Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1385&sort=other_investigators
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=other_investigators", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1424&sort=other_investigators", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1386&sort=other_investigators", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1384&sort=other_investigators" }, "data": [ { "type": "Grant", "id": "12383", "attributes": { "award_id": "1R24AI165424-01A1", "title": "Establishment of a Bat Resource for Infectious Disease Research", "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": 7711, "first_name": "SARA ELAINE", "last_name": "Woodson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-22", "end_date": "2028-08-31", "award_amount": 1694054, "principal_investigator": { "id": 859, "first_name": "Jonathan H", "last_name": "Epstein", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 234, "ror": "", "name": "Ecohealth Alliance inc.", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22678, "first_name": "William A", "last_name": "Schountz", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 323, "ror": "https://ror.org/03k1gpj17", "name": "Colorado State University", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 323, "ror": "https://ror.org/03k1gpj17", "name": "Colorado State University", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true }, "abstract": "/ Abstract Bats are reservoirs, or suspected reservoirs, of many zoonotic viruses, including SARS, SARS2 and MERS coronaviruses, Nipah and Hendra viruses, and Ebola and Marburg viruses. Little is known about how these viruses circulate in their bat reservoirs, principally because of a lack of bat colonies that can be used for the development of experimental infection models. To address this deficiency, we will capture horseshoe bats and Indian flying foxes, respective reservoir hosts of Nipah virus and SARS-related coronaviruses, in Bangladesh where they will be quarantined and provided veterinary care as they adapt to captivity. Bats will be shipped to CSU to establish the breeding colonies as a resource for investigators who study these viruses. We will generate primary cell cultures and immortalized cell lines from various tissues and freeze live bone marrow that will be useful for studying how these viruses infect bat cells, and how the viruses may modulate the innate immune responses. Recombinant cytokines will also be produced for the research community, including those for generating macrophages and dendritic cells (GM-CSF, Flt3L), T cells (IL-2) and for in vivo modulation of the adaptive immune response (IFN, IL-4). Moreover, we will generate monoclonal antibodies for use in cytokine detection assays and flow cytometry of immune cell subsets and in vivo neutralization. Finally, we will perform experimental infection studies of Nipah virus, SARS-CoV-2 and the SARS-related coronavirus, RaTG13, to study the infection kinetics, virus distribution and transcriptomic, proteomic and metabolomic profiles of bats during infection, and escalation and resolution of the immune response. Tissues, cells and sera from naïve and infected bats will be archived in a biobank that will be made available to the research community. The establishment of this resource will lead to a better understanding of how bats host highly pathogenic viruses without disease and may shed light on events that increase spillover risks to humans. In turn, this information could lead to development of mitigation strategies to prevent future virus spillover and uncover new strategies for therapeutic treatment of coronavirus and Nipah virus diseases.", "keywords": [ "2019-nCoV", "Address", "Affect", "Animal Model", "Animals", "Archives", "Asia", "Bangladesh", "Biology", "Bone Marrow", "Breeding", "Caring", "Cell Culture Techniques", "Cell Line", "Cells", "Chiroptera", "Clinical", "Colorado", "Communities", "Coronavirus", "Coronavirus Infections", "Dendritic Cells", "Development", "Disease", "Disease Outbreaks", "Ebola virus", "Encephalitis", "Event", "FLT3 ligand", "Family Pteropodidae", "Filovirus", "Flow Cytometry", "Freezing", "Future", "Genus Pteropus", "Granulocyte-Macrophage Colony-Stimulating Factor", "Health", "Hendra Virus", "Henipavirus", "Henipavirus Infections", "Hepatitis C virus", "Human", "Immune", "Immune response", "Immunology", "In Vitro", "Individual", "Infection", "Infection Control", "Infectious Diseases Research", "Innate Immune Response", "Interleukin-2", "Interleukin-4", "Kinetics", "Knowledge", "Laboratories", "Macrophage", "Mammals", "Marburgvirus", "Measles", "Methodological Studies", "Middle East Respiratory Syndrome Coronavirus", "Modeling", "Monoclonal Antibodies", "Mumps", "Natural Immunity", "Nipah Virus", "Outcome", "Paramyxovirus", "Pathogenicity", "Pathology", "Physiology", "Predisposition", "Primary Cell Cultures", "Proteins", "Proteomics", "Quarantine", "Reagent", "Recombinant Cytokines", "Recombinant Proteins", "Research", "Research Personnel", "Resolution", "Resources", "Risk", "SARS coronavirus", "Sarbecovirus", "Severe Acute Respiratory Syndrome", "Study models", "Surface Antigens", "T-Lymphocyte", "Testing", "Therapeutic", "Tissues", "Universities", "Viral", "Virus", "Virus Diseases", "Work", "Zoonoses", "adaptive immune response", "bat-borne", "betacoronavirus", "biobank", "cell immortalization", "coronavirus treatment", "cytokine", "deep sequencing", "detection assay", "experimental study", "germ free condition", "improved", "in vitro testing", "in vivo", "metabolomics", "mortality", "novel", "novel therapeutic intervention", "offspring", "pandemic potential", "pathogen", "pathogenic virus", "prevent", "trait", "transcriptomics" ], "approved": true } }, { "type": "Grant", "id": "6846", "attributes": { "award_id": "1R21AI169548-01", "title": "Development and function of humoral immunity in the Jamaican fruit bat, Artibeus jamaicensis", "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": 8224, "first_name": "Kentner L.", "last_name": "Singleton", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-02-18", "end_date": "2024-01-31", "award_amount": 279000, "principal_investigator": { "id": 22677, "first_name": "Hannah Kim", "last_name": "Frank", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 811, "ror": "", "name": "TULANE UNIVERSITY OF LOUISIANA", "address": "", "city": "", "state": "LA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22678, "first_name": "William A", "last_name": "Schountz", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 323, "ror": "https://ror.org/03k1gpj17", "name": "Colorado State University", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 811, "ror": "", "name": "TULANE UNIVERSITY OF LOUISIANA", "address": "", "city": "", "state": "LA", "zip": "", "country": "United States", "approved": true }, "abstract": "Bats host many viruses, seemingly without disease, that cause lethal infections in humans and other non-bat species, including rabies, Marburg fever virus and SARS-related coronaviruses. A greater understanding of the bat immune system – how