Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=4&sort=-end_date
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-end_date", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=-end_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=5&sort=-end_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=3&sort=-end_date" }, "data": [ { "type": "Grant", "id": "15777", "attributes": { "award_id": "1R01AR085033-01", "title": "Improving the diagnosis and outcome of diffuse alveolar hemorrhage in systemic lupus erythematosus", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 32850, "first_name": "MARIE", "last_name": "MANCINI", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-06", "end_date": "2030-06-30", "award_amount": 538755, "principal_investigator": { "id": 32851, "first_name": "WESTLEY H", "last_name": "REEVES", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32852, "first_name": "Haoyang", "last_name": "Zhuang", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2642, "ror": "", "name": "UNIVERSITY OF FLORIDA", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true }, "abstract": "The variable clinical manifestations of SLE patients are largely unexplained. Although severe diffuse alveolar hemorrhage (DAH) with pulmonary capillaritis is unusual in lupus, more than half of patients with this complication die and focal lung hemorrhage occurs in 30-66% of patients. Using a mouse model (pristane-induced lupus) developed in our laboratory, we will ask why C57BL/6 (B6) mice are susceptible to pristane-induced DAH/vasculitis whereas BALB/c and DBA/2 mice are resistant. DAH is initiated by lung endothelial cell (EC) injury followed by recruitment of bone marrow-derived monocytes to the lung. We found that dysregulation of the extrinsic coagulation pathway also is involved and that lung disease is abolished by early treatment with MEK1/2 or ERK1/2 inhibitors. The overall hypothesis is that genetically- determined lung microvascular EC injury evolves into DAH because of monocyte infiltration into the lung and abnormal regulation of the extrinsic coagulation pathway. Aim 1 addresses susceptibility to DAH. We will ask whether EC injury and bleeding are lung-specific and investigate gene expression patterns associated with DAH by single-cell RNA-sequencing. Genes conferring susceptibility/resistance to EC injury and bleeding be mapped in recombinant inbred BXD (B6 X D2) mice. Aim 2 examines the MEK1/2-ERK1/2 pathway in pristane-induced DAH. We will define the sequence of events leading to DAH and develop blood-based diagnostic tests for the diagnosis of incipient DAH prior to the onset of bleeding. This is important, because the disease process is irreversible once hemorrhage begins. We will look for tests that distinguish early DAH (pre-bleeding) from other forms of lung injury, such as sepsis with acute respiratory distress syndrome. Aim 3 translates what is learned in mice to human DAH. We hypothesize that the disease process is similar except that the initial EC injury is caused by respiratory viral infections rather than pristane. We will ask if a predisposition to lung EC injury determines susceptibility, as in mice, and whether diagnostic approaches developed in the mouse model are relevant to human DAH. Lung EC injury will be examined in SLE patients with influenza or COVID infection and the role of mild bleeding disorders will be explored. The ability to diagnose incipient DAH (pre- bleeding) may permit future therapeutic trials using FDA-approved MEK1/2 inhibitors, such as trametinib, which are highly effective in pristane-induced DAH.", "keywords": [ "ANCA vasculitis", "Acute Respiratory Distress Syndrome", "Address", "Adopted", "Alveolar", "Antineutrophil Cytoplasmic Antibodies", "Autoantibodies", "Autoimmune", "Autoimmune Diseases", "BALB/cJ Mouse", "Biological Assay", "Blood", "Blood Coagulation Disorders", "Blood Vessels", "Bone Marrow", "C57BL/6 Mouse", "COPA syndrome", "Cell Line", "Clinical", "Coagulation Process", "Complex", "Complication", "DBA/2 Mouse", "Data", "Defect", "Dependence", "Development", "Diagnosis", "Diagnostic tests", "Diffuse", "Disease", "Disease susceptibility", "Early Diagnosis", "Early treatment", "Endothelial Cells", "Environmental Risk Factor", "Enzyme-Linked Immunosorbent Assay", "Event", "Exanthema", "Exhibits", "FDA approved", "Future", "Gene Expression", "Gene Expression Profile", "Genes", "Genetic", "Genetic Predisposition to Disease", "Hemorrhage", "Hemostatic function", "Human", "Immune", "Immunologics", "Inbred BALB C Mice", "Inbreeding", "Infiltration", "Inflammation", "Inherited", "Injury", "Intervention", "Kidney", "Laboratories", "Learning", "Life", "Link", "Lung", "Lung Diseases", "Lupus", "Lupus Nephritis", "MAP2K1 gene", "MAPK3 gene", "Malignant Neoplasms", "Maps", "Mediating", "Mitogen-Activated Protein Kinases", "Modeling", "Monitor", "Mouse Strains", "Mus", "NUP214 gene", "Outcome", "Pathogenesis", "Pathway interactions", "Patients", "Plasma", "Predisposition", "Pristane", "Process", "Prognosis", "Public Health", "Qualifying", "Recombinants", "Regulation", "Resistance", "Respiratory Tract Infections", "Retinal blind spot", "Role", "SARS-CoV-2 infection", "Sepsis", "Serum", "Severity of illness", "Systemic Lupus Erythematosus", "Testing", "Therapeutic Trials", "Tissues", "Translating", "Vascular Diseases", "Vasculitis", "Viral Respiratory Tract Infection", "cell injury", "diagnostic strategy", "ds-DNA", "experience", "genome wide association study", "immune function", "improved", "influenza infection", "inhibitor", "injured", "lung injury", "lung microvascular endothelial cells", "monocyte", "mouse model", "novel therapeutics", "prevent", "protein expression", "pulmonary", "recruit", "sepsis induced ARDS", "single-cell RNA sequencing", "treatment response" ], "approved": true } }, { "type": "Grant", "id": "15718", "attributes": { "award_id": "1R01AI190359-01", "title": "Effects of Vaccination on Acute and Post-Acute Respiratory Viral Infection Outcomes in Solid Organ 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": 32597, "first_name": "BROOKE ALLISON", "last_name": "BOZICK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-06-13", "end_date": "2030-05-31", "award_amount": 1442898, "principal_investigator": { "id": 32598, "first_name": "William", "last_name": "Werbel", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 344, "ror": "https://ror.org/00za53h95", "name": "Johns Hopkins University", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Respiratory viral infections (RVI) including SARS-CoV-2, RSV, and influenza, are major threats to the health of solid organ transplant recipients (SOTRs), who live at the intersection of chronic comorbidity, frailty, and heavy immunosuppression. These factors contribute to high rates of clinically observed severe RVI and pose risks for poorly understood post-acute syndromes including organ dysfunction and protracted infections associated with immune evasive mutations of", "keywords": [ "2019-nCoV", "Accounting", "Acute", "Address", "Age", "Allografting", "Antibody Response", "Antimetabolites", "Authorization documentation", "Binding", "Biological Assay", "Blood specimen", "COVID-19", "COVID-19 pandemic", "COVID-19 vaccination", "Cessation of life", "Chronic", "Clinical", "Data", "Detection", "Development", "Diagnosis", "Disease", "Dose", "Enrollment", "Event", "Exclusion", "Frequencies", "Functional disorder", "Health", "Heterogeneity", "Hospital Mortality", "Hospitalization", "Immune Evasion", "Immunocompromised Host", "Immunoglobulin G", "Immunologics", "Immunosuppression", "Immunosuppressive Agents", "Infection", "Influenza", "Influenza A Virus H1N1 Subtype", "Intervention", "Knowledge", "Liquid substance", "Long COVID", "Longitudinal cohort", "Lung", "Measures", "Modeling", "Morbidity - disease rate", "Mucosal Immune Responses", "Mucosal Immunity", "Mucous Membrane", "Mutation", "Nose", "Organ", "Outcome", "Outcome Measure", "Participant", "Pattern", "Persons", "Phenotype", "Plasma", "Policies", "Population", "Prospective Studies", "Prospective cohort", "Public Health", "Regimen", "Reporting", "Research", "Respiratory Syncytial Virus Vaccines", "Risk", "Risk Assessment", "Risk Factors", "Sampling", "Schedule", "Secretory Immunoglobulin A", "Severity of illness", "Signal Transduction", "Solid", "Subgroup", "Surveys", "Swab", "Symptoms", "Syndrome", "Time", "Transplantation", "Vaccination", "Vaccine Antigen", "Vaccines", "Viral", "Viral Respiratory Tract Infection", "Virus Diseases", "Virus Shedding", "breakthrough infection", "chronic infection", "cohort", "comorbidity", "effectiveness evaluation", "experience", "frailty", "high risk", "immunogenic", "immunoprophylaxis", "improved", "infection burden", "infection risk", "influenza infection", "mortality", "nasal swab", "neutralizing antibody", "novel", "novel vaccines", "organ transplant recipient", "organ transplant rejection", "post SARS-CoV-2 infection", "programs", "prospective", "response", "vaccine effectiveness", "vaccine platform", "vaccine response", "vaccine trial" ], "approved": true } }, { "type": "Grant", "id": "15719", "attributes": { "award_id": "1R01AI190286-01", "title": "Novel B cell epitope discovery against human coronaviruses", "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": 32599, "first_name": "MICHELLE MARIE", "last_name": "ARNOLD", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-06-10", "end_date": "2030-05-31", "award_amount": 899935, "principal_investigator": { "id": 32600, "first_name": "IAN A", "last_name": "WILSON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 745, "ror": "", "name": "SCRIPPS RESEARCH INSTITUTE, THE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Human coronaviruses have caused devastating global pandemics and epidemics and continue to threaten global public health. Coronaviruses are highly variable, which has led evasion of most neutralizing antibodies and reduction in vaccine effectiveness. Many potent antibodies to coronaviruses have very limited breadth, while some of the broadest neutralizing antibodies described to date exhibit notably lower neutralization potency. Thus, the exigency to capitalize on what we have learned during the SARS-CoV-2 pandemic to find novel epitopes that elicit broad and potent antibodies against the coronavirus family and enhance pandemic preparedness. We have developed a highly integrated platform for identification of B cell epitopes against coronaviruses. Our previous studies revealed over ten B cell epitopes on the SARS-CoV-2 spike, through comprehensive characterization and high-resolution structure determination. This project aims to identify novel B cell epitopes on SARS-CoV-2 and other human coronaviruses, focusing on conserved and cryptic epitopes that elicit broadly neutralizing antibodies. Specifically, we will (1) identify unexplored epitopes on the SARS-CoV-2 spike protein, (2) uncover cryptic epitopes that have been largely understudied, and (3) identify pan-sarbecovirus, pan- betacoronavirus, and pan-coronavirus epitopes. Collectively, utilizing diverse donor samples, state-of-the-art multi-bait B cell isolation strategies, and high-throughput structural biology, this research aims to uncover novel B cell epitopes that inform on the design of next-generation vaccines and therapeutics, enhancing our preparedness for future coronavirus pandemics.", "keywords": [ "2019-nCoV", "Antibodies", "Apical", "B-Lymphocyte Epitopes", "B-Lymphocytes", "Binding Sites", "COVID-19 pandemic", "Cell Separation", "Coronavirus", "Coronavirus spike protein", "Disease Outbreaks", "Electron Microscopy", "Epidemic", "Epitope Mapping", "Epitopes", "Exhibits", "FDA Emergency Use Authorization", "Face", "Family", "Future", "Goals", "Grant", "Human", "Immune response", "Immunodominant Epitopes", "Knowledge", "Learning", "Maps", "Messenger RNA", "Middle East Respiratory Syndrome", "Molecular Conformation", "Peptides", "Population", "Prevention", "Proteins", "Public Health", "Readiness", "Research", "Resolution", "SARS coronavirus", "SARS-CoV-2 antibody", "SARS-CoV-2 positive", "SARS-CoV-2 spike protein", "Sampling", "Sarbecovirus", "Severe Acute Respiratory Syndrome", "Sierra Leone", "Site", "Structure", "Syndrome", "Therapeutic", "Vaccine Design", "Vaccines", "Variant", "Virus", "betacoronavirus", "coronavirus pandemic", "design", "experimental study", "future pandemic", "human coronavirus", "immunogenicity", "neutralizing antibody", "novel", "novel vaccines", "pandemic coronavirus", "pandemic disease", "pandemic preparedness", "polyclonal antibody", "receptor binding", "respiratory", "stem", "structural biology", "vaccine effectiveness", "variants of concern", "zoonotic coronavirus" ], "approved": true } }, { "type": "Grant", "id": "15701", "attributes": { "award_id": "1U54AI191253-01", "title": "Center for Multiscale Immune Systems Modeling", "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": 32567, "first_name": "MEGHAN