Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=5&sort=-end_date
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-end_date", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1442&sort=-end_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=6&sort=-end_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=4&sort=-end_date" }, "data": [ { "type": "Grant", "id": "16098", "attributes": { "award_id": "1K08AG098035-01", "title": "Identification of molecular-neuropathological signatures in AD, FTLD and Long COVID", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Aging (NIA)" ], "program_reference_codes": [], "program_officials": [ { "id": 44574, "first_name": "CHELSEA MARIE", "last_name": "HAAKENSON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-07-01", "end_date": "2031-04-30", "award_amount": 146750, "principal_investigator": { "id": 44575, "first_name": "Ting", "last_name": "Zhang", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3502, "ror": "", "name": "UNIVERSITY OF CALIFORNIA LOS ANGELES", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Neurodegenerative diseases, including Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), exhibit neuropathological features (e.g., amyloid and p-tau accumulation) that disproportionately affect certain brain regions and subsets of cells. This selective vulnerability to neuropathological features has been recognized for decades, yet its underlying molecular mechanisms remain unclear. Long COVID, a prevalent post-pandemic condition with largely unknown disease mechanisms, is reported to exhibit p-tau pathology, linking it to neurodegeneration. Current methods, including single-nucleus RNA sequencing, are unable to integrate spatial and pathological contexts with transcriptomic profiles, limiting direct molecular characterization of disease pathology at the single cell level. Here, I propose to leverage single-cell spatial multi-omics on postmortem brain tissues to in-situ capture molecular and cellular alterations that directly linked to selective vulnerability to neuropathological features across AD, FTLD, and Long COVID at single-cell resolution—insights previously unattainable. I will also identify potential pathological modulators using functional genomics in human induced pluripotent stem cell (iPSC)-derived neurons. In this proposal, Aim1 will characterize neuropathological and transcriptomic alterations in Long COVID and compare findings to AD and FTLD. Aim2 will leverage same- slide single-cell spatial multi-omics with neuropathology phenotyping (Xenium 5K + Phenocycler-Fusion) and define the molecular-neuropathological signatures specific to amyloid, neuronal p-tau, and glial p-tau pathology in AD, FTLD and Long COVID. Aim3 will employ CRISPRi/a screening in iPSC-derived neurons to identify neuronal p-tau modifiers from signatures uncovered in Aim2. By integrating single-cell spatial multi-omics with functional genomics, this project will bridge the gap between neuropathology and molecular profiling, provide novel insights into selective vulnerability to neuropathological features and identify pathological modulators. My long-term goal is to become a physician(neuropathologist)-scientist leading a NIH-funded research laboratory focused on neurodegenerative diseases and COVID-19. This five-year mentored career development plan will provide the necessary training for my transition to independence, emphasizing expertise in single-cell spatial transcriptomics and proteomics, bioinformatics, imaging analysis, iPSC technology and CRISPR-based functional genomics. Additionally, I will deepen my knowledge of neuropathology, molecular genetics, and clinical aspects of AD, FTLD, and Long COVID. I have assembled a multidisciplinary mentorship team of distinguished physician-scientists that includes Dr. Daniel Geschwind (primary mentor), Drs. Harry Vinters and Shino Magaki (co-mentors), and advisory members Drs. Inma Cobos, Vivek Swarup, and Edward Lee. With UCLA's cutting- edge facilities, exceptional research environment, and strong clinical resources, this award will prepare me to become a competitive neuropathologist-scientist, advancing our understanding of neurodegenerative diseases and COVID-19 while informing therapeutic strategies.", "keywords": [ "Address", "Affect", "Aging", "Alzheimer's Disease", "Alzheimer's disease brain", "Amyloid", "Astrocytes", "Autopsy", "Award", "Bioinformatics", "Brain", "Brain region", "COVID-19", "CRISPR interference", "Cell Communication", "Cell Death", "Cell model", "Cells", "Clinical", "Clustered Regularly Interspaced Short Palindromic Repeats", "Code", "Coiled Bodies", "Couples", "Data", "Dementia", "Development Plans", "Diagnosis", "Diffuse", "Disease", "Disease Progression", "Environment", "Etiology", "Exhibits", "Flow Cytometry", "Frontotemporal Lobar Degenerations", "Functional disorder", "Funding", "Genes", "Goals", "Image", "Immunofluorescence Immunologic", "In Situ", "Individual", "Induced pluripotent stem cell derived human neuron", "Induced pluripotent stem cell derived neurons", "Knowledge", "Laboratory Research", "Link", "Long COVID", "Mentors", "Mentorship", "Methods", "Molecular", "Molecular Genetics", "Molecular Profiling", "Nature", "Nerve Degeneration", "Neurodegenerative Disorders", "Neurofibrillary Tangles", "Neurons", "Onset of illness", "Pathologic", "Pathology", "Patients", "Phenotype", "Physicians", "Pick Disease of the Brain", "Pick body", "Progressive Supranuclear Palsy", "Proteins", "Proteomics", "Reporting", "Research", "Resolution", "Resources", "Scientist", "Senile Plaques", "Slide", "Stimulus", "Tauopathies", "Technology", "Therapeutic", "Tissues", "Training", "United States National Institutes of Health", "Work", "acute COVID-19", "amyloid pathology", "brain cell", "brain tissue", "career development", "cell type", "cohort", "four repeats tau", "functional genomics", "human induced pluripotent stem cells", "hyperphosphorylated tau", "induced pluripotent stem cell", "induced pluripotent stem cell technology", "insight", "member", "multidisciplinary", "neuropathology", "novel", "post-pandemic", "resilience", "response", "screening", "single nucleus RNA-sequencing", "spatial integration", "spatial omics", "spatial transcriptomics", "tau Proteins", "tau aggregation", "tau-1", "transcriptome sequencing", "transcriptomics" ], "approved": true } }, { "type": "Grant", "id": "16128", "attributes": { "award_id": "1R01AI190919-01A1", "title": "Vectored Immunoprophylaxis of SARS-CoV-2 with receptor decoys", "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": 32536, "first_name": "DIPANWITA", "last_name": "BASU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-19", "end_date": "2031-04-30", "award_amount": 836484, "principal_investigator": { "id": 44610, "first_name": "Nathaniel R.", "last_name": "Landau", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 832, "ror": "", "name": "NEW YORK UNIVERSITY SCHOOL OF MEDICINE", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Monoclonal