence. Aim 2 will determine how CBP/p300 inhibition alters enhancer accessibility and promotes RevSC formation and lineage plasticity using in vitro organoid models and in vivo pharmacologic and genetic perturbations. This work will generate a high-resolution atlas of early regenerative chromatin states and uncover enhancer-centric mechanisms that govern epithelial reprogramming. Importantly, it will elucidate how enhancer accessibility and histone modifications orchestrate cell fate transitions during intestinal regeneration, uncovering early epigenetic regulators of RevSC formation. These findings will identify molecular markers of regenerative potential and inform strategies to enhance mucosal repair in radiation enteropathy and inflammatory bowel disease. As part of a structured training plan, I will receive hands-on instruction in single-nucleus multi-omics, enhancer mapping, and organoid-based assays, complemented by formal coursework, clinical shadowing, and mentorship from physician-scientists. This integrated approach will provide the technical, analytical, and professional foundation necessary for a successful career as a physician-scientist in gastroenterology.

Up to $43K

2030-07-31

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Early Head Start

Talbot County, Maryland

Early Head Start

Up to $800K

Rolling

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

Early Head Start

Talbot County, Maryland

Early Head Start

Up to $800K

Rolling

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

EARLY HEAD START CHILD CARE PARTNERSHIP

Department of Family and Support Services

EARLY HEAD START CHILD CARE PARTNERSHIP

Up to $11.2M

2026-11-30

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EARLY HEADSTART EXPANSION

Department of Family and Support Services

EARLY HEADSTART EXPANSION FY26

Up to $4.2M

2026-11-30

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Early Identification and Treatment of Mental Disorders in Children and Adolescents (R01)

National Institutes of Health

Purpose. This Funding Opportunity Announcement (FOA) issued by the National Institute of Mental Health (NIMH), National Institutes of Health (NIH), invites investigator-initiated research grant applications for studies focused on the early identification and treatment of mental disorders in children and adolescents. Specific examples include studies focused on: the validation of early diagnosis of mental disorders in youth, especially in young children; the development of new interventions to treat mental disorders and prevent the exacerbation of associated functional impairment; the efficacy and safety of new and existing treatments; the identification and evaluation of predictors of treatment response and underlying mechanisms of action for new and existing treatments; the long-term effectiveness and impact of early intervention on later course; and the factors that promote or impede access to services and impact the effectiveness of services for these patients in community and practice settings. Assessment methods may include behavioral, neuropsychological, neuroimaging, and other physiological measures or markers. Intervention strategies to be studied may include pharmacological, psychosocial, and rehabilitative interventions, separately or in combination. Mechanism of Support. This FOA will use the NIH Research Project Grant (R01) award mechanism. Applications of related or identical scientific scope are also solicited under the NIH Small Research Grant (R03), the NIH Exploratory/Developmental Grant (R21), and the NIMH Clinical Exploratory Research Grant (R34), responding to FOAs PA-06-180, PA-06-181, and PAR-06-248, respectively. Funds Available and Anticipated Number of Awards. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. The total amount awarded and the number of awards will depend upon the mechanism numbers, quality, duration, and costs of the applications received. Eligible Institutions/Organizations. Public/State Controlled Institution of Higher Education; Private Institution of Higher Education; Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education); Nonprofit without 501(c)(3) IRS Status (Other than Institution of Higher Education); Small Business; For-Profit Organization (Other than Small Business); State Government; U.S. Territory or Possession; Indian/Native American Tribal Government (Federally Recognized); Indian/Native American Tribal Government (Other than Federally Recognized); Indian/Native American Tribally Designated Organization; Non-domestic (non-U.S.) Entity (Foreign Organization); Hispanic-serving Institution; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); Alaska Native and Native Hawaiian Serving Institutions; Regional Organization; Other(s): Eligible agencies of the Federal government; Faith-based or community based organizations.

rolling

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Early Immune Signatures of COPD: Linking Inflammation to Disease Progression

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY/ABSTRACT The R03 application builds upon Dr. Yun’s K08-funded study, which investigated how hedgehog interacting protein (HHIP) deficiency contributes to lymphocytic inflammation in chronic obstructive pulmonary disease (COPD). Through that work, we identified unique CD8+T cell populations in both a murine model and human COPD lungs. In this proposal we will focus on a specific CD8+T cell subset expanded in mild to moderate (early) COPD and investigate its contribution to COPD development and progression. By leveraging longitudinal cohorts and single-cell immune profiling, we will determine 1) whether this subset is associated with COPD development and progression, and 2) the clonal and antigenic drivers that underlying its expansion. Our emphasis on defining the transcriptomic, clonal, and antigenic properties of this CD8+T cell subset in COPD will advance our understanding of inflammatory pathogenesis and potentially provide a foundation for novel therapeutic strategies aimed at slowing disease progression.

