Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1405&sort=program_officials
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=program_officials", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1424&sort=program_officials", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1406&sort=program_officials", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1404&sort=program_officials" }, "data": [ { "type": "Grant", "id": "15989", "attributes": { "award_id": "1R21AI191169-01A1", "title": "Intelligent biosensing system for automated real-time monitoring of airborne pathogens for safe indoor environments", "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": "2026-02-05", "end_date": "2028-01-31", "award_amount": 396448, "principal_investigator": { "id": 28438, "first_name": "Vishal", "last_name": "Verma", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 31634, "first_name": "Na", "last_name": "Wei", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 3439, "ror": "", "name": "UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "The increasing frequency of respiratory infectious diseases, such as influenza and COVID-19, which can spread rapidly and lead to severe outbreaks, necessitates that we re-envision our approaches to monitor pathogen exposures in the indoor environments. Current surveillance methods mostly depend on syndromic data from hospital admissions, clinic visits, and school absenteeism rates. However, these approaches can lead to underestimation and delay in disease surveillance due to no reporting of mild or asymptomatic cases, lack of access to healthcare, and time-consuming lab and diagnostic processes. A proactive approach in combating airborne diseases requires early detection of target pathogens. Here, we propose to innovate an intelligent system capable of real-time, efficient, and cost-effective monitoring of airborne pathogens in the environment. We will build upon our preliminary success in automated bioaerosol sampling and pathogen detection, to create an Airborne Pathogen Sensing (APS) system. This goal will be achieved by focusing on two specific aims. First, we will create a novel class of modular whole-cell biosensors for sensitive, rapid, and robust detection of multiple critical airborne pathogens. The pathogen detection will be achieved by creating quenchbody (Q-body) display biosensors, where target specific quenchbody is expressed and displayed on the surface of microbial host cells. When the Q-body binds to its antigen (target pathogen), the fluorescence intensity substantially increases via the antigen-dependent removal of the quenching effect on the fluorophore. Second, we will design and build a portable and automated bioaerosol sampling device that can be coupled to the biosensing and signal detection systems. To this end, we will evaluate and optimize two sampling devices: mist chamber and biosampler, and choose the device with the highest bioaerosol capture efficiency. Finally, we will integrate the biosensing component with the bioaerosol sampling device and an automated flow-through fluorescence detection system to achieve automated real-time monitoring of airborne pathogens.", "keywords": [ "Absenteeism", "Address", "Antibodies", "Antigens", "Binding", "Biosensing Techniques", "Biosensor", "COVID-19", "COVID-19 pandemic", "Cell membrane", "Cell surface", "Cells", "Cessation of life", "Characteristics", "Clinic Visits", "Communicable Diseases", "Consumption", "Coupled", "Coupling", "Data", "Detection", "Development", "Devices", "Diagnostic", "Disease", "Disease Outbreaks", "Disease Surveillance", "Early Diagnosis", "Economic Burden", "Education", "Engineering", "Environment", "Environmental Monitoring", "Enzyme-Linked Immunosorbent Assay", "Epidemic", "Equipment", "Excision", "Exhibits", "Expert Systems", "Exposure to", "Fluorescence", "Fostering", "Frequencies", "Future", "Goals", "Health", "Health Care Costs", "Health protection", "Hospitalization", "Human Resources", "Incidence", "Indoor environment", "Influenza", "Laboratories", "Lead", "Machine Learning", "Measurement", "Methods", "Monitor", "Mutate", "Output", "Pathogen detection", "Play", "Polymerase Chain Reaction", "Prevention", "Procedures", "Process", "Public Health", "Reaction", "Readiness", "Reagent", "Reporting", "Research Personnel", "Resources", "Respiratory syncytial virus", "Risk Assessment", "Risk Reduction", "Sampling", "Schools", "Seasons", "Signal Transduction", "Social Well-Being", "Societies", "Streptococcus pyogenes", "Surface", "Surveillance Methods", "System", "Technology", "Time", "Work", "air sampling", "clinical diagnostics", "cost", "cost effective", "design", "detection limit", "detection method", "detection platform", "fluorophore", "health care availability", "improved", "indoor air", "influenzavirus", "innovation", "microbial", "microbial host", "novel", "novel strategies", "pandemic disease", "pathogen", "pathogen exposure", "pathogenic virus", "portability", "real time monitoring", "respiratory", "respiratory aerosol", "response", "seasonal influenza", "skills", "success", "syndromic surveillance", "synthetic biology", "transmission process", "virology" ], "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": "15749", "attributes": { "award_id": "1R21AI188683-01A1", "title": "Contribution of adipose tissue immune cells to Influenza pathogenesis", "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": "2025-08-18", "end_date": "2027-07-31", "award_amount": 240750, "principal_investigator": { "id": 32805, "first_name": "Senad", "last_name": "Divanovic", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2620, "ror": "", "name": "CINCINNATI CHILDRENS HOSP MED CTR", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "Epidemiological evidence establishes obesity as an independent risk factor for increased severity of viral respiratory pneumonias including influenza virus infection. Dysregulated systemic and tissue inflammation is critical to the pathogenesis of both influenza- and