antibody therapy for severe COVID-19 and for prophylaxis in immunocompromised individuals was initially of great value but was sidelined by the rapid emergence of virus variants with mutations in the spike gene that rendered the antibodies ineffective. Receptor decoys offer a means to overcome this problem. Because the viral spike protein needs to conserve its high affinity for ACE2, there is a high genetic barrier for the virus to escape from neutralization by the decoy. The project will develop vectored immunoprophylaxis (VIP) in which high affinity ACE2 receptor decoys will be expressed by adeno-associated virus (AAV) and lentiviral viral vectors. These will be used to protect against and to treat SARS-CoV-2 infection. The decoys consist of the extracellular domain of ACE-2 fused to a truncated immunoglobulin heavy chain Fc region. The “microbody” neutralizes the virus by binding to the viral spike protein and will be active against all variants. Because the decoys are composed entirely of human-derived protein components, they will be well-tolerated by the human immune system. The decoys will be optimized to increase their affinity for the spike protein and will be produced with Fc regions that alter their tissue localization, half-life, antiviral activity and antibody effector functions. The decoys will be tested as recombinant protein for prophylactic and therapeutic efficacy in ACE2 transgenic mouse and hamster models against a panel of SARS-CoV-2 variants. Tissue localization and half-life of vector-expressed decoy proteins will be determined by live-imaging of decoy–luciferase fusions. Long-term protection against infection will be established with decoy-expressing AAV and lentiviral vectors in mice and hamsters by intranasal instillation and intramuscular injection. The animals will then be challenged with live virus up to a year post- administration. Serum and lung concentrations of the decoy will be measured and the host antibody response to the decoy protein will be tested. An optimized decoy will be designed based on the findings obtained with modified decoy proteins and its effectiveness will be studied in rhesus macaques, a model that closely resembles humans. The decoy approach will be valuable for rapidly establishing long-term protection, and will be of value to immunocompromised individuals for whom vaccination is less effective. The approach offers an off-the-shelf means with which to rapidly protect the population in the event of a novel zoonotic coronavirus pandemic. The lessons learned will be broadly applicable to other viruses for which a decoy receptor can be generated.", "keywords": [ "2019-nCoV", "ACE2", "Acquired Immunodeficiency Syndrome", "Aerosols", "Affect", "Affinity", "Amino Acids", "Animal Model", "Animals", "Antibodies", "Antibody Response", "Binding", "Binding Proteins", "COVID-19 treatment", "COVID-19 vaccination", "Cell Surface Receptors", "Data", "Death Rate", "Dependovirus", "Development", "Disease", "Effectiveness", "Epitopes", "Event", "Evolution", "Exposure to", "Extracellular Domain", "Future", "Gene Transduction Agent", "Generations", "Genes", "Genetic", "Genetic Diseases", "Half-Life", "Hamsters", "Heavy-Chain Immunoglobulins", "Human", "Image", "Immune response", "Immune system", "Immunization Programs", "Immunocompromised Host", "Individual", "Infection", "Intramuscular", "Intramuscular Injections", "Investments", "Length", "Lentivirus Vector", "Luciferases", "Lung", "Macaca", "Macaca mulatta", "Malignant Neoplasms", "Measures", "Modeling", "Monoclonal Antibodies", "Monoclonal Antibody Therapy", "Mus", "Mutation", "Pathogenicity", "Pharmaceutical Preparations", "Physiological", "Population", "Predisposition", "Production", "Prophylactic treatment", "Proteins", "Recombinant Proteins", "Recombinants", "Resistance", "Respiratory System", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "SARS-CoV-2 variant", "Serotyping", "Serum", "Testing", "Therapeutic", "Therapeutic Effect", "Tissues", "Transgenic Mice", "Transplantation", "Treatment Efficacy", "Update", "Vaccination", "Vaccines", "Variant", "Viral", "Viral Antibodies", "Viral Physiology", "Viral Vector", "Viral load measurement", "Virus", "Virus Diseases", "Virus Receptors", "Virus Replication", "acute COVID-19", "acute infection", "adeno-associated viral vector", "compare effectiveness", "coronavirus pandemic", "delivery vehicle", "design", "effectiveness evaluation", "emerging virus", "future pandemic", "hospitalization rates", "immunoprophylaxis", "microbody", "nonhuman primate", "nonhuman primate models", "novel", "pandemic virus", "prevent", "prophylactic", "receptor", "severe COVID-19", "success", "transmission process", "vaccine immunogenicity", "vector", "weapons", "zoonotic coronavirus" ], "approved": true } }, { "type": "Grant", "id": "16127", "attributes": { "award_id": "1R25AI189409-01", "title": "The National Summer Undergraduate Research Project: Virtual Programming and Mentoring in Biomedical Microbiology and Immunology", "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": 44608, "first_name": "CARMEN", "last_name": "MOTEN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-13", "end_date": "2031-04-30", "award_amount": 368681, "principal_investigator": { "id": 44609, "first_name": "Michael David Leslie", "last_name": "Johnson", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3378, "ror": "", "name": "UNIVERSITY OF ARIZONA", "address": "", "city": "", "state": "AZ", "zip": "", "country": "United States", "approved": true }, "abstract": "The National Summer Undergraduate Research Project (NSURP) was created as an eight-week virtual summer research program in the microbial sciences that matches underrepresented minorities in STEM undergraduate students nationwide with faculty mentors worldwide to address the barriers presented by COVID-19 cancelations. NSURP mentees conduct research from any location with an internet connection, allowing students to learn how to conduct impactful research by forming and testing hypotheses. As individuals returned to in-person programs, NSURP found a population unable to travel, independent of COVID-19, due to financial, familial, geography, and health constraints. As we see an increased demand from these individuals, post-pandemic, who can’t travel to in-person opportunities, we seek to expand our ability to serve these undergraduates with research opportunities in our program and provide them with year-long mentoring and professional development. NSURP seeks to apply its virtual research model to human health-related topics, such as the basic and applied disease research conducted within the purview of the NIAID, both in microbiology and immunology. Implementing NSURP within the NIAID infrastructure will create more opportunities for URM scientists and ultimately aid in developing a diverse biomedical research workforce. The central premise of NSURP is to meet undergraduates where they