it responds to viruses, how it differs from the human immune system – could lead to improved approaches for treating or even avoiding infection in humans. The immune response consists of two major branches: the nonspecific innate response and the pathogen-specific adaptive response. Although numerous studies have investigated innate immunity in bats, very little is known about their adaptive immune system. The long-term objective of the proposed research is to enhance understanding of adaptive immunity in bats. A key feature of adaptive immunity is humoral immunity; this immune response is mediated by antibodies, also known as immunoglobulins. The hyper-diverse immunoglobulin repertoire is generated through a combination of gene recombination, DNA insertions and deletions, and somatic mutation of the antibody sequence. While immunoglobulins have been detected in several serological studies of bats, the true extent of the diversity of bat immunoglobulin repertoires, the degree to which bats rely on gene rearrangement vs. somatic mutation to generate these repertoires, how mutation of the immunoglobulins correlates with neutralization of pathogens, or the B cell subsets that arise in response to infection remain unknown. The proposed study will use rabies virus vaccination followed by rabies virus infection in Jamaican fruit bats to generate the most comprehensive understanding of B cell-mediated adaptive immunity in bats to date. Jamaican fruit bats are common across Central and South America, where rabies remains a serious threat, and are naturally infected by rabies virus. This research will use long-read sequencing to characterize the germline genes that provide the starting diversity for the immunoglobulin repertoire. Next generation genomic techniques will be used to track the development of rearranged immunoglobulin repertoires, monitor expansion of specific B cell clones, and quantify the degree of somatic mutation in antigen-exposed antibodies across vaccination and challenge with rabies. Single-cell transcriptomics will be used to characterize the B cell subsets that arise in response to immune challenges, and binding assays and rabies neutralization tests will facilitate an understanding of how antibody maturation correlates with function. Comparison of the immune responses of bats to vaccination and infection will be used to investigate immunity in controlled and natural contexts. This research will provide important information on the adaptive immune system of bats that is currently lacking. These data will provide insight into the differences in immune responses between bats and humans to a shared pathogen and can be used to develop new rabies prevention or intervention approaches. The framework and immunological data generated by this project will also allow for specific investigations of B-cell mediated immunity to any infection.", "keywords": [ "Adaptive Immune System", "Address", "Affinity", "Aliquot", "Animals", "Antibodies", "Antibody Repertoire", "Antibody Response", "Antibody titer measurement", "Antigens", "Avidity", "B-Cell Antigen Receptor", "B-Cell Development", "B-Lymphocyte Subsets", "B-Lymphocytes", "Binding", "Biological Assay", "Blood specimen", "Body Size", "Cell Culture Techniques", "Cells", "Cellular Immunity", "Central America", "Chiroptera", "Clonal Expansion", "Clone Cells", "Communicable Diseases", "Comparative Genomic Analysis", "DNA", "Data", "Deletion Mutation", "Development", "Disease", "Exposure to", "Fever", "Frequencies", "Fruit", "Future", "Gene Combinations", "Gene Rearrangement", "Genes", "Genetic", "Genetic Recombination", "Genomic DNA", "Genomics", "Health", "Human", "Humoral Immunities", "Immune", "Immune response", "Immune system", "Immunity", "Immunoglobulin Class Switching", "Immunoglobulin G", "Immunoglobulin Isotypes", "Immunoglobulin Somatic Hypermutation", "Immunoglobulin Switch Recombination", "Immunoglobulins", "Immunologic Memory", "Immunologics", "Individual", "Infection", "Insertion Mutation", "Intervention", "Investigation", "Jamaican", "Knowledge", "Lead", "Malignant Neoplasms", "Marburgvirus", "Measures", "Mediating", "Memory", "Memory B-Lymphocyte", "Monitor", "Mutate", "Mutation", "Natural Immunity", "Neutralization Tests", "Organ", "Organism", "Population", "Prevention", "Public Health", "Rabies", "Rabies virus", "Reagent", "Research", "Research Personnel", "Role", "SARS coronavirus", "Serology", "Somatic Mutation", "South America", "T-Lymphocyte", "Techniques", "Testing", "Time", "Vaccinated", "Vaccination", "Vaccines", "Viral", "Virus", "Virus Diseases", "Zoonoses", "adaptive immunity", "bat-borne", "cell mediated immune response", "cell type", "cohort", "experience", "experimental study", "immunoglobulin receptor", "improved", "insight", "next generation", "pathogen", "peripheral blood", "prevent", "receptor", "response", "transcriptome", "transcriptomics" ], "approved": true } }, { "type": "Grant", "id": "11184", "attributes": { "award_id": "1R21HL168142-01", "title": "Validation of a Genetic-based Biomarker Panel for Stratification of Mortality Risk in ARDS Patients", "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": 22589, "first_name": "CHRISTIAN RENE", "last_name": "Gomez", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-04-01", "end_date": "2024-03-31", "award_amount": 115125, "principal_investigator": { "id": 26527, "first_name": "Christian", "last_name": "Bime", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 22687, "first_name": "Joe G. N.", "last_name": "Garcia", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 438, "ror": "https://ror.org/03m2x1q45", "name": "University of Arizona", "address": "", "city": "", "state": "AZ", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 438, "ror": "https://ror.org/03m2x1q45", "name": "University of Arizona", "address": "", "city": "", "state": "AZ", "zip": "", "country": "United States", "approved": true }, "abstract": "PROJECT SUMMARY: The COVID-19 pandemic has dramatically highlighted serious unmet needs of ARDS including the absence of effective FDA-approved pharmacologic interventions that address ARDS mortality. ARDS phenotype heterogeneity, the complexity of dysregulated inflammation, and the absence of predictive biomarkers have all contributed to failed ARDS therapeutic clinical trials. Predictive biomarkers, either protein- or genomic-based, that identify specific ARDS sub-phenotypes and likely responders to specific ARDS therapeutics, could significantly influence effective clinical trial designs to assess novel therapeutics and therefore benefit the outcomes of ARDS trials. Our group has long championed the utility of genomic-intensive approaches to identify multiple novel ARDS therapeutic targets. We previously identified eNAMPT (extracellular nicotinamide phosphoribosyl transferase) as a novel ARDS therapeutic target/gene which serves as a damage-associated molecular pattern protein (DAMP) and ligand for Toll-like receptor 4 (TLR4). NAMPT SNPs predict ARDS severity and eNAMPT amplifies dysregulated lung/systemic inflammatory responses that contribute to multi- organ injury/failure. We demonstrated the utility of a humanized eNAMPT-neutralizing mAb as a therapeutic strategy in ARDS and other inflammatory conditions. Plasma eNAMPT, along with IL-6, IL-8, IL-1RA, MIF, and Ang-2, was highly predictive of 28-day ARDS mortality. We also identified variants in selectin P ligand gene (SELPLG) encoding P-selectin glycoprotein ligand 1 (PSGL1), and P-selectin gene (SELP) as associated with increased susceptibility to ARDS in Blacks. PSGL1/P-selectin interactions are critical to lung inflammation via leukocyte trafficking, platelet aggregation, and thrombosis. Plasma PSGL1 and P-selectin levels are significantly elevated in sepsis, ARDS, and COVID-19 pneumonia patients and PSGL1 inhibition (mAb, TSGL-Ig) significantly attenuates preclinical lung injury in ARDS. This R-21 application will utilize over 900 plasma samples and genotyping results available from the NHLBI Prevention and Early Treatment of Acute Lung Injury (PETAL) Network Reevaluation of systemic Early neuromuscular blockade (ROSE) study (see NHLBI BioLINCC letter). We will validate two highly novel stratification tools to improve patient stratification in the design of future ARDS clinical trials targeting eNAMPT/TLR4 and PSGL1/P-Selectin interactions. Specific Aim (SA) #1 will develop a genotype-based biomarker assay combining: i) carefully selected SELPLG/SELP variants with plasma PSGL1/P-selectin levels, and ii) NAMPT variants with plasma eNAMPT levels. These genotypes will identify ARDS subjects as candidates for future clinical trials targeting PSGL-1/P-selectin interactions and the eNAMPT/TLR4 signaling pathway. SA #2 will validate the predictive capacity of a seven-biomarker panel (eNAMPT, IL-6, IL-8, IL-1RA, PSGL-1, IL-1β, Ang-2) for ARDS mortality. Successful completion of this highly innovative R21 grant will generate a novel ‘point of care’ pharmacogenetic enrichment tools to be leveraged in designing human ARDS clinical trials targeting PSGL1/P-selectin and eNAMPT/TLR4 interactions.", "keywords": [ "Acute Lung Injury", "Acute Respiratory Distress Syndrome", "Address", "Angiopoietin-2", "Attenuated", "Biological Assay", "Biological Markers", "Black Populations", "COVID-19 pandemic", "COVID-19 pneumonia", "COVID-19/ARDS", "Clinical Trials", "Clinical Trials Design", "Data", "Early treatment", "Evaluation", "FDA approved", "Failure", "Future", "Genes", "Genetic", "Genomics", "Genotype", "Grant", "Heterogeneity", "Human", "IL8 gene", "Immunoglobulins", "Induction of neuromuscular blockade", "Inflammation", "Inflammatory", "Interleukin-1 beta", "Interleukin-6", "Intervention", "Letters", "Leukocyte Trafficking", "Ligands", "Lung", "Mediation", "Mendelian randomization", "Modeling", "Molecular", "Monoclonal Antibodies", "National Heart Lung and Blood Institute", "Niacinamide", "Outcome", "P-Selectin", "P-selectin ligand protein", "Participant", "Patients", "Pattern", "Pharmacogenetics", "Phenotype", "Plasma", "Platelet aggregation", "Predisposition", "Prevention", "Proteins", "Pulmonary Inflammation", "Risk", "SELP gene", "Sampling", "Selectins", "Severities", "Signal Pathway", "Stratification", "TLR4 gene", "Therapeutic", "Therapeutic Clinical Trial", "Thrombosis", "Transferase", "Validation", "Variant", "anakinra", "biomarker panel", "clinically relevant", "design", "extracellular", "genetic variant", "health disparity", "improved", "innovation", "insight", "lung injury", "member", "mortality", "mortality risk", "multiorgan injury", "neutralizing monoclonal antibodies", "novel", "novel marker", "novel therapeutics", "patient stratification", "pharmacologic", "point of care", "pre-clinical", "predictive marker", "predictive test", "radiological imaging", "sepsis induced ARDS", "systemic inflammatory response", "therapeutic target", "tool" ], "approved": true } }, { "type": "Grant", "id": "12123", "attributes": { "award_id": "1R44AI179371-01", "title": "Monoclonal Antibody Cocktail for Treatment of Marburg Virus Disease", "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": 27983, "first_name": "JULIE", "last_name": "Dyall", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-08-11", "end_date": "2024-01-31", "award_amount": 293392, "principal_investigator": { "id": 27984, "first_name": "M Javad", "last_name": "Aman", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 22691, "first_name": "Thomas William", "last_name": "Geisbert", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 851, "ror": "", "name": "UNIVERSITY OF TEXAS MED BR GALVESTON", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 2065, "ror": "", "name": "ABVACC, INC.", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Ebola (EBOV) and Marburg (MARV) viruses cause hemorrhagic fever disease in humans and nonhuman primates (NHPs) with case-fatality rates as high as 90%. The 2013-2016 Ebola Virus Disease (EVD) outbreak led to over 28,000 cases and 11,000 deaths and took an enormous toll on the economy of West African nations, in the absence of any vaccine or therapeutic options. This outbreak spurred an unprecedented global effort for development of vaccines and therapeutics for EVD and led to an approved vaccine and two monoclonal antibody (mAb) therapeutics. Importantly studies with EBOV mAbs and later SARS-CoV2 mAbs established the value of mAb cocktails for effective treatment of viral diseases. In contrast to EVD, development of therapeutics for Marburg Virus Disease (MVD) has been lagging despite several MVD outbreaks including one in 2022. The investigators on this MPI Phase I/II Fast Track SBIR application have developed two classes of mAbs targeting non-overlapping epitopes within the receptor binding site (RBS) and the internal fusion loop (IFL) of MARV glycoprotein (GP). The RBS-binding mAb (MR186), provides protection primarily through effector functions, while the IFL-binder (R217) is the most potent neutralizing MARV mAb discovered to-date. MR186 has been engineered to enhance bioavailability using YTE mutation in the Fc portion, and produced in a fucosyl- transferase deficient CHO cell line to enhance effector functions (MR186-YTEAF). We are currently introducing YTE mutations into R217 Fc to generate the therapeutic candidate R217-YTE. In this proposed project we harness these complementary mechanisms of action to develop a highly effective cocktail of these two mAbs for MVD treatment. Use of mAb cocktail is also expected to reduce the risk of escape variant. The proposal has four Specific Aims. In Aim 1 (Phase I portion), R217-YTE will be produced in ExpiCHO cells and fully characterized. Superior efficacy of the cocktail will be demonstrated in a guinea pig model of MARV-Angola and this milestone will serve for transition to Phase II SBIR. Phase II Portion starts with Aim 2, in which the efficacy of the cocktail will be tested in NHP models in series of adaptively designed NHP experiments and finally the superior efficacy will be formally demonstrated in comparison with the individual mAbs. In Aim 3 we will evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of the antibodies in sera from a number of NHP efficacy studies including