obesity-comorbidities. However, the critical processes that govern increased influenza severity in obesity remain undefined. The expansion of white adipose tissue (WAT) along with activation of WAT-residing immune cells inflammation promotes tissue/organ damage severity in obesity. Of note, WAT depots differ in their anatomical location and function—characteristics that are directly linked with the pathogenesis of disease-impacted organs. Using a model that combines obesity and influenza A virus (IAV) infection we reported that obese mice exhibit in greater mortality and worsened lung inflammation and tissue pathology compared to lean controls. Focusing on immune cells, we showed that IAV infection changes epididymal WAT (eWAT; a depot distal to the lungs) and lung immune cell composition and function, and favors accrual of a macrophage (MØ) subset in the lungs that shares a transcriptomic signature with eWAT residing inflammatory MØs. However, although transfer of eWAT MØ from obese into lean IAV infected mice amplified host immune cell infiltration to the lungs, it was not sufficient to increase influenza severity. Thus, eWAT MØ, although important, either do not possess the full extent of pathogenic traits or other WAT-residing immune cells are dominant contributors to influenza severity in obesity. Importantly, the presence of thoracic WAT (tWAT; a depot that is proximal to the lungs) was reported in individuals living with obesity and in obese mice. Notably, adipocytes and MØ within tWAT support IAV replication and produce proinflammatory factors during IAV infection. However, whether the character and function of tWAT and eWAT immune cells, including MØ, differs during IAV infection has not been studied. Our preliminary studies comparing tWAT and eWAT immune cells show that: (i) transfer of tWAT immune cells from obese mice into IAV infected lean mice induces mortality; (ii) tWAT is highly enriched in phenotypically distinct immune cell types; and (iii) tWAT MØ exhibit greater ability to produce proinflammatory cytokines relevant in influenza pathogenesis. Together, our novel data and existing literature support the overarching hypothesis that tWAT MØ become progressively more proinflammatory during obesity and IAV infection, and that activation of tWAT MØ unique pathogenic traits is sufficient to increases influenza severity. To test this hypothesis, we will: (1) Determine cellular traits of tWAT immune cells in obesity and influenza severity; and (2) Determine pathological processes whereby tWAT macrophages exacerbate influenza severity. Given the global increase in the incidence of obesity and viral pneumonias (e.g., Influenza, SARS-CoV-2) our high-risk/high-reward proposal will provide keen insights into previously unexplored processes that govern inflammation-associated disease severity in obesity.", "keywords": [ "2019-nCoV", "Adipocytes", "Adipose tissue", "Adoptive Transfer", "Adult", "Affect", "Anatomy", "Blood", "Cardiovascular Diseases", "Cell Physiology", "Cells", "Cessation of life", "Characteristics", "Chest", "Chronic Kidney Failure", "Communicable Diseases", "Crohn's disease", "Data", "Development", "Disease", "Distal", "Enzyme-Linked Immunosorbent Assay", "Epidemiology", "Evolution", "Exhibits", "Exploratory/Developmental Grant", "Flow Cytometry", "Future", "Gene Modified", "Goals", "Heart", "Histopathology", "Hospitalization", "Immune", "Incidence", "Individual", "Infection", "Inflammation", "Inflammatory", "Influenza", "Influenza A virus", "Kidney", "Link", "Literature", "Location", "Lung", "Lung Diseases", "Macrophage", "Modeling", "Mus", "Obese Mice", "Obesity", "Organ", "PTPRC gene", "Pathogenesis", "Pathogenicity", "Pathologic Processes", "Pathology", "Persons", "Phenotype", "Pneumonia", "Preventive", "Process", "Production", "Public Health", "Pulmonary Inflammation", "Pulmonary Pathology", "Reporting", "Risk", "Risk Factors", "Severities", "Severity of illness", "Shapes", "Source", "Structure of parenchyma of lung", "Testing", "Therapeutic", "Thinness", "Thoracic cavity structure", "Tissues", "Viral", "Viral Load result", "Viral Pneumonia", "Virus Diseases", "Virus Replication", "Visceral", "Wild Type Mouse", "Youth", "cell type", "clinically significant", "comorbidity", "cytokine", "experimental study", "high reward", "high risk", "immune cell infiltrate", "immune function", "improved", "influenza infection", "insight", "mortality", "novel", "pandemic disease", "pulmonary function", "respiratory", "systemic inflammatory response", "trait", "transcriptome", "transcriptomics" ], "approved": true } }, { "type": "Grant", "id": "15829", "attributes": { "award_id": "1F31AI191758-01", "title": "MAC formation and Cell-Specific Inflammasome Activation in COVID-19", "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": "2025-09-16", "end_date": "2028-08-15", "award_amount": 49538, "principal_investigator": { "id": 44242, "first_name": "Calder R", "last_name": "Ellsworth", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 811, "ror": "", "name": "TULANE UNIVERSITY OF LOUISIANA", "address": "", "city": "", "state": "LA", "zip": "", "country": "United States", "approved": true }, "abstract": "Program summary: The objective of this training proposal is to determine how enhanced complement activation and increased membrane attack complex (MAC) formation exacerbate severe COVID-19. The complement system, a key component of the innate immunity, can be initiated by three pathways (lectin, alternative, and classical), potentially leading to MAC formation. MAC's primary function is to lyse pathogens via pore formation. However, clinical evidence indicates that complement activation and MAC formation, while normally protective, can be detrimental in SARS-CoV-2 infection and contribute to COVID-19 pathogenesis. Currently, the cellular and molecular mechanisms underlying MAC-accelerated severe COVID-19 remain unexplored. To address this question, we have characterized a murine model of severe COVID-19 using a mouse-adapted