ANN", "last_name": "HARTWICK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-06-13", "end_date": "2030-05-31", "award_amount": 4874388, "principal_investigator": { "id": 32568, "first_name": "Cliburn C", "last_name": "Chan", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 20611, "first_name": "Roger Keith", "last_name": "Reeves", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 246, "ror": "https://ror.org/00py81415", "name": "Duke University", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 246, "ror": "https://ror.org/00py81415", "name": "Duke University", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "The Center of Excellence (CoE) is a research initiative that brings together experts from various fields to develop innovative solutions for multi-scale modeling in infectious and immune-mediated disease (IID). The CoE consists of the: Administrative Core (AC), Community Development and Education Core (CDEC), Model and Data Sharing Core (MDSC), and three Research Projects (RP). Each component plays a crucial role. The AC serves as a central hub, connecting various entities, and plays a critical role in pivoting CoE resources during disease outbreaks. It administers the Opportunities Fund, supporting proposals from investigators across NIAID- sponsored modeling groups. The CDEC will develop educational resources, build communities of practice and learning, organize research experiences for graduate students and postdoctoral fellows, and set up document sharing facilities, messaging platforms, and a centralized website to facilitate knowledge sharing. The MDSC will develop an informatics infrastructure that enables seamless integration of data and models across different scales, facilitating more accurate predictions and informed decision-making. The RPs focus on bridging models of host-virus interactions across biological scales. RP1 models humoral defense against viral pathogens, using antibody-antigen molecular dynamics at the molecule scale to understand the constraints limiting the evolution of immune repertoires at the individual scale. RP2 models the immune cell as a target of viral infection, using agent-based models of lymphoid tissue at the cell scale to inform host-pathogen dynamics at the individual scale. RP3 models the interactions between individuals and populations, using agent based models of host-pathogen interactions at the individual scale to inform stochastic epidemic models at the population scale. The research focuses on modeling a set of clinically important viruses, including HIV-1, SARS-CoV-2, Epstein Barr Virus (EBV), and others. The models can be used to study disease pathogenesis, the effect of medical interventions, and disease transmission in heterogeneous population networks. Key strengths of the proposed CoE are (1) the ability to coordinate administrative approaches and technologies for the infectious disease modeling community; (2) a collaborative environment that encourages knowledge sharing, innovation, and the development of cutting- edge solutions; (3) balanced representation of the experimental and computational communities within each Core and RP; (4) extensive experience with IID modeling, team science, education, and community development; (5) robust informatics infrastructure for model and data sharing that already hosts large-scale NIH- funded projects; (6) exceptional strengths integrating generative deep learning with computational modeling in the MDSC and RPs, and (7) the importance of the proposed research to develop more accurate IID models that can inform public health policy and decision-making. The unique strengths of the proposed CoE make it an ideal platform for advancing IID research, developing innovative solutions to complex problems, and responding during infectious disease outbreaks, epidemics and pandemics.", "keywords": [ "2019-nCoV", "Acceleration", "Address", "Antibodies", "Antibody Repertoire", "Antibody Response", "Antigens", "Artificial Intelligence enhanced", "Biological", "Biological Models", "Cells", "Clinical", "Cloud Computing", "Code", "Collaborations", "Communicable Diseases", "Communication", "Communities", "Community Developments", "Community Health Education", "Community of Practice", "Complex", "Computer Models", "Data", "Data Set", "Decision Making", "Dedications", "Development", "Disease", "Disease Outbreaks", "Education", "Educational workshop", "Emergency Situation", "Ensure", "Epidemic", "Escape Mutant", "Event", "Evolution", "Fostering", "Funding", "Funding Opportunities", "Goals", "Grant", "HIV-1", "Heterogeneity", "Human Herpesvirus 4", "Immune", "Immune system", "Immunological Models", "Individual", "Infection", "Information Systems", "Infrastructure", "Intervention", "Knowledge", "Leadership", "Learning", "Licensing", "Link", "Lymphoid Tissue", "Mediating", "Medical", "Mentors", "Metadata", "Modeling", "National Institute of Allergy and Infectious Disease", "Organism", "Outcome", "Pathogenesis", "Play", "Policies", "Policy Making", "Population", "Population Heterogeneity", "Positioning Attribute", "Postdoctoral Fellow", "Printing", "Public Health", "Publications", "Reproducibility", "Research", "Research Personnel", "Research Project Grants", "Resources", "Retrieval", "Role", "Running", "Science", "Scientific Advances and Accomplishments", "Services", "Strategic Planning", "Students", "System", "Technology", "Therapeutic Intervention", "Training", "Training Programs", "United States National Institutes of Health", "Viral", "Virus", "Virus Diseases", "Virus-Cell Membrane Interaction", "career", "collaborative environment", "community building", "computational platform", "computer framework", "data infrastructure", "data integration", "data modeling", "data resource", "data sharing", "deep learning", "design", "disease model", "disease transmission", "education resources", "experience", "experimental study", "graduate student", "higher education", "immunological intervention", "in silico", "infectious disease model", "informatics infrastructure", "innovation", "interdisciplinary approach", "learning community", "meetings", "molecular dynamics", "multi-scale modeling", "new epidemic", "novel", "open source", "outbreak preparedness", "outbreak response", "pandem" ], "approved": true } }, { "type": "Grant", "id": "15705", "attributes": { "award_id": "1R24AI186970-01A1", "title": "Enhancing the utility of deer mice as an infectious disease model", "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": 