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NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY/ABSTRACT Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS). Susceptibility to MS is significantly associated with Class II alleles, in particular DRB1*15:01:01(DR15). Autoimmune response of the self-reactive CD4 T cells to myelin antigens is a major component of MS immunopathogenesis. Several CNS antigens are thought to be the targets for CD4 T cells and there are numerous viral and bacterial peptides that activate myelin basic protein (MBP)-specific T cells. This suggests that cross-reactivity of CD4 T cells might represent one mechanism whereby infections trigger disease. Myelin antigens are widely used to induce Experimental autoimmune encephalomyelitis (EAE). The actual myelin-reactive CD4 T cells potential cross- reactivity is very poorly characterized. To better define the T cell receptor (TCR) repertoire and its specificity in MS, we applied single cell paired TCR sequencing method, an algorithm to determine convergence of TCRs across individuals, and a robust platform for antigen discovery. Without enriching the T cells for any particular antigen specificity, we performed unbiased TCR sequencing of activated T cells from the blood and cerebrospinal fluid (CSF) of MS patients and healthy controls. In MS patients, we found higher clonal expansion and overlap of CD4 T cells in the blood and CSF, convergence of CD4 TCRs among multiple DR15 MS patients with common sequences/motifs, and cross-reactivity to human adenovirus (HAdV) peptide and with MBP. We generated DR15 tetramer with HAdV-peptide and in a small new cohort of DR15 patients and controls show the existence of HAdV and MBP cross-reactive CD4 T cells in the blood. Moreover, we generated a new HAdV-TCR transgenic mice to test hypothesis of cross-reactivity. Altogether, we show that a convergent CD4 TCR from multiple MS patients react with MBP and a peptide from viral origin and these cells can be detected in the blood of patients. Altogether, our results showed that CD4 T cells in MS cross-react to MBP and a peptide from viral origin. Therefore, our central hypothesis is that cross-reactive myelin specific CD4 TCR repertoire in a subpopulation of MS patients is triggered by adenovirus antigen. We will test this hypothesis with the following aims: Aim 1. To assess the cross-reactive CD4 TCR repertoire between MBP- and HAdV in MS patients and healthy individuals. Aim 2. To mechanistically determine the impact of a HAdV- and MBP-cross-reactive CD4-TCR in mouse model.

NIAID - National Institute of Allergy and Infectious Diseases

Abstract Support is requested for a Keystone Symposia conference entitled “Myeloid Cells: Functional Heterogeneity with Therapeutic Promise,” organized by Drs. Charlotte L. Scott, Shalin H. Naik and Thomas Fabre, with scientific programming input from Keystone Symposia. The meeting will take place February 23–26, 2026 at the Keystone Resort in Keystone, Colorado, USA. Myeloid cells play crucial roles in the innate immune system, responding to infections and maintaining tissue homeostasis. Despite their significant therapeutic promise, the potential of myeloid cells is yet to be fully realized. This Keystone Symposia meeting aims to bring together key leaders in academia and industry to discuss recent insights regarding myeloid cell functional heterogeneity and how to target these cells for therapeutic interventions. This conference will highlight recent advances in our understanding of the role of myeloid cells in different disease settings, including cancer, infection and other immune-mediated disorders, which will enable new translational perspectives for understanding, treating, and preventing infectious and immunologic diseases. The meeting program will provide opportunities for attendees to gain a deeper understanding of unique and conserved myeloid cell populations across tissues and diseases and explore how these might be leveraged therapeutically. Through rigorous discussions, this meeting aims to outline key questions for future research that will harness the power of myeloid cells and showcase current and emerging technologies. A key feature of this meeting is that it will be co-located with another Keystone Symposia conference, “Hematopoiesis.” This partnership will provide valuable insights into the interconnected roles of hematopoietic stem cells and myeloid lineages in both health and disease. Inclusive poster sessions, panel discussions, shared meals and social activities will promote networking, encourage the sharing of cross-disciplinary insights and provide broader scientific perspectives important for future research collaborations towards the development of successful therapeutic strategies.

DEPT OF DEFENSE.DEPT OF THE NAVY.NAVSUP.NAVSUP WEAPON SYSTEMS SUPPORT.NAVSUP WSS PHILADELPHIA.NAVSUP WEAPON SYSTEMS SUPPORT

N0038326PR0R076_ FMS REPAIR ACO

National Alliance to End Homelessness

Funding for communities improving their homeless response systems through data integration and performance measurement.