strain (MA30) that recapitulates key aspects of SARS-CoV2 infection, including lung edema and epithelial cell tropism. Using this MA30 strain to infect an array of complement deficient mice (C3-/- and C7-/-) and mice deficient in the critical MAC regulator CD59 (mCd59-/-), I demonstrated a causative role of MAC on severe COVID-19. However, the cell targets and molecular mechanism of MAC-mediated severe COVID-19 remain unknown. Our preliminary data show increased activity of Caspase-1, a downstream event of NLRP3 inflammasome formation, in LPS- challenged mCD59-/- mice. Additionally, NLRP3 inflammasome formation and Caspase-1 activation, leading to the release of IL-1β and IL-18, contributes to the cytokine storm and severe immunopathology in COVID-19. Our single-cell and bulk RNA sequencing data show increased transcription of the casp-1, IL-18 and Gsdmd in endothelial cells and macrophages of MA30 infected mice at 2 days-post infection. Therefore, my overarching hypothesis is that MAC targets endothelial cells and macrophages, accelerating severe COVID-19 through the activation of Caspase-1 pathway. To test this central hypothesis, I propose the following aims. Aim 1 is to determine the pathogenic role of MAC-mediated Casp1 activation in severe COVID-19. Aim 2 is to determine the MAC-mediated cellular effects on COVID-19 and associate the disease severity with cell specific casp1 activation. With our prior work we established a causative role for MAC in severe COVID-19 pathogenesis. This proposal advances that work by determining the cellular and molecular mechanisms by which MAC causes severe COVID-19. By elucidating the role of the MAC/Casp1 axis in specific cell types during severe COVID-19, this research will further our understanding of the disease's immunopathology, and better prepare us for new SARS variants and emerging diseases. A better understanding is crucially needed to identify novel therapeutic targets for mitigating cytokine storm and improving outcomes for critically ill patients.", "keywords": [ "Acceleration", "Address", "Attenuated", "Autopsy", "Blood", "Body Weight", "Bone Marrow Transplantation", "CASP1 gene", "CD46 Antigen", "COVID-19", "COVID-19 monitoring", "COVID-19 pathogenesis", "Cardiovascular Diseases", "Cells", "Clinical", "Complement", "Complement 3a", "Complement 5a", "Complement Activation", "Complement Membrane Attack Complex", "Critical Illness", "Cytolysis", "Data", "Deposition", "Disease", "Disease Progression", "Endothelial Cells", "Epithelial Cells", "Equilibrium", "Erythrocytes", "Event", "GPI Membrane Anchors", "Genetic Transcription", "Hematopoietic", "Hemolysis", "IL18 gene", "In Vitro", "Infection", "Inflammasome", "Inflammatory", "Interleukin-1 beta", "Ion Pumps", "Ions", "Knock-out", "Lectin", "Leukocytes", "Link", "Lung", "Macrophage", "Macrophage Activation", "Measures", "Mediating", "Membrane", "Molecular", "Mus", "Myeloid Cells", "Natural Immunity", "Neurodegenerative Disorders", "Pathogenicity", "Pathway interactions", "Patients", "Periodicals", "Production", "Proteins", "Pulmonary Edema", "Pulmonary Pathology", "Regulation", "Research", "Role", "SARS-CoV-2 infection", "SARS-CoV-2 variant", "Sampling", "Serum", "Severe Acute Respiratory Syndrome", "Severity of illness", "Testing", "Tissues", "Training", "Tropism", "Variant", "Vulnerable Populations", "Work", "cell type", "complement deficiency", "complement system", "cytokine", "cytokine release syndrome", "endothelial dysfunction", "immunopathology", "improved", "improved outcome", "in vivo", "mouse model", "new pandemic", "new therapeutic target", "paroxysmal nocturnal hemoglobinuria", "pathogen", "programs", "severe COVID-19", "transcriptome sequencing", "tumorigenesis", "variants of concern" ], "approved": true } }, { "type": "Grant", "id": "15881", "attributes": { "award_id": "1K99AI190056-01", "title": "Regulation and Function of respiratory mucosal immunity post SARS-CoV-2 vaccination and infection", "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": "2025-09-03", "end_date": "2027-08-31", "award_amount": 108273, "principal_investigator": { "id": 44314, "first_name": "Jinyi", "last_name": "Tang", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3391, "ror": "", "name": "UNIVERSITY OF VIRGINIA", "address": "", "city": "", "state": "VA", "zip": "", "country": "United States", "approved": true }, "abstract": "Current intramuscular COVID-19 vaccines, despite eliciting robust systemic immune responses, generate suboptimal neutralizing antibody (nAb), IgA Ab, and cellular responses in the respiratory mucosal. This is likely why current vaccines are less effective at preventing infection and transmission. The role of mucosal immunity in protecting against respiratory viral infection remains largely unexplored. The long-term goal of this research is to comprehensively understand the differentiation, function, regulation, and interaction of respiratory immune cells. Pilot data revealed that people with hybrid immunity from SARS-CoV-2 infection and vaccination exhibit significantly high levels of antigen-specific IgA and nAbs in the respiratory mucosa, compared to those who got vaccinated or infected alone. Further, recent research and our initial findings suggest that mucosal IgA is locally produced by lung-resident B cells during both primary infection and reinfection, yet the specific role and development of mucosal IgA are not fully understood. Therefore, the overall objectives of this application are to a) understand systemic and mucosal immunity in people with hybrid immunity, b) define immune compartments that confer protection and transmission in animal models, and c) unravel the mechanisms underlying the respiratory protection of mucosal immunity. The central hypothesis is that respiratory IgA provides neutralization and protection against heterologous infection, facilitated by an orchestrated interaction between macrophages, CD4 Th1 cells, and IgA+ B cells in the respiratory mucosa. This hypothesis will be tested by