Grant List
Represents Grant table in the DB
GET /v1/grants?sort=-id
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-id", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1442&sort=-id", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=2&sort=-id", "prev": null }, "data": [ { "type": "Grant", "id": "16179", "attributes": { "award_id": "5F31DA063126-02", "title": "A statewide examination of the address-level relationships between residential eviction proceedings and overdose events in Rhode Island", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Drug Abuse (NIDA)" ], "program_reference_codes": [], "program_officials": [ { "id": 44305, "first_name": "ERIN MARGARET", "last_name": "PARKER", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-01", "end_date": "2027-08-31", "award_amount": 50114, "principal_investigator": { "id": 44306, "first_name": "Alexandra", "last_name": "Skinner", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3365, "ror": "", "name": "BROWN UNIVERSITY", "address": "", "city": "", "state": "RI", "zip": "", "country": "United States", "approved": true }, "abstract": "PROPOSAL SUMMARY In the wake of the COVID-19 pandemic, overdose mortality and affordable housing shortages have reached unprecedented levels in Rhode Island and across the United States. Housing insecurity is a known risk factor for overdose, yet the effects of residential eviction—a structural and policy-sensitive cause of housing insecurity—on overdose risks are understudied. Eviction is a complex legal process composed of a series of stages, each of which may impact overdose risk and thus offers opportunity for public health intervention. The objective of this proposal is to pursue a thorough examination of the relationship between residential eviction proceedings (i.e., filing, hearing, and enforcement) and overdose at the address level in Rhode Island, to better inform eviction prevention policies that complement ongoing harm reduction and overdose prevention efforts. The proposed research will leverage the wealth of centralized, high-resolution data available in Rhode Island—and our team’s established relationship with the state health department—to construct a longitudinal dataset with data linked from several administrative sources. We will first characterize the prevalence and time course of eviction proceedings relative to non-fatal or fatal overdose events by conducting sequence and cluster analyses to operationalize variation in the order, duration, and timing of eviction proceedings before and after a given overdose event (AIM 1). We will then estimate the address-level causal effect of residential eviction proceedings on risk of non-fatal and fatal overdose, both overall and by race and ethnicity of overdose decedents, using a sequential target trial approach (AIM 2). The proposed research will be among the first of its kind to link eviction records with address-level health data to characterize heterogeneity in the duration and timing of eviction proceedings, to examine a causal link between eviction and overdose, and to explore differential impacts of eviction on overdose death by race and ethnicity. Because eviction is an intervenable mechanism of housing vulnerability that may be associated with overdose risk, findings from this work may elucidate novel avenues for addressing the intersecting housing and overdose crises in tandem. The proposed research will be completed by the principal investigator with support and mentorship from collaborators with substantial expertise in advanced quantitative methods for life course epidemiology and causal inference. The training activities detailed in this application, focused on advancing skills in epidemiologic study design and longitudinal data analysis and developing a deep contextual knowledge of the social and legal implications of eviction proceedings, will prepare the principal investigator for a career as an independent social epidemiologist and academic researcher.", "keywords": [ "Acute", "Address", "Alaska Native population", "American Indian Population", "Applied Skills", "Black race", "COVID-19 pandemic", "Censuses", "Characteristics", "Cluster Analysis", "Complement", "Complex", "County", "Data", "Data Linkages", "Data Set", "Discrimination", "Dose", "Drug user", "Economics", "Epidemiologic Research Design", "Epidemiologist", "Ethnic Origin", "Event", "Exposure to", "Funding", "Goals", "Harm Reduction", "Health", "Hearing", "Heterogeneity", "Hispanic", "Housing", "Individual", "Intervention", "Knowledge", "Learning", "Legal", "Life course epidemiology", "Link", "Mentorship", "Methodology", "Methods", "Neighborhoods", "Overdose", "Patients", "Policies", "Prevalence", "Prevention", "Principal Investigator", "Process", "Race", "Records", "Research", "Research Personnel", "Rhode Island", "Risk", "Risk Factors", "Sequence Analysis", "Series", "Shapes", "Source", "Structural Models", "Time", "Training", "Training Activity", "United States", "United States National Institutes of Health", "Variant", "Work", "career", "causal inference", "chronic exposures", "data management", "epidemiology training", "health data", "high-resolution", "housing insecurity", "legal implication", "life course", "longitudinal analysis", "longitudinal dataset", "longitudinal research", "marginalized community", "mortality", "neglect", "novel", "overdose death", "overdose prevention", "overdose risk", "psychosocial", "public health intervention", "residence", "response", "risk prediction", "segregation", "skills", "social", "social implication", "stressor", "structural health determinants" ], "approved": true } }, { "type": "Grant", "id": "16178", "attributes": { "award_id": "5K23AI185318-02", "title": "Defining vaccine immunogenicity and adoptive transfer in hematopoietic stem cell transplant recipients", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32556, "first_name": "TIMOTHY A", "last_name": "GONDRE-LEWIS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-15", "end_date": "2029-08-31", "award_amount": 194400, "principal_investigator": { "id": 44302, "first_name": "Amy Caryn", "last_name": "Sherman", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3545, "ror": "", "name": "BRIGHAM AND WOMEN'S HOSPITAL", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Allogeneic hematopoietic stem cell transplant (HCT) recipients are at high risk of severe morbidity and mortality due to respiratory viral illnesses, including COVID-19. Despite two mRNA SARS-CoV-2 vaccines that are highly effective for the general population, HCT recipients have reduced immune responses to vaccines and remain at risk. This population’s ongoing risk is amplified by the emergence and circulation of SARS-CoV- 2 variant strains, relaxation of mask mandates and other public health measures, and waning effectiveness of SARS-CoV-2 monoclonal antibodies. New vaccination strategies are urgently needed for patients with hematologic malignancies, both to protect these patients and to reduce viral reservoirs that otherwise would allow for generation of new variants. To inform these strategies, we will evaluate the unique role of adoptive transfer of humoral and cellular immunity in HCT recipients, which will simultaneously use vaccine response as a mechanism to evaluate immune reconstitution. These studies will test our overarching hypothesis that these patients have distinct and altered immune responses to mRNA SARS-CoV-2 vaccination, resulting from their underlying disease, past immunomodulatory therapies, and the unique donor-to-recipient immune dynamics. The Specific Aims of this proposal are: Aim 1: Characterize the relationship between donor and recipient SARS-CoV-2 immunity in matched-related donor allogeneic HCT patients through analysis of humoral responses and transfer of immunity post-transplant from banked samples; Aim 2: Describe the correlation between donors’ pre-harvest cellular responses and recipients’ post-transplant humoral SARS-CoV-2 vaccine responses through creation of a prospective study of HCT recipients and their matched-related donors; and Aim 3: Evaluate donor v. recipient Ag-specific T and B cells and SARS-CoV-2 clonal breadth and depth after re-vaccination post-transplant to assess immune reconstitution, using T and B cell receptor repertoire analyses methods. We expect that completion of these aims and the associated training objectives will generate clinically applicable preliminary data to inform vaccine development and policy for patients with hematologic malignancies. My long-term career goal is to become an independently funded clinician-scientist and leader in translational vaccinology with a focus on developing precision vaccines for immunocompromised adults. I will achieve this through: 1) investigation of immunologic pathways that promote or inhibit vaccine-induced responses for patients with hematological malignancies, and 2) translation of these findings into novel vaccines via early-phase clinical trials. Brigham and Women’s Hospital and the Precision Vaccines Program at Boston Children’s Hospital are highly collaborative research environments within the broader Harvard Medical School community that will provide abundant resources and institutional support to complete the described aims.", "keywords": [ "2019-nCoV", "Adoptive Transfer", "Adult", "Affinity", "Allogenic", "Antibodies", "Antibody Response", "Antigens", "B cell clonality", "B cell reconstitution", "B-Cell Antigen Receptor", "B-Lymphocytes", "Bioinformatics", "Biometry", "Blood specimen", "Boston", "COVID-19", "COVID-19 vaccination", "COVID-19 vaccine", "Cell Physiology", "Cells", "Cellular Immunity", "Centers for Disease Control and Prevention (U.S.)", "Childhood", "Chimerism", "Circulation", "Clinical", "Clinical Research", "Cohort Studies", "Communicable Diseases", "Communities", "Data", "Defect", "Development", "Disease", "Dissection", "Dose", "Effectiveness", "Environment", "Evolution", "Fostering", "Frequencies", "Funding", "Gene Amplification", "General Population", "Generations", "Goals", "Guidelines", "Harvest", "Hematologic Neoplasms", "Hematopoietic Stem Cell Transplantation", "Histocompatibility Antigens", "Hospitals", "Humoral Immunities", "Immune", "Immune response", "Immunity", "Immunocompromised Host", "Immunoglobulin G", "Immunologics", "Immunology", "Impairment", "Individual", "Infection", "Influenza", "Institution", "Investigation", "K-Series Research Career Programs", "Kinetics", "Laboratories", "Laboratory Study", "Learning", "Link", "Longitudinal", "Longitudinal cohort", "Masks", "Measures", "Memory B-Lymphocyte", "Mentors", "Mentorship", "Methods", "Modeling", "Monoclonal Antibodies", "Morbidity", "Mutate", "Pathway interactions", "Patients", "Pediatric Hospitals", "Phenotype", "Plasma", "Policies", "Population", "Predisposition", "Prevention", "Prevention Guidelines", "Prospective Studies", "Prospective cohort", "Public Health", "RNA vaccine", "Recommendation", "Recording of previous events", "Relaxation", "Research", "Research Design", "Resources", "Risk", "Role", "SARS-CoV-2 antigen", "SARS-CoV-2 exposure", "SARS-CoV-2 immunity", "SARS-CoV-2 mRNA vaccination", "SARS-CoV-2 mRNA vaccine", "SARS-CoV-2 variant", "Sampling", "Scientist", "Seasons", "Series", "Serum", "Stem cell transplant", "T-Cell Receptor", "T-Cell Receptor Genes", "T-Lymphocyte", "Technology", "Testing", "Training", "Translations", "Transplant Recipients", "Transplantation", "Vaccinated", "Vaccination", "Vaccines", "Variant", "Viral", "Viral reservoir", "Virus", "Vulnerable Populations", "Woman", "Work", "antigen-specific T cells", "career", "chemotherapy", "clinical application", "clinical translation", "early phase clinical trial", "e" ], "approved": true } }, { "type": "Grant", "id": "16177", "attributes": { "award_id": "5R01AI194318-02", "title": "Infectiousness and social mixing in asymptomatic TB as a driver of population-level transmission", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 44239, "first_name": "NICOLE JOY", "last_name": "ESPY", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-16", "end_date": "2030-08-31", "award_amount": 1173748, "principal_investigator": { "id": 27650, "first_name": "Nippie Sarita", "last_name": "Shah", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3388, "ror": "", "name": "EMORY UNIVERSITY", "address": "", "city": "", "state": "GA", "zip": "", "country": "United States", "approved": true }, "abstract": "Achieving substantial reductions in TB incidence will require innovative strategies for halting TB transmission, which have been hampered by a critical knowledge gap of where, when, and by whom transmission is occurring. We and others have shown that only 9-30% of TB cases can be linked to a close contact, suggesting most transmission occurs outside of household settings and with more limited (or casual) contact. Because individuals have more community contacts than household contacts, there is greater opportunity for exposure and infection outside the home, despite a lower intensity of the interactions. Thus, implementing effective measures to prevent transmission requires a comprehensive understanding of when someone becomes infectious and where they are encountering the largest number of susceptible individuals. It is increasingly