are, facilitate exposure and pursuit of a scientific opportunity, and give them the tools and confidence to continue in their scientific careers. To maximize the contribution of NSURP within the NIAID mission, we will 1) provide virtual biomedical-specific summer research opportunities within the NIAID mission for minoritized undergraduates, 2) facilitate synergistic virtual scientific and career multi-level mentoring relationships, and 3) assess program impact by evaluating educational outcomes of NSURP participants and conducting longitudinal studies on the effects of culturally-responsive virtual mentorship training.", "keywords": [ "Address", "American", "Arizona", "Basic Science", "Biological Sciences", "Biomedical Research", "Black race", "COVID-19", "Caliber", "Collaborations", "Development", "Discipline", "Disease", "Education", "Education Projects", "Enrollment", "Faculty", "Family", "First Generation College Students", "Foundations", "Funding", "Geography", "Health", "Health Professional", "Human", "Immunology", "Indigenous", "Individual", "Infrastructure", "Internet", "Interview", "Latina", "Latino", "Latinx", "Learning", "Location", "Longitudinal Studies", "Low income", "Mentors", "Mentorship", "Microbiology", "Minority Groups", "Mission", "Modeling", "National Institute of Allergy and Infectious Disease", "Outcome", "Participant", "Persons", "Population", "Positioning Attribute", "Productivity", "Readiness", "Research", "Research Project Grants", "Research Training", "Resources", "STEM career", "STEM field", "Scholars Program", "Science", "Science Technology Engineering and Mathematics", "Societies", "Students", "Surveys", "Testing", "Training", "Training Activity", "Trajectory", "Travel", "Underrepresented Minority", "Underrepresented Populations", "United States", "Universities", "career", "design", "experience", "faculty mentor", "improved", "interest", "meetings", "microbial", "minority scientist", "minority undergraduate", "peer", "peer coaching", "post-pandemic", "programs", "skill acquisition", "summer research", "tool", "training opportunity", "undergraduate student", "undergraduate summer research", "underrepresented minority student", "virtual" ], "approved": true } }, { "type": "Grant", "id": "16132", "attributes": { "award_id": "1P01AI195327-01", "title": "Organoid and Primary Culture Core", "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": [], "start_date": "2026-05-11", "end_date": "2031-04-30", "award_amount": 324500, "principal_investigator": { "id": 44614, "first_name": "Melanie Maria", "last_name": "Ott", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3523, "ror": "", "name": "J. DAVID GLADSTONE INSTITUTES", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "CORE 2: ORGANOID AND HUMAN CELL CULTURE CORE SUMMARY The Organoid and Human Cell Culture Core is a critical component of the Gladstone PhAIge Therapy Center, designed to accelerate the clinical development of phage-based therapeutics targeting ESKAPE pathogens, with a particular focus on Klebsiella pneumoniae (Kp). Antimicrobial resistance is a growing global health crisis, contributing to over a million deaths annually. Phage therapy represents a promising solution to this challenge, especially as the discovery of antibiotics with novel mechanisms of action continues to lag. However, the lack of advanced preclinical models that adequately replicate human physiology and host responses hinders the translation of phage therapy to clinical use. The Organoid and Human Cell Culture Core will address this unmet need by developing and implementing cutting-edge ex vivo human cell culture systems, including 3D human airway organoids (HAOs), 2D air-liquid interface (ALI) cultures, and other primary cell models. These models offer significant advantages over traditional in vitro models by closely mimicking the complexity of human lung tissues, including cellular diversity, barrier integrity, and innate immune responses, enabling more precise evaluation of phage efficacy and safety in a clinically relevant context. The Core will accomplish this goal in two specific aims. Aim 1 focuses on establishing robust infection models for Kp in 3D HAOs and 2D ALI cultures and leveraging high-throughput sequencing-based assays to assess phage adsorption, entry efficiency, and specificity to support Project 1. By identifying phages with high on-target effects against bacteria and minimal off-target effects on human cells, this aim will streamline the selection of optimal candidates for clinical development. Aim 2 will evaluate mammalian host responses to phage therapy, including bacterial clearance, epithelial damage, host cell viability, Kp strain variation, and inflammatory cytokine expression, a critical step to advance the most promising phage cocktails to future clinical trials. The Core will also incorporate patient-derived organoids, including those from individuals with cystic fibrosis, to investigate how pre-existing epithelial dysfunction affects therapeutic outcomes. The Core leverages Dr. Melanie Ott’s recognized expertise in organoid technology, with a proven track record of using HAOs to model infectious diseases, including SARS-CoV-2, HCV, HIV, and influenza. This foundational expertise, applied to Kp infections, will help develop rigorous quantitative assays to evaluate phage efficacy and safety independent from human donor bias. By integrating human models into the Center’s research pipeline in Projects 1–2 and the Advanced Computational Core, the Organoid and Human Cell Culture Core will accelerate the translation of phage therapies from bench to bedside.", "keywords": [ "2019-nCoV", "3-Dimensional", "Acceleration", "Address", "Adsorption", "Affect", "Aftercare", "Air", "Animal Model", "Antibiotic Resistance", "Antibiotics", "Antimicrobial Resistance", "Architecture", "Bacteria", "Bacteriophages", "Bar Codes", "Binding Proteins", "Bioinformatics", "Biological Assay", "Cell Culture System", "Cell Culture Techniques", "Cell Survival", "Cell model", "Cells", "Cessation of life", "Clinical", "Clinical Trials", "Colony-Forming Units Assay", "Complex", "Consumption", "Cosmids", "ESKAPE pathogens", "Electrical Resistance", "Engineering", "Environment", "Epithelium", "Evaluation", "Failure", "Functional disorder", "Future", "Gene Expression", "Genome", "Goals", "HIV", "Hepatitis C virus", "High-Throughput Nucleotide Sequencing", "Human", "Immune response", "Immune system", "Immunofluorescence Immunologic", "In Vitro", "Infection", "Inflammatory", "Influenza", "Innate Immune Response", "Klebsiella pneumoniae", "Lactate Dehydrogenase", "Liquid substance", "Lung", "Mammalian Cell", "Measures", "Methodology", "Methods", "Modeling", "Molecular", "Multi-Drug Resistance", "Organ", "Organoids", "Patients", "Physiological", "Physiology", "Pre-Clinical Model", "Preclinical data", "Primary Cell Cultures", "Prophages", "Quantitative Reverse Transcriptase PCR", "Research", "Safety", "Services", "Site", "Specificity", "Stains", "Structure