pursuing three specific aims: 1) To identify the respiratory mucosal immunity in people with hybrid immunity, 2) To study protection and transmission following SARS-CoV-2 breakthrough infection or mucosal vaccine booster in animal models primed with mRNA vaccines, and 3) To elucidate the mechanisms underlying the mucosal protection of respiratory immunity. Aim 1 will systematically profile the immune signatures in the blood, nasal cavity, and lower airway in children with hybrid immunity. Aim 2 will utilize mouse and hamster models of hybrid immunity and mucosal vaccine booster to study protection and transmission. Under Aim 3, we will investigate the mechanism of mucosal protection in both humans and mice. This research will advance our understanding of respiratory immunology and vaccinology, potentially impacting the global fight against SARS-CoV-2 and future respiratory viruses. This project will provide the applicant, Dr. Jinyi Tang, with experimental and conceptual training to develop his research program and ensure his transition to an independent tenure- track position. Dr. Tang will be mentored by a committee of experienced immunologist, virologist and clinician-scientist specializing in mucosal viral immunology, led by primary mentor Dr. Jie Sun. The planned career development activities will ensure Dr. Tang achieves his long-term goals of consistent manuscript publishing, achieving independent funding, and training of the next generation of scientists.", "keywords": [ "2019-nCoV", "Address", "Animal Model", "Antibody Formation", "Antibody Response", "Antibody-mediated protection", "Antigens", "B-Lymphocytes", "Blood", "Bronchoscopy", "CD4 Positive T Lymphocytes", "COVID-19 pandemic", "COVID-19 vaccination", "COVID-19 vaccine", "Cells", "Cellular Immunity", "Cessation of life", "Child", "Circulation", "Coculture Techniques", "Communicable Diseases", "Data", "Development", "Disease", "Ensure", "Exhibits", "Funding", "Future", "Generations", "Genetic", "Goals", "Hamsters", "Human", "Hybrids", "Immune", "Immune Evasion", "Immune response", "Immunity", "Immunoglobulin A", "Immunologist", "Immunology", "In Vitro", "Infection", "Infection prevention", "Innate Immune Response", "Intramuscular", "Knowledge", "Lung", "Macrophage", "Manuscripts", "Memory B-Lymphocyte", "Mentors", "Methods", "Modeling", "Morbidity - disease rate", "Mucosal Immunity", "Mucous Membrane", "Mus", "Nasal cavity", "Outcome", "Pediatric cohort", "Persons", "Plasma Cells", "Play", "Positioning Attribute", "Preventive measure", "Primary Infection", "Production", "Public Health", "Publishing", "RNA vaccine", "Regulation", "Research", "Respiratory Mucosa", "Respiratory Tract Infections", "Respiratory physiology", "Role", "SARS-CoV-2 immunity", "SARS-CoV-2 infection", "SARS-CoV-2 variant", "Scientist", "T-Lymphocyte", "Testing", "Th1 Cells", "Training", "Transforming Growth Factor beta", "Vaccinated", "Vaccination", "Vaccinee", "Vaccines", "Variant", "Viral", "Viral Respiratory Tract Infection", "Viral Vector", "Work", "adaptive immune response", "booster vaccine", "breakthrough infection", "career", "career development", "cross reactivity", "cytokine", "design", "experience", "fighting", "high dimensionality", "human model", "improved", "in vivo", "insight", "interleukin-21", "mortality", "mouse model", "mucosal vaccine", "multiple omics", "neutralizing antibody", "next generation", "novel", "novel vaccines", "pathogen", "prevent", "programs", "respiratory", "respiratory virus", "response", "tenure track", "transmission process", "vaccine-induced immunity", "vaccinology", "variants of concern" ], "approved": true } }, { "type": "Grant", "id": "15913", "attributes": { "award_id": "1R21AI194204-01", "title": "Notch regulation of airway epithelial-immune cell cross-talk in SARS-CoV-2 infection", "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": "2025-07-09", "end_date": "2027-06-30", "award_amount": 448688, "principal_investigator": { "id": 44356, "first_name": "Susan", "last_name": "Kovats", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 44357, "first_name": "Matthew Stuart", "last_name": "Walters", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 3399, "ror": "", "name": "OKLAHOMA MEDICAL RESEARCH FOUNDATION", "address": "", "city": "", "state": "OK", "zip": "", "country": "United States", "approved": true }, "abstract": "Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19. Infection with SARS-CoV-2 begins in epithelial cells of the upper airways, which triggers multiple antiviral responses that activate myeloid immune cells, coordinate the early innate immune response, and limit viral spread. Notably, our understanding of the cell signaling mechanisms that regulate early epithelial-immune cell interactions and induction of tissue pathology during SARS-CoV-2 infection of the human airway remains limited. To investigate these processes, we have developed a novel in vitro all human 3D model of the upper airways (HUA) composed of layers of primary differentiated airway epithelial cells expressing ACE2, lung fibroblasts in a collagen matrix, and pulmonary endothelial cells, with myeloid cells present in each layer. SARS-CoV-2 infection of the HUA model results in virus replication and induction of an immune response reminiscent of in vivo infection, and the presence of myeloid cells limits viral replication. Therefore, we will use the HUA model to perform kinetic studies of the mechanisms by which human airway cells interact to regulate virus-host interactions, inflammation, and tissue pathology associated with SARS-CoV-2. We will focus on the Notch pathway, which acts via direct cell- to-cell signaling to regulate airway epithelial cell fate decisions as well as myeloid cell maintenance, Toll-like receptor signaling, pro-inflammatory polarization, and antiviral functions. However, the mechanisms by which Notch signaling regulates airway epithelial-myeloid cell interactions during SARS-CoV-2 infection remain unknown. Our preliminary analyses showed