32576, "first_name": "NADINE", "last_name": "BOWDEN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-06-01", "end_date": "2030-05-31", "award_amount": 466725, "principal_investigator": { "id": 32577, "first_name": "Ioulia", "last_name": "Chatzistamou", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 23713, "first_name": "Kiesha", "last_name": "Wilson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 930, "ror": "", "name": "UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA", "address": "", "city": "", "state": "SC", "zip": "", "country": "United States", "approved": true } ] }, { "id": 31996, "first_name": "Hippokratis", "last_name": "Kiaris", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 930, "ror": "", "name": "UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA", "address": "", "city": "", "state": "SC", "zip": "", "country": "United States", "approved": true }, "abstract": "Deer mice (genus Peromyscus) are the most abundant mammals in North America. In biomedical research, their most prominent use is in the field of infectious diseases, because they are the natural reservoir of infectious agents such as Borrelia burgdorferi which causes Lyme disease, for Hantaviruses, Sin Nombre Virus, and SARS-CoV-2 that caused the COVID-19 pandemic. The University of South Carolina operates, for more than 40 years, the Peromyscus Genetic Stock Center (PGSC) that is charged with the mission of maintaining different stocks of Peromyscus, supplying them to outside investigators and exploiting deer mouse- related research. The present proposal addresses 3 major unmet needs of the Peromyscus community of researchers that impede the use of deer mice as a model and are related to the poor breeding program that does not enable rapid availability if deer mice to users, the lack of Peromyscus-specific antibodies, and the lack of readily access to breeding records for pedigree analyses. Here, we request funds to enhance the utility of deer mice as a model of relevance to NIAID’s interests by (1) strengthening the breeding capacities of the PGSC, (2) by developing specialized immunological reagents such as Peromyscus-specific antibodies, and (3) by curating our electronic databases and rendering them easily accessible to outside users. Plans for the project’s sustainability have been developed, and it is anticipated that upon completion it will be supported fully by the income generated.", "keywords": [ "2019-nCoV", "Address", "Animal Model", "Animals", "Antibodies", "Antigens", "Back", "Behavior", "Biomedical Research", "Books", "Borrelia burgdorferi", "Breeding", "COVID-19 pandemic", "Charge", "Communicable Diseases", "Communities", "Consultations", "Databases", "Deer Mouse", "Ecology", "Electronics", "Evolution", "Funding", "Generations", "Genetic", "Genetic Enhancement", "Genetic Variation", "Genomics", "Goals", "Hantavirus", "Human Resources", "Immune response", "Immune system", "Immunologics", "Inbreeding", "Income", "Infectious Agent", "Infectious Diseases Research", "Inflammation", "Lyme Disease", "Maintenance", "Mammalian Cell", "Mammals", "Manuals", "Mental Depression", "Metabolism", "Mission", "Modeling", "Monitor", "Monoclonal Antibodies", "Mus", "National Institute of Allergy and Infectious Disease", "North America", "Operations Research", "Pathology", "Peromyscus", "Plasmids", "Predisposition", "Production", "Reagent", "Records", "Request for Proposals", "Research", "Research Contracts", "Research Personnel", "Resources", "Sin Nombre virus", "South Carolina", "Surveys", "Testing", "Time", "United States National Institutes of Health", "Universities", "Validation", "Work", "experimental study", "genetic pedigree", "genome resource", "genomic tools", "infectious disease model", "interest", "model organism", "programs", "repository", "tool", "user-friendly" ], "approved": true } }, { "type": "Grant", "id": "11419", "attributes": { "award_id": "1UM1TR004407-01", "title": "Scripps Clinical and Translational Science Hub", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Center for Advancing Translational Sciences (NCATS)" ], "program_reference_codes": [], "program_officials": [ { "id": 21379, "first_name": "SOJU", "last_name": "Chang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-05-01", "end_date": "2030-04-30", "award_amount": 6029792, "principal_investigator": { "id": 23339, "first_name": "Eric Jeffrey", "last_name": "Topol", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 745, "ror": "", "name": "SCRIPPS RESEARCH INSTITUTE, THE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 745, "ror": "", "name": "SCRIPPS RESEARCH INSTITUTE, THE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT The Scripps Research Translational Institute (SRTI) is the foundation for the Scripps hub and is dedicated to accelerating science that will improve human health. SRTI’s emphasis on genomics, digital medicine, and informatics/analytics fosters a multi-dimensional understanding of individualized human health. The Scripps hub has previously included the Scripps Research Institute (SR) and Scripps Health (SH) as principal partners, including Rady Children’s Institute of Genomic Medicine (RCIGM) for genomic medicine initiatives and California Institute for Medical Research (Calibr) for drug repurposing / discovery. In the new CTSA cycle, our partners have expanded to include San Diego State University (SDSU), enabling us to combine forces in computer science, artificial intelligence, biosensors, and diversity inclusion and equity initatives. SRTI’s expertise in genomics was highlighted during the pandemic. We became one of the country’s most productive sequencing centers for SARS-CoV-2 by rapidly forming the “SEARCH” alliance to process samples with the San Diego County Department of Health, UCSD, Sharp Health, California Department of Public Health, Helix, and our partners RCIGM and SH. Digital medicine has been one of SRTI’s core strengths, having pioneered the first remote, site-less digital clinical trial and now expanding this methodology to address many other medical conditions such as health during pregnancy and sleep disorders. Our Digital Trials Center launched the Digital Engagement & Tracking for Early Control and Treatment Scripps (DETECT) study, and in a matter of weeks our team was able to accurately predict the likelihood of Covid with SARS-CoV-2 using passively collected resting heart rate data from wristband sensors and later to identify a physiologic