of parenchyma of lung", "System", "Techniques", "Technology", "Testing", "Therapeutic", "Time", "Tissues", "Training", "Translations", "Variant", "assay development", "bench to bedside", "bronchial epithelium", "clinical candidate", "clinical development", "clinically relevant", "combat", "cystic fibrosis patients", "cytokine", "design", "droplet digital PCR", "effective therapy", "efficacy evaluation", "ex vivo", "global health", "high throughput screening", "human model", "in vitro Model", "in vivo Model", "infectious disease model", "innovation", "insight", "multi-drug resistant pathogen", "novel", "outcome prediction", "pre-clinical", "preclinical study", "predictive modeling", "rapid test", "rational design", "receptor binding", "research clinical testing", "resistant Klebsiella pneumoniae", "therapeutic target", "therapy outcome" ], "approved": true } }, { "type": "Grant", "id": "15952", "attributes": { "award_id": "1K25AI196259-01", "title": "Modeling SARS-CoV-2 variant emergence from immunocompromised hosts", "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": 32891, "first_name": "MARY KATHERINE BRADFORD", "last_name": "PLIMACK", "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": 161946, "principal_investigator": { "id": 44397, "first_name": "Katherine", "last_name": "Owens", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3410, "ror": "", "name": "FRED HUTCHINSON CANCER CENTER", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "This proposal describes a five-year research training program that will facilitate my ongoing transition from an applied mathematician to an independent, quantitative, multidisciplinary biomedical researcher. I will work closely with clinicians, mathematical modelers, bioinformaticians, evolutionary biologists, virologists and immunologists to develop a suite of mathematical models which will be validated against viral, immune, phylogenetic and epidemiolocal datasets. The goals of my proposal will be to: 1) understand the mechanisms facilitating generation of SARS-CoV-2 variants of concern (VOC) during prolonged infections in immunocompromised (IC) individuals, and 2) identify key bottle necks that limit the number of VOCs that predominate in the general population. SARS-CoV-2 is the appropriate virus for which to develop this modeling framework due to the availability of data, and ongoing incidence, but the approach will be widely applicable to other pathogens. The training program includes an outstanding group of mentors and collaborators. My scientific advisory committee consists of experts in modeling infectious diseases (Dr Josh Schiffer and Dr Dan Reeves), clinical care for IC individuals (Dr Josh Schiffer and Dr. Alpana Wahgmare), epidemiology (Dr Cheryl Cohen and Dr Dobromir Dimitrov), viral evolution (Dr JT McCrone and Dr Mahan Ghafari), and biostatistics and machine learning (Dr Ollivier Hyrien). This group is dedicated to ensuring the success of my project, and my career development as an independent researcher. The specific learning goals required for my successful transition to biomedical research will be accomplished through didactic coursework in virology, immunology, epidemiology and phylogenetics as well as conferences and professional training in the skills of a successful mentor and group leader. The research plan addresses a critically important clinical and public health issue. Prolonged SARS-CoV- 2 infections in IC individuals are the most likely source of most novel VOC, which have extended and strongly exacerbated the impact of the pandemic. Though these infections have had an outsized public health impact, clear guidance regarding clinical management and safety measures is lacking. Understanding the within-host evolution of SARS-CoV-2 is paramount to addressing these issues. Through accomplishing the aims of this proposal, Dr Owens will address critical gaps in our knowledge of SARS-CoV-2 evolution and create an in silico framework to study SARS-CoV-2 interventions at both individual and population level. Ultimately, this proposal will allow Dr Owens to influence the future of pandemic response research as well as build a self-sustaining program at the interface of mathematical modeling, immunology, viral dynamics, and viral evolution.", "keywords": [ "2019-nCoV", "Address", "Advisory Committees", "Aftercare", "Anatomy", "Award", "Biomedical Research", "Biometry", "COVID-19 impact", "COVID-19 incidence", "Calibration", "Cessation of life", "Clinical", "Clinical Management", "Clinical Trials", "Data", "Data Set", "Dedications", "Effectiveness of Interventions", "Ensure", "Epidemiology", "Evolution", "Frequencies", "General Population", "Generations", "Genetic", "Genetic Drift", "Genetic Recombination", "Goals", "Guidelines", "Health Policy", "Heterogeneity", "Immune", "Immune response", "Immunity", "Immunocompromised Host", "Immunologics", "Immunologist", "Immunology", "Incidence", "Individual", "Infection", "Intervention", "Kinetics", "Knowledge", "Learning", "Link", "Machine Learning", "Mathematics", "Measures", "Mentors", "Mentorship", "Modeling", "Mutate", "Mutation", "Neck", "Nucleotides", "Output", "Pattern", "Phylogenetic Analysis", "Population", "Program Sustainability", "Public Health", "Published Comment", "Recording of previous events", "Research", "Research Personnel", "Research Training", "Risk", "Risk Factors", "SARS-CoV-2 infection", "SARS-CoV-2 variant", "Safety", "Scientist", "Social Distance", "Source", "Testing", "Training", "Training Programs", "United States National Institutes of Health", "Vaccination", "Variant", "Viral", "Viral Genes", "Viral Load result", "Virus", "Virus Replication", "Work", "career", "career development", "chronic infection", "clinical care", "community transmission", "design", "epidemiologic data", "experience", "fitness", "future pandemic", "immunological status", "in silico", "ineffective therapies", "infectious disease model", "insight", "machine learning method", "mathematical model", "multidisciplinary", "novel", "pandemic impact", "pandemic preparedness", "pandemic response", "pathogen", "patient oriented", "pressure", "skills", "success", "symposium", "tool", "transmission process", "vaccine distribution", "variants of concern", "viral rebound", "virology" ], "approved": true } }, { "type": "Grant", "id": "15950", "attributes": { "award_id": "1K08AI196255-01", "title": "Neutralizing antibody pressure on the evolution of SARS-CoV-2 variants.