studies performed in Aim 1. Correlations between PK/PD data and clinical outcome will be explored. Aim 4 we will be focused on generation of stable manufacturing cell lines in CHO cells and at lease four clones of each mAb will be produced to be used for future GMP cell banks. If successful, we anticipate further development of the product under DoD or BARDA funding and approval under FDA Animal Rule.", "keywords": [ "2019-nCoV", "Africa", "African", "Aman", "Angola", "Animal Model", "Antibodies", "Antibody Therapy", "Binding", "Binding Sites", "Biological Availability", "Biological Products", "Biological Response Modifier Therapy", "Blood Chemical Analysis", "Case Fatality Rates", "Cavia", "Cell Line", "Cells", "Cessation of life", "Chinese Hamster Ovary Cell", "Clinical", "Collaborations", "Comparative Study", "Complete Blood Count", "Data", "Development", "Disease", "Disease Outbreaks", "Disease Outcome", "Dose", "Drug Kinetics", "Ebola", "Ebola Hemorrhagic Fever", "Ebola virus", "Engineering", "Epitopes", "Exhibits", "FDA approved", "Fatality rate", "Filovirus", "Fucosyltransferase", "Funding", "Future", "GP2 gene", "GTPBP1 gene", "Generations", "Glycoproteins", "Human", "Immunotherapy", "Individual", "Infection", "Injections", "Lead", "Macaca fascicularis", "Marburg Virus Disease", "Marburgvirus", "Measures", "Modeling", "Monitor", "Monoclonal Antibodies", "Mutation", "Outcome", "Pharmacodynamics", "Phase", "Property", "Regression Analysis", "Reporting", "Research", "Research Personnel", "Risk Reduction", "Sampling Studies", "Series", "Serum", "Small Business Innovation Research Grant", "Surface", "Survival Analysis", "Testing", "Therapeutic", "Therapeutic Monoclonal Antibodies", "Time", "Transfection", "Vaccines", "Variant", "Viral", "Viral Hemorrhagic Fevers", "Viremia", "Virus", "Virus Diseases", "Zaire Ebola virus", "animal efficacy", "animal rule", "antibody immunotherapy", "base", "cell bank", "clinical development", "design", "drug candidate", "effective therapy", "efficacy evaluation", "efficacy study", "experimental study", "guinea pig model", "manufacture", "neutralizing antibody", "neutralizing monoclonal antibodies", "nonhuman primate", "novel", "pathogen", "pharmacokinetics and pharmacodynamics", "primary endpoint", "product development", "protective efficacy", "prototype", "receptor binding", "secondary endpoint", "sobriety", "stable cell line", "success", "therapeutic candidate", "therapeutic development", "therapeutically effective", "vaccine development", "viral outbreak" ], "approved": true } }, { "type": "Grant", "id": "15517", "attributes": { "award_id": "1R01AI183645-01A1", "title": "Assessing functional immunity to influenza infection by quantifying BCR binding avidities", "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": 26918, "first_name": "Michelle Marie", "last_name": "Arnold", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-11-13", "end_date": "2029-10-31", "award_amount": 811009, "principal_investigator": { "id": 22692, "first_name": "Nicole", "last_name": "Baumgarth", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 746, "ror": "", "name": "UNIVERSITY OF CALIFORNIA AT DAVIS", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22693, "first_name": "Steven CARL", "last_name": "George", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 32060, "first_name": "Venktesh", "last_name": "Shirure", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 32061, "first_name": "Xiangdong", "last_name": "Zhu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 746, "ror": "", "name": "UNIVERSITY OF CALIFORNIA AT DAVIS", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Activation, clonal expansion, and affinity maturation of antigen-specific B cells are considered the hallmarks of adaptive immunity; hence, the assessment of B cell responses is thought to provide correlates of immune protection. Antigen-specific B cell responses have traditionally been observed indirectly, by examining the serum antibody pool using ELISA, or in the case of influenza the hemagglutinin inhibition assay (HIA). Direct measurements of antibody-secreting cells have also been done using ELISPOT, or more recently by flow cytometry. However, there are currently no tools to assess the functionality of the non-antibody (Ab) secreting memory B cell (Bmem) pool. This is an important limitation as Bmem, more than the circulating Ab pool, contain cross-reactive and cross-protective cells that could respond to a challenge infection with a mutated pathogen variant, such as occurs during the seasonal yearly influenza surges. Knowing the extent to which Bmem cells exist and can bind to the original or emerging variants of a pathogen would greatly help, for example, with decisions about when to update vaccines to the circulating seasonal influenza or SARS-COV-2 strains. The primary objective of this proposal is to generate such a tool. Our recent work demonstrates the proof-of- concept that a simple microfluidic platform can capture the full avidity spectrum of antigen-specific B cells, and that the equilibrium binding avidity of the BCR correlates strongly with the binding affinity of the secreted antibody. We have dubbed this approach and technology the Shear-force Avidity-based Cell Selector (SACS). These findings provide the foundation of our central hypothesis: capture, separation, and quantification of peripheral B cells based on the force-dependent BCR binding avidity can be used as a measure of functional immune status. To test our hypothesis, and fully develop the SACS technology, the specific aims of this project are to: 1) enhance the design and optimize a microfluidic device with the capacity to capture and separate a complex pool of B cells based on BCR binding avidity to a defined antigen; and 2) characterize the relationship between binding avidity dynamics of influenza-specific peripheral B cells and immune status following influenza virus infection. Our platform will demonstrate the functionality of a rapid and easily adaptable system to evaluate the dynamics of the B cell response to influenza, but is completely adaptable to host of other pathogens such as SARS-Cov-2. Expected results would provide a new measurement platform (SACS) that would allow for the first time the rapid assessment of the range of functional BCR-antigen interaction strengths of individual B cells within the complex pools of peripheral B cells and B cell subsets to predict functional immunity.