Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=3&sort=-awardee_organization
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-awardee_organization", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1442&sort=-awardee_organization", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=4&sort=-awardee_organization", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=2&sort=-awardee_organization" }, "data": [ { "type": "Grant", "id": "16136", "attributes": { "award_id": "1R15GM164973-01", "title": "Decoding the Sulfation Code: Selectively Sulfated Glycomacromolecules as Tools to Investigate Viral Protein-Carbohydrate Recognition", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 22244, "first_name": "MICHAEL", "last_name": "SAKALIAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-15", "end_date": "2029-04-30", "award_amount": 487727, "principal_investigator": { "id": 44620, "first_name": "Nicole Leigh", "last_name": "Snyder-Lee", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3525, "ror": "", "name": "DAVIDSON COLLEGE", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "Heparan sulfate proteoglycans (HSPGs) are a complex group of glycosylaminoglycans (GAGs) that are involved in several important biological processes including embryonic development, inflammation, angiogenesis, neurodegeneration, cardiovascular disorders, cancer. HSPGs have also been shown to play various roles in the infection of a number of viruses including HSV-1 and HSV-2, Human Papilloma Viruses (HPV), Human Immunodeficiency Virus (HIV), Dengue viruses (DENV), Hepatitis B Viruses (HBV), Hepatitis C Virus (HCV), Hepatitis E Virus, (HEV), Merkel Cell Polyomavirus (MCPyV), Rabies Virus (RABV), Respiratory Syncytial Virus (RSV), coronaviruses such as SARS-CoV-2 and HCoV-NL63, and Human Cytomegalovirus (HCMV). The important role of HSPGs in the viral life cycle has prompted numerous investigations into the use of HS and structural analogues of HS as potential compounds to study HSPG-viral engagement often with the goal of developing a better understanding of sulfation code. In most cases, these structures have been derived from natural sources or prepared synthetically. However, there remain several limitations to their use. First, structures generated from native HSPGs are often heterogeneous, making it difficult to perform the types of structure- function analyses that might unlock the sulfation code. Synthetic and semisynthetic glycans with precise sulfation patterns can be used to overcome this limitation, but they are difficult to prepare. Synthetic sulfated glycomacromolecules (oligomers and polymers) designed to serve as tools to mimic heparan sulfate have helped to overcome some of these limitations, particularly in their relative ease of synthesis. However, it is often difficult to replicate the unique sulfation patterning observed in HS. To address these shortcomings, our team will develop a library of glycomacromolecules (oligomers and polymers) bearing selectively sulfated sugars to more rapidly explore how factors such as carbohydrate content, sulfation patterns, sulfation density, and presentation (flexibility/rigidity) influence viral recognition. We also propose performing an initial assessment of the ability of our library of compounds to engage viral surface proteins of three model respiratory viruses: HPV16, SARS- CoV-2 and IAV. Finally, this proposal will provide exceptional research experiences for multiple undergraduates, fostering the training of the next generation of glycoscientists.", "keywords": [ "2019-nCoV", "Address", "Amines", "Anabolism", "Anti-viral Agents", "Binding", "Biochemistry", "Biological Assay", "Biological Process", "Carbohydrates", "Cardiovascular Diseases", "Cell surface", "Code", "Complex", "Core Protein", "Coronavirus", "Cytomegalovirus", "Deacetylation", "Dengue Virus", "Development", "Embryonic Development", "Enzyme-Linked Immunosorbent Assay", "Fostering", "Funding", "Glucosamine", "Glucuronic Acids", "Glycosaminoglycans", "Goals", "HIV", "Heparan Sulfate Proteoglycan", "Heparitin Sulfate", "Hepatitis B Virus", "Hepatitis C virus", "Hepatitis E virus", "Herpesvirus 1", "Human", "Human Herpesvirus 2", "Human Papillomavirus", "Human papillomavirus 16", "Iduronic Acid", "Infection", "Inflammation", "Investigation", "Libraries", "Life Cycle Stages", "Malignant Neoplasms", "Membrane Proteins", "Merkel Cells", "Modeling", "Modification", "Molecular", "Morphology", "Natural Source", "Nature", "Nerve Degeneration", "Pattern", "Play", "Polymers", "Polyomavirus", "Polysaccharides", "Process", "Proteins", "Rabies virus", "Research", "Research Personnel", "Respiratory syncytial virus", "Role", "Series", "Sialic Acids", "Signal Transduction", "Structure", "Sulfate", "Surface", "Techniques", "Training", "United States National Institutes of Health", "Viral", "Viral Proteins", "Virion", "Virus", "Virus Receptors", "Work", "analog", "angiogenesis", "density", "design", "epimerization", "experience", "flexibility", "human coronavirus", "innovation", "insight", "interest", "next generation", "novel", "receptor", "respiratory virus", "scaffold", "sugar", "tool", "undergraduate student" ], "approved": true } }, { "type": "Grant", "id": "16133", "attributes": { "award_id": "1F32AI191726-01A1", "title": "Subversion of intercellular coupling during respiratory virus 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": 