\"", "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": 32891, "first_name": "MARY KATHERINE BRADFORD", "last_name": "PLIMACK", "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": 194160, "principal_investigator": { "id": 44394, "first_name": "Ian Alexander", "last_name": "Mellis", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3409, "ror": "", "name": "COLUMBIA UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT: Rationale: SARS-CoV-2 evolution has led to the emergence of viral variants that evade existing immunity in the human population, which continue to pose a threat to global public health. It has proven challenging to predict which mutations will arise in future dominant viral variants, and, as a result, it is difficult to design vaccines that provide adequate protection against viruses that will circulate in future waves of infections. Our preliminary data show that viral variant evolution is most closely correlated with evasion of serum neutralizing antibodies, and that serum neutralizing antibody responses are shaped by immune imprinting to the ancestral D614G strain. This mentored career project aims to leverage these observations to develop an in vitro model for predicting where mutations will appear in the virus and to use that information to design updated vaccines. Candidate: As a Transfusion Medicine fellow with a PhD in Genomics and Computational Biology and two years of experience in virology and immunology research, I bring a unique complement of perspectives and skills to the analysis of viral and antigenic evolution and to vaccine design strategies. Further training in advanced BSL-2-compatible pseudovirus culture, mouse immunization, and computational structural biology will be central to the completion of the proposed project and to my development as an independent physician-scientist aiming to improve our understanding and mitigation of pathogen evolution. My primary mentor, Dr. David Ho, an international leader in virology, and my complementary multidisciplinary advisory team, will ensure my research and career development progress. Environment: The Ho laboratory at the Columbia University Irving Medical Center (CUIMC) is a world leader in the study of pandemic viruses, including SARS-CoV-2, with expertise in the characterization of viral variants and serum antibody analysis. The Ho lab has access to abundant resources and many collaborators, including leaders in pseudovirus construction, structural biology, and vaccine design. CUIMC also has a long track record of supporting junior physician-scientists on their paths to successful independent careers in academic medicine. Approach: We will test the central hypothesis that widespread early exposure to ancestral SARS-CoV-2 shapes the evolutionary trajectory of the virus and that such a trajectory can be modeled in vitro. In Aim 1 we will assess the impact of mouse serum neutralizing antibodies elicited by different immunization histories on mutational profiles in cultured BSL-2-rated pseudoviruses and correlate mutations with historical public health databases. In Aim 2, we will identify whether particular epitopes on the spike protein are particularly susceptible to the emergence of mutations under serum antibody selective pressure. In Aim 3, we will design and test novel COVID-19 vaccine candidates in mice based on observed mutations that arise in pseudoviruses. This project will enhance our understanding of SARS-CoV-2, provide a framework for in vitro modeling of antigenically variable pathogens, and contribute to vaccine design strategies.", "keywords": [ "2019-nCoV", "Advisory Committees", "Antibodies", "Antibody Response", "Antigenic Variation", "Antigens", "Biological Assay", "COVID-19", "COVID-19 booster", "COVID-19 vaccine", "Cessation of life", "Complement", "Computational Biology", "Data", "Databases", "Dengue", "Development", "Doctor of Philosophy", "Ensure", "Environment", "Epitopes", "Escape Mutant", "Evolution", "Exposure to", "Formulation", "Frequencies", "Future", "Genomics", "Growth", "Human", "Immune", "Immune response", "Immunity", "Immunization", "Immunize", "Immunology", "Impairment", "In Vitro", "Individual", "Infection", "Influenza", "International", "Junior Physician", "Laboratories", "Machine Learning", "Maps", "Measures", "Medical center", "Medicine", "Mentors", "Modeling", "Monoclonal Antibodies", "Mus", "Mutation", "Physicians", "Population", "Predisposition", "Proteins", "Public Health", "RNA vaccine", "Recording of previous events", "Research", "Resolution", "Resources", "SARS-CoV-2 spike protein", "SARS-CoV-2 variant", "Scientist", "Serum", "Shapes", "Structural Models", "System", "Testing", "Training", "Universities", "Update", "Vaccination", "Vaccine Design", "Vaccines", "Variant", "Vesicular stomatitis Indiana virus", "Viral", "Viral Genome", "Virus", "Work", "booster vaccine", "candidate identification", "career", "career development", "cohort", "design", "emerging virus", "experience", "exposure mixture", "genome sequencing", "imprint", "improved", "in vitro Model", "innovation", "multidisciplinary", "mutant", "mutation screening", "neutralizing antibody", "novel", "novel vaccines", "pandemic disease", "pandemic virus", "pathogen", "predictive modeling", "pressure", "public health intervention", "recurrent infection", "research and development", "skills", "structural biology", "therapy development", "transfusion medicine", "vaccine candidate", "vaccine development", "variants of concern", "virology" ], "approved": true } }, { "type": "Grant", "id": "15946", "attributes": { "award_id": "1R01AI196117-01", "title": "Advancing Analytical Tools to Quantify and Mitigate the Risk for Transitioning from Episodic to Endemic Transmission for Emerging Infections", "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": 32873, "first_name": "MISRAK", "last_name": "GEZMU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-04-10", "end_date": "2031-03-31", "award_amount": 787837, "principal_investigator": { "id": 26281, "first_name": "Seth", "last_name": "Blumberg", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3405, "ror": "", "name": "UNIVERSITY OF CALIFORNIA, SAN FRANCISCO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "This project will develop and apply computational tools for assessing the risk that diseases with episodic transmission become established in the general population. Our project is relevant to emerging zoonoses, re-emerging vaccine-preventable diseases, and healthcare-associated infections. Timely identification and control of such diseases could have significantly altered the course of mpox, SARS-CoV-2, and antimicrobial resistance. It is therefore important to have methods available to monitor and fully elucidate the transmission patterns of infectious diseases that can develop increased burden through pathogen evolution, reduced population immunity, or other sociodemographic changes. Any such method needs to consider patchy surveillance and differences in risk among those who are exposed to the disease. Furthermore, diseases that cause episodic outbreaks might require specific control strategies that are different from those that apply to epidemic or endemic diseases. Existing models that explore some of these aspects typically omit key factors, rely on untested assumptions, or are validated in a circular fashion using simulations based on the same assumptions they aim to test. This limits their reliability for real-world