signature that correlates with Long Covid (Post-Acute Sequelae or SARS-CoV-2 Infection). The Scripps hub will innovate clinical and translational science to improve human health across the lifespan and diverse racial, ethnic, geographic and socioeconomic communities. The hub will provide a nurturing environment for education, training, and career development with a focus on individualized health domains of genomics, digital medicine, and biomedical informatics, to empower tomorrow’s diverse workforce.", "keywords": [ "2019-nCoV", "Acceleration", "Address", "Area", "Artificial Intelligence", "Awareness", "Biosensor", "California", "Child", "Clinical Research", "Clinical Sciences", "Clinical Trials", "Collaborations", "Communities", "Country", "County", "Data", "Data Aggregation", "Data Set", "Dedications", "Democracy", "Diagnostic", "Dimensions", "Dissemination and Implementation", "Diverse Workforce", "Drug Screening", "Ecosystem", "Education", "Elements", "Ethics", "Ethnic Origin", "Fostering", "Foundations", "Genomic medicine", "Genomics", "Geography", "Goals", "Health", "Healthcare", "Heart Rate", "Human", "Human Resources", "Industry Collaboration", "Informatics", "Institute of Medicine (U.S.)", "Institution", "Intervention", "Longevity", "Medical", "Medical Research", "Methodology", "Modeling", "Outcome", "Patients", "Physiological", "Population", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Preventive", "Process", "Productivity", "Program Development", "Public Health", "Public Health Informatics", "Race", "Research", "Research Institute", "Research Project Grants", "Resource Informatics", "Resources", "Rest", "SARS-CoV-2 infection", "Sampling", "Science", "Services", "Site", "Sleep Disorders", "Structure", "Techniques", "Time", "Training", "Translational Research", "Universities", "Vision", "Voice", "biomedical informatics", "career development", "community engaged research", "community engagement", "computer science", "computerized data processing", "cost effective", "data standards", "digital", "digital medicine", "digital models", "digital twin", "diversity and inclusion", "drug repurposing", "educational atmosphere", "empowerment", "equity diversity and inclusion", "ethnic diversity", "health data", "health equity", "health inequalities", "improved", "individualized medicine", "innovation", "interoperability", "multimodal data", "multimodality", "pandemic disease", "pregnancy disorder", "programs", "public health emergency", "racial diversity", "real time model", "response", "secondary analysis", "sensor", "socioeconomics", "tool", "translational approach" ], "approved": true } }, { "type": "Grant", "id": "15757", "attributes": { "award_id": "1R01HD114714-01A1", "title": "Bone age determination for the 21st Century: Using AI to broaden and diversify a 60-year-old gold standard and overcome reader bias", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 21091, "first_name": "KAREN", "last_name": "WINER", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2030-04-30", "award_amount": 448280, "principal_investigator": { "id": 32820, "first_name": "Anouck", "last_name": "Girard", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32821, "first_name": "JOSEPHINE Z", "last_name": "KASA-VUBU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 32822, "first_name": "Niko Albert", "last_name": "Kaciroti", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2626, "ror": "", "name": "UNIVERSITY OF MICHIGAN AT ANN ARBOR", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "/ Abstract Bone age (BA) is a measure of maturation of a child’s skeleton, and, as such, a key clinical indicator of growth used by pediatricians and pediatric endocrinologists. As a person’s body ages, from birth through childhood, puberty, and adulthood, the size and shape of the bones of the skeleton change. Growth plates, initially wide open, fuse progressively in childhood. The BA is meant to be the “average” age at which the skeleton reaches a certain degree of maturation. In combination with other measures, it can be used to predict future adult height and detect possible growth disorders or abnormal pubertal maturation. The estimation of BA with a radiological image of the left hand and wrist describes the degree of maturation of a child’s skeleton. The most commonly available standards for the BA estimation, such as the Greulich and Pyle (G&P) Atlas (1959) and the Tanner-Whitehouse method, involve visual inspection of X-ray images of the person’s left hand and wrist, followed by its comparison with the set of reference images. This manual inspection is not only time- consuming, but subjective, and the estimation among radiologists may vary depending upon experience / expertise. Moreover, the data collected in these approaches is outdated: the current population of the United States has been much reshaped in the last 60 years, due to a larger number of children of international ancestry and a nutritional environment, particularly during the COVID pandemic, that has resulted in an obesity pandemic that affects the growth and rate of physical maturation of children. Thus, there is a need to renovate these bone age standards such that the reference is representative of the current population and develop an AI-assisted system for the accurate prediction of bone age. Moreover, the research team for the proposed project will develop an adjustment factor to incorporate the BMI Z-score for more clinical relevance of the AI- assisted outcome. The proposed technical approach is three-pronged. Specific Aim 1 is to establish a database for BA assessment in children that addresses racial and ethnic disparities and reduces spacing between available standards. Specific Aim 2 is to develop and validate an AI-assisted classification system for BA readings from the X-ray images. Finally, Specific Aim 3 is to enhance BA determination by an adjustment factor reflecting the impact of BMI Z-score on skeletal maturation. In support of all three aims, a web designer will build and deploy a web application capable of incorporating the AI algorithm for the adjusted Bone Age determination with qualitative data provided by users.", "keywords": [ "Address", "Adoption", "Adrenal Gland Diseases", "Adult", "Affect", "Age", "Anxiety", "Artificial Intelligence enhanced", "Atlases", "Automobile Driving", "Birth", "Black race", "Body mass index", "COVID-19 pandemic", "Child", "Child Health", "Childhood", "Chronology", "Classification", "Clinical", "Computerized