that airway epithelial cells and myeloid cells express multiple Notch ligands and receptors in uninfected HUA models, suggesting that the Notch pathway will mediate bidirectional crosstalk during the airway response to infection. We will test the central hypothesis that Notch receptor signaling in myeloid cells regulates their pro-inflammatory phenotype, thereby promoting the host innate antiviral immune response and contributing to airway epithelial cell damage and remodeling during SARS-CoV-2 infection. Using lentivirus vectors and inducible expression systems, we will attenuate expression of individual Notch ligands and receptors in a cell-type specific and temporal manner. Following SARS-CoV-2 infection, we will quantify the impact of reducing Notch signaling activity on virus replication, myeloid cell phenotypes, the host immune response, and airway epithelial remodeling. The data collected in this study will advance our understanding of the mechanisms that regulate airway epithelial-immune cell interactions during SARS-CoV-2 infection and may identify candidate therapeutic targets in the Notch pathway to enhance antiviral immunity and reduce epithelial injury and remodeling in the upper airway.", "keywords": [ "2019-nCoV", "ACE2", "Address", "Anti-viral Response", "Anti-viral Therapy", "Attenuated", "COVID-19", "COVID-19 treatment", "Cell Communication", "Cell Differentiation process", "Cell Maintenance", "Cell Separation", "Cells", "Cessation of life", "Collagen", "Data", "Dendritic Cells", "Endothelial Cells", "Environment", "Epithelial Cells", "Epithelium", "Fibroblasts", "Gene Modified", "Human", "Immune", "Immune response", "In Vitro", "Individual", "Infection", "Inflammation", "Inflammatory", "Innate Immune Response", "Kinetics", "Lentivirus Vector", "Ligands", "Lung", "Macrophage", "Maintenance", "Mediating", "Membrane", "Modeling", "Myelogenous", "Myeloid Cells", "NOTCH1 gene", "Notch Signaling Pathway", "Pathology", "Pathway interactions", "Phenotype", "Play", "Process", "Receptor Signaling", "Regulation", "Role", "SARS-CoV-2 infection", "Shapes", "Signal Transduction", "Structure of parenchyma of lung", "System", "Testing", "Tissue Model", "Tissues", "Toll-like receptors", "Viral", "Viral Physiology", "Virus", "Virus Activation", "Virus Replication", "airway epithelium", "antiviral immunity", "candidate identification", "cell injury", "cell type", "epithelial injury", "human disease", "in vivo", "inducible gene expression", "lung injury", "lung microvascular endothelial cells", "lung repair", "monocyte", "notch protein", "novel", "pandemic disease", "post SARS-CoV-2 infection", "pulmonary", "receptor", "respiratory infection virus", "respiratory virus", "response", "single-cell RNA sequencing", "therapeutic target", "three-dimensional modeling", "virus host interaction" ], "approved": true } }, { "type": "Grant", "id": "15931", "attributes": { "award_id": "1K99AI193238-01", "title": "Investigating the role of T cells in promoting post-acute memory deficits after COVID-19 in mice", "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": "2025-07-07", "end_date": "2027-06-30", "award_amount": 107995, "principal_investigator": { "id": 26728, "first_name": "Abigail Rose", "last_name": "Vanderheiden", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 827, "ror": "", "name": "WASHINGTON UNIVERSITY", "address": "", "city": "", "state": "MO", "zip": "", "country": "United States", "approved": true }, "abstract": "Millions of individuals in the United States suffer from post-acute symptoms of COVID-19 (PASC), many of which are neurological in origin. Although SARS-CoV-2 does not cause widespread infection of the central nervous system (CNS), significant neuroinflammation, decreased adult neurogenesis, alterations in synaptic proteins, decreased total brain volume, and poor performance on tests of learning and memory have all been observed in COVID-19 patients. However, the mechanisms by which a respiratory virus is causing persistent neurological dysfunction are not well understood. Studies of PASC patients identified ongoing dysregulation of T cell responses in the serum and imaging studies confirmed that PASC patients have activated T cells in the CNS. Homeostatic T cells in the meninges are known to influence learning, memory, and anxiety-like behavior through the secretion of cytokines, however the impact of T cells on neurological symptoms after COVID-19 is unknown. Thus, I hypothesize that systemic inflammation promotes recruitment of antigen-specific T cells to the CNS after SARS-CoV-2 infection, and these cells contribute to persistent deficits in learning and memory via secretion of cytokines and other pro-inflammatory mediators. To investigate this, I will utilize my recently developed mouse model of neurological dysfunction after COVID-19, in which intranasal infection of wild-type mice with SARS-CoV-2 causes robust infection of the respiratory tract, but not the CNS, post-acute memory deficits, loss of hippocampal neurogenesis, and increased pro-inflammatory cytokines in the CNS. Preliminary data found that CD4+ T cells are recruited to the meningeal dura after infection and promote post-acute memory deficits as determined via the Novel Object recognition test. In the K99 phase of this proposal, (Aim 1) I will investigate the phenotype of CD4+ T cells in the CNS after SARS-CoV-2 infection and determine how cytokines secreted by CD4+ T cells may contribute to memory deficits using a behavioral test battery and investigation of neurogenesis and tri-synaptic circuit function. In Aim 2, I will test if T cell priming and differentiation impact pathogenicity in the CNS after COVID-19 by first, determining if antigen specificity is required for recruitment to and effector functions in the CNS and second, investigating which CD4+ T cell effector subset is driving post-acute memory deficits. In the R00 phase, I will utilize a previously established murine model of breakthrough vaccination to investigate how priming of