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": "2026-05-25", "end_date": "2028-05-24", "award_amount": 76780, "principal_investigator": { "id": 44615, "first_name": "Chelsea 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": 3524, "ror": "", "name": "VIRGINIA POLYTECHNIC INST AND ST UNIV", "address": "", "city": "", "state": "VA", "zip": "", "country": "United States", "approved": true }, "abstract": "Coronavirus infections comprise 15 – 30% of common colds, with four human coronaviruses circulating seasonally. While respiratory and gastrointestinal symptoms are usually self-limiting, increased disease severity, such as bronchitis and pneumonia, can occur. This increased coronavirus disease severity is also highlighted by the most recent coronavirus outbreak, emphasizing the importance of understanding mechanisms of coronaviral replication and propagation. Interestingly, coronaviruses have been reported to disrupt intercellular coupling, suggesting a conserved mechanism used to promote coronaviral replication and propagation. This is unsurprising, as mechanical and metabolic coupling contribute to the cell-intrinsic antiviral immune response. Epithelial barriers established in part by tight junctions prevent viral access to receptors required for cell entry and the underlying tissue. Meanwhile, gap junction intercellular communication facilitates the spread of immune signaling molecules to prime the cell-intrinsic innate antiviral response in neighboring cells. Despite these antiviral roles of junctional complexes, how coronaviruses target and perturb host junctional complexes to facilitate viral infection and spread remains unknown. My proposed research will address this gap in knowledge through investigating coronaviral-mediated manipulation of epithelial cell mechanical and metabolic coupling and the mechanism through which this occurs. Aim 1: Determine mechanisms of coronaviral-mediated alterations to epithelial cell mechanical coupling. Organization of tight junction complexes following coronaviral infection will be assessed, along with the sufficiency of individual viral proteins to induce pathological remodeling of tight junction complexes and the mechanism through which tight junction remodeling occurs. Aim 2: Delineate the mechanism through which coronaviruses perturb epithelial cell metabolic coupling. Signaling pathways driving decreased gap junction function during coronavirus infection will be identified, and the sufficiency of coronaviral proteins to impair metabolic coupling will be determined. The effect of gap junction intercellular communication on coronaviral spread and disease severity will also be assessed. Completion of this project will reveal mechanisms of how coronavirus infection affects both mechanical and metabolic intercellular coupling. Ultimately, this work will broaden our understanding of coronavirus pathogenesis, identifying molecular substrates for novel anti-coronaviral therapeutics. Specifically, targeting coronavirus-mediated mechanisms of cell junction perturbation may serve as a viable future direction for antivirals to decrease recovery time by limiting viral spread while preserving host antiviral immune responses.", "keywords": [ "Affect", "Anti-viral Agents", "Anti-viral Response", "Bronchitis", "COVID-19 outbreak", "COVID-19 severity", "Cells", "Common Cold", "Complex", "Connexin 43", "Connexins", "Coronavirus", "Coronavirus Infections", "Coupling", "Data", "Disease", "Disease Outbreaks", "Electrical Resistance", "Epithelial Cells", "Epithelium", "Future", "Gap Junctions", "Goals", "Immune response", "Immune signaling", "Impairment", "In Vitro", "Individual", "Infection", "Intercellular Junctions", "Knowledge", "Mechanics", "Mediating", "Metabolic", "Modeling", "Molecular", "Mus", "Mutation", "Pathogenesis", "Pathologic", "Patients", "Pneumonia", "Post-Translational Protein Processing", "Proteins", "Public Health", "Recovery", "Regulation", "Reporting", "Research", "Respiratory Signs and Symptoms", "Role", "SARS-CoV-2 infection", "Scaffolding Protein", "Seasons", "Serine", "Severity of illness", "Signal Pathway", "Signal Transduction", "Signaling Molecule", "Testing", "Therapeutic", "Tight Junctions", "Time", "Tissues", "Viral", "Viral Proteins", "Virus", "Virus Diseases", "Virus Replication", "Work", "coronavirus outbreak", "gastrointestinal symptom", "human coronavirus", "in vitro Model", "in vivo", "intercellular communication", "live cell imaging", "monolayer", "new therapeutic target", "novel", "pandemic disease", "preservation", "prevent", "protein expression", "receptor", "respiratory infection virus", "superresolution microscopy", "zonula occludens-1 protein" ], "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": "16130", "attributes": { "award_id": "1R01NS148641-01", "title": "Mechanistic Investigation of Chronic Neuropathologic Interaction Between Viral Infection and Progression of Lewy Pathology and Dementia", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Neurological Disorders and Stroke (NINDS)" ], "program_reference_codes": [], "program_officials": [ { "id": 32579, "first_name": "WILLIAM PATRICK", "last_name": "DALEY", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-13", "end_date": "2030-04-30", "award_amount": 582172, "principal_investigator": { "id": 31851, "first_name": "Xiaohong", "last_name": "Lu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3522, "ror": "", "name": "LOUISIANA