Medical Record", "Consultations", "Consumption", "Data", "Databases", "Decision Making", "Elements", "Endocrinologist", "Environment", "Epiphysial cartilage", "Ethnic Origin", "European ancestry", "Evaluation", "FDA approved", "Fostering", "Future", "Growth", "Growth Disorders", "Hand", "Health", "Health Care Costs", "Height", "Hormonal", "Image", "International", "Internet", "Left", "Link", "Machine Learning", "Manuals", "Marketing", "Measures", "Medical", "Methods", "Michigan", "North America", "Nutritional", "Obesity", "Obesity Epidemic", "Ohio", "Outcome", "Pattern", "Performance", "Persons", "Population", "Precocious Puberty", "Predisposition", "Procedures", "Puberty", "Race", "Radiology Specialty", "Reader", "Reading", "Research", "Roentgen Rays", "Sampling", "Selection Bias", "Shapes", "Skeletal bone", "Skeleton", "Societies", "Somatotropin", "Specialist", "Standardization", "System", "Technology", "Testing", "Time", "Underweight", "United States", "Universities", "Variant", "Visual", "Weight", "Wrist", "X-Ray Medical Imaging", "artificial intelligence algorithm", "bone age", "boys", "care providers", "clinical practice", "clinically relevant", "cost", "database expansion", "ethnic disparity", "experience", "girls", "health disparity", "infancy", "innovation", "novel", "novel strategies", "obesity in children", "pandemic disease", "pediatrician", "racial disparity", "racial diversity", "radiological imaging", "radiologist", "skeletal maturation", "stem", "tool", "web app", "young adult" ], "approved": true } }, { "type": "Grant", "id": "11203", "attributes": { "award_id": "1UG1HD112092-01", "title": "Maternal Fetal Medicine Units Network: University of California, San Francisco", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 22555, "first_name": "Nahida Abdo", "last_name": "Chakhtoura", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-04-01", "end_date": "2030-03-31", "award_amount": 355300, "principal_investigator": { "id": 27221, "first_name": "MARY E", "last_name": "NORTON", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 768, "ror": "https://ror.org/043mz5j54", "name": "University of California, San Francisco", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Significant disparities in maternal and infant mortality and morbidity exist in the U.S, and the MFMU Network aims to reduce the rates of preterm birth, fetal growth abnormalities, newborn morbidity, and maternal complications of pregnancy. Novel strategies, including new therapies and technologies, innovative study designs and interventions, attention to implementation science, inclusion of adequately diverse study participants into clinical trials, and input from the stakeholders impacted by health disparities are needed to improve outcomes for pregnant and lactating people. Although California accounts for nearly one eighth of annual U.S. births, the MFMU Network lacks a West Coast site. The University of California, San Francisco (UCSF) has a racially and ethnically diverse patient population, including many individuals with differing gender identities. The inclusion of historically marginalized communities, including segments of the population that are highly represented in California, will ensure the MFMU Network study results are generalizable, and will promote health equity for all persons. UCSF is a pioneer in innovative research techniques, such as genomics and metagenomics, as well as clinical research methods, including community partnership and implementation science. In addition, UCSF has a robust research infrastructure that has supported numerous translational investigations including epigenetics and infection studies, metagenomic sequencing in pregnant patients with obstetric complications, studies of environmental contaminants such as wildfire smoke on reproductive outcomes, and placental biology, including the impact of COVID-19 and COVID vaccines. UCSF has an extensive network of affiliated practices and referring hospitals that provide care for diverse patient populations with a myriad of pregnancy- related complications and together with its affiliate, Zuckerberg San Francisco General Hospital, performs nearly 4000 deliveries per year in mostly high-risk patients. Therefore, to support the mission of the MFMU Network, we will 1) Enroll a large and uniquely diverse, west coast participant population; 2) Contribute multidisciplinary expertise of UCSF investigators to high priority areas of public health that impact pregnant people and/or their infants, such as the COVID pandemic, the opioid crisis, and the impacts of climate change; and 3) Leverage our affiliation with the MFMU Network to develop a diverse group of young academic investigators. UCSF will bring a host of novel and innovative opportunities, including clinical populations and unique technological and research approaches that will strengthen the work of the MFMU Network.", "keywords": [ "Address", "Area", "Attention", "Basic Science", "Birth", "Black race", "COVID-19 impact", "COVID-19 pandemic", "California", "Caring", "Clinic", "Clinical", "Clinical Research", "Clinical Services", "Clinical Trials", "Collection", "Comprehensive Health Care", "Conscious", "DNA", "Diabetes Mellitus", "Education", "Endocrinology", "Enrollment", "Ensure", "Environment", "Environmental Impact", "Environmental Pollutants", "Epigenetic Process", "Ethnic Origin", "Ethnic group", "Fetal Growth", "Gender Identity", "General Hospitals", "Genetic", "Genomics", "Goals", "Health system", "Heart Diseases", "Hospitals", "Housing", "Hypertension", "Individual", "Infant", "Infection", "Infrastructure", "Intervention", "Investigation", "Lactation", "Maternal Mortality", "Maternal complication", "Maternal-Fetal Medicine Units Network", "Maternal-fetal medicine", "Metagenomics", "Methodology", "Mission", "Molecular", "Morbidity - disease rate", "Multi-Institutional Clinical Trial", "Multicenter Trials", "Neurology", "Newborn Infant", "Outcome", "Outpatients", "Participant", "Patients", "Perinatal", "Perinatal Care", "Persons", "Pharmacogenomics", "Placental Biology", "Plasma", "Population", "Pregnancy Complications", "Pregnancy Outcome", "Premature Birth", "Prenatal Diagnosis", "Public Health", "Race", "Recruitment Activity", "Reproductive Endocrinology", "Research", "Research Design", "Research Infrastructure", "Research Methodology", "Research Personnel", "Research Technics", "Resources", "Safety", "San Francisco", "Site", "Smoke", "Technology", "Tissues", "Training