Up to $121K

2027-12-31

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Early Immune System Development and Ontogeny (R01 Clinical Trial Optional)

National Institutes of Health

The purpose of this Notice of Funding Opportunity (NOFO) is tofurther elucidate the mechanisms of early immune development in utero, during the early post-natal period and during early childhood in neonates, infants, and children and adolescents with or without in-utero exposure to HIV or Anti-Retroviral Therapeutics (ART).This initiative aims to understand intricate mechanisms of immune cells at the maternal-fetal interface, T and B cell development and maturation in offspring, and local immune responses and the role of systemic immunity.

Up to $400K

2028-11-05

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

Early Immune System Development and Ontogeny (R01 Clinical Trial Optional)

Healthincome_security_and_social_services

National Institutes of Health

<p>The purpose of this Notice of Funding Opportunity (NOFO) is tofurther elucidate the mechanisms of early immune development in utero, during the early post-natal period and during early childhood in neonates, infants, and children and adolescents with or without in-utero exposure to HIV or Anti-Retroviral Therapeutics (ART).This initiative aims to understand intricate mechanisms of immune cells at the maternal-fetal interface, T and B cell development and maturation in offspring, and local immune responses and the role of systemic immunity.</p>

Up to $400K

2028-11-05

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

Early Life Lead Exposure and Later Life Cognitive Function: Biological and Psychosocial Pathways

NIEHS - National Institute of Environmental Health Sciences

PROJECT SUMMARY/ABSTRACT Lead is a well-established neurotoxicant known for its adverse effects on neurodevelopment and cumulative impacts on adult cognition. Emerging evidence suggests that early life lead exposure may also increase the risk of later-life cognitive decline and neurodegenerative disease, independent of adult exposures. However, critical gaps remain in understanding how early life lead exposure contributes to cognitive aging, particularly regarding sensitive windows of vulnerability, interactions with social factors, and underlying mechanisms. The objective of this project is to elucidate the biological and psychosocial pathways linking early life lead exposures and later life cognitive function, focusing on identifying time-specific intervention points over the life course. We will test the central hypothesis that lead exposure during specific early developmental periods contributes to worse cognitive function in later life, which may be modified by psychosocial factors in childhood and adulthood and mediated through epigenetic alterations and adult health conditions. Leveraging the unique study design of the St. Louis Baby Tooth (SLBT) Study, which provides unprecedented early-life measures of lead exposure across prenatal and early postnatal periods in a population of older adults and cognitive assessments, health surveys, and blood samples in later life - this project will: (K99) Aim 1: Evaluate how psychosocial factors in childhood and adulthood modify the association between early life lead exposure and later-life cognitive function; (R00) Aim 2: Investigate whether adult cardiovascular, metabolic, and psychiatric comorbidities mediate the relationship between early life lead exposure and cognitive deficits; and (R00) Aim 3: Identify epigenetic signatures associated with early life lead exposure and their relation to cognitive outcomes. This K99/R00 will provide mentored training to gain expertise in cognitive aging and related comorbidities, social epidemiology, causal inference, and bioinformatics for epigenomics data analysis. Findings will offer immediate insight into risk factors for later-life cognitive impairment, sensitive windows of early life lead exposure, susceptible populations, and pathways through which lead exposures impact later-life cognitive dysfunction. This project, nested within the ongoing SLBT cohort study, will also be a launching point for future R01s examining clinical cardiometabolic measures, cognitive decline, and the cognitive exposome.