STATE UNIV HSC SHREVEPORT", "address": "", "city": "", "state": "LA", "zip": "", "country": "United States", "approved": true }, "abstract": "Neuropathological interactions between COVID-19 and ADRD suggest shared molecular and cellular mechanisms. A recent case series study revealed striking cutaneous Lewy pathology (phosphorylated α- synuclein) in Long-COVID Postural orthostatic tachycardia syndrome (POTS) patients. Animal studies consistently show that viral infection can trigger α-synucleinopathies in hamster and macaque SARS-CoV-2 infection models. SARS-CoV-2 N-and Spike protein can bind to α-Synuclein to induce Lewy pathology in vitro. Recent human single-neuron sequencing findings of accumulation of non-germline inherited somatic mutations associated with neurodegenerative disorders support the pathogenic role of genotoxic stress in age-dependent long-lasting neurologic deficits and cognitive decline. These observations support the role of infection in the pathogenesis of synucleinopathy, a pathological intracellular proteinaceous α-Synuclein (α-Syn) inclusions that are characteristic of neurological disorders, including dementia with Lewy body (DLB), with DLB being the second most common type of dementia after AD. Ours and other studies have begun to reveal the role of genotoxic stress interplaying with autophagy-lysosome function in synucleinopathy. To study the impact of virus infection on synucleinopathy in vivo, we generated a human ACE2 transgenic mouse model with full-length human ACE2 regulatory regions that faithfully recapitulated the structure, tissue distribution, and gene regulation of the human gene. SARS-CoV-2 infection in ABSL-3 facility established the feasibility of our model to study post-acute sequelae of COVID-19 (PASC) and age-dependent progression of neuropathology without viral neuroinvasion and lethal encephalitis, providing distinct advantages over the existing animal models. Compelling vivo data indicates that inhibiting genotoxic stress can effectively lessen inflammation, cell senescence, accumulation of α-Synuclein, autophagy deficits, neuroinflammation, and cognitive and anosmia symptoms in an immunopathology model without viral neural invasion. ATM inhibition only in genotoxic stressed cells via a novel genetic strategy also rescued α-Synuclein aggregates spreading and cognitive deficits, suggesting a causal pathogenic role of genotoxic stress in synucleinopathy and long COVID symptoms. We hypothesize viral infection-driven brain genotoxic stress mediates the pathologic interaction between COVID-19 and DLB via perpetuating DDR/cell senescence, autophagy/lysosome acidification dysfunction, and neuroinflammation that sustains chronic cognitive and neurological deficits. To test the hypothesis, Aims 1 and 2 will determine how viral infection as an etiologic factor can drive chronic olfactory and cognitive deficits, as well as Lewy pathology, with genotoxic stress as a prominent feature and key initiating factor. Aim 3 will establish the causal role of brain genotoxic stress and pathogenic mechanisms in PASCs, Lewy pathology, and dementia. The findings will transform the current paradigm of the viral origin of neurodegeneration and advance the therapeutic targeting of genotoxic stress for PASCs, Lewy pathology, and dementia.", "keywords": [ "2019-nCoV", "ACE2", "Acceleration", "Address", "Alzheimer's disease related dementia", "Animal Model", "Animals", "Anosmia", "Autophagocytosis", "Binding", "Braak's hypothesis", "Brain", "COVID-19", "COVID-19 pandemic", "COVID-19 sequelae", "COVID-19 susceptibility", "Case Series", "Cell Aging", "Cells", "Cellular Stress", "Cessation of life", "Characteristics", "Chronic", "Chronic Fatigue Syndrome", "Cognitive", "Cognitive Manifestations", "Cognitive deficits", "Cutaneous", "DNA Damage", "DNA Repair", "Data", "Dementia", "Dementia with Lewy Bodies", "Development", "Disease Progression", "Dissection", "Drug or chemical Tissue Distribution", "Encephalitis", "Epigenetic Process", "Etiology", "Functional disorder", "Gene Expression Regulation", "Genes", "Genetic", "Genetic Techniques", "Genotoxic Stress", "Hamsters", "Hospitalization", "Human", "Huntington Disease", "Impaired cognition", "Impairment", "In Vitro", "Individual", "Infection", "Inflammation", "Inherited", "Intervention", "Invaded", "Investigation", "Length", "Lewy body pathology", "Long COVID", "Longitudinal", "Lysosomes", "Macaca", "Mediating", "Modeling", "Molecular", "Mus", "Nerve Degeneration", "Nervous System Disorder", "Neurodegenerative Disorders", "Neurologic", "Neurologic Deficit", "Neurologic Symptoms", "Neuronal Dysfunction", "Neurons", "Nucleic Acid Regulatory Sequences", "Olfactory dysfunction", "Pathogenesis", "Pathogenicity", "Pathologic", "Pathology", "Patients", "Peptide Initiation Factors", "Persian Gulf Syndrome", "Pharmacology", "Phenotype", "Phosphorylation", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Postural Orthostatic Tachycardia Syndrome", "Proteins", "Reporter", "Research", "Resolution", "Risk", "Role", "SARS-CoV-2 infection", "Severities", "Somatic Mutation", "Structure", "Symptoms", "Telomere Shortening", "Testing", "Transgenic Mice", "Viral", "Viral Pathogenesis", "Viral reservoir", "Virus", "Virus Diseases", "age acceleration", "age related", "aging brain", "alpha synuclein", "cell injury", "chemobrain", "chronic condition", "clinically relevant", "experience", "genetic