clear that TB exists along a dynamic spectrum between latent TB infection and active TB disease, with several intervening states characterized by absence of symptoms in the setting of Mtb replication and host response. It is estimated that asymptomatic TB may account for up to half of bacteriologically confirmed TB globally, yet there is limited understanding of infectiousness during this stage. Recent studies have shown that cough may not be necessary for TB to be transmitted. TB bacilli detected in bioaerosols generated by less forceful respiratory maneuvers, such as tidal breathing, are associated with incident TB in close contacts. Since asymptomatic TB remains undiagnosed for an average of two years—during which time people maintain their normal activities and social mixing behaviors—this may explain the large proportion of transmission occurring in community settings. Understanding social contact patterns during early stages of TB has important implications for determining where and when TB is spread. There are limited data on asymptomatic TB transmission; however, research on contact patterns during the COVID-19 pandemic demonstrated community transmission by asymptomatic cases, in part because social contact patterns are unchanged while feeling well. Asymptomatic spread is an established paradigm for several infectious diseases but is yet to be characterized for TB. We will conduct a prospective cohort study of 1,000 close contacts to determine the onset of infectiousness (Aim 1) and measure social contact patterns (Aim 2) along the spectrum of TB disease. Aim 3 will utilize these data to model the proportion of TB transmission that occurs during early-stage disease, particularly in community settings. We have been conducting community-wide TB screening, diagnosis, and transmission research for over two decades, leading to transformative findings that shaped patient care and policy. Our team brings together global leaders in field-based epidemiologic research, transmission science, aerobiology, multi-omics, and modeling to examine fundamental questions in TB transmission science. Together these findings will provide critical information to guide interventions that will more effectively reduce TB incidence", "keywords": [ "Bacillus", "Bacteriology", "Behavior", "Biological Markers", "Breathing", "COVID-19 pandemic", "Cause of Death", "Cessation of life", "Communicable Diseases", "Communities", "Coughing", "Country", "Data", "Detection", "Diagnosis", "Diagnostic tests", "Disease", "Disease Progression", "Epidemiologic Research", "Frequencies", "Functional disorder", "Goals", "Health Policy", "Home", "Household", "Immune response", "Incidence", "Individual", "Infection", "Inflammatory", "Intervention", "Knowledge", "Link", "Location", "Measures", "Microbiology", "Modeling", "Mycobacterium tuberculosis", "Pathway Analysis", "Patient Care", "Pattern", "Persons", "Policies", "Population", "Predisposition", "Prevalence Study", "Prevention Measures", "Prospective Studies", "Prospective cohort study", "Radiology Specialty", "Research", "Sampling", "Science", "Shapes", "South Africa", "Sputum", "Survey Methodology", "Symptoms", "Time", "Tuberculosis", "Well in self", "aerosolized", "community setting", "community transmission", "experience", "face mask", "genome sequencing", "indexing", "innovation", "multiple omics", "mycobacterial", "observational cohort study", "prevent", "prospective", "radiological imaging", "respiratory", "screening", "social", "social contact", "transcriptomics", "transmission process", "whole genome" ], "approved": true } }, { "type": "Grant", "id": "16176", "attributes": { "award_id": "5R01HL179084-02", "title": "Identifying Novel Roles and the Therapeutic Potential of the Thrombin Receptor Protease Activated Receptor-1 (PAR1) in Lung Lymphatic Function and Acute Respiratory Distress Syndrome", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 44269, "first_name": "GUOFEI", "last_name": "ZHOU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-15", "end_date": "2029-06-30", "award_amount": 750280, "principal_investigator": { "id": 44296, "first_name": "Hasina Outtz", "last_name": "Reed", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 825, "ror": "", "name": "WEILL MEDICAL COLL OF CORNELL UNIV", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Acute Respiratory Distress Syndrome (ARDS) is a devastating disease with high morbidity and mortality. The COVID-19 pandemic and the yearly toll of viral and bacterial pneumonia underscore the urgent need for a mechanistic understanding of ARDS that would lead to new therapies. ARDS is characterized by a prothrombotic state and activation of the thrombin receptor protease activated receptor 1 (PAR1). PAR1 is perhaps the most important mediator of inflammation and coagulation in ARDS, as it coordinates the interplay between platelets, endothelial cells, and the immune response. However, targeting PAR1 therapeutically has thus far been unsuccessful, highlighting our knowledge gaps in understanding the pleiotropic roles of this critical receptor. The premise of proposal is that PAR1 plays a previously unappreciated role in the lymphatic vasculature in ARDS that offers a novel therapeutic strategy to prevent lung injury. The lymphatic vasculature mediates the inflammatory response of the lung through both fluid drainage and trafficking of immune cells. However, the molecular pathways that drive these functions have not been fully uncovered. Lymphatics have specialized endothelial cell junctions that mediate fluid and cell uptake into the vessel lumen. Loss of these permeable ‘button’ junctions impairs lymphatic function by preventing the drainage and cell trafficking function of these vessels. Using mouse models, we have found that PAR1 is necessary for button junction formation during lung injury. Lymphatic-specific loss of PAR1 leads to immune cell accumulation and worse lung injury, which our studies suggest is due to loss of button junctions that promote lymphatic function. These data point to a previously unknown role of PAR1 in lung injury that improves lymphatic drainage and promotes resolution of inflammation. In this proposal, we will test the hypothesis that PAR1 is necessary for lymphatic buttons and function (Aim 1), that thrombin-mediated PAR1 signaling in lymphatics is protective during lung injury due to its role in promoting lymphatic buttons and drainage (Aim 2), and that agonists of PAR1 that promote beneficial PAR1 signaling in lymphatics while persevering blood vessel function are a novel therapeutic strategy for ARDS (Aim 3). When completed these studies