applications. To address this gap, we will combine statistical inference with simulation approaches to address key questions in quantifying and mitigating the risk from infectious diseases. We will extend methods for inference using branching process models to take into account imperfect observations and heterogeneity in both transmission and susceptibility. We will apply these methods to a range of applications to improve our ability to learn from data describing sporadic infection clusters. We will also use mobility and demographic data to construct synthetic populations representing situations where infections cause occasional outbreaks. This will permit stress-testing of inference methods and evaluation of control strategies. Our iterative approach will allow us to refine model assumptions, improve inference robustness, and identify the most informative data types for public health surveillance and control. The work will result in a greater understanding of how public health agencies can best use data from episodic disease transmission and computational tools for applying this understanding to coming threats. To demonstrate the breadth of applicability, we will apply our methodological advancements to (1) quantify the transmissibility of H5N1 influenza, (2) determine the probability of large measles outbreaks occurring annually, and (3) evaluate control strategies for reducing transmission of virulent, healthcare-associated MRSA strains. To promote scientific reproducibility, we will produce user-friendly software that integrates with existing packages and share synthetic population data. Our team is well-positioned to conduct this work since we have developed many existing tools and paradigms for analyzing episodic transmission, including branching process models and outbreak simulations in synthetic populations. By advancing the science of disease transmission and equipping public health agencies with actionable results, this work will reduce the risk of future pandemics.", "keywords": [ "2019-nCoV", "Address", "Antimicrobial Resistance", "Behavior", "COVID-19 pandemic", "California", "Cations", "Clinical Data", "Communicable Diseases", "Communities", "County", "Data", "Data Collection", "Disease", "Disease Outbreaks", "Effectiveness", "Emerging Communicable Diseases", "Emerging infection", "Endemic Diseases", "Epidemic", "Epidemiology", "Evaluation", "Evolution", "Exhibits", "Exposure to", "Future", "General Population", "Goals", "Health Care", "Heterogeneity", "Household", "Human", "Immunity", "Individual", "Infection", "Influenza", "Influenza A Virus H5N1 Subtype", "Intervention", "Learning", "Link", "Measles", "Methodology", "Methods", "Modeling", "Modernization", "Monitor", "Monkeypox", "Pattern", "Population", "Population Surveillance", "Positioning Attribute", "Predisposition", "Probability", "Process", "Public Health", "Reproducibility", "Reproduction", "Research", "Resources", "Risk", "Risk Assessment", "Risk Reduction", "Route", "Science", "Statistical Methods", "Stress Tests", "Structure", "Study models", "Techniques", "Testing", "United States", "Vaccines", "Virulent", "Work", "Zoonoses", "advanced analytics", "analytical tool", "computerized tools", "data streams", "disease transmission", "disorder control", "disorder risk", "evidence base", "future pandemic", "generative artificial intelligence", "health care associated infections", "improved", "innovation", "mathematical model", "methicillin resistant Staphylococcus aureus", "model development", "models and simulation", "novel", "pathogen", "predicting response", "prevent", "previous pandemic", "public health intervention", "real world application", "risk mitigation", "simulation", "sociodemographics", "synthetic construct", "tool", "transmission process", "user friendly software" ], "approved": true } }, { "type": "Grant", "id": "16143", "attributes": { "award_id": "1K24AI198098-01", "title": "Mentoring patient-oriented research on point-of-care diagnostics for infectious diseases", "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": 32875, "first_name": "INKA I", "last_name": "SASTALLA", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-04-17", "end_date": "2031-03-31", "award_amount": 209758, "principal_investigator": { "id": 44625, "first_name": "Paul K", "last_name": "Drain", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2645, "ror": "", "name": "UNIVERSITY OF WASHINGTON", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "This midcareer investigator award in patient-oriented research is intended to provide the candidate, Dr. Paul Drain, MD, MPH; Associate Professor at the University of Washington (UW), with protected time to develop a structured and effective approach for research mentorship. He is Director of Clinical Research for the International Clinical Research Center in UW’s Department of Global Health, and Director of the Clinical Core for the Seattle Tuberculosis Research Advancement Center (Sea-TRAC). His clinical research group has been conducting diagnostic studies and clinical trials to advance rapid point-of-care diagnostics for infectious diseases, including HIV, tuberculosis (TB), malaria, and SARS-CoV-2. His research activities are grounded in clinical epidemiology and implementation science frameworks to evaluate a central hypothesis that improved diagnostic screening and testing methods, including novel point-of-care technologies, can advance clinical care and patient- centered outcomes for infectious diseases. However, the design of novel clinical studies, implementation science frameworks, use of mobile technologies, and development of machine learning and AI-guided algorithms have been rapidly evolving for patient-oriented research in the recent years. His research program and group are supported by 3 R01-funded studies, as well as several grants from the Gates Foundation and industry sponsors. From these ongoing and upcoming studies, he will develop a structured research mentoring program with three mentor-specific aims: (1) to identify and support emerging leaders to pursue patient-oriented research, (2) to develop a structured patient-oriented research mentorship program, and (3) to foster mentee research by facilitating access to exiting clinical datasets and advanced statistical research methods. He will also seek to advance patient-oriented research with three research-specific aims: (1) to define the value of diagnostics when implemented for various infections and indications, (2) to assess the demand and acceptance for using rapid diagnostics in community and home-based settings, (3) to utilize machine learning, AI-guided algorithms, and decision-analytic modeling to advance frameworks and utilization of novel point-of-care diagnostics for screening and testing. Achieving these aims will significantly advance his career and his mentees, while providing important contributions to the field of diagnostics. Expanding his capacity to mentor trainees in using the