Up to $120K

2028-06-30

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

Early Life Stress, Cellular Vulnerability, and the Developmental Programming of Metabolic Disease

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

PROJECT SUMMARY Early life stress (ELS), particularly during fetal development, is a critical risk factor for long-term health, including obesity and metabolic disorders. This project investigates how prenatal stress exposure is biologically embedded, leading to increased vulnerability to abdominal adiposity and metabolic dysfunction. Our long-term goal is to eluci- date cellular and molecular pathways that mediate the developmental origins of metabolic disease, supporting early identification and prevention strategies for at-risk children. Despite known associations between ELS and adult dis- ease, current research is limited by inconsistent findings in early life, inadequate biomarkers of fetal stress exposure, and poor measurement of adiposity in infants. Traditional reliance on weight-based metrics fails to capture fat dis- tribution, which is key to metabolic risk. Moreover, stress exposure during pregnancy is typically estimated from basal circulating biomarkers, neglecting dynamic physiological stress responses. To address these gaps, we employ a translational, multi-level design integrating basic science and clinical research. Using umbilical-derived mesenchy- mal stromal cells (MSCs) from human newborns, we will model individualized cellular vulnerability to ELS. In par- allel, we will track in vivo adipose development using serial MRI assessments and metabolic profiling in infants. Our specific aims are: Aim 1: Determine if biological stress during pregnancy predicts infant adiposity, distribution, and metabolic function using state-of-the-art MR imaging at birth and 5–6 months. Aim 2: Test whether MSCs from high-stress exposed infants exhibit greater cellular vulnerability under in vitro adi- pogenic challenge conditions. Stress exposure will be comprehensively quantified using ex vivo glucocorticoid-cytokine stimulation, diurnal sali- vary cortisol sampling, and maternal blood assays during early and late pregnancy. These data will be synthesized into a composite (PCA) biological stress exposure score. We hypothesize that dynamic, functionally derived measures of maternal stress will better predict infant abdominal adiposity and metabolic function than static bi- omarkers, and that stem cells from high-stress-exposed infants will exhibit greater vulnerability—reflected by in- creased lipid accumulation and hypertrophy—especially under in vitro challenge conditions. This integrated ap- proach will illuminate mechanisms of biological embedding and identify novel markers of metabolic risk. Findings will advance precision health by enabling targeted early-life interventions. This project will also establish a scalable human newborn stem cell biobank for future studies of stress-related disease pathways.

Up to $777K

2031-03-31

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

Early Re-Initiation of Semaglutide After Metabolic and Bariatric Surgery in Youth: A Randomized Clinical Trial

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

Youth with severe obesity are less likely to reach, and maintain, body mass index (BMI) reduction with lifestyle modification and obesity pharmacotherapy alone.1–5 Metabolic and bariatric surgery (MBS) remains the most effective intervention for managing severe pediatric obesity.6 Up to one in four youth do not respond to MBS, whereas others experience weight regain.7 Until recently, few alternative options existed for these young people other than another technique of MBS.4,5 Recent research highlights that lower post-surgical levels of glucagon- like peptide-1 (GLP-1) and increased reward-based eating behaviors contribute to suboptimal early weight loss and weight gain reoccurence.8–11 A multi-pronged approach, immediately postoperatively, that adds GLP-1 receptor agonists (GLP-1RA), like semaglutide, to lifestyle modification may improve weight trajectories by targeting appetite and satiety mechanisms early in the postoperative course, yet this has never been tested in youth.2,12,13 To date, there are no standard of care guidelines for how to incorporate obesity pharmacotherapy after MBS in youth. Accordingly, this study aims to address this gap in evidence-based guidelines involving early re-initiation of semaglutide in youth, who have undergone MBS. Based on novel data from our pediatric MBS program14, we have designed a 24-month randomized controlled trial involving 80 youth, ages 12-18 years, with class III obesity, who have been on semaglutide preoperatively and are undergoing MBS. Youth will be randomly assigned to (1) early reintroduction of semaglutide (MBS + semaglutide) two-weeks postoperatively or (2) MBS alone with no semaglutide. All participants will receive intensive lifestyle modification counseling per standard of care guidelines throughout the trial period.15,16 Assessments will be conducted over a 24-month period to capture changes in anthropometric, cardiometabolic, and food intake outcomes. Aim 1: Evaluate the efficacy of early re-initiation of semaglutide immediately after MBS on weight reduction and body composition. H1: We hypothesize that early semaglutide re-initiation is associated with significantly greater weight loss and reduction in fat mass compared to MBS alone. Aim 2: Examine the efficacy of early semaglutide re-initiation immediately after MBS on GLP-1 and glucose profiles following a frequently sampled oral glucose tolerance test. H2: We hypothesize that early semaglutide re-initiation will increase modified percent time in glucose range, captured with continuous glucose monitoring and increase stimulated GLP-1 levels compared to MBS alone. Aim 3: Assess the effect of early semaglutide re-initiation after MBS on objective measures of ad libitum food intake and food reinforcement using validated, experimental procedures (Eating in the Absence of Hunger, palatable buffet meal, and relative reinforcing value of food task). H3: Compared to MBS alone, youth who receive early semaglutide re-initiation will decrease ad libitum food intake and decrease food motivation. This study will generate the first RCT evidence to inform early, phenotype-driven GLP-1RA use after adolescent MBS— advancing urgently needed, evidence-based protocols with direct implications for clinical practice. 1