approach", "immunopathology", "in vivo", "innovation", "insight", "life span", "mouse model", "neural", "neuroinflammation", "neuropathology", "novel", "older adult", "older patient", "olfactory bulb", "postmitotic", "pre-formed fibril", "response", "senescence", "sensor", "spatiotemporal", "symptomatology", "synuclein" ], "approved": true } }, { "type": "Grant", "id": "16129", "attributes": { "award_id": "1R35GM162331-01", "title": "Advancing Low-Cost Synthetic Biosensor Arrays for Rapid Multiplex Biomarker Detection", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 44611, "first_name": "CAROLINA", "last_name": "SALVADOR MORALES", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-01", "end_date": "2031-02-28", "award_amount": 383801, "principal_investigator": { "id": 44612, "first_name": "Yixin", "last_name": "Liu", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3521, "ror": "", "name": "MICHIGAN TECHNOLOGICAL UNIVERSITY", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "The complexity and heterogeneity of diseases such as sepsis and allergy arise from diverse pathophysiological mechanisms and variable patient responses to treatment. Traditional diagnostic approaches relying on clinical phenotypes fail to capture the underlying molecular variability, leading to ineffective therapies and high healthcare costs. Host response-based diagnostics, driven by endotype classification, offer a promising solution by enabling disease stratification and personalized treatment through biomarker-based profiling. However, current biosensing platforms lack the scalability, affordability, and multiplexing capacity necessary for widespread clinical implementation. This research program aims to revolutionize biomarker-based diagnostics by developing a cost-effective, scalable, and multiplexed biosensing platform based on Molecularly Imprinted Polymers (MIPs). MIPs, synthetic receptors mimicking antibody recognition, offer superior stability and lower production costs compared to conventional immunosensors. The PI's lab has already demonstrated MIP-based electrochemical sensors for small molecules and protein targets, including SARS-CoV-2 spike protein and stress biomarkers. Building on this foundation, the next five years will focus on three key objectives: 1) Establishing an adaptable imprinting platform for the rapid synthesis of MIP-based biosensors tailored to amino acids, peptides, and proteins, inspired by nature’s antibody generation system. This approach will integrate computational modeling, machine learning, and experimental validation to predict and optimize imprinting efficiency in physiological environments. 2) Advancing multiplexed biosensing technology by integrating novel transduction mechanisms with scalability, such as redox- integrated MIP sensors and extended-gate field-effect transistors (EG-FETs)-based MIP sensors, coupled with machine learning-driven signal deconvolution for multiplex biomarker detection. 3) Developing a seamless sample-to-answer platform incorporating electrospun nanofiber-based whole blood separation and passive fluidic delivery to facilitate biomarker detection directly from complex biological samples without extensive preprocessing. Our research will initially focus on two key applications: (1) an amino acid biosensor array targeting branched-chain and aromatic amino acids, which are biomarkers for metabolic and neurological disorders; and (2) a multiplexed biosensor for sepsis biomarkers, integrating cytokines, acute-phase proteins, and metabolic indicators for early diagnosis and patient stratification. By integrating expertise in materials science, computational chemistry, electronics, and machine learning, our program will establish a next-generation biosensing framework that is cost-effective, scalable, and adaptable to diverse disease applications. The proposed work will bridge fundamental molecular recognition with real-world clinical translation, accelerating biomarker-based diagnostics, improving patient outcomes, and advancing precision medicine.", "keywords": [ "Acceleration", "Acute-Phase Proteins", "Allergy", "Amino Acids", "Antibodies", "Aromatic Amino Acids", "Biological", "Biological Markers", "Biosensing Techniques", "Biosensor", "Classification", "Complex", "Computer Models", "Coupled", "Detection", "Diagnostic", "Disease", "Disease stratification", "E-learning", "Early Diagnosis", "Enhancement Technology", "Environment", "Foundations", "Generations", "Health Care Costs", "Immune response", "Intervention", "Machine Learning", "Metabolic", "Metabolic Diseases", "Molecular", "Nature", "Nervous System Disorder", "Oxidation-Reduction", "Patient-Focused Outcomes", "Peptides", "Physiological", "Polymers", "Production", "Proteins", "Research", "SARS-CoV-2 spike protein", "Sampling", "Sepsis", "Signal Transduction", "Stress", "System", "Technology", "Transistors", "Validation", "Whole Blood", "Work", "biomarker panel", "clinical implementation", "clinical phenotype", "clinical translation", "computational chemistry", "cost", "cost comparison", "cost effective", "cytokine", "diagnostic platform", "diagnostic strategy", "disease heterogeneity", "imprint", "improved", "ineffective therapies", "materials science", "molecular recognition", "nanofiber", "next generation", "novel", "patient stratification", "patient variability", "personalized diagnostics", "personalized medicine", "precision