Programs", "Translational Research", "Underrepresented Minority", "Universities", "Vaccines", "Wildfire", "Work", "climate change", "climate impact", "clinical care", "community partnership", "coronavirus disease", "ethnic diversity", "experience", "fetal", "health disparity", "health equity promotion", "high risk", "implementation science", "improved", "improved outcome", "in utero", "infant morbidity/mortality", "innovation", "marginalized community", "medical specialties", "metagenomic sequencing", "microbial", "multidisciplinary", "new technology", "novel", "novel strategies", "novel therapeutics", "obstetric care", "obstetrical complication", "opioid epidemic", "patient oriented", "patient population", "perinatal medicine", "perinatal mental health", "personalized approach", "precision medicine", "pregnancy heal" ], "approved": true } }, { "type": "Grant", "id": "15704", "attributes": { "award_id": "1P30AG092752-01", "title": "North Texas ADRC", "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": 32575, "first_name": "CERISE", "last_name": "ELLIOTT", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-06-15", "end_date": "2030-03-31", "award_amount": 4663946, "principal_investigator": { "id": 26206, "first_name": "IHAB M", "last_name": "HAJJAR", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1215, "ror": "", "name": "UT SOUTHWESTERN MEDICAL CENTER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "This new application is to establish the North Texas Alzheimer’s Disease Research Center (NT-ADRC) which will serve North Texas, one of the most-populous catchment areas in the country. This application describes how we plan to build a unique and interconnected multidisciplinary center that will create an environment that enables and supports innovative research, training and eventually enhance the care and lives of those dealing with Alzheimer's Disease (AD) and related dementias (ADRD). It is built on a strong foundation of AD and ADRD research and will synergize and connect multiple AD/ADRD investigators and their programs at University of Texas (UT) Southwestern Medical Center, UT Dallas, and UT Arlington. The NT-ADRC will benefit from the strong institutional support to advance AD and ADRD research, our long history of studying cardiometabolic factors, particularly hypertension, in AD/ADRD, our recent expansion of the cutting-edge neuroimaging, informatics, machine learning, and artificial intelligence (ML/AI) capabilities in neurosciences, and the recruitment of multiple key leaders in the Neurocognitive space. The NT-ADRC thematic focus is on examining the roles and mechanisms of hypertension and other cardiometabolic factors in the early phases of AD/ADRD, developing innovative biomarkers for early detection, and identifying related therapeutic targets. We have an exceptional engagement in our diverse communities that is amplified by the participation of Parkland Health and its community ties. We also create novel ways to enhance inclusiveness in ADRD research particularly Lumbar Punctures acceptance and Brain Donation enrollment. These amplify the Center’s abilities to create a highly diverse UDS cohort representative of our diverse population as evidenced by our affiliated studies (Dallas Heart Study and the NIA-funded Post-COVID Neuro-Cognitive Manifestations in Older African Americans). The NT-ADRC Center addresses multiple elements in the National Alzheimer's Project Act (NAPA) and its Implementation Milestones by enabling ongoing and new research in the preclinical and prodromal stages centered around the discovery of novel disease mechanisms underlying the role of hypertension and other cardiometabolic factors in increasing the risk of AD/ADRD; implementing novel ML/AI approaches to biomarker developments; and paving the way for novel therapeutic developments. The NT- ADRC will enhance scientific and clinical collaborations by sharing of biosamples and data with local and national investigators, dissemination of research findings to professional and lay audiences and create education opportunities for researchers, clinicians, learners, and the general North Texas community focused on enhancing caregivers’ education and support. Our commitment to diversity, innovation and rigor to ADRD research will build a new local environment of cutting-edge research and training. It will also position us to make important contributions to the ADRC network and to advance the national agenda towards meeting the NAPA goals.", "keywords": [ "Acceleration", "Action Research", "Address", "African American population", "Alzheimer disease detection", "Alzheimer&apos", "s Disease", "Alzheimer&apos", "s disease related dementia", "Alzheimer&apos", "s disease risk", "Angiography", "Artificial Intelligence", "Awareness", "Behavioral", "Biological Markers", "Brain", "Brain imaging", "COVID-19 neurocognitive sequelae", "Caregivers", "Caring", "Catchment Area", "Clinical", "Cohort Studies", "Collaborations", "Communities", "Community Health Education", "Country", "Coupled", "Data", "Data Science", "Data Set", "Dementia", "Development", "Disease", "Early Diagnosis", "Education", "Elements", "Enrollment", "Environment", "Foundations", "Funding", "Goals", "Health", "Heart", "Hypertension", "Image", "Informatics", "Institution", "Intervention", "Liquid substance", "Machine Learning", "Measures", "Medical center", "Mentors", "Nerve Degeneration", "Neurocognitive", "Neurosciences", "Pathogenesis", "Peripheral", "Persons", "Phase", "Population", "Population Heterogeneity", "Positioning Attribute", "Proteins", "Recording of previous events", "Research", "Research Infrastructure", "Research Personnel", "Resources", "Risk Factors", "Role", "Schools", "Science", "Social Work", "Speech", "Spinal Puncture", "Standardization", "System", "Texas", "Therapeutic Trials", "Training", "Translational Research", "Universities", "Voice", "arterial stiffness", "biobank", "biomarker development", "cardiometabolism", "caregiver education", "caregiving", "cerebrovascular reactivity", "clinical center", "cohort", "community engagement", "community partnership", "data management", "data sharing", "early detection biomarkers", "education research", "health equity", "innovation", "meetings", "multidisciplinary", "neuroimaging", "neuropathology", "new therapeutic target", "next generation", "novel", "novel marker", "novel therapeutics", "outreach", "post-COVID-19", "pre-clinical", "programs", "protein