will result in an entirely new paradigm for the pathogenesis of ARDS by uncovering a link between PAR1, lymphatic function, and the inflammatory response, leading to a novel therapeutic strategy for this devastating disease.", "keywords": [ "Acute Lung Injury", "Acute Respiratory Distress Syndrome", "Address", "Agonist", "Automobile Driving", "Autopsy", "Bacterial Pneumonia", "Biological Assay", "Blood", "Blood Platelets", "Blood Vessels", "Breathing", "COVID-19", "COVID-19 pandemic", "COVID-19/ARDS", "Cells", "Chronic Obstructive Pulmonary Disease", "Coagulation Process", "Confocal Microscopy", "Coupling", "Cytoprotection", "Data", "Disease", "Drainage procedure", "Endothelial Cells", "Event", "Fibrosis", "G-Protein-Coupled Receptors", "GTP-Binding Proteins", "Homeostasis", "Human", "Hyperoxia", "Immune", "Immune response", "Impairment", "Infection", "Inflammation", "Inflammation Mediators", "Inflammatory Response", "Influenza", "Injury", "Intercellular Junctions", "Knowledge", "Leukocyte Trafficking", "Link", "Liquid substance", "Lung", "Lung Diseases", "Lung Transplantation", "Lymphatic", "Lymphatic Capillaries", "Lymphatic Endothelial Cells", "Lymphatic function", "Mediating", "Modeling", "Molecular", "Morbidity", "Movement", "Mus", "PAR-1 Receptor", "Pathogenesis", "Pathologic", "Pathway interactions", "Patients", "Peptide Hydrolases", "Permeability", "Play", "Proteins", "Publishing", "Reporter", "Reporting", "Resolution", "Role", "Signal Transduction", "Slice", "Specimen", "Testing", "Therapeutic", "Thrombin", "Thrombin Receptor", "Time", "Tissues", "Toxicant exposure", "Trauma", "Viral Pneumonia", "Work", "aspirate", "beta-arrestin", "comparison control", "ex vivo imaging", "improved", "in vitro Assay", "in vivo", "inhibitor", "lung injury", "lymph nodes", "lymphatic drainage", "lymphatic dysfunction", "lymphatic vasculature", "lymphatic vessel", "mortality", "mouse model", "novel", "novel therapeutic intervention", "novel therapeutics", "prevent", "receptor", "rho", "single-cell RNA sequencing", "targeted agent", "trafficking", "uptake" ], "approved": true } }, { "type": "Grant", "id": "16175", "attributes": { "award_id": "5P20GM156712-02", "title": "Project 3: Modified RNA and LNP formulation as immunomodulatory agents for cellular immunity", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [], "start_date": "2025-09-01", "end_date": "2030-08-31", "award_amount": 249851, "principal_investigator": { "id": 44293, "first_name": "Theresa M", "last_name": "Raimondo", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3365, "ror": "", "name": "BROWN UNIVERSITY", "address": "", "city": "", "state": "RI", "zip": "", "country": "United States", "approved": true }, "abstract": "PROJECT 3 ABSTRACT RNA has become a new and successful therapeutic modality that entails the introduction of in vitro transcribed (IVT) modified mRNA into cells via lipid nanoparticle (LNP) delivery vehicles. RNA modifications and LNP formulation both critically impact RNA translation, immunogenicity, biodistribution, and the efficacy of such therapeutics. While incorporation of N1-methylpseudouridine (m1ψ) modifications into IVT mRNA in COVID-19 vaccines has demonstrated safety and potent antibody generation, the fundamental concepts underlying RNA modification and LNP formulation for the generation of cellular immunity are unknown. Unlike vaccination, such cellular (macrophage and T cell) immunity will be required for efficacious application of mRNA-LNPs to cancer immunotherapy. Macrophages are ideal targets for mRNA-LNP cancer therapeutics due to their propensity to internalize nanoparticles, central role in modulating the tumor immune microenvironment, and capacity to present cancer antigen to T cells. We propose that optimization of mRNA modifications and LNP formulations will lead to the generation of improved effector anti-cancer chimeric antigen receptor-macrophages (CAR-M) (aim 1) or promote macrophage cross-presentation of cancer antigens leading to T cell immunity (aim 2). We propose simultaneously screening IVT mRNA modifications, beyond m1ψ, and LNP formulation parameters to optimize anti-cancer macrophage immunity. Anti-HER2 CAR sequences (aim 1) or model cancer antigen (aim 2) will be encoded into IVT mRNA, IVT reactions with T7 RNA polymerase will allow incorporation of modified nucleosides with expected variability in immune stimulatory to antagonistic behavior. These modified IVT mRNAs will be incorporated LNPs with varying immunostimulatory properties. MC3, a lipid used in the FDA approved RNA-LNP therapeutic Onpattro®, will be a ‘non-inflammatory’ control LNP, to compare experimental lipids with heterocyclic head groups, previously shown to promote immune activation. Libraries generated by varying both RNA modification and LNP formulation will be screened in vitro, to identify mRNA-LNPs that maximize CAR-M cancer phagocytosis (aim 1) or antigen presentation (aim 2). Finally, top mRNA-LNPs will be tested for therapeutic efficacy in murine models of peritoneal disseminated ovarian cancer (aim 1) or OVA-antigen expressing melanoma (aim 2). Ultimately, we expect to identify mRNA modification and LNP formulations capable of optimizing macrophage-driven anti-cancer cellular immunity. The insights generated by this proposal will be critical to understanding how IVT mRNA and LNPs modify immunity in the tumor microenvironment and will elucidate fundamental concepts underlying the design of RNA-LNP therapeutics for diverse clinical applications.", "keywords": [ "Antibodies", "Antibody Response", "Antigen Presentation", "Antigens", "B16F10", "Behavior", "Biodistribution", "Biology", "CD8-Positive T-Lymphocytes", "COVID-19 vaccine", "Cancer Model", "Cell Separation", "Cell Therapy", "Cells", "Cellular Immunity", "Centers of Research Excellence", "Coculture Techniques", "Cross Presentation", "Cytosine", "DNA", "Data", "Disease", "ERBB2 gene", "Experimental Designs", "FDA approved", "Formulation", "Gene Silencing", "Generations", "Genetic Transcription", "Health", "Immune", "Immunity", "In Vitro", "Intraperitoneal Injections", "Libraries", "Lipids", "Macrophage", "Macrophage Activation", "Malignant Neoplasms", "Malignant neoplasm of ovary", "Melanoma", "Messenger RNA", "Metastatic Malignant Neoplasm to the Ovary", "Methodology", "Modality", "Moderna COVID-19 vaccine", "Modification", "Mus", "Neoplasm Metastasis", "Nucleosides", "PTPNS1 gene", "Peritoneal", "Peritoneal Macrophages", "Phagocytosis", "Pharmaceutical Preparations", "Play", "Property", "RNA", "Reaction", "Role", "Safety", "Small Interfering RNA", "T-Cell Activation", "T-Lymphocyte", "T7 RNA