medicine", "programs", "receptor", "sensor", "small molecule", "treatment response", "treatment strategy" ], "approved": true } }, { "type": "Grant", "id": "16126", "attributes": { "award_id": "1R01AI199482-01", "title": "Maternal Respiratory Infection Shapes Fetal Lung Epithelial Immune Memory: Implications for Postnatal Inflammatory Lung 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": 44292, "first_name": "MERCY R", "last_name": "PRABHUDAS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-11", "end_date": "2031-04-30", "award_amount": 822060, "principal_investigator": { "id": 11021, "first_name": "Hongpeng", "last_name": "Jia", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 344, "ror": "https://ror.org/00za53h95", "name": "Johns Hopkins University", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 44607, "first_name": "Xi", "last_name": "Ren", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 3520, "ror": "", "name": "JOHNS HOPKINS UNIVERSITY", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Maternal immune activation (MIA) during pregnancy, particularly from viral infections like SARS-CoV-2 (SCV2), poses significant risks to fetal development, resulting in long-term immune dysfunction in offspring. Our findings suggest that maternal SCV2 infection predisposes offspring to chronic inflammatory lung diseases, such as asthma, through the formation of prenatal lung epithelial immune memory linked to epigenetic modifications in key inflammatory genes like IL-33. This project aims to define the mechanisms by which prenatal lung epithelial immune memory is established and contributes to chronic inflammatory lung diseases. We hypothesize that maternal SCV2 infection disrupts the SDF-1/CXCR4 axis in fetal lung mesenchyme via maternal IL-6, leading to epigenetic changes in fetal epithelial cells, including increased chromatin accessibility at inflammatory genes such as IL-33. To test this, we will (1) investigate how the timing of maternal SCV2 infection impacts immune memory formation, (2) examine mesenchymal-epithelial cell interactions in immune memory formation, and (3) explore signaling pathways that mediate SDF-1/CXCR4-driven epigenetic changes. The results of this research will uncover novel mechanisms of non-immune cell immune memory and provide insights for developing preventive strategies for chronic inflammatory lung diseases in offspring exposed to maternal viral infections.", "keywords": [ "2019-nCoV", "Acute Respiratory Distress Syndrome", "Asthma", "CXCR4 Receptors", "CXCR4 gene", "Caring", "Cell Communication", "Cell Maturation", "Cells", "Characteristics", "Chromatin", "Cohort Studies", "Complex", "DNA Methylation", "Data", "Development", "Epigenetic Process", "Epithelial Cells", "Epithelium", "Exhibits", "Exposure to", "Fetal Development", "Fetal Lung", "Foundations", "Future Generations", "Genes", "Goals", "Human", "Immune System Diseases", "Immunologic Memory", "Inflammation", "Inflammatory", "Inflammatory Response", "Interleukin-6", "Link", "Lung", "Mediating", "Memory", "Mesenchymal", "Mesenchyme", "Modification", "Molecular", "Molecular Target", "Mothers", "Play", "Pregnancy", "Prevention strategy", "Preventive", "Production", "Regulation", "Research", "Respiratory Tract Infections", "Risk", "Role", "SARS-CoV-2 infection", "Shapes", "Signal Pathway", "Signal Transduction", "Stimulus", "Testing", "Therapeutic", "Virus Diseases", "chronic inflammatory lung disease", "cytokine", "epithelial stem cell", "fetal", "histone modification", "immune activation", "inflammatory lung disease", "insight", "lung development", "mouse model", "neonate", "novel", "offspring", "postnatal", "prenatal", "prevent", "public health intervention", "pulmonary", "respiratory", "response", "stem cell function", "viral transmission" ], "approved": true } }, { "type": "Grant", "id": "16125", "attributes": { "award_id": "1R21CA301202-01A1", "title": "Innate & Adaptive Determinants of Post-CAR Cytokine Release Syndrome", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Cancer Institute (NCI)" ], "program_reference_codes": [], "program_officials": [ { "id": 44605, "first_name": "YIN", "last_name": "LIU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-01", "end_date": "2028-04-30", "award_amount": 452540, "principal_investigator": { "id": 44606, "first_name": "KATHARINE C", "last_name": "HSU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3519, "ror": "", "name": "SLOAN-KETTERING INST CAN RESEARCH", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Advances in cell therapies have drastically changed treatment algorithms for hematologic malignancies, broadening curative approaches from the previously singular option of allogeneic hematopoietic cell transplantation to now include the highly effective chimeric antigen receptor (CAR) T cell therapies. Despite the promise of CAR T cell therapies, which harness the patient’s own T cell compartment upon the direction of a transduced antigen-specific receptor, they are still accompanied by significant morbidity. Referred to as “cytokine release syndrome” (CRS) due to rapid increases in multiple cytokines, including IL-6, IFN-γ, IL-2, and TNF, the disordered inflammatory response accompanying CAR T-cell therapies manifests clinically as fever, hypotension, hypoxia, and dyspnea. Overall occurrence of CRS is 93% following CAR T-cell administration (23% severe, with potential for fatal outcome), resulting