misfolding", "recruit", "repository", "statistics", "success", "synergism", "therapeutic development", "therapeutic target", "tomography", "vascular injury" ], "approved": true } }, { "type": "Grant", "id": "15707", "attributes": { "award_id": "1R01NS138600-01A1", "title": "The role of SARS-CoV-2-induced senescence in the development of Alzheimer's Disease", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Neurological Disorders and Stroke (NINDS)" ], "program_reference_codes": [], "program_officials": [ { "id": 32579, "first_name": "WILLIAM PATRICK", "last_name": "DALEY", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-06-09", "end_date": "2030-03-31", "award_amount": 369823, "principal_investigator": { "id": 23833, "first_name": "Eleni", "last_name": "Markoutsa", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 235, "ror": "https://ror.org/032db5x82", "name": "University of South Florida", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 235, "ror": "https://ror.org/032db5x82", "name": "University of South Florida", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true }, "abstract": "SARS-CoV-2 has been associated with neurological symptoms, although there is no strong evidence of a direct viral infection in the brain. Recent reports indicate that SARS-CoV-2-induced systemic inflammation and the cleaved S1 subunit of the S protein remain detectable in patients with COVID-19 for months after diagnosis and may cause neurological manifestations. Also, COVID-19 tends to be more severe in older people, and although various biological responses change with aging, the induction of cellular senescence (SC) is predominant. New findings indicate that SARS-CoV-2 induces senescence in the lung epithelium with an exacerbated senescence- associated secretory phenotype (SASP) in response to the S1 subunit of the SARS-CoV-2 spike protein. Here, we will investigate how SARS-CoV-2 promotes CS in the brain and the role of SASP components in conveying senescence and promoting AD pathogenesis. Our preliminary data show that the S1 protein enters the systemic circulation and accumulates in the choroid plexus (CP) epithelium that expresses the ACE2 receptor. When S1 is combined with systemic inflammation, it induces a senescence-like phenotype in the brain of aged mice, initially restricted to epithelial cells in the CP, but it spreads to other brain regions, including the cortex and hippocampus, within a month. Transcriptome analysis in the brains of aged S1-challenged mice with systemic inflammation 30 days post S1 administration identified the \"metabolic pathways,\" \"pathways in neurodegeneration,\" and \"Alzheimer's disease\" among the top 10 enriched pathways. We also investigated how the S1 cleaved subunit induces cellular senescence (CS) in the choroid plexus epithelial cells when combined with systemic inflammation, and our results indicate that S1 induces dysfunction of the Nrf2-antioxidant response, which leads to accelerated CS when it is accompanied by LPS-induced ROS production. Most importantly, SASP analysis revealed the role of soluble factors SASP and EV-miRNA SASP components in conveying CS of neurons and regulating CS and AD pathways, respectively. Therefore, our goal is to explore whether miRNA replacement therapy can abrogate secondary SASP-induced senescence and AD pathogenesis and progression. Furthermore, analysis of postmortem brain sections and CSF from AD patients revealed the presence of CS markers in the CP long before the robust accumulation of β-amyloid and tau tangles in HPC, suggesting that CS may play an important role in Alzheimer's pathogenesis. Analysis of CSF from the early stages of AD also showed high levels of soluble SASP factors, which correlates well with the cellular senescent burden in the CP that produces the CSF. These findings prompted us to examine the relationship between CS and SARS-CoV-2 infection further and how it may increase the risk for AD. Our hypothesis is that SARS-CoV- 2-induced SASP in the CSF induces neuronal senescence and increases AD risk. Patients with severe COVID- 19 may be predisposed to develop AD later in life. These studies will allow us to identify better diagnostic markers and therapeutic targets and enable early intervention to prevent the development and progression of AD.", "keywords": [ "2019-nCoV", "ACE2", "Acceleration", "Aging", "Alzheimer disease prevention", "Alzheimer&apos", "s Disease", "Alzheimer&apos", "s Disease Pathway", "Alzheimer&apos", "s disease brain", "Alzheimer&apos", "s disease pathology", "Alzheimer&apos", "s disease patient", "Alzheimer&apos", "s disease risk", "Antibodies", "Antioxidants", "Astrocytes", "Autopsy", "Behavior assessment", "Biological", "Blood", "Brain", "Brain region", "COVID-19", "COVID-19 patient", "Cell Aging", "Cell Senescence Induction", "Choroid Plexus Epithelium", "Circulation", "Data", "Development", "Diagnosis", "Disease Progression", "Early Intervention", "Enzyme-Linked Immunosorbent Assay", "Enzymes", "Epithelial Cells", "Epithelium", "Exposure to", "Functional disorder", "Genes", "Goals", "Hippocampus", "Human", "In Vitro", "Inflammation", "Intervention", "Lead", "Long-Term Effects", "Lung", "Measures", "Mediating", "Metabolic Pathway", "MicroRNAs", "Microglia", "Mus", "Nerve Degeneration", "Neurofibrillary Tangles", "Neurologic Symptoms", "Neurons", "Older Population", "Pathogenesis", "Pathway interactions", "Patients", "Pattern", "Phenotype", "Play", "Production", "Protein Subunits", "Proteins", "Reporting", "Research", "Role", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "Senile Plaques", "Severe Acute Respiratory Syndrome", "Structure of choroid plexus", "Testing", "Virus Diseases", "Western Blotting", "abeta accumulation", "aged", "amyloid precursor protein processing", "brain cell", "brain endothelial cell", "cell type", "cognitive testing", "deep sequencing", "diagnostic biomarker", "in vivo", "inflammatory marker", "later life", "miRNA expression profiling", "microRNA replacement therapy", "mouse model", "nerve stem cell", "old mice", "oligodendrocyte progenitor", "paracrine", "prevent", "receptor", "response", "senescence", "senescence associated secretory phenotype", "senescent cell", "severe COVID-19", "spatiotemporal", "systemic inflammatory response", "tau Proteins", "tau aggregation", "tau-1", "therapeutic target", "transcriptome", "transcriptome sequencing" ], "approved": true } } ], "meta": { "pagination": { "page": 4, "pages": 1405, "count": 14046 } } }