polymerase", "Therapeutic", "Translations", "Treatment Efficacy", "Tumor Antigens", "Tumor-associated macrophages", "Uridine", "Vaccination", "Viral Vector", "anti-cancer", "base editing", "cancer immunotherapy", "chimeric antigen receptor", "clinical application", "cost", "delivery vehicle", "design", "ex vivo", "immune RNA", "immune activation", "immune modulating agents", "immunogenicity", "improved", "in vivo", "insight", "lipid nanoparticle", "mRNA Transcript Degradation", "mRNA lipid nano particle vaccine", "mouse model", "nanoparticle", "nanoparticle delivery", "novel", "phosphorothioate", "screening", "sensor", "siRNA delivery", "therapeutic evaluation", "therapeutic nanoparticles", "timeline", "translational impact", "tumor", "tumor microenvironment", "tumor-immune system interactions", "vaccine safety" ], "approved": true } }, { "type": "Grant", "id": "16174", "attributes": { "award_id": "1R01AI183446-01A1", "title": "Assessing mechanisms for the persistence of RNA viruses in bats using a captive and wild Eidolon helium colonies", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32795, "first_name": "EUN-CHUNG", "last_name": "PARK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-24", "end_date": "2030-08-31", "award_amount": 146125, "principal_investigator": { "id": 44632, "first_name": "Osbourne", "last_name": "Quaye", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3544, "ror": "", "name": "UNIVERSITY OF GHANA", "address": "", "city": "", "state": "", "zip": "", "country": "GHANA", "approved": true }, "abstract": "Emerging viruses are an important threat to humans, with serious implications for both public health and the global economy. These viruses have emerged from having stable relationships with other animals, and although the spillovers can occur anywhere, studies have shown that there are geographic hotspots (e.g., high diversity ecosystems with frequent interactions between animals and humans) where emergence is more common, and all of these hotpots are located outside of the United States (US). However, because of the interconnectedness of the global economy, emerging viruses can rapidly spread and directly impact the US by causing an outbreak that could originate from anywhere in the world (e.g., the COVID-19 pandemic). Bats, in particular, have been linked to many high consequence emerging viruses, including SARS coronaviruses, as well as filoviruses, Hendra and Nipah viruses. This proposal seeks to address fundamental knowledge gaps regarding bat-hosted viruses through an innovative combination of longitudinal molecular surveillance, highlymultiplexed serology, and whole genome virus sequencing. The study will utilize straw-colored fruit bat (Eidolon helvum) as a model system for studying mechanisms of virus persistence and transmission within bats. E. helvum is widely distributed throughout the West and Central African hotspots for virus emergence, known to host a variety of viruses from groups with known capacity for human infection, and there are multiple documented interfaces for the transmission of viruses from E. helvum to humans, livestock, and other wild animals. Specifically, we propose to work in Accra, Ghana because of the long-term captive breeding colony of E. helvum that has been maintained at the Accra Zoo for research purposes. This globally unique facility will enable us to longitudinally track individual bats and their viruses, in a manner that is not possible when working only with wild populations. Since the facility is located within E. helvum’s endemic range, the impact of population size on virus diversity and shedding can also be directly tested by comparing the captive colony with geographically proximal wild bat populations, something that would not be possible to replicate within the US. Longitudinal sample collection and broad-range PCR will be used to monitor virus shedding over time, and highly-multiplexed serology will be used to obtain an unprecedented view of the viruses infecting E. helvum bats. Differences in infection histories between captive and wild animals will be identified, and whole genome sequencing will be used to track the evolution of viruses shed in the captive colony (with individual-level resolution) and those circulating in wild bats. By providing fundamental knowledge about the dynamics of zoonotic viruses within their natural hosts, this project will help in the design of targeted diagnostics, vaccines, and spillover risk mitigation strategies against viral diseases in the US including rabies, Camp Hill virus (a recently identified henipavirus in Alabama), and other henipaviruses infections, and protect the US population from the damaging impacts of these viruses.", "keywords": [ "Address", "Africa South of the Sahara", "Agriculture", "Animals", "Arizona", "Avian Influenza A Virus", "Biological Assay", "Breeding", "Chiroptera", "Chronic", "Collaborations", "Color", "Coronavirus", "Custom", "Data", "Disease", "Ebola virus", "Ecology", "Emerging Communicable Diseases", "Emerging infection", "Environmental Risk Factor", "Epidemiology", "Event", "Family", "Family Pteropodidae", "Frequencies", "Fruit", "Genomics", "Geographic Distribution", "Ghana", "Habitats", "Health", "Helium", "Hendra Virus", "Human", "Incidence", "Individual", "Infection", "International", "Investigation", "Knowledge", "Livestock", "Maintenance", "Mammals", "Methodology", "Middle East Respiratory Syndrome Coronavirus", "Modernization", "Molecular", "Monitor", "Monkeypox virus", "Nipah Virus", "Paramyxovirus", "Pathogenicity", "Phylogenetic Analysis", "Play", "Population", "Population Density", "Population Growth", "Population Sizes", "Prevalence", "RNA Viruses", "Recording of previous events", "Rectum", "Recurrence", "Research", "Research Institute", "Resolution", "Risk", "Risk Assessment", "Role", "SARS coronavirus", "Serology", "Serology test", "Site", "Swab", "System", "Testing", "Time", "Universities", "Viral", "Viral Epidemiology", "Viral Genome", "Virus", "Virus Diseases", "Virus Shedding", "Wild Animals", "Work", "Zika Virus", "Zoonoses", "chronic infection", "design", "economic impact", "emerging virus", "genome sequencing", "health economics", "innovation", "land use", "member", "prevent", "public health relevance", "sample collection", "socioeconomics", "tool", "transmission process", "viral transmission", "virome", "whole genome" ], "approved": true } }, { "type": "Grant", "id": "16173", "attributes": { "award_id": "5R21AI191193-02", "title": "Mobilizing Innovative Strategies to Improve TB Diagnosis and Retention in the TB Care Cascade for Migrant Communities in New York City", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32562, "first_name": "KAREN A", "last_name": "LACOURCIERE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-09", "end_date": "2027-08-31", "award_amount": 173249, "principal_investigator": { "id": 44290, "first_name": "Yael R", "last_name": "Hirsch-Moverman", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 44291, "first_name": "Max", "last_name": "O'Donnell", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 781, "ror": "", "name": "COLUMBIA UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Since 2021, TB incidence in New York City (NYC) has surged partly due to decreased attenƟon during the COVID-19 pandemic and in part due to increased migraƟon across the southern US border. Approximately 205,000 migrants from TB-endemic regions arrived in NYC since April 2022. In 2023, TB incidence in NYC rose by 28%, the highest rates in over a decade, with 89% of cases among individuals born outside the US. Our proposal aims to evaluate innovaƟve methods to improve TB detecƟon, prevenƟon, and treatment among migrants in NYC. IniƟal work by our team in NYC migrant shelters has demonstrated high numbers of persons with of latent TB infecƟon (LTBI) and acƟve TB. Current clinic-based approaches to TB surveillance are ineffecƟve since few high-risk persons complete TB screening and fewer are retained in the TB cascade of care. The proposed intervenƟon, SPOT-TB (Screening with Portable X-rays for rapid recOgniTion of TB), evaluates the use of mobile diagnosƟc teams integraƟng ultraportable digital chest radiography paired with arƟficial intelligence-assisted interpretaƟon, upfront tesƟng for TB (interferon gamma release assay) and HIV, and community engagement to improve iniƟaƟon and retenƟon in the TB cascade of care compared to convenƟonal, clinic- based approaches to TB surveillance. Aim 1 is to idenƟfy acƟve and latent TB in migrant communiƟes using this mobile detecƟon platiorm, hypothesizing that it will increase the proporƟon of migrants compleƟng diagnosƟc evaluaƟon compared to convenƟonal approaches. Aim 2 is to determine the feasibility and acceptability of the SPOT-TB strategy using mixed methods, hypothesizing that it will be highly feasible and acceptable to both care workers and parƟcipants. Aim 3 is to evaluate structural and behavioral barriers to TB care in NYC migrant communiƟes, hypothesizing that unstable housing will be a fundamental barrier and that perceived TB sƟgma will predict subsequent loss to retenƟon in the care cascade. This project employs mixed methods to evaluate the intervenƟon’s feasibility, acceptability, and effecƟveness, uƟlizing advanced staƟsƟcal techniques to understand complex relaƟonships. The scalable SPOT-TB model aims to provide a robust framework for improving TB care in urban settings, with data supporƟng future NIH R01 submissions for larger trials. By enhancing TB detecƟon and care retenƟon, the project seeks to reduce TB transmission and improve health outcomes for NYC's migrant populaƟon.", "keywords": [ "Address", "Advocacy", "Artificial Intelligence enhanced", "Behavioral", "Biological Assay", "COVID-19 pandemic", "Caring", "Cessation of life", "Chest", "Clinic", "Clinical Sciences", "Communities", "Complex", "Country", "Data", "Detection", "Diagnosis", "Emergency Situation", "Epidemiology", "Evaluation", "Fostering", "Future", "HIV", "HIV/TB", "Health", "Hospitals", "Human immunodeficiency virus test", "Image", "Improve Access", "Incidence", "Individual", "Infrastructure", "Intelligence", "Interferon Type II", "Intervention", "Interview", "Knowledge", "Mental Health", "Methods", "Migrant", "Modeling", "New York City", "Outcome", "Participant", "Persons", "Prevention", "Public Health", "Resources", "Risk", "Risk Assessment", "Roentgen Rays", "Science", "Services", "Shelter facility", "Site", "Social Sciences", "Symptoms", "System", "Techniques", "Thoracic Radiography", "Tuberculosis", "Tuberculosis diagnosis", "Uganda", "United States", "United States National Institutes of Health", "Universities", "Work", "acceptability and feasibility", "barrier to care", "case finding", "community collaboration", "community engagement", "community setting", "digital", "follow-up", "future implementation", "high risk population", "housing instability", "image guided", "improved", "innovation", "insight", "low and middle-income countries", "novel", "portability", "programs", "screening", "social stigma", "transmission process", "tuberculosis diagnostics", "urban setting" ], "approved": true } }, { "type": "Grant", "id": "16172", "attributes": { "award_id": "5R01AI187511-02", "title": "Integrating genomic architecture and tuberculosis (TB) immunity in Africa", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32562, "first_name": "KAREN A", "last_name": "LACOURCIERE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-17", "end_date": "2030-08-31", "award_amount": 788499, "principal_investigator": { "id": 24650, "first_name": "Paul John", "last_name": "Norman", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 784, "ror": "https://ror.org/02hh7en24", "name": "University of Colorado Denver", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 3543, "ror": "", "name": "UNIVERSITY OF COLORADO DENVER", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true }, "abstract": "Modified Project Summary/Abstract Section The human obligate bacterium Mycobacterium tuberculosis (M.tb) infects approximately a quarter of the world's population, leading to chronic disease with an annual death toll exceeding 1.6 million. The disruption of services during the COVID-19 pandemic resulted in a 4.5% increase in cases, exceeding 6 million new cases in 2021, with Africa bearing a critical burden. The incidence in USA is increasing by 16% per year. Not all infected individuals progress to active disease, and we have shown in genome-wide association studies (GWAS) that human host genetic factors contribute to disease outcome. To identify new ways to improve disease outcome, human studies to characterize the genetic factors involved in TB and its interaction with the immune system are urgently needed. Here, we focus on the genetic susceptibility to active TB, focusing on HLA and its interactions with the KIR genes of natural killer (NK) cells, critical in shaping the immune response against TB. In this study, we propose to uniquely leverage the diversity of South African populations (sub-Saharan African, European, and South-East Asian ancestries) to perform multi-ethnic associations with broad applicability. Specifically, we aim to: 1) Generate population-level data (HLA, KIR, and SNP array) on 5,000 case/control