in use of costly antibody therapeutics and intensive monitoring and translating to a financial burden on the healthcare system. Despite its frequency, CRS lacks a widely accepted definition, a clear molecular mechanism, and reliable markers predictive of its occurrence. Most critically, it is known that the CAR itself is not sufficient to elicit CRS. Our central hypothesis is that the origins of CRS are both effector cell- and environment-intrinsic: critical differences between the CAR effector lymphocytes are what elicit CRS from myeloid cells that have become susceptible in certain patients and that absence of either the stimulus or the response mitigates the initiation and propagation of CRS. Natural killer (NK) cells endowed with the same CAR as T cells do not elicit CRS, despite being capable of achieving complete tumor remission. This crucial difference between the two effector lymphocytes is further highlighted by our own findings that NK-like T cells (TKLR), a lymphocyte population demonstrating features of each, also fail to cause CRS in a mouse model for CAR therapy despite robust anti-tumor efficacy. The overlapping spectrum of these three populations with different CRS outcomes permits a more focused dissection in Aim 1 of the features initiating, propagating or suppressing CRS, including differences in response kinetics. Using in vitro models, we will test combinations of cellular components for their ability to elicit cytokine production and transcriptional changes leading to CRS. CRS-associated cytokine and molecular candidates will then be validated in a murine xenograft CRS model. In addition, the toxicity profile of CAR T cell therapy ranges from no CRS to severe CRS, even when treating the same disease with the same CAR T product. Thus, patient-specific factors, particularly the myeloid cell population critical for the pathological feedback loop of CRS, will be analyzed. In Aim 2, we will identify the pre-treatment risk signatures (phenotypic functional, and transcriptional) in the myeloid cell population in matched CAR T recipients who did and did not develop CRS. This comprehensive profiling will reveal novel points of intervention and prevention for CRS and ultimately lead CAR therapies to greater safety.", "keywords": [ "Allogenic", "Antigens", "Binding", "Breathing", "CAR T cell therapy", "Cell Communication", "Cell Compartmentation", "Cell Lineage", "Cell Therapy", "Cells", "Clinical", "Development", "Disease", "Disease remission", "Dissection", "Dyspnea", "Effector Cell", "Endowment", "Environment", "Event", "Evolution", "Fatal Outcome", "Feedback", "Fever", "Financial Hardship", "Frequencies", "Gene Expression Profile", "Genetic Transcription", "Health Care Systems", "Hematologic Neoplasms", "Hematopoietic Neoplasms", "Hematopoietic Stem Cell Transplantation", "Hour", "Hypotension", "Hypoxia", "Immune system", "In Vitro", "Individual", "Inflammatory", "Inflammatory Response", "Interferon Type II", "Interleukin-2", "Interleukin-6", "Intervention", "Kinetics", "Lead", "Lymphocyte", "Macrophage", "Malignant Neoplasms", "Mediating", "Medical", "Modeling", "Molecular", "Monitor", "Morbidity", "Mus", "Myelogenous", "Myeloid Cells", "Natural Killer Cells", "Outcome", "Pathologic", "Patients", "Phenotype", "Population", "Predisposition", "Prevention", "Production", "Proteomics", "Risk", "Role", "Safety", "Sampling", "Stimulus", "Syndrome", "T-Lymphocyte", "TNF gene", "Testing", "Therapeutic antibodies", "Toxic effect", "Translating", "Xenograft procedure", "chimeric antigen receptor", "chimeric antigen receptor T cells", "chimeric antigen receptor natural killer cells", "cost", "cytokine", "cytokine release syndrome", "cytotoxic", "design", "experience", "humanized mouse", "in vitro Model", "in vivo", "insight", "monocyte", "mouse model", "neoplastic cell", "novel", "predictive marker", "receptor", "response", "sample archive", "side effect", "transcriptomic profiling", "transcriptomics", "treatment algorithm", "treatment risk", "tumor" ], "approved": true } }, { "type": "Grant", "id": "16122", "attributes": { "award_id": "1R01AI192916-01A1", "title": "Shark nanobodies identify pan-coronavirus spike sites of vulnerability fortherapeutic intervention", "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": "2026-05-06", "end_date": "2031-04-30", "award_amount": 896045, "principal_investigator": { "id": 27043, "first_name": "Helen M.", "last_name": "Dooley", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [] }, "other_investigators": [ { "id": 27044, "first_name": "Michael Gordon", "last_name": "Joyce", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 3518, "ror": "", "name": "UNIVERSITY OF MARYLAND BALTIMORE", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Coronaviruses (CoVs) cause significant disease in humans and have the propensity to shift between zoonotic reservoirs and into human populations, making them a continual global health threat. To date, seven different strains of CoVs have been found to infect humans, of which SARS-CoV-1, SARS-CoV-2, and MERS-CoV (all betacoronaviruses) have previously caused pandemics and still pose severe threats to global health. Worldwide efforts during the COVID-19 pandemic (caused by SARS-CoV-2) led to the rapid development of vaccines and monoclonal antibody therapies (mAbs) that showed great effectiveness in reducing disease severity and preventing death in vulnerable