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "6858", "attributes": { "award_id": "5R21AI161041-02", "title": "Quantifying the spectrum and dynamics of B-cell binding avidity in response to influenza", "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": 6050, "first_name": "Mary Chelsea", "last_name": "Lane", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-02-01", "end_date": "2023-01-31", "award_amount": 235500, "principal_investigator": { "id": 22692, "first_name": "Nicole", "last_name": "Baumgarth", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 746, "ror": "", "name": "UNIVERSITY OF CALIFORNIA AT DAVIS", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22693, "first_name": "Steven CARL", "last_name": "George", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 746, "ror": "", "name": "UNIVERSITY OF CALIFORNIA AT DAVIS", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Activation, clonal expansion, and affinity maturation of antigen-specific B cells are considered the hallmarks of adaptive immunity; hence, the assessment of B cell responses is thought to provide correlates of immune protection. Antigen-specific B cell responses have traditionally been observed indirectly, through the study of the magnitude of the serum antibody pool using ELISA. Direct measurements of antibody-secreting cells have also been done using ELISPOT, or more recently by flow cytometry (FC). None of these methods, however, provide a measure of a B cell’s overall binding avidity for its cognate antigen, despite the fact that this measure is frequently acknowledged as prognostic of immune protection and may be critical for the evaluation of functional immunity. The primary goals of this project are to i) develop a microfluidic platform to capture and isolate B cells according to their binding avidity for viral antigens, and ii) use the platform to examine how B cell binding avidity changes in time (affinity maturation) following infection and correlates with functional immunity. Our long-term objective is to develop new tools with which to rapidly and effectively assess immune cell function. This project expands on our previous work with tumor-specific T cells, and specifically examines the B cell response to influenza A in hybridoma and murine model systems. The specific aims of this project are to: 1) Design and optimize a microfluidic device to determine the specificity and binding avidities of influenza virus nuclear protein (NP)- and hemagglutinin (HA)-specific monoclonal B cells; and 2) characterize binding avidity dynamics of HA- and NP-specific peripheral B cells following influenza virus infection. Our platform will demonstrate the functionality of a rapid and easily adaptable system to evaluate the dynamics of the B cell response to influenza but is completely adaptable to host of other pathogens such as SARS-Cov-2. Furthermore, the project will begin to vigorously test long-held dogmas regarding the potential critical importance of affinity maturation in the complex setting of an acute infection that induces polyclonal extrafollicular and germinal center B cell responses, as well as local and systemic B cell immunity, where related earlier studies have failed to demonstrate affinity maturation as a main driver of protective immunity.", "keywords": [ "2019-nCoV", "Affinity", "Antibodies", "Antibody Affinity", "Antibody Therapy", "Antigens", "Avidity", "B-Cell Antigen Receptor", "B-Cell Receptor Binding", "B-Lymphocytes", "Binding", "Biological Assay", "Biological Models", "Biometry", "Cell physiology", "Cells", "Clinical", "Clonal Expansion", "Communicable Diseases", "Communities", "Complex", "Detection", "Devices", "Enzyme-Linked Immunosorbent Assay", "Evaluation", "Flow Cytometry", "Frequencies", "Goals", "Hemagglutination", "Hemagglutinin", "Hybridomas", "Immune", "Immunity", "Immunoglobulin-Secreting Cells", "Individual", "Infection", "Influenza", "Influenza A Virus H1N1 Subtype", "Influenza A virus", "Kinetics", "Label", "Liquid substance", "Measurement", "Measures", "Memory B-Lymphocyte", "Methods", "Microfluidic Microchips", "Microfluidics", "Modeling", "Mus", "Nuclear Protein", "Peripheral", "Plasma Cells", "Plasmablast", "Population", "Process", "Puerto Rico", "Recombinants", "Research", "Sensitivity and Specificity", "Serum", "Specificity", "Spleen", "Structure of germinal center of lymph node", "Surface", "System", "T-Lymphocyte", "Techniques", "Technology", "Testing", "Time", "Vaccination", "Viral Antigens", "Virus", "Work", "acute infection", "adaptive immunity", "antigen binding", "base", "bone", "density", "design", "enzyme linked immunospot assay", "immunological status", "indexing", "influenza infection", "influenzavirus", "lymph nodes", "microfluidic technology", "mouse model", "pathogen", "prognostic", "response", "therapeutic development", "tool", "tumor" ], "approved": true } }, { "type": "Grant", "id": "8075", "attributes": { "award_id": "1R21AI161041-01", "title": "Quantifying the spectrum and dynamics of B-cell binding avidity in response to influenza", "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": 6050, "first_name": "Mary Chelsea", "last_name": "Lane", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-02-01", "end_date": "2023-01-31", "award_amount": 196250, "principal_investigator": { "id": 22692, "first_name": "Nicole", "last_name": "Baumgarth", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 746, "ror": "", "name": "UNIVERSITY OF CALIFORNIA AT DAVIS", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22693, "first_name": "Steven CARL", "last_name": "George", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 746, "ror": "", "name": "UNIVERSITY OF CALIFORNIA AT DAVIS", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Activation, clonal expansion, and affinity maturation of antigen-specific B cells are considered the hallmarks of adaptive immunity; hence, the assessment of B cell responses is thought to provide correlates of immune protection. Antigen-specific B cell responses have traditionally been observed indirectly, through the study of the magnitude of the serum antibody pool using ELISA. Direct measurements of antibody-secreting cells have also been done using ELISPOT, or more recently by flow cytometry (FC). None of these methods, however, provide a measure of a B cell’s overall binding avidity for its cognate antigen, despite the fact that this measure is frequently acknowledged as prognostic of immune protection and may be critical for the evaluation of functional immunity. The primary goals of this project are to i) develop a microfluidic platform to capture and isolate B cells according to their binding avidity for viral antigens, and ii) use the platform to examine how B cell binding avidity changes in time (affinity maturation) following infection and correlates with functional immunity. Our long-term objective is to develop new tools with which to rapidly and effectively assess immune cell function. This project expands on our previous work with tumor-specific T cells, and specifically examines the B cell response to influenza A in hybridoma and murine model systems. The specific aims of this project are to: 1) Design and optimize a microfluidic device to determine the specificity and binding avidities of influenza virus nuclear protein (NP)- and hemagglutinin (HA)-specific monoclonal B cells; and 2) characterize binding avidity dynamics of HA- and NP-specific peripheral B cells following influenza virus infection. Our platform will demonstrate the functionality of a rapid and easily adaptable system to evaluate the dynamics of the B cell response to influenza but is completely adaptable to host of other pathogens such as SARS-Cov-2. Furthermore, the project will