samples, characterizing genetic diversity across multi-ancestry individuals from South Africa; 2) Perform binding and cytotoxic assays to functionally test/develop interaction scores for newly discovered alleles, and determine their specific NK impact on NK cell function 3) Develop appropriate, well-powered statistical models for association of HLA/KIR variation and HLA/KIR interaction with disease susceptibility. The Northern Cape Province, South Africa provides an ideal location to perform this study; the extremely high community TB incidence results in lower misclassification bias introduced by unknown or low infectious disease exposure. Outcomes include: a) studying a large TB case-control dataset of DNA, clinically-active cases and epidemiological variables of 5,000 participants; b) clarifying the role of NK cells in TB pathogenesis; c) appropriately calibrated statistical models of HLA/KIR association in admixed populations. We have an outstanding track record of collaboration, including ≥ 40 co-authored publications, as well as expertise in clinical epidemiology, statistical and population genetics, and immunogenetics, uniquely positioning us to address this critical research question using innovative methods -- including direct HLA and KIR allele sequencing and functional validation of their interactions. Through direct genetic assays, complex interaction analyses, and advanced statistical approaches, this study aims to shed light on the genetic risk factors and the immunogenetic landscape critical for understanding and combatting TB.", "keywords": [ "Address", "Adult", "Africa", "African", "Alleles", "Antibody Formation", "Architecture", "Asian ancestry", "Bacteria", "Binding", "Biological Assay", "COVID-19", "COVID-19 pandemic", "Calibration", "Cause of Death", "Cell Communication", "Cell Line", "Cell Physiology", "Cells", "Cessation of life", "Characteristics", "Chronic", "Chronic Disease", "Clinical", "Collaborations", "Collection", "Communicable Diseases", "Communities", "Complex", "Country", "DNA", "Data", "Data Set", "Development", "Disease", "Disease Outcome", "Disease susceptibility", "Environment", "Epidemiology", "European", "Freedom", "Functional disorder", "Gene Fusion", "Genes", "Genetic", "Genetic Polymorphism", "Genetic Predisposition to Disease", "Genetic Variation", "Genomics", "HLA Antigens", "Heritability", "Heterogeneity", "Histocompatibility Antigens Class I", "Histocompatibility Antigens Class II", "Human", "Immune response", "Immune system", "Immunity", "Immunogenetics", "Immunoglobulins", "Incidence", "Individual", "KIR3DS1", "Killer Cells", "Laboratories", "Ligands", "Location", "Maps", "Methods", "Mycobacterium tuberculosis", "Natural Killer Cells", "Outcome", "Participant", "Pathogenesis", "Peptides", "Population", "Population Genetics", "Positioning Attribute", "Predisposition", "Prevalence", "Province", "Publications", "Receptor Cell", "Receptor Gene", "Research", "Resistance", "Role", "SNP array", "Sample Size", "Sampling", "Services", "Shapes", "Signal Transduction", "South Africa", "South African", "Southern Africa", "Statistical Models", "Testing", "Tuberculosis", "Tuberculosis diagnosis", "Validation", "Variant", "case control", "clinical epidemiology", "cohort", "combinatorial", "cytotoxic", "disease exposure", "dosage", "ex vivo", "genetic association", "genetic risk factor", "genome wide association study", "genome-wide", "genomic locus", "high-resolution", "human model", "improved", "innovation", "insight", "large datasets", "microbial", "multi-ethnic", "nanopore sequencing", "novel", "population stratification", "public health relevance", "receptor", "receptor expression", "reference genome", "response", "segregation", "southeast Asian", "structural mutation", "tuberculosis immunity" ], "approved": true } }, { "type": "Grant", "id": "16171", "attributes": { "award_id": "5R44AG097298-02", "title": "Scaling a network of small community-based care homes as a high-value alternative to institutional care", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Aging (NIA)" ], "program_reference_codes": [], "program_officials": [ { "id": 44631, "first_name": "JOSEPH JEFFREY", "last_name": "CHIARENZELLI", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-16", "end_date": "2027-05-31", "award_amount": 1169847, "principal_investigator": { "id": 44289, "first_name": "Vipan", "last_name": "Nikore", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3542, "ror": "", "name": "HOMECARE HUB US INC", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "The United States faces a severe long-term services and supports (LTSS) crisis as the senior population grows rapidly, with the number of seniors expected to nearly double by 2060. Approximately 70% of these individuals will require some form of LTSS, putting unprecedented pressure on a system that is already costly and strained. Traditional nursing homes, while necessary, frequently exceed $100,000 annually per patient and often lead to issues such as social isolation, high readmission rates, and lower resident satisfaction. The COVID-19 pandemic underscored the fragility of these centralized care models, which saw higher infection rates, limited adaptability, and increasing burdens on families and health systems. There is an urgent need for cost-effective, high-quality, and scalable non-institutional LTSS alternatives that are adaptable to the needs of seniors. Homecare Hub (HCH) offers an innovative solution through its network of small, community-based 2-12 person residential care homes. By creating a technology and services platform that allows caring nurses and caregivers to create new supply of high-quality small care homes, and then connecting seniors to these new and existing vetted small homes that deliver personalized, cost-effective care, HCH aims to provide a decentralized, supportive alternative to institutional LTSS. This model leverages a robust technology platform to monitor real-time bed availability in the network of homes, facilitate efficient patient transitions, and uphold high standards of quality. This makes HCH a natural fit within the healthcare ecosystem. HCH’s solution has already demonstrated notable success, achieving reduced hospital readmissions, shorter lengths of stay, and high family satisfaction across multiple pilot studies. The project’s specific aims are: 1) to demonstrate improved health outcomes for seniors by tracking measures in physical health (chronic disease management), mental health, and overall well-being, as well as reductions in ER visits and re-admissions; 2) to quantify the cost-effectiveness of HCH’s model through