OD - NIH Office of the Director

Specific Aims: NAMs Technology Development Center for Women’s Health, “NAMs TDC-WH” The “NAMs TDC-WH” brings together an international multidisciplinary team, from basic scientists to clinical practitioners, lower the barriers for developing new drugs to treat a spectrum of gynecology disorders ranging from endometriosis to heavy menstrual bleeding and polycystic ovary syndrome (PCOS). This overarching goal will be facilitated by an existing well-funded core infrastructure at MIT in Center for Gynepathology Research that links clinicians, engineers, and scientists in academia and industry to build living patient avatars for endometriosis, adenomyosis and other gynecology diseases (Figure 1. The living patient avatars that will be rigorously tested and translated in the NAMS TDC-WH have been developed since their inception as “combinatorial NAMs”. Computational systems biology and bioinformatics analysis of clinical data (deep phenotyping and -omics) guided the design and operation of microphysiological systems (MPS) to capture key biological phenomena involved in disease and response to drugs, with performance of the MPS benchmarked against in vivo data. For this proposed project, we expand the computational and the clinical teams to capture a more comprehensive picture of the patient population, including genetic diversity and evolving aspects of the pain phenotype. We focus primarily here on combinatorial NAMs for female reproductive tissues, but include liver and other organ systems, recognizing the systemic nature of these diseases and the requirement that any drugs developed with gynecology tissues as a target require metabolic and safety assessments in a systemic manner. We test the hypothesis that pain phenotypes in humans relevant for endometriosis can be captured adequately via the combinatorial NAMs approach. The aims of the TDC-WH are to (i) elevate these technologies to the rigorous criteria needed for regulatory activities related to planning and interpreting human clinical trials for these drugs (ii) further strengthen the ties to the clinical phenotyping, genetics and bioinformatics communities whose input are needed to design physiologically relevant NAMs and benchmark them against in vivo for specific therapeutic targets (iii) translate the NAMs into use via example pre-clinical use cases in collaboration with Pharma. Finally, in addition to the technologies that have already been commercialized or in the process of being commercialized, we aim to translate the new platform technologies under development into wide availability through commercial partners. This will be accomplished through a comprehensive spectrum of education and outreach activities, including videos, hands-on tutorials, and translation of alpha versions of technologies for early feedback on user experience.

OD - NIH Office of the Director

PROJECT SUMMARY The NAMs Decisions Center is a multidisciplinary team of scientists, engineers, modelers, and educators working to integrate New Approach Methodologies (NAMs) into regulatory decision-making for chemical safety assessment. The primary goal of the Center is to develop defined approaches for using mature combinatorial in vitro and in silico NAMs to enhance read-across methods, reducing reliance on animal testing. A key challenge in replacing traditional animal tests is proving sufficient similarity between chemicals, which is required for regulatory acceptance of read-across approaches. A systematic review of over 1,100 industry-proposed read- across adaptations submitted to the European Chemicals Agency (ECHA) found that only 8% were accepted, primarily due to insufficient toxicokinetic and toxicodynamic data—gaps that NAMs could help fill. To address this, the Center proposes five Specific Aims. Aim 1: Center Management and International Integration, will ensure effective governance through an Internal Steering Committee and guidance from an External Advisory Committee with international representation from regulatory agencies, industry and NGOs. Aim 2: Developing Population-Based NAMs for Read-Across, will be focused on improving read-across approaches using population-based in vitro and in silico NAMs. This work will include complex in vitro models for gut permeability, liver metabolism, and renal clearance, population variability studies using human-derived cell panels, ion mobility spectrometry-mass spectrometry as a rapid tool for toxicokinetics, toxicodynamic variability assessment with human lymphoblast cell lines, these will be combined into population-toxicokinetics/toxicodynamics NAMs. Three pilot projects focused on Center-relevant studies will be also included. Aim 3: NAMs Technology Development and Commercialization, will consist of three cores: Administrative Core will provide Center oversight, Data Management & Bioinformatics Core will be responsible for data integration and biostatistics support, and NAMs Resources Core will include resources for Device Fabrication and Transcriptomics. Aim 4: NAMs Qualification and Regulatory Acceptance, will ensure the robustness and reproducibility of the individual and combinatorial NAMs. With expertise in regulatory qualification, this Aim will help facilitate regulatory acceptance of Center- developed NAMs-based approaches. Aim 5: Training, Outreach, and Stakeholder Engagement, will conduct Ethical, Legal, and Social Implications (ELSI) research (identify stakeholder concerns, clarify validation expectations, and refine communication strategies), workforce development & training (create NAMs education materials for high-school/college students, regulators, industry professionals, and academics), and Community Engagement (encourage regulatory adoption through targeted workshops and read-across case studies). Overall, the NAMs Decisions Center aims to revolutionize chemical safety assessments by integrating NAMs into defined read-across approaches. By accelerating chemical evaluations and reducing reliance on animal testing, this initiative will make a significant impact on public health and regulatory decision-making.