populations. However, viral variants of concern (VOC) have continued to emerge, many of which have escaped the previously approved mAbs, while the pandemic potential of new coronavirus spillover events remains high. Thus, the overall aim of this project is the development of broadly-protective immunotherapeutic molecules that can be easily deployed should a CoV spillover of pandemic potential occur. To achieve this, we will interrogate VNAR nanobody repertoires derived from nurse sharks that have received sequential immunizations with heterologous CoV SpFNs, i.e., primed with SARS-CoV-2 SpFN, then recalled with SARS-CoV-1 SpFN, MERS-CoV, or 229E SpFN immunogens, to identify broadly conserved, neutralizing epitopes. Isolated nanobodies will be produced in recombinant form and evaluated for function and specificity using binding, affinity, and competition mapping assays, followed by pseudovirus and live-viral neutralization, and in vivo protection studies with animal models that mimic high-risk human populations. Based upon our preliminary studies we anticipate that we will find VNAR nanobodies that can target (i) pan-sarbecovirus epitopes, (ii) pan-merbecovirus epitopes, and (iii) pan-alphacoronavirus epitopes. Using X-ray crystallography and Cryo-EM imaging we will determine the binding epitope of each VNAR. This atomic-level information will allow a complete understanding of the molecular recognition of antibody specificity and cross-reactivity, as exposed by the unique recognition capabilities of shark VNARs. Using a structure-guided approach the most potent nanobodies will be combined to create multi-valent molecules with prophylactic and therapeutic activity. These will be tested in vivo with administration routes expanded to explore intranasal administration for increased efficacy and ease-of-use in future situations of pandemic potential.", "keywords": [ "2019-nCoV", "Affinity", "Animal Model", "Animals", "Antibodies", "Antibody Specificity", "Antigen-Antibody Complex", "Antigens", "Binding", "Biological Assay", "COVID-19 pandemic", "Cessation of life", "Collaborations", "Complex", "Coronavirus", "Cryoelectron Microscopy", "Data", "Development", "Disease", "Effectiveness", "Elderly", "Epitopes", "Ferritin", "Future", "Goals", "Human", "Image", "Immune response", "Immunization", "Immunize", "Immunoglobulin G", "Immunoglobulin M", "Immunology", "Immunotherapeutic agent", "Intervention", "Intranasal Administration", "Lead", "Link", "Maps", "Merbecovirus", "Middle East Respiratory Syndrome Coronavirus", "Modeling", "Monoclonal Antibody Therapy", "Negative Staining", "Nurses", "Obese Mice", "Phage Display", "Population", "Proteins", "Recombinants", "Resistance", "Route", "SARS coronavirus", "SARS-CoV-2 spike protein", "Sarbecovirus", "Scientist", "Severity of illness", "Shark", "Site", "Specificity", "Structure", "Techniques", "Therapeutic", "Transgenic Organisms", "Viral", "Viral Respiratory Tract Infection", "Vulnerable Populations", "X-Ray Crystallography", "Zoonoses", "alphacoronavirus", "betacoronavirus", "coronavirus vaccination", "cross reactivity", "design", "diabetic", "experience", "global health", "high risk", "high-resolution", "immunogen", "improved", "in vivo", "in vivo evaluation", "innovation", "molecular recognition", "mouse model", "nanobodies", "nanoparticle", "novel", "novel coronavirus", "pandemic disease", "pandemic potential", "prevent", "prophylactic", "spillover event", "structural biology", "vaccine development", "vaccine-induced antibodies", "variants of concern" ], "approved": true } }, { "type": "Grant", "id": "16121", "attributes": { "award_id": "1R21AI194473-01A1", "title": "Multi-scale Computational Analysis of Structure, Dynamics and Function of Protein E from Corona Viruses", "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": "2026-05-19", "end_date": "2028-04-30", "award_amount": 204375, "principal_investigator": { "id": 44600, "first_name": "Qiang", "last_name": "Cui", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3517, "ror": "", "name": "BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Project Summary: To help develop effective strategies to battle and prevent future breakouts of corona viruses, it is essential to understand the functions of their proteins. In this proposal, we focus on the envelope protein (E) from SARS-CoV-2 and MERS-CoV, which is involved in virus assembly and budding, and the ion channel activity associated with the transmembrane domain in the endoplasmic reticulum Golgi intermediate compartment (ERGIC) leads to Ca2+ and H+ imbalance, which in turn induces ER stress, NLRP3 inflamma- some activation and excessive secretion of inflammatory cytokines. These functions make the E protein an attractive drug target. There are, however, major questions regarding the underlying molecular mechanism for channel activation and ion permeation, as well as factors that drive the clustering of E proteins and its connection to the generation of local membrane curvature, which is essential to viral particle formation. We have the following specific aims: Aim 1: Conduct atomistic and hybrid QM/MM simulations to define the con- duction mechanism of an individual pentameric channel formed by protein E; this includes elucidating the roles of calcium/proton binding and transient ion-pairing in regulating channel opening and catalyzing ion(s) perme- ation, respectively, and establishing contribution