CD4+ T cells in the periphery influences differentiation into a pathogenic CD4+ effector subset. In Aim 3, I will explore how severe, systemic inflammation may be driving recruitment of these pathogenic T cells to the CNS and which chemokine: receptor pairs are critical for this process. Combined, this project will determine the mechanisms by which pathogenic CD4+ T cells are recruited to the CNS after COVID-19 and how they promote post-acute learning and memory deficits. These data could identify fundamental mechanisms by which immunity to viral infections controls neurological function and potential druggable targets for treatment of PASC.", "keywords": [ "2019-nCoV", "Acute", "Address", "Antigens", "Attentional deficit", "Automobile Driving", "Autopsy", "Brain", "CD4 Positive T Lymphocytes", "CD8-Positive T-Lymphocytes", "CD8B1 gene", "COVID-19", "COVID-19 patient", "COVID-19 therapeutics", "CXCL10 gene", "Cells", "Central Nervous System", "Central Nervous System Infections", "Cerebrospinal Fluid", "Clonal Expansion", "Cognitive deficits", "Data", "Development", "Disease", "Dura Mater", "Flow Cytometry", "Genetic", "Gliosis", "Hippocampus", "Immune", "Immune response", "Immunity", "Impairment", "Incidence", "Individual", "Infection", "Infection Control", "Inflammation", "Inflammation Mediators", "Inflammatory", "Investigation", "Knockout Mice", "Learning", "Location", "Long COVID", "Measures", "Mediating", "Memory", "Memory impairment", "Meningeal", "Meninges", "Mental Depression", "Microscopy", "Modeling", "Mus", "Myeloid Cell Activation", "Myeloid Cells", "Nervous System Physiology", "Neurodegenerative Disorders", "Neurologic", "Neurologic Dysfunctions", "Neurologic Symptoms", "Organ", "Pathogenicity", "Patients", "Performance", "Peripheral", "Phase", "Phenotype", "Population", "Process", "Proteins", "Recovery", "Respiratory Tract Infections", "Risk", "Risk Reduction", "Role", "SARS-CoV-2 B.1.351", "SARS-CoV-2 infection", "SARS-CoV-2 variant", "Serum", "Severity of illness", "Sorting", "Specificity", "Symptoms", "Synapses", "System", "T cell response", "T-Cell Activation", "T-Cell Depletion", "T-Cell Immunologic Specificity", "T-Lymphocyte", "T-Lymphocyte Subsets", "T-cell receptor repertoire", "Testing", "United States", "Vaccinated", "Vaccination", "Viral Respiratory Tract Infection", "Virus", "Virus Diseases", "Wild Type Mouse", "acute COVID-19", "acute symptom", "adult neurogenesis", "antigen-specific T cells", "anxiety-like behavior", "behavior test", "brain volume", "candidate identification", "chemokine", "comparison control", "conditional knockout", "congenic", "cytokine", "druggable target", "effector T cell", "experience", "experimental study", "imaging study", "improved", "insight", "microscopic imaging", "mouse model", "neural circuit", "neural correlate", "neurogenesis", "neuroinflammation", "neuropsychiatric disorder", "novel", "object recognition", "performance tests", "post SARS-CoV-2 infection", "prevent", "receptor", "recruit", "respiratory virus", "single-cell RNA sequencing", "systemic inflammatory r" ], "approved": true } }, { "type": "Grant", "id": "15953", "attributes": { "award_id": "1K08AI196260-01", "title": "Human upper airway immune memory kinetics and durability against respiratory pathogens", "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": "2026-04-02", "end_date": "2031-03-31", "award_amount": 159300, "principal_investigator": { "id": 44398, "first_name": "Sydney Ilima", "last_name": "Ramirez", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3411, "ror": "", "name": "LA JOLLA INSTITUTE FOR IMMUNOLOGY", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Peripheral blood is the primary sample type collected to evaluate a vast range of medical conditions. However, peripheral blood testing may not reflect processes occurring in tissue, like the upper airway. The SARS- CoV-2 (SARS2) pandemic highlighted the importance of being able to sample the upper airway for purposes including evaluation of viral infection and clearance. Although the upper airway represents the primary site of infection for many human pathogens, critical questions remain regarding upper airway immunity and protection. Nasal cavity swab sampling can be used to bridge knowledge gaps regarding upper airway immunity to important respiratory pathogens like SARS2 and to address important immunologic questions where peripheral blood sampling is inherently insufficient. I established novel methods for reproducible, longitudinal sampling of upper airway immune cell populations using swabs and demonstrated that sufficient numbers of viable immune cells could be collected to allow for high resolution downstream analyses, including multiparametric flow cytometry and single cell RNA sequencing. Upper airway resident memory B and T cell populations, including SARS2- specific memory B and T cells were characterized using these methods. There is great interest in developing next generation vaccines, including vaccines that can elicit robust mucosal immune responses. This requires knowledge of the immunologic contexts in which mucosal immunity is generated and the requirements for maintenance of upper airway immune memory. I hypothesize that local antigen exposure is required to develop durable upper airway immune memory, and intramuscular immunization alone may fail to elicit upper airway immunity despite generating circulating immunity. I will test this hypothesis by studying upper airway memory B and T cell frequencies, diversity, kinetics and durability in distinct immunologic contexts including SARS2 breakthrough infection (BTI) and COVID-19 booster vaccination using this award. Other respiratory pathogens of public health importance will also be examined. If funded, this K08 will assist with my transition to becoming a successful independent physician scientist investigator in human immunology and infectious diseases. The La Jolla Institute for Immunology (LJI) is a superb training environment and located on the campus of another