existing clinical studies will help strengthen the next generation of clinical researchers for global health and infectious diseases. This work will lead to a series of future proposed clinical studies and grant applications that will seek to further advance diagnostic technologies and testing to have a maximal impact on reducing morbidity/mortality for HIV, TB, malaria, and diseases of global importance.", "keywords": [ "2019-nCoV", "Algorithms", "Applications Grants", "Biometry", "Biostatistical Methods", "Career Mobility", "Catalogs", "Cessation of life", "Clinical", "Clinical Data", "Clinical Investigator", "Clinical Research", "Clinical Trials", "Collaborations", "Communicable Diseases", "Communities", "Data", "Data Analyses", "Data Collection", "Data Set", "Development", "Diagnosis", "Diagnostic", "Diagnostic Services", "Diagnostic tests", "Discipline", "Disease", "Educational Curriculum", "Epidemiologic Methods", "Faculty", "Fostering", "Foundations", "Funding", "Future", "Goals", "Grant", "HIV", "Home", "Human immunodeficiency virus test", "Industry", "Infection", "International", "Knowledge", "Learning Module", "Machine Learning", "Malaria", "Mentors", "Mentorship", "Methods", "Mid-Career Clinical Scientist Award (K24)", "Midcareer Investigator Award in Patient-Oriented Research", "Modeling", "Morbidity", "Patient-Focused Outcomes", "Point of Care Technology", "Rapid diagnostics", "Research", "Research Activity", "Research Methodology", "Research Personnel", "Research Project Grants", "Series", "Specimen", "Structure", "Students", "Support Groups", "Testing", "Time", "Tuberculosis", "Universities", "Washington", "Work", "biobank", "career", "clinical care", "clinical epidemiology", "clinical implementation", "design", "diagnostic algorithm", "diagnostic screening", "diagnostic technologies", "diagnostic value", "disease model", "global health", "implementation framework", "implementation science", "improved", "infectious disease treatment", "interest", "mid-career faculty", "mobile computing", "mortality", "next generation", "novel", "novel diagnostics", "patient oriented research", "point of care testing", "point-of-care diagnostics", "preference", "professor", "programs", "screening", "skills" ], "approved": true } }, { "type": "Grant", "id": "16140", "attributes": { "award_id": "1R01NS147100-01", "title": "Blood-Brain Barrier Integrity and Immune Dynamics in Neuropsychiatric Sequelae of Post-SARS-CoV-2 onset ME/CFS versus Pre-Pandemic ME/CFS Patients", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Neurological Disorders and Stroke (NINDS)" ], "program_reference_codes": [], "program_officials": [ { "id": 44622, "first_name": "VICKY R", "last_name": "WHITTEMORE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-04-16", "end_date": "2031-03-31", "award_amount": 633378, "principal_investigator": { "id": 44623, "first_name": "Alba Miranda", "last_name": "Azola", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2615, "ror": "", "name": "JOHNS HOPKINS UNIVERSITY", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is a long-term disabling condition with a wide range of symptoms, often triggered by acute infection. The CDC estimates that in 2022, over 3.5 million Americans are living with ME/CFS, and this number continues to increase as many Long COVID patients develop ME/CFS. Profound neurocognitive sequelae are highly prevalent in ME/CFS. The underlying pathophysiologic mechanism that drives neurocognitive impairments in post-infectious chronic conditions remains poorly understood, hindering the development of therapeutic interventions. Studies in chronic viral infections recognize that the trafficking of proinflammatory monocytes in the brain drives disruption of the blood-brain barrier and promotes a neuroinflammatory state. We hypothesize that post-SARS-CoV-2 onset ME/CFS patients and pre- pandemic ME/CFS patients have similar blood-brain barrier (BBB) disruption that is mechanistically linked to circulating proinflammatory analytes (cytokines and chemokines), altered BBB endothelial integrity, and a subtype of proinflammatory peripheral blood mononuclear cells (PBMCs) known as intermediate monocytes. Thus, disruption in BBB integrity promotes persistent neuroinflammation and altered neuronal activity, contributing to neuropsychiatric sequelae in both pre- and post-pandemic ME/CFS patients.Additionally, there is evidence supporting glymphatic system dysfunction in ME/CFS, which further contributes to the perpetuation of the neuroinflammatory state. We propose cross-sectional imaging to assess BBB integrity, with neuropsychiatric assessments and immunophenotyping in 100 post-SARS-CoV-2 onset ME/CFS patients and 100 who have pre- pandemic ME/CFS patients. In addition, we will incorporate 100 participants as a control group of SARS-CoV-2 infected individuals who fully recovered without lingering symptoms from our team NIH-funded similar study in a Long COVID cohort. First, we aim to assess BBB integrity in post-pandemic ME/CFS (vs. pre-pandemic ME/CFS) and its contribution to neuropsychiatric conditions. BBB integrity will be evaluated with a non-contrast magnetic resonance imaging technique that uses water-extraction-with-phase-contrast-arterial-spin-tagging (WEPCAST), to determine BBB permeability to small molecules. We have shown this to be sensitive to BBB change in mild cognitive impairment and are currently using this technique in other neuro-infectious diseases. Second, we aim to assess cross-sectional links between circulating soluble markers, PBMC-associated markers, and BBB permeability to small molecules in post SARS CoV-2 onset ME/CFS patients and pre pandemic ME/CFS. We hypothesize that both groups will exhibit similar levels of soluble markers promoting PBMC trafficking to brain and promoting monocyte activation, disruption of soluble markers that promote endothelial integrity & higher levels of cell-surface proteins that promote PBMC diapedesis into brain will be associated with higher PS values and greater alterations in the cognitive and psychiatric domains. Findings will inform next steps in the development of therapeutic approaches to minimize neuroinflammation in Long COVID.", "keywords": [ "2019-nCoV", "Adult", "American", "Anxiety", "Area", "Attention", "Biological Markers", "Blood", "Blood - brain barrier anatomy", "Body System", "Brain", "Brain imaging", "Brain-Derived Neurotrophic Factor", "CCL2 gene", "CD14 gene", "COVID-19", "COVID-19 patient", "CX3CL1 gene", "CXCL10 gene", "CXCR3 gene", "Cell Surface Proteins", "Cells", "Central Nervous System", "Chronic", "Chronic Disease", "Chronic Fatigue Syndrome", "Cognition", "Cognitive", "Cohort Studies", "Complex", "Control Groups", "Depressed mood", "Disabling condition", "Disease", "Endothelium", "Exertion", "Exhibits", "FCGR3B gene", "Fatigue", "Fractalkine", "Funding", "IL18 gene", "Illness impact", "Image", "Imaging Techniques", "Immune", "Immunophenotyping", "Impaired