begin to vigorously test long-held dogmas regarding the potential critical importance of affinity maturation in the complex setting of an acute infection that induces polyclonal extrafollicular and germinal center B cell responses, as well as local and systemic B cell immunity, where related earlier studies have failed to demonstrate affinity maturation as a main driver of protective immunity.", "keywords": [ "2019-nCoV", "Affinity", "Antibodies", "Antibody Affinity", "Antibody Therapy", "Antigens", "Avidity", "B-Cell Antigen Receptor", "B-Cell Receptor Binding", "B-Lymphocytes", "Binding", "Biological Assay", "Biological Models", "Biometry", "Cell physiology", "Cells", "Clinical", "Clonal Expansion", "Communicable Diseases", "Communities", "Complex", "Detection", "Devices", "Enzyme-Linked Immunosorbent Assay", "Evaluation", "Flow Cytometry", "Frequencies", "Goals", "Hemagglutination", "Hemagglutinin", "Hybridomas", "Immune", "Immunity", "Immunoglobulin-Secreting Cells", "Individual", "Infection", "Influenza", "Influenza A Virus H1N1 Subtype", "Influenza A virus", "Kinetics", "Label", "Liquid substance", "Measurement", "Measures", "Memory B-Lymphocyte", "Methods", "Microfluidic Microchips", "Microfluidics", "Modeling", "Mus", "Nuclear Protein", "Peripheral", "Plasma Cells", "Plasmablast", "Population", "Process", "Puerto Rico", "Recombinants", "Research", "Sensitivity and Specificity", "Serum", "Specificity", "Spleen", "Structure of germinal center of lymph node", "Surface", "System", "T-Lymphocyte", "Techniques", "Technology", "Testing", "Time", "Vaccination", "Viral Antigens", "Virus", "Work", "acute infection", "adaptive immunity", "antigen binding", "base", "bone", "density", "design", "enzyme linked immunospot assay", "immunological status", "indexing", "influenza infection", "influenzavirus", "lymph nodes", "microfluidic technology", "mouse model", "pathogen", "prognostic", "response", "therapeutic development", "tool", "tumor" ], "approved": true } }, { "type": "Grant", "id": "6871", "attributes": { "award_id": "1R01DE031928-01A1", "title": "Initiation of immune responses to SARS COV2 in the oral cavity and upper airway", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Dental and Craniofacial Research (NIDCR)" ], "program_reference_codes": [], "program_officials": [ { "id": 22517, "first_name": "Preethi", "last_name": "Chander", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-04-01", "end_date": "2027-03-31", "award_amount": 822036, "principal_investigator": { "id": 22696, "first_name": "GILL", "last_name": "DIAMOND", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1506, "ror": "", "name": "UNIVERSITY OF MISSISSIPPI MED CTR", "address": "", "city": "", "state": "MS", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22697, "first_name": "SARAH C", "last_name": "GLOVER", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 22698, "first_name": "BRUCE H.", "last_name": "HORWITZ", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1506, "ror": "", "name": "UNIVERSITY OF MISSISSIPPI MED CTR", "address": "", "city": "", "state": "MS", "zip": "", "country": "United States", "approved": true }, "abstract": "Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a life-threatening illness with multi-system involvement in a subset of infected individuals. Oral and nasopharyngeal (NP) epithelial cells express the SARS-CoV-2 receptor ACE2, and infection of the oral/nasopharyngeal cavity (ONP) is likely an obligate step in the development of COVID-19. Immune responses first generated in the ONP are almost certainly crucial for viral clearance but may also play a central role in the development of hyperinflammatory injury observed in many infected individuals. We have used single cell (sc)- RNA sequencing from a racially diverse prospective cohort of COVID-19 patients to identify distinct subsets of ciliated epithelial cells within the NP that are direct targets for SARS-CoV-2 infection and have described innate anti-viral responses generated by those cells within both directly infected as well as non-infected bystander cells. Interestingly this analysis demonstrates that increased mortality is linked to blunted anti-viral gene response in the NP, suggesting that a successful innate response to viral infection in the nose is a critical component of a successful anti-viral response. In addition to the nose, there is strong evidence that SARS-CoV-2 can infect the oral epithelium. While there are several anatomic sites within the mouth that are likely involved in anti-viral responses, the gingival sulcus is a unique immunologically active location that is crucial for maintaining oral health. The gingival epithelium expresses both the SARS-CoV-2 receptor ACE2 as well as the host protease TMPRSS2 necessary for viral entry, but exhibits important immunological differences compared to the nasal epithelium including a bias towards IL-17 associated neutrophil responses. Thus, our overall hypothesis is that identifying and enhancing successful innate and adaptive cellular immune responses of the nasal and gingival epithelium will lead to novel therapeutic avenues for COVID-19. To address this hypothesis, propose the following aims: 1. Stratify cell states and viral dynamics across mucosal surfaces following SARS-CoV-2 infection and vaccination; 2. Compare memory T cell responses within the nose and gingiva that are associated with successful or pathogenic responses to SARS-CoV-2; and 3. Characterize the regulation of host innate immune defense mechanisms that are essential to limit propagation of SARS-CoV-2 infection within ONP epithelial cells. To accomplish these aims, we will analyze human ONP samples from individuals with COVID- 19, recovered from COVID-19, and vaccinated for COVID-19 using sc-RNA-seq, flow cytometry, and other molecular biology techniques. At completion, the project will define the protective innate and adaptive immune mechanisms operating in the ONP of patients infected with SARS-CoV-2, improve our overall understanding of viral induced immunity in the ONP, and provide insight into how these pathways influence disease pathogenesis.", "keywords": [ "2019-nCoV", "3-Dimensional", "ACE2", "Acute", "Address", "Aerodigestive Tract", "Affect", "Anatomy", "Antiviral Agents", "Antiviral Response", "Area", "Bioinformatics", "COVID-19", "COVID-19 patient", "Cells", "Cessation of life", "Clinical", "Complement", "Congestive", "Coughing", "Defect", "Defense Mechanisms", "Development", "Disease", "Enrollment", "Epithelial", "Epithelial Cells", "Exhibits", "Fever", "Flow Cytometry", "Functional disorder", "Future", "Gene Expression", "Generations", "Genes", "Gingiva", "Goals", "Host Defense", "Human", "Immune", "Immune response", "Immunity", "Immunization", "Immunologics", "Immunology", "Immunomodulators", "Individual", "Infection", "Inflammatory", "Inflammatory Response", "Injury", "Interdisciplinary Study", "Interferons", "Interleukin-17", "Knowledge", "Life", "Link", "Location", "Metadata", "Molecular Biology Techniques", "Morbidity - disease rate", "Mucous Membrane", "Nasal Epithelium", "Nose", "Oral", "Oral