comparative analyses with traditional LTSS, showing potential for significant healthcare savings; and 3) to highlight how this model supports enhanced hospital throughput and transitions by enabling faster, more efficient and higher quality discharges. By fostering a model that addresses both the financial and human challenges of LTSS, HCH is poised to make a transformative impact on the healthcare system, providing a sustainable, person-centered approach to senior care that enhances quality, reduces costs, and aligns with the future of value-based healthcare.", "keywords": [ "Acute", "Address", "Adoption", "Assisted Living Facilities", "Beds", "COVID-19 pandemic", "Care given by nurses", "Caregivers", "Caring", "Chronic Disease", "Client satisfaction", "Communities", "Computer software", "Continuity of Patient Care", "Country", "Data", "Death Rate", "Decentralization", "Disease Management", "Ecosystem", "Emergency department visit", "Ensure", "Face", "Family", "Financial Hardship", "Fostering", "Future", "Gerontology", "Goals", "Growth", "Health", "Health Care", "Health Care Costs", "Health Care Systems", "Health Surveys", "Health system", "Home", "Hospitalization", "Hospitals", "Human", "Individual", "Infection", "Infrastructure", "Institution", "Interview", "Length of Stay", "Life Style", "Link", "Long-Term Care", "Mainstreaming", "Marketing", "Measurable", "Measures", "Medical Care Team", "Mental Health", "Modeling", "North America", "Nursing Homes", "Outcome", "Paper", "Pathway interactions", "Patient-Focused Outcomes", "Patients", "Personal Satisfaction", "Persons", "Phase", "Pilot Projects", "Population", "Positioning Attribute", "Process", "Quality of Care", "Residential Treatment", "Resources", "Risk", "Savings", "Services", "Skilled Nursing Facilities", "Social isolation", "Support System", "Surveys", "System", "Technology", "Time", "Traction", "United States", "Visit", "Wisconsin", "aging population", "care costs", "care outcomes", "care systems", "clinical care", "community based care", "comparative", "cost", "cost effective", "cost effectiveness", "cost efficient", "experience", "family burden", "flexibility", "health record", "high standard", "hospital readmission", "improved", "infection rate", "innovation", "patient home care", "person centered", "personalized care", "physical conditioning", "preference", "pressure", "readmission rates", "real time monitoring", "resilience", "satisfaction", "social", "success", "technology platform", "value-based care" ], "approved": true } }, { "type": "Grant", "id": "16170", "attributes": { "award_id": "5R35GM156197-02", "title": "Pathological Autoantibodies Contribute to Immune Suppression in Sepsis", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 44630, "first_name": "CHIEN-CHUNG", "last_name": "CHAO", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-01", "end_date": "2030-07-31", "award_amount": 410000, "principal_investigator": { "id": 44286, "first_name": "Gerard J", "last_name": "Nau", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3541, "ror": "", "name": "RHODE ISLAND HOSPITAL", "address": "", "city": "", "state": "RI", "zip": "", "country": "United States", "approved": true }, "abstract": "Sepsis is a severe illness associated with high morbidity and mortality in the US and globally. Complications of multi-organ dysfunction, acute respiratory distress syndrome, and infections have a significant impact on late survival. With limited therapeutic interventions, it is essential to understand the fundamental biology of sepsis. Immune dysfunction and immunosuppression are characteristic of sepsis, especially with late complications where lymphopenia predicts a poor prognosis. Gaps remain, however, in the understanding of the mechanisms underlying prolonged immune suppression. Recently, there has been a greater appreciation of autoimmune antibodies that lead to pathological immune consequences in the setting of critical illness. For example, sepsis due to COVID-19 leads to anti-cytokine autoantibodies (ACAAs) that correlate with greater disease severity. In our preliminary data we have also defined ACAAs post-COVID along with ACAAs in ICU patients with sepsis. We have also made the novel discovery of anti-Fas autoantibodies (FasAAs) induced during sepsis, representing a novel mechanism for lymphopenia associated with critical illness. Our overarching hypothesis is that severe conditions like sepsis induce pathological autoimmunity that alters immune function and increases infections. Our hypothesis predicts that sepsis patients with higher levels of autoantibodies will have more immune dysregulation and secondary infectious complications. The objective of this proposal is to determine the prevalence of ACAAs, define mechanism(s) by which they contribute to immunosuppression, and identify sites where their activity could be disrupted for therapeutic purposes. We propose using complementary immune and computational approaches to identify autoantibodies from the blood of sepsis patients and how they correlate with clinical status. We will investigate the biological function of these antibodies on human cytokines and human cells in vitro, along with developing strategies to interfere with deleterious autoantibodies. To address these issues, we have obtained over 350 serum specimens for this study to discriminate between the effects of preexisting autoantibodies and those with a net increase during sepsis. In addition, we have access to deep RNA-seq data from over 100 sepsis patients for computational studies. The long-term objective is to apply this information to assess prognosis of sepsis patients and create precision therapeutics to sustain and restore immune function.", "keywords": [ "Acute Respiratory Distress Syndrome", "Address", "Antibodies", "Autoantibodies", "Autoimmunity", "Biological Process", "Biology", "Blood", "COVID-19", "Cells", "Characteristics", "Clinical", "Critical Illness", "Data", "Functional disorder", "Human", "Immune", "Immune System Diseases", "Immune system", "Immunosuppression", "In Vitro", "Infection", "Lymphopenia", "Modality", "Morbidity", "Organ", "Pathologic", "Patients", "Precision therapeutics", "Prevalence", "Prognosis", "Proteins", "Research", "Sepsis", "Serum", "Severity of illness", "Site", "Specimen", "Therapeutic", "Therapeutic Intervention", "computer studies", "cytokine", "immune function", "infection risk", "mortality", "novel", "novel therapeutics", "post sepsis", "post-COVID-19", "preservation", "septic patients", "transcriptome sequencing" ], "approved": true } } ], "meta": { "pagination": { "page": 1, "pages": 1442, "count": 14420 } } }