cognition", "Individual", "Infection", "Infiltration", "Inflammation", "Inflammatory", "Infrastructure", "Interleukin-6", "Link", "Long COVID", "Magnetic Resonance Imaging", "Malaise", "Measures", "Memory", "Mental Health", "Moods", "Neurocognitive", "Neurocognitive Deficit", "Neurons", "Participant", "Pathway interactions", "Patients", "Peripheral Blood Mononuclear Cell", "Phase", "Reporting", "Residual state", "Role", "Severe Acute Respiratory Syndrome", "Surface", "Symptoms", "TNF gene", "Techniques", "Therapeutic", "Therapeutic Intervention", "United States National Institutes of Health", "Vascular Endothelial Growth Factors", "Virus Diseases", "Water", "acute COVID-19", "acute infection", "arterial spin labeling", "blood-brain barrier disruption", "blood-brain barrier permeabilization", "brain fog", "cell motility", "chemokine", "chronic condition", "cognitive disability", "cognitive function", "cohort", "cytokine", "depressive symptoms", "experience", "functional restoration", "glymphatic dysfunction", "innovation", "migration", "mild cognitive impairment", "monocyte", "neuroAIDS", "neuroinflammation", "neuropsychiatry", "novel", "perceived stress", "post-pandemic", "pre-pandemic", "response", "rumination", "small molecule", "therapeutic development", "trafficking" ], "approved": true } }, { "type": "Grant", "id": "15944", "attributes": { "award_id": "1R01AI195454-01", "title": "Hijacking the neonatal Fc receptor: the novel biology of arterivirus entry, transmission, and persistence", "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": 44307, "first_name": "RODOLFO M", "last_name": "ALARCON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-04-03", "end_date": "2031-03-31", "award_amount": 615446, "principal_investigator": { "id": 31459, "first_name": "Adam Lee", "last_name": "Bailey", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3403, "ror": "", "name": "UNIVERSITY OF WISCONSIN-MADISON", "address": "", "city": "", "state": "WI", "zip": "", "country": "United States", "approved": true }, "abstract": "Understanding novel mechanisms by which animal viruses enter cells, evade immunity, and cause disease has scientific and public health importance. Arteriviruses are an understudied family of RNA viruses (related to coronaviruses) that infect a wide variety of mammals. The host and viral factors that determine arterivirus disease, persistence, and cross-species transmission remain unknown and unpredictable. This lack of understanding has implications for predicting/thwarting arterivirus emergence in humans, as some arteriviruses have been shown to infect human cells. Macrophages are exclusively infected by most arteriviruses, but the subpopulation(s) of macrophages that support arterivirus replication remain poorly defined. The process by which arteriviruses enter cells is highly novel and also poorly understood. Each virion displays an unusually large set of surface glycoproteins (7-11 depending on the virus) that are unlike any known viral fusion machinery. The macrophage-specific molecule CD163 is a required arterivirus receptor, yet CD163 by itself is insufficient to mediate arterivirus entry. We recently identified the neonatal Fc receptor (FcRn) as an important entry factor that arteriviruses use together with CD163 to gain entry into cells. Aim 1 of this project builds upon this discovery to define the molecular details of the arterivirus:FcRn interaction. In Aim 1a, we will map the site(s) on FcRn that are critical for arterivirus engagement by creating chimeric FcRn molecules that incorporate features of arterivirus-permissive and -resistant FcRn orthologs, with the goal of defining the domains, motifs, and residues involved in arterivirus/FcRn interactions. In Aim 1b, we will generate chimeric arteriviruses that contain combinations of glycoproteins from different arteriviruses, seeking to define the viral glycoproteins, domains, motifs, and residues involved in FcRn engagement. In Aim 1c, we will continue to develop our understanding of the host factors required for arterivirus entry by performing screens to identify additional host factors that are functionally redundant with FcRn for the viral entry process. In Aim 2, we will use the murine arterivirus (lactate dehydrogenase-elevating virus, LDV), which causes life-long viremia in adult mice, to understand several aspects of arterivirus infection in vivo. In Aim 2a, we will use a nanoluciferase-expressing LDV to perform body-wide imaging and identify the tissues that support LDV infection over time. In Aim 2b, we will hone in key tissues and identify the macrophage populations within these tissues that support LDV infection and determine how persistent arterivirus infection impacts recovery of target cell populations. Finally, in Aim 2c we will use FcRn-knockout mice to determine whether arteriviruses hijack FcRn’s physiologic role in placental biology, potentially explaining the high efficiency with which arteriviruses transmit vertically. This project will provide insights into novel mechanisms of viral entry, macrophage infection and dysfunction, viral persistence, and vertical transmission through the study of the neglected “pre-emergent” family of mammalian viruses, the arteriviruses.", "keywords": [ "Acute", "Acute Disease", "Adult", "Anatomy", "Animals", "Arterivirus", "Arterivirus Infections", "Biology", "Cell Culture Techniques", "Cell Line", "Cell Surface Receptors", "Cells", "Clustered Regularly Interspaced Short Palindromic Repeats", "Complex", "Coronavirus", "Development", "Disease", "Distant", "Family", "Family suidae", "Farm", "Fc Receptor", "Fetus", "Functional disorder", "Glycoproteins", "Goals", "Human", "Image", "Immune system", "Immunity", "Immunoglobulin G", "Industry", "Infection", "Integration Host Factors", "Knock-out", "Knockout Mice", "Knowledge", "Laboratories", "Lactate dehydrogenase-elevating virus", "Life Cycle Stages", "Link", "Macrophage", "Mammals", "Maps", "Mediating", "Membrane Glycoproteins", "Modeling", "Molecular", "Mus", "Orthologous Gene", "Phase", "Physiological", "Placenta", "Placental Biology", "Pneumonia", "Population", "Positioning Attribute", "Predisposition", "Primates", "Process", "Public Health", "RNA Viruses", "Recovery", "Reporter", "Research", "Resistance", "Retinal blind spot", "Role", "Site", "Structure", "Surface", "Syncytiotrophoblast", "System", "Time", "Tissues", "Tropism", "Vertical Transmission", "Viral", "Viral Hemorrhagic Fevers", "Viremia", "Virion", "Virus", "Virus Receptors", "Virus Replication", "Whole Organism", "cell immortalization", "chronic infection", "cross-species transmission", "economic impact", "fetal", "genome-wide", "in utero", "in vivo", "insight", "medical countermeasure", "model organism", "nanoluciferase", "neglect", "neonatal Fc receptor", "novel", "permissiveness", "pregnant", "receptor", "reverse genetics", "time use", "transmission process" ], "approved": true } } ], "meta": { "pagination": { "page": 5, "pages": 1442, "count": 14420 } } }