Up to $884K

2031-04-30

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Early regulation of T follicular helper cell differentiation via stroma-derived Notch signals

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY The germinal center (GC) is a specialized microanatomical structure forming in secondary lymphoid organs in response to pathogens and immunogens. T follicular helper (Tfh) cells are a specialized subset of CD4+ T cells providing help to B cells within GCs. Tfh differentiation occurs in a stepwise fashion, first via polarization during initial priming by antigen-presenting cells and then via interactions with cognate B cells. The GC response provides a two-pronged system to generate durable protective immunity, as its main cellular outputs are antigen- specific memory B cells and long-lived plasma cells. While many key regulators of Tfh differentiation have been identified, many aspects of early Tfh differentiation remain to be elucidated. The Notch signaling pathway is highly conserved from mice to humans and has been demonstrated to play a role in effector T cell differentiation. This pathway is comprised of multiple ligand:receptor pairs which are differentially expressed across cell and tissue types. Of note, a subset of lymph node stromal cells termed fibroblastic reticular cells (FRCs) that are lineage traced by Ccl19-cre have been shown to be essential for both Tfh and effector CD8 differentiation. My own preliminary data indicates the same subset of cells provide necessary signals to antigen-specific, differentiating CD4 T cells within the first three days post immunization to drive the Tfh fate. In the absence of early Notch signals, differentiating T cells adopt a TH1-biased effector fate, evidenced by increased expression of the canonical TH1 transcription factor Tbet and increased production of TH1-associated cytokines such as IL-2, interferon gamma and tumor necrosis factor alpha. My preliminary data also suggests that the key Notch receptor, Notch1, and the key ligand, Delta like ligand 4, are upregulated 24 hours post immunization. Through a uLIPSTIC-based approach where cells in direct contact are irreversibly labeled, I have demonstrated that antigen-specific CD4 T cells interact with Ccl19-cre-expressing FRCs at the same 24 hour timepoint. However, little is known about the exact mechanisms behind receptor upregulation and the direct transcriptional targets following receptor:ligand interactions. Thus, I hypothesize that FRC niches control the early stages of Tfh differentiation and subsequent magnitude of GC responses via spatially regulated access to Dll4 Notch ligands. To explore this hypothesis, I will determine how the upregulation of Notch receptors is regulated post immunization. I will also define how differentiating Tfh cells interact with cellular partners, and how these interactions change in the absence of Notch signaling. Finally, I will determine how the Notch signaling pathway influences the transcription of known Tfh target genes through retroviral transduction and Cleavage Under Targets and Release using Nuclease (CUT&RUN) to identify the direct transcriptional targets of the Notch signaling pathway. Altogether, this proposal will identify direct Notch transcriptional targets in mature T cells for the first time and situate these events amongst the steps of Tfh differentiation, further elucidating the early mechanisms behind commitment to the Tfh fate.

Up to $50K

2028-03-31

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EARLY STAGE INNOVATIONS (ESI26)