cavity", "Oral health", "Pathogenesis", "Pathogenicity", "Pathway interactions", "Peptide Hydrolases", "Peptides", "Pharyngeal structure", "Phenotype", "Play", "Preventive", "Production", "Prospective cohort", "Regulation", "Respiratory Signs and Symptoms", "Role", "SARS coronavirus", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "Sampling", "Severity of illness", "Site", "Sore Throat", "Structure of gingival sulcus", "Surface", "System", "Systemic disease", "T cell receptor repertoire sequencing", "T cell response", "T memory cell", "T-Cell Receptor", "T-Lymphocyte", "T-cell receptor repertoire", "TMPRSS2 gene", "Talents", "Therapeutic", "Tissues", "Type 2 Angiotensin II Receptor", "Vaccinated", "Vaccination", "Vaccines", "Viral", "Viral Genes", "Virus", "Virus Diseases", "antiviral immunity", "base", "cohort", "cytokine", "density", "ethnic diversity", "exhaustion", "improved", "in vivo", "insight", "intercellular communication", "mitochondrial dysfunction", "mortality", "neutrophil", "next generation", "novel therapeutics", "oral biology", "oral cavity epithelium", "oral infection", "pathogen", "patient population", "patient subsets", "racial diversity", "receptor", "response", "single-cell RNA sequencing", "virology" ], "approved": true } }, { "type": "Grant", "id": "11609", "attributes": { "award_id": "5R01DE031928-02", "title": "Initiation of immune responses to SARS COV2 in the oral cavity and upper airway", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Dental and Craniofacial Research (NIDCR)" ], "program_reference_codes": [], "program_officials": [ { "id": 22517, "first_name": "Preethi", "last_name": "Chander", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-04-01", "end_date": "2027-03-31", "award_amount": 764740, "principal_investigator": { "id": 22696, "first_name": "GILL", "last_name": "DIAMOND", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1506, "ror": "", "name": "UNIVERSITY OF MISSISSIPPI MED CTR", "address": "", "city": "", "state": "MS", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22697, "first_name": "SARAH C", "last_name": "GLOVER", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 22698, "first_name": "BRUCE H.", "last_name": "HORWITZ", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1506, "ror": "", "name": "UNIVERSITY OF MISSISSIPPI MED CTR", "address": "", "city": "", "state": "MS", "zip": "", "country": "United States", "approved": true }, "abstract": "Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a life-threatening illness with multi-system involvement in a subset of infected individuals. Oral and nasopharyngeal (NP) epithelial cells express the SARS-CoV-2 receptor ACE2, and infection of the oral/nasopharyngeal cavity (ONP) is likely an obligate step in the development of COVID-19. Immune responses first generated in the ONP are almost certainly crucial for viral clearance but may also play a central role in the development of hyperinflammatory injury observed in many infected individuals. We have used single cell (sc)- RNA sequencing from a racially diverse prospective cohort of COVID-19 patients to identify distinct subsets of ciliated epithelial cells within the NP that are direct targets for SARS-CoV-2 infection and have described innate anti-viral responses generated by those cells within both directly infected as well as non-infected bystander cells. Interestingly this analysis demonstrates that increased mortality is linked to blunted anti-viral gene response in the NP, suggesting that a successful innate response to viral infection in the nose is a critical component of a successful anti-viral response. In addition to the nose, there is strong evidence that SARS-CoV-2 can infect the oral epithelium. While there are several anatomic sites within the mouth that are likely involved in anti-viral responses, the gingival sulcus is a unique immunologically active location that is crucial for maintaining oral health. The gingival epithelium expresses both the SARS-CoV-2 receptor ACE2 as well as the host protease TMPRSS2 necessary for viral entry, but exhibits important immunological differences compared to the nasal epithelium including a bias towards IL-17 associated neutrophil responses. Thus, our overall hypothesis is that identifying and enhancing successful innate and adaptive cellular immune responses of the nasal and gingival epithelium will lead to novel therapeutic avenues for COVID-19. To address this hypothesis, propose the following aims: 1. Stratify cell states and viral dynamics across mucosal surfaces following SARS-CoV-2 infection and vaccination; 2. Compare memory T cell responses within the nose and gingiva that are associated with successful or pathogenic responses to SARS-CoV-2; and 3. Characterize the regulation of host innate immune defense mechanisms that are essential to limit propagation of SARS-CoV-2 infection within ONP epithelial cells. To accomplish these aims, we will analyze human ONP samples from individuals with COVID- 19, recovered from COVID-19, and vaccinated for COVID-19 using sc-RNA-seq, flow cytometry, and other molecular biology techniques. At completion, the project will define the protective innate and adaptive immune mechanisms operating in the ONP of patients infected with SARS-CoV-2, improve our overall understanding of viral induced immunity in the ONP, and provide insight into how these pathways influence disease pathogenesis.", "keywords": [ "2019-nCoV", "3-Dimensional", "ACE2", "Acute", "Address", "Aerodigestive Tract", "Affect", "Anatomy", "Antiviral Response", "Area", "Bioinformatics", "COVID-19", "COVID-19 patient", "Cells", "Cessation of life", "Clinical", "Complement", "Coughing", "Defect", "Defense Mechanisms", "Development", "Disease", "Enrollment", "Epithelial", "Epithelial Cells", "Exhibits", "Fever", "Flow Cytometry", "Functional disorder", "Future", "Gene Expression", "Generations", "Genes", "Gingiva", "Goals", "Host Defense", "Human", "IL17 gene", "Immune", "Immune response", "Immunity", "Immunization", "Immunologics", "Immunology", "Immunomodulators", "Individual", "Infection", "Inflammatory", "Inflammatory Response", "Injury", "Interdisciplinary Study", "Interferons", "Interleukin-17", "Knowledge", "Life", "Link", "Location", "Metadata", "Molecular Biology Techniques", "Morbidity - disease rate", "Mucous Membrane", "Nasal Epithelium", "Nasopharynx", "Nose", "Oral", "Oral cavity", "Oral health", "Pathogenesis", "Pathogenicity", "Pathway interactions", "Peptide Hydrolases", "Peptides", "Pharyngeal structure", "Phenotype", "Play", "Preventive", "Production", "Prospective cohort", "Regulation", "Respiratory Signs and Symptoms", "Role", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "Sampling", "Severe Acute Respiratory Syndrome", "Severity of illness", "Signal Transduction", "Site", "Sore Throat", "Structure of gingival sulcus", "Surface", "System", "Systemic disease", "T cell receptor repertoire sequencing", "T cell response", "T memory cell", "T-Cell Receptor", "T-Lymphocyte", "T-cell receptor repertoire", "TMPRSS2 gene", "Talents", "Therapeutic", "Tissues", "Type 2 Angiotensin