NASA

NASA SBIR Phase I funds innovative aerospace and technology R&D including data analytics, autonomous systems, and advanced computing. Post-reauthorization solicitations expected Spring 2026.

National 4-H Council

Funds 4-H youth development programs including STEM, healthy living, and agriculture.

U.S. Fish and Wildlife Service

The National Coastal Wetlands Conservation Grant Program annually provides grants of up to $1 million to coastal and Grant Lakes states, as well as U.S. Territories to protect, restore and enhance coastal wetland ecosystems and associated uplands. The grants are funded through the Sport Fish Restoration and Boating Trust Fund, which is supported by excise taxes on fishing equipment an motorboat fuel.

NGCP

Supports collaborative STEM programs for girls and women.

National Grid Foundation

Supports energy affordability, workforce development, STEM education, and environmental sustainability in National Grid service areas.

National Rural Water Association

Water system operator training and capacity building for small rural systems

National Aeronautics and Space Administration

National Space Grant College and Fellowship Program - Opportunities in NASA STEM FY 2020 – 2024

NSAC

Grants for farm and food policy advocacy, focusing on conservation, beginning farmer support, and local food systems.

NC Department of Agriculture and Consumer Services

The NC Department of Agriculture provides grants to farmers, agribusinesses, food banks, and rural organizations for agricultural development, food system infrastructure, farmland preservation, and rural community support.

NC Department of Public Instruction

STEM education initiative grants for NC to expand science, technology, engineering, and mathematics programs in K-12 and postsecondary institutions.

Washington Headquarters Services

NDEP STEM Open NFO

NDN Collective

Part of a $50M commitment to build Indigenous power. Funds organizing, narrative change, policy, and direct investment in Native communities for systemic change.

Nebraska Department of Economic Development

The Business Innovation Act provides grants to Nebraska small businesses and startups for prototype development, innovation, and commercialization of new technologies, supporting the state's entrepreneurial ecosystem.

Neighborhood House

Work with middle and high school age youth around the High Point low-income housing community in Southwest Seattle to develop and implement a community needs survey and then create app, website, or podcast projects to address identified needs and build awareness of Science, Technology, Engineering and Math (STEM) careers.

NEST+m New Explorations into Science, Technology + Math

Build a science lab equipped with hydroponic farmingtechnology with nutrient film technique, vertical growing systems, integrated pest management, a fish farm and a rain water cachment system.

NIMH - National Institute of Mental Health

Project Summary Biological accounts of reinforcement learning posit that dopamine encodes reward prediction errors (RPEs), which are multiplied by a learning rate to update state or action values. The learning rate is often assumed to be constant, but studies in humans, monkeys, rats, and mice, have found behavioral evidence for dynamic learning rates. In volatile environments, dynamic learning rates allow animals to learn faster when the world is changing, and more slowly when the world is stable. While dopamine is thought to instantiate RPEs, we recently found that dopamine release in the ventral striatum did not reflect learning rates, suggesting that dopamine-independent mechanisms determine the rate of error-driven learning. Moreover, we present strong preliminary data showing that inactivation of the orbitofrontal cortex (OFC) eliminates dynamic learning rates behaviorally, and that OFC neurons that project to the ventral striatum seem to encode the learning rate in their firing rates. In this proposal, we will determine how OFC projections to the ventral striatum dictate the rate of error-driven learning at behavioral and neural levels. This proposal will use a novel behavioral paradigm in rats, in which reward statistics vary over latent blocks of trials. We previously found strong behavioral signatures of dynamic learning rates in rats performing this task. High-throughput behavioral training will generate dozens of trained subjects for experiments in parallel, accelerating the rate of research progress. We will use optogenetics and electrophysiology to record from and manipulate OFC neurons that project to the ventral striatum, to determine if this projection pathway dictates behavioral learning rates (Aim 1). We will use electrophysiology and optogenetics to relate behavioral learning rates and activation of OFC neurons that project to the ventral striatum to trial-by-trial changes in evoked spiking in the striatum (Aim 2). We will use optical methods to measure dopamine release in the striatum and activation of OFC axon terminals, while simultaneously recording action potentials from the ventral striatum, to relate endogenous fluctuations in coincident dopamine and OFC inputs to trial-by-trial plasticity of evoked spiking (Aim 3). These experiments will test key predictions of “three-factor” plasticity rules in behaving animals. These experiments will address a major open question, which is how specific output pathways from OFC interact with downstream circuits to coordinate value-based decisions and learning. Neuromodulatory systems including dopamine are implicated in myriad neuropsychiatric disorders including schizophrenia and depression. A greater understanding of the circuit mechanisms by which they coordinate different aspects of behavior and interact holds promise for revealing novel therapeutic targets for these disorders.