NASA Headquarters

The National Aeronautics and Space Administration (NASA) Headquarters has released the solicitation Early Stage Innovations (ESI), as an appendix to the Research and Technology Mission Directorate (RTMD) umbrella NASA Research Announcement (NRA) titled "Space Technology Research, Development, Demonstration, and Infusion 2026 (SpaceTech REDDI 2026). . The solicitation is available by opening the NSPIRES homepage at https://nspires.nasaprs.com/, selecting Open under "Solicitations," and searching "Early Stage Innovations (ESI26) under Keywords, or directly via https://solicitation.nasaprs.com/NNH26ZTR001N-26ESI_B2. Through ESI26, Space Technology Research Grants (STRG) Program within RTMD solicits proposals from U.S. institutions of higher education (IHEs) for innovative, early-stage space technology research of high priority to NASA. Proposals are sought on specific space technologies that are currently at low Technology Readiness Levels (TRLs). The solicitation exclusively seeks proposals that are primarily responsive to civil-space needs and use cases and not terrestrial and/or non-civil-space applications. The solicitation exclusively seeks proposals that are responsive to one of the following eight topics: Acceleration of Computational Fluid Dynamics of High-Enthalpy Hypersonic Flows Using Advanced Numerics and Machine Learning Advancements in Autonomous Maintenance and Manufacturing Technologies for the Moon and Mars Computational Techniques for the Design and Characterization of Oxidation-Resistant Refractory Alloys for Aerospace Applications Entry-Induced Fracture Modeling of Thermal Protection Materials Experimental Characterization of Supersonic Retropropulsion Flows at Subscale Innovative and Adaptive Filtering Approaches for Onboard Autonomous Spacecraft Navigation Large Surface Area Electrospray Thruster Robotic Construction and Outfitting for Surface Power Grids on the Moon and Mars Only U.S. IHEs are eligible to submit proposals to this Appendix. The Principal Investigator (PI) must be either a tenured faculty member or an untenured faculty member on the tenure track from the proposing IHE. Teaming and collaboration are permitted, subject to the restrictions described in the solicitation. The financial and programmatic support for ESI comes from the STRG Program within RTMD. Awards are planned to start in June 2027. NASA plans to make approximately 24 awards as a result of this ESI solicitation, subject to the receipt of meritorious proposals and the availability of funds. The actual number of awards will depend on the quality of the proposals received; NASA reserves the right to make no awards under this solicitation. All proposals must be submitted electronically through NSPIRES by an authorized organizational representative. Proposals are being solicited via a two-step process where preliminary proposals are mandatory and only those invited may submit a full proposal. Mandatory preliminary proposals are due on or before August 13, 2026, 5 pm Eastern, and the target deadline for invited full proposals is December 16, 2026, 5 pm Eastern. Detailed submission instructions and due dates are provided in the solicitation. Potential proposers and their proposing organizations are urged to familiarize themselves with the submission system, ensure they are registered in NSPIRES, and submit the required proposal materials well in advance of the deadline. Technical and programmatic comments and questions may be addressed by email to the Space Technology Research Grants Program Executive at hq-esi-call@mail.nasa.gov. Responses to inquiries will be answered by email and may also be included in the Frequently Asked Questions (FAQ) documents located on the NSPIRES page associated with the solicitation; anonymity of persons/institutions who submit questions will be preserved.

Up to $750K

2026-08-13

sciencetechnology

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EARLY STAGE INNOVATIONS FOR IN SITU RESOURCE UTILIZATION (ESI26-ISRU)

NASA Headquarters

The National Aeronautics and Space Administration (NASA) Headquarters has released the solicitation Early Stage Innovations for In Situ Resource Utilization (ESI26-ISRU), as an appendix to the Research and Technology Mission Directorate (RTMD) umbrella NASA Research Announcement (NRA) titled "Space Technology Research, Development, Demonstration, and Infusion 2026 (SpaceTech REDDI 2026). . The solicitation is available by opening the NSPIRES homepage at https://nspires.nasaprs.com/, selecting Open under "Solicitations," and searching "Early Stage Innovations (ESI26) under Keywords, or directly via https://solicitation.nasaprs.com/NNH26ZTR001N-26ESI_B7. Through ESI, Space Technology Research Grants (STRG) Program within RTMD solicits proposals from U.S. institutions of higher education (IHEs) for innovative, early-stage space technology research of high priority to NASA. Proposals are sought on specific space technologies that are currently at low Technology Readiness Levels (TRLs). The solicitation exclusively seeks proposals that are primarily responsive to civil-space needs and use cases and not terrestrial and/or non-civil-space applications. The solicitation exclusively seeks proposals that are responsive to the following topic: Lunar In Situ Resource Utilization Water Purification. Only U.S. IHEs are eligible to submit proposals to this Appendix. The Principal Investigator (PI) must be either a tenured faculty member or an untenured faculty member on the tenure track from the proposing IHE. Teaming and collaboration are permitted, subject to the restrictions described in the solicitation. The financial and programmatic support for ESI comes from the STRG Program within RTMD. Awards are planned to start in June 2027. NASA plans to make approximately 3 awards as a result of this ESI solicitation, subject to the receipt of meritorious proposals and the availability of funds. The actual number of awards will depend on the quality of the proposals received; NASA reserves the right to make no awards under this solicitation. All proposals must be submitted electronically through NSPIRES by an authorized organizational representative. Proposals are being solicited via a two-step process where preliminary proposals are mandatory and only those invited may submit a full proposal. Mandatory preliminary proposals are due on or before August 13, 2026, 5 pm Eastern, and the target deadline for invited full proposals is December 16, 2026, 5 pm Eastern. Detailed submission instructions and due dates are provided in the solicitation. Potential proposers and their proposing organizations are urged to familiarize themselves with the submission system, ensure they are registered in NSPIRES, and submit the required proposal materials well in advance of the deadline. Technical and programmatic comments and questions may be addressed by email to the Space Technology Research Grants Program Executive at hq-esi-call@mail.nasa.gov. Responses to inquiries will be answered by email and may also be included in the Frequently Asked Questions (FAQ) documents located on the NSPIRES page associated with the solicitation; anonymity of persons/institutions who submit questions will be preserved.