excellent academic research and medical institution, the University of California, San Diego (UCSD). I will receive ongoing mentorship from an established investigator with a track record for producing successful mentees, Professor Shane Crotty, PhD, a world- renowned expert in the field of immunology. LJI and UCSD are closely affiliated, and Dr. Crotty has an adjunct appointment at UCSD. I will have access to resources at both LJI and UCSD for this career development award. As an Associate Physician in UCSD’s Division of Infectious Diseases I will receive additional mentorship in academic career development, and maintain my clinical acumen by providing part-time medical care and consultation services for medically complex patients.", "keywords": [ "2019-nCoV", "Address", "Adult", "Animal Model", "Antibodies", "Antibody Response", "Antibody titer measurement", "Antigens", "Appointment", "Award", "B-Lymphocytes", "Blood Tests", "Blood specimen", "CD8-Positive T-Lymphocytes", "COVID-19 booster", "COVID-19 pandemic", "COVID-19 vaccination", "California", "Caring", "Cell Survival", "Cell secretion", "Cells", "Clinical", "Common Cold", "Communicable Diseases", "Complex", "Consultations", "Coronavirus", "Coronavirus Infections", "Data", "Development", "Disease", "Doctor of Philosophy", "Enrollment", "Environment", "Epitopes", "Evaluation", "Flow Cytometry", "FluMist", "Frequencies", "Funding", "Human", "Immune", "Immunity", "Immunization", "Immunoglobulin A", "Immunologic Memory", "Immunologics", "Immunology", "Immunophenotyping", "Infection", "Infection Control", "Infection prevention", "Influenza", "Institution", "Intramuscular", "Investigation", "K-Series Research Career Programs", "Kinetics", "Knowledge", "Left", "Licensing", "Maintenance", "Mediating", "Medical", "Memory", "Memory B-Lymphocyte", "Mentorship", "Methods", "Morbidity", "Mucosal Immune Responses", "Mucosal Immunity", "Mucous Membrane", "Nasal cavity", "Nasal turbinate bone structure", "Nasopharynx", "Nose", "Patients", "Physicians", "Play", "Population", "Primates", "Process", "Public Health", "Reproducibility", "Research", "Research Personnel", "Resolution", "Resources", "Role", "SARS-CoV-2 exposure", "SARS-CoV-2 immunity", "SARS-CoV-2 infection", "SARS-CoV-2 variant", "Sampling", "Scientist", "Secondary Immunization", "Services", "Severity of illness", "Site", "Source", "Swab", "T cell response", "T-Cell Receptor", "T-Lymphocyte", "Testing", "Time", "Tissues", "Training", "Universities", "Vaccination", "Vaccine Design", "Vaccines", "Viral", "Virus Diseases", "acquired immunity", "adaptive immunity", "breakthrough infection", "career development", "cohort", "cross reactivity", "cytokine", "experimental study", "flu", "human pathogen", "influenza virus vaccine", "insight", "interest", "live attenuated influenza vaccine", "minimally invasive", "mortality", "mucosal vaccine", "nasopharyngeal swab", "neutralizing antibody", "novel", "novel strategies", "novel therapeutics", "novel vaccines", "pandemic disease", "peripheral blood", "professor", "respiratory pathogen", "respiratory virus", "response", "severe COVID-19", "single-cell RNA sequencing" ], "approved": true } }, { "type": "Grant", "id": "15982", "attributes": { "award_id": "1R01AI189532-01A1", "title": "Biophysical constraints on antibody affinity maturation to SARS-CoV-2", "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": "2026-02-19", "end_date": "2031-01-31", "award_amount": 815762, "principal_investigator": { "id": 44437, "first_name": "Angela Marie", "last_name": "Phillips", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2635, "ror": "", "name": "UNIVERSITY OF CALIFORNIA, SAN FRANCISCO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The objective of this proposal is to develop a quantitative understanding of how the biophysical properties of antibodies impact their capacity to evolve affinity to divergent SARS-CoV-2 spike variants. Though there is substantial evidence that mutations acquired during affinity maturation impact antibody expression, affinity for distinct viral variants, and self-reactivity, we lack a quantitative understanding of (1) how mutations impact these biophysical properties and (2) how these properties, and trade-offs between them, collectively determine the fate of the corresponding B-cell lineage. Here, we propose three Aims to test our hypothesis that mutations differentially impact antibody expression, affinity, and self-reactivity, resulting in biophysical trade-offs that constrain the evolution of antibodies that bind divergent SARS-CoV-2 spike variants. In Aim 1, we quantitate the biophysical effects of mutations in anti-SARS-CoV-2 spike antibodies, using high-throughput mammalian cell- display methods we recently developed. By measuring the expression, affinity, and self-reactivity for millions of anti-spike antibodies, including broadly neutralizing antibodies (bnAbs) that bind divergent spike variants, their evolutionary predecessors, and systematically mutagenized antibody sequences, we will unveil biophysical constraints that shape affinity maturation to rapidly evolving viral antigens. In Aim 2, we evaluate the contributions of antibody biophysical properties to B-cell fitness, or proliferation, using longitudinally-sampled patient B-cells following exposure to divergent strains of SARS-CoV-2. This approach will reveal the relative importance of distinct antibody biophysical properties in driving B-cell evolutionary dynamics in human repertoires and enable development of quantitative models for predicting the outcomes of affinity maturation. In Aim 3, we define the impact of selection pressure during affinity maturation on the biophysical properties of the resulting antibodies, focusing on selection regimes known to favor the maturation of bnAbs that bind distinct spike variants. To this end, we leverage a B-cell directed evolution platform that mimics the mutagenic load of somatic hypermutation, enables fine-tuning of the antibody selection conditions, and supports