NIDCR - National Institute of Dental and Craniofacial Research

PROJECT SUMMARY/ABSTRACT Deep tooth injuries and inflammation affect millions of Americans, often progressing into pulp necrosis and treated by removing, i.e. devitalizing, and replacing the dental pulp tissue with artificial materials. Vital pulp therapies (VPTs) have the potential to promote cell signaling that stops the infection and restores pulp health, but their effectiveness is limited once pulpitis is established. This is largely due to the large gap in knowledge of what signaling cascades regulate the immune response to defend the pulp versus promote tertiary dentino- genesis to repair the damage. Studies have demonstrated that sensory axons sprout during infection and injury and communicate with immune and stem cell populations during tissue healing. Insights into how neurons pro- tect and enable dentin repair can therefore create therapeutic strategies that harness this axis to heal, rather than remove, the dental pulp tissue. The long-term goal of this project is to understand the cellular mecha- nisms that protect teeth via immune and mineralizing cell responses to inflammation and damage. The applica- tion objective is to determine the role of calcitonin gene-related peptide (CGRP) in activating immune and min- eralizing cells during tooth healing, i.e. reparative dentinogenesis. Our central hypothesis is that neuronal-de- rived CGRP regulates the function of neutrophils & monocytes, surviving odontoblasts and odontoblast progen- itors via its receptor, receptor activity modifying protein 1 (Ramp1), during reparative dentinogenesis. The ra- tionale for this project is that a detailed scientific framework of cellular crosstalk during reparative dentinogene- sis is likely to identify cell-specific mechanisms that sustain and enhance tooth health. The central hypothesis will be tested with the following specific aims: 1) Determine the cell-specific effects of CGRP signaling after deep dentin trauma; 2) Identify the role of CGRP signaling in regulating inflammation and subsequent tertiary dentinogenesis after direct pulp capping procedures; and 3) Evaluate the effect of increased RAMP1 expres- sion and/or exogenous CGRP on promoting pulp healing and homogeneous mineralized tissue barrier for- mation after direct pulp capping. In aim 1, direct pulp capping will be performed on mice with conditional dele- tions of the CGRP receptor, RAMP1, in immune or mineralizing cells. The dentin pulp complex will be analyzed throughout the healing period of 1-56 days for inflammatory and mineralization responses. For aim 2, a model of pulpal inflammation will be created with an initial shallow injury on molars with lipopolysaccharide applied. This will be drilled out and restored 24 hours later, followed by a similar timeline of investigations into pulpal responses. The last aim proposes to enhance RAMP1 and therefore the ability to respond to CGRP released during injury and inflammation to establish whether this can promote pulp healing and tissue barrier formation. The research proposed in this application is innovative because it provides a clinically relevant model of deep dentin damage and repair with which to study cell-specific repair mechanisms. The proposal is significant be- cause it is expected to identify cellular mechanisms that sustain tooth vitality to advance the development of next-generation VPTs.

NINDS - National Institute of Neurological Disorders and Stroke

Project Summary The NeuroNauts Scholars program seeks to cultivate the next generation of neuroscience researchers by providing eight high school students with immersive, hands-on research experiences in areas central to neurological health. The long-term goal is to expand the biomedical workforce by sparking early interest in neuroscience and equipping students with the skills to advance our understanding of brain and nervous system function. Under the expert guidance of UWF faculty, students will participate in an intensive eight-week summer program that integrates authentic laboratory research and interactive seminars. The program’s goals are to: 1. Provide hands-on training in experimental design, data collection, and analysis using cutting-edge neuroscience methodologies. 2. Enhance students’ understanding of neural mechanisms including neuroplasticity and neural network dynamics that underlie brain function and the pathogenesis of neurological disease. 3. Develop complementary skills in scientific writing, presentation, and critical analysis to prepare students for advanced studies and careers in neuroscience. 4. Foster a supportive research environment through personalized mentoring, continuous monitoring of student progress, and regular evaluation of program effectiveness. Program outcomes will be rigorously assessed through quantitative metrics and qualitative feedback using an online assessment system (EvaluateUR),, ensuring that the curriculum remains responsive to student needs. By bridging theoretical knowledge with practical research, the NeuroNauts Scholars program directly supports NINDS’s mission to advance our understanding of the brain and reduce the burden of neurological disease, while building a robust future biomedical research workforce.