Up to $1.5M

2026-08-13

sciencetechnology

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Early Stage Testing of Pharmacologic or Neuromodulatory Device-based Interventions for the Treatment of Mental Disorders (R33- Clinical Trial Required)

National Institutes of Health

NIMH requires an experimental therapeutics approach for the development and testing of therapeutic interventions, in which studies both evaluate the clinical effect of an intervention and generate information about the mechanisms underlying a disorder or an intervention response. As part of NIMHs Clinical Trial Pipeline, this NOFO encourages early stage testing of pharmacologic interventions with novel mechanisms of actions or device-based interventions. More specifically, this NOFO is intended to support early stage testing of pharmacologic or device-based interventions using a protocol design where the presumed mechanism of action of the intervention is adequately tested, to provide meaningful information where target modulation yields a dose-dependent neurophysiological/clinical/behavioral effect.

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Early Stage Testing of Pharmacologic or Neuromodulatory Device-based Interventions for the Treatment of Mental Disorders (R33- Clinical Trial Required)

National Institutes of Health

Health

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

Early Stage Testing of Pharmacologic or Neuromodulatory Device-based Interventions for the Treatment of Mental Disorders (R61/R33 Clinical Trial Required)

National Institutes of Health

Health

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

Early Stage Testing of Pharmacologic or Neuromodulatory Device-based Interventions for the Treatment of Mental Disorders (R61/R33 Clinical Trial Required)

National Institutes of Health

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

Early TMS-EEG potentials as biomarkers for personalized neuromodulation in treatment-resistant depression

NIMH - National Institute of Mental Health

PROJECT SUMMARY A major advance for treating depression, the leading cause of disability worldwide, has been the non- pharmacological development of repetitive transcranial magnetic stimulation (rTMS). While rTMS is effective for some, only about half of patients demonstrate a sustained clinical response. This is partly due to stimulation parameters not being fully optimized. While recent research has focused on personalizing where to stimulate, a critical gap remains in optimizing how to stimulate for each patient. This study aims to improve rTMS treatment for depression by using prefrontal electrophysiological biomarkers to personalize stimulation. We seek to enhance target engagement and better understand how brain changes relate to clinical response. Our method centers on early local TMS-evoked potentials (EL-TEPs), which provide reliable measurements of prefrontal excitability at the individual level. Prefrontal EL-TEPs are altered in depression, correlate with treatment outcomes, and respond to neuroplastic interventions like intermittent theta-burst stimulation (iTBS). Our team has pioneered a novel method to optimize EL-TEP acquisition, significantly improving signal quality and reliability. We hypothesize that personalizing iTBS pulse count and intensity to maximize EL-TEP suppression will optimize neural effects and improve clinical outcomes. We propose a R61/R33 study to develop and validate a personalized iTBS protocol. The R61 phase will demonstrate target engagement based on prefrontal excitability changes in 80 patients with treatment-resistant depression (TRD). We will characterize how iTBS parameters affect EL-TEPs in an abbreviated protocol, focusing on acute neurophysiological effects. The R33 phase will confirm target engagement and relate brain changes to clinical response in 106 new patients with TRD, comparing EL-TEP-guided personalized iTBS treatment to non-personalized iTBS treatment. This phase will involve a randomized, triple-blind design with comprehensive neurophysiological, clinical, cognitive, and functional assessments at multiple timepoints. This research is innovative as it uses prefrontal electrophysiology to deliver personalized iTBS treatment. The significance lies in its potential to select treatment parameters based on brain changes. Impact: This project aims to improve iTBS treatment through neurophysiology-guided personalization. By demonstrating target engagement and relating brain changes to clinical outcomes of personalized iTBS treatment, we seek to advance our understanding of the neural mechanisms of depression. If successful, this research could lead to more effective and efficient personalized treatments for depression.

Up to $1.1M

2028-01-31