longitudinal B-cell sampling to profile the evolutionary dynamics of the B-cell response and the biophysical properties of the corresponding antibody lineages. The resulting data will be used to define the impact of the selection regime on the biophysical determinants of B-cell fitness. Successful completion of these Aims will yield quantitative insight into (1) how antibody biophysical properties change during affinity maturation, (2) how they collectively determine B-cell fate in human repertoires, and (3) how their relative importance varies across distinct selection regimes. Thus, this work will advance our fundamental understanding of the biophysical mechanisms that shape antibody affinity maturation to rapidly evolving pathogens like SARS-CoV-2, supporting efforts to design and elicit antibodies that bind existing and novel viral variants.", "keywords": [ "2019-nCoV", "Affinity", "Antibodies", "Antibody Affinity", "Antibody Repertoire", "Antigens", "Autoantibodies", "Automobile Driving", "B-Cell Antigen Receptor", "B-Lymphocytes", "Binding", "Biophysical Process", "Biophysics", "Cell Lineage", "Cell membrane", "Cell surface", "Data", "Development", "Directed Molecular Evolution", "Engineering", "Epitopes", "Evolution", "Exposure to", "Frequencies", "Future", "Goals", "Human", "Immunoglobulin Somatic Hypermutation", "Knowledge", "Mammalian Cell", "Measures", "Membrane", "Methods", "Modeling", "Molecular", "Mutagens", "Mutation", "Outcome", "Patients", "Population", "Process", "Proliferating", "Property", "Protein Engineering", "Proteins", "Regimen", "Relaxation", "Research", "SARS-CoV-2 antibody", "SARS-CoV-2 exposure", "SARS-CoV-2 spike protein", "SARS-CoV-2 variant", "Sampling", "Shapes", "Surface", "Testing", "Vaccines", "Variant", "Viral", "Viral Antigens", "Virus", "Work", "adaptive immunity", "antigen binding", "biophysical properties", "design", "efficacy evaluation", "empowerment", "fitness", "improved", "insight", "interest", "neutralizing antibody", "novel", "outcome prediction", "pathogen", "predictive modeling", "pressure", "response", "trafficking", "vaccine development" ], "approved": true } }, { "type": "Grant", "id": "15725", "attributes": { "award_id": "2527135", "title": "Collaborative Research: eMB: The immunological signature of a changing world: mathematical models to infer historical patterns of infectious disease", "funder": { "id": 3, "ror": "https://ror.org/021nxhr62", "name": "National Science Foundation", "approved": true }, "funder_divisions": [ "Mathematical and Physical Sciences (MPS)", "MATHEMATICAL BIOLOGY" ], "program_reference_codes": [], "program_officials": [ { "id": 32775, "first_name": "Vu", "last_name": "Dinh", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-15", "end_date": null, "award_amount": 224888, "principal_investigator": { "id": 27856, "first_name": "Scott", "last_name": "Nuismer", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 4470, "first_name": "Christopher H", "last_name": "Remien", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 627, "ror": "", "name": "Regents of the University of Idaho", "address": "", "city": "", "state": "ID", "zip": "", "country": "United States", "approved": true }, "abstract": "Spillover of infectious diseases from wildlife to humans and livestock is a pervasive risk to the health and welfare of human populations around the world. Effective management of this risk is facilitated by early detection of changes in the frequency of spillover events. This research will develop new mathematical models and statistical methods that allow changes in the rate of spillover to be detected from the fossil record of past infection that remains imprinted on human and animal immune systems. The general methodology developed by this project will be rigorously tested using simulated data and applied to Rift Valley fever virus, a pathogen that poses a high risk of global expansion with potentially devastating consequences for human health and agriculture. Work on this project will train students in cutting edge mathematical and statistical methods and support an international workshop where software developed by the project will be introduced and instruction on its use provided. Predicting how zoonotic infectious diseases change over time is a fundamentally important challenge with few general mathematical solutions. Central to addressing this problem is disentangling historical changes in the rate or “force” of spillover from background biological processes, such as age-specific infection and wanning immunity, which can cloak or mimic the signal of temporal change. Existing statistical methods to infer historical changes in the force of spillover for zoonotic pathogens rely on piecemeal solutions tailored to specific scenarios, ignore interacting background processes, use only single immunological markers, and have failed to rigorously evaluate parameter identifiability. To fill this gap, this project will develop a general mathematical framework describing the probability that an individual is in a specific multivariate immune state as a function of age and time using a coupled system of partial differential equations (PDEs). Approximate and numerical solutions to this system of PDEs will enable a Bayesian statistical framework for inferring recent historical changes in the force of spillover in the presence of alternative biological processes. Testing this statistical framework using extensive, biologically realistic simulated datasets will allow the identifiability of historical change in force of spillover to be evaluated. Application of this methodology to Rift Valley fever virus, a pathogen with significant pandemic potential, will determine whether increasing case counts in East Africa result from fundamental shifts in disease epidemiology or from increased disease surveillance. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.", "keywords": [], "approved": true } } ], "meta": { "pagination": { "page": 1405, "pages": 1424, "count": 14236 } } }