II Receptor", "Vaccinated", "Vaccination", "Vaccinee", "Vaccines", "Viral", "Viral Genes", "Virus", "Virus Diseases", "antiviral immunity", "body system", "cohort", "cytokine", "density", "ethnic diversity", "exhaustion", "improved", "in vivo", "insight", "mitochondrial dysfunction", "mortality", "neutrophil", "next generation", "novel therapeutics", "oral biology", "oral cavity epithelium", "oral infection", "pathogen", "patient population", "patient subsets", "post SARS-CoV-2 infection", "racial diversity", "receptor", "response", "single-cell RNA sequencing", "virology" ], "approved": true } }, { "type": "Grant", "id": "14775", "attributes": { "award_id": "5R01DE031928-04", "title": "Initiation of immune responses to SARS COV2 in the oral cavity and upper airway", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Dental and Craniofacial Research (NIDCR)" ], "program_reference_codes": [], "program_officials": [ { "id": 22517, "first_name": "Preethi", "last_name": "Chander", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-11-20", "end_date": "2027-03-31", "award_amount": 677350, "principal_investigator": { "id": 22696, "first_name": "GILL", "last_name": "DIAMOND", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1506, "ror": "", "name": "UNIVERSITY OF MISSISSIPPI MED CTR", "address": "", "city": "", "state": "MS", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22697, "first_name": "SARAH C", "last_name": "GLOVER", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 22698, "first_name": "BRUCE H.", "last_name": "HORWITZ", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 811, "ror": "", "name": "TULANE UNIVERSITY OF LOUISIANA", "address": "", "city": "", "state": "LA", "zip": "", "country": "United States", "approved": true }, "abstract": "Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a life-threatening illness with multi-system involvement in a subset of infected individuals. Oral and nasopharyngeal (NP) epithelial cells express the SARS-CoV-2 receptor ACE2, and infection of the oral/nasopharyngeal cavity (ONP) is likely an obligate step in the development of COVID-19. Immune responses first generated in the ONP are almost certainly crucial for viral clearance but may also play a central role in the development of hyperinflammatory injury observed in many infected individuals. We have used single cell (sc)- RNA sequencing from a racially diverse prospective cohort of COVID-19 patients to identify distinct subsets of ciliated epithelial cells within the NP that are direct targets for SARS-CoV-2 infection and have described innate anti-viral responses generated by those cells within both directly infected as well as non-infected bystander cells. Interestingly this analysis demonstrates that increased mortality is linked to blunted anti-viral gene response in the NP, suggesting that a successful innate response to viral infection in the nose is a critical component of a successful anti-viral response. In addition to the nose, there is strong evidence that SARS-CoV-2 can infect the oral epithelium. While there are several anatomic sites within the mouth that are likely involved in anti-viral responses, the gingival sulcus is a unique immunologically active location that is crucial for maintaining oral health. The gingival epithelium expresses both the SARS-CoV-2 receptor ACE2 as well as the host protease TMPRSS2 necessary for viral entry, but exhibits important immunological differences compared to the nasal epithelium including a bias towards IL-17 associated neutrophil responses. Thus, our overall hypothesis is that identifying and enhancing successful innate and adaptive cellular immune responses of the nasal and gingival epithelium will lead to novel therapeutic avenues for COVID-19. To address this hypothesis, propose the following aims: 1. Stratify cell states and viral dynamics across mucosal surfaces following SARS-CoV-2 infection and vaccination; 2. Compare memory T cell responses within the nose and gingiva that are associated with successful or pathogenic responses to SARS-CoV-2; and 3. Characterize the regulation of host innate immune defense mechanisms that are essential to limit propagation of SARS-CoV-2 infection within ONP epithelial cells. To accomplish these aims, we will analyze human ONP samples from individuals with COVID- 19, recovered from COVID-19, and vaccinated for COVID-19 using sc-RNA-seq, flow cytometry, and other molecular biology techniques. At completion, the project will define the protective innate and adaptive immune mechanisms operating in the ONP of patients infected with SARS-CoV-2, improve our overall understanding of viral induced immunity in the ONP, and provide insight into how these pathways influence disease pathogenesis.", "keywords": [ "2019-nCoV", "3-Dimensional", "ACE2", "Acute", "Address", "Aerodigestive Tract", "Affect", "Anatomy", "Anti-viral Response", "Area", "Bioinformatics", "Body System", "COVID-19", "COVID-19 patient", "Cells", "Cessation of life", "Clinical", "Complement", "Coughing", "Defect", "Defense Mechanisms", "Development", "Disease", "Enrollment", "Epithelial Cells", "Epithelium", "Exhibits", "Fever", "Flow Cytometry", "Functional disorder", "Future", "Gene Expression", "Generations", "Genes", "Gingiva", "Goals", "Host Defense", "Human", "IL17 gene", "Immune", "Immune response", "Immunity", "Immunization", "Immunologics", "Immunology", "Individual", "Infection", "Inflammatory", "Inflammatory Response", "Injury", "Interdisciplinary Study", "Interferons", "Knowledge", "Life", "Link", "Location", "Metadata", "Molecular Biology Techniques", "Morbidity - disease rate", "Mucous Membrane", "Nasal Epithelium", "Nasopharynx", "Nose", "Oral", "Oral cavity", "Oral health", "Pathogenesis", "Pathogenicity", "Pathway interactions", "Peptide Hydrolases", "Peptides", "Pharyngeal structure", "Phenotype", "Play", "Preventive", "Production", "Prospective cohort", "Regulation", "Respiratory Signs and Symptoms", "Role", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "Sampling", "Severe Acute Respiratory Syndrome", "Severity of illness", "Signal Transduction", "Site", "Sore Throat", "Structure of gingival sulcus", "Surface", "System", "Systemic disease", "T cell receptor repertoire sequencing", "T cell response", "T memory cell", "T-Cell Receptor", "T-Lymphocyte", "T-cell receptor repertoire", "TMPRSS2 gene", "Talents", "Therapeutic", "Tissues", "Type 2 Angiotensin II Receptor", "Vaccinated", "Vaccination", "Vaccinee", "Vaccines", "Viral", "Viral Genes", "Virus", "Virus Diseases", "antiviral immunity", "cohort", "cytokine", "density", "ethnic diversity", "exhaustion", "immune modulating agents", "improved", "in vivo", "insight", "mitochondrial dysfunction", "mortality", "neutrophil", "next generation", "novel therapeutics", "oral biology", "oral cavity epithelium", "oral infection", "pathogen", "patient population", "patient subsets", "post SARS-CoV-2 infection", "racial diversity", "receptor", "response", "single-cell RNA sequencing", "virology" ], "approved": true } } ], "meta": { "pagination": { "page": 1385, "pages": 1424, "count": 14236 } } }