from key polar and aromatic residues to the regulation of pore hydration and ion exit. Aim 2: Conduct atomistic and coarse-grained simulations to probe the mechanism of protein E clustering and the coupling with membrane curvature. In particular, the simulations will help better define the roles of cholesterol and phosphoinositides, and establish the causal relationship between protein E clustering and membrane curvature generation, including the structural features (! strand vs. ↵ helical) of the C-terminal cytoplasmic domain. The proposed computational studies take advantage of our recent methodol- ogy advances and expertise established in related studies, and predictions that emerge from the computational analyses will be readily tested experimentally through collaboration with the Hong group. The mechanistic in- sights and computational strategies established in this work are potentially applicable to the analysis of other envelope proteins in viruses.", "keywords": [ "2019-nCoV", "Anti-viral Agents", "Binding", "C-terminal", "Calcium", "Cations", "Cholesterol", "Collaborations", "Computer Analysis", "Coronavirus", "Coupling", "Cytoplasmic Tail", "Defective Viruses", "Drug Design", "Drug Targeting", "E protein", "Endoplasmic Reticulum", "Future", "Generations", "Genes", "Golgi Apparatus", "Grain", "HIV-1", "Hybrids", "Hydration status", "Hydrophobicity", "Individual", "Infection", "Inflammasome", "Inflammatory", "Ion Channel", "Ions", "Letters", "Life Cycle Stages", "Lipids", "Mediating", "Membrane", "Membrane Proteins", "Methodology", "Middle East Respiratory Syndrome Coronavirus", "Molecular", "Mutation", "Nature", "Pathogenicity", "Phosphatidylinositols", "Process", "Proteins", "Protons", "Recording of previous events", "Regulation", "Role", "SARS coronavirus", "Structural Models", "Structural Protein", "Structure", "System", "Testing", "Transmembrane Domain", "Uncertainty", "Viral", "Viral Physiology", "Viral Proteins", "Virus", "Virus Assembly", "Work", "computer studies", "cytokine", "design", "endoplasmic reticulum stress", "env Gene Products", "high-resolution", "influenza M2", "inhibitor", "insight", "pandemic disease", "particle", "pathogenic virus", "prevent", "protein E", "protein function", "reduce symptoms", "simulation", "solid state nuclear magnetic resonance", "virus envelope" ], "approved": true } }, { "type": "Grant", "id": "16119", "attributes": { "award_id": "1P20GM162339-01", "title": "Interrogating immune response and coronavirus infection in a migratory bat model", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [], "start_date": "2026-05-15", "end_date": "2031-01-31", "award_amount": 210086, "principal_investigator": { "id": 25386, "first_name": "Daniel", "last_name": "Becker", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3516, "ror": "", "name": "UNIVERSITY OF OKLAHOMA", "address": "", "city": "", "state": "OK", "zip": "", "country": "United States", "approved": true }, "abstract": "Bats harbor many zoonotic viruses, including both genera of coronaviruses (CoVs) pathogenic in humans (α- and β-CoVs). Limited evidence to-date suggests that periods of active infection in bats—and thus opportunities to transmit zoonotic viruses to humans—are driven by stressors that modulate immunological tolerance of infection and facilitate viral replication and shedding. Yet such work has mostly ignored immune mechanisms and remains observational. This project will combine experimental field studies with bioinformatic analyses and mathematical modeling to test migration as a stressor in bats and its impact on CoV infection and shedding. We will focus on Mexican free-tailed bats (Tadarida brasiliensis), a common and widespread migratory bat species in North America for which we and others have detected CoVs similar to HCoV-229E and that is susceptible to SARS-CoV-2. In Aim 1, we will sample T. brasiliensis monthly at our established study site in Oklahoma, capturing energetic stressors of spring migration from Mexico, birth and lactation, and fall migration back to Mexico. In vivo challenge with polyIC, mimicking a natural RNA virus infection, will be used to query the bat antiviral response in the face of these different stressors. Established transcriptomic and proteomic assays will be performed at the OCIE ImmunoModulation Technology Core (IMTC) to quantify shifts in immune gene expression and protein abundance, characterizing both global response as well as the response of select antiviral components such as interferons. In Aim 2, we will characterize CoV infection from oral and rectal swabs using RT-PCR. Working closely with the OCIE Omics Data Science Core (ODSC), we will assess differential abundance of genes and proteins with CoV infection. Further, we will identify candidate gene and protein biomarkers of CoV infection using simple classifiers and robust machine learning algorithms. In Aim 3, we will adapt our previously established susceptible–infected–latent–infected mathematical model to our migratory bat system, integrating key immunological findings from Aims 1 and 2. We will further capitalize on our Motus Wildlife Tracking System infrastructure in Oklahoma and monitor bat migration using lightweight, suture-attached PowerTags. We will use resulting data on bat migration routes to run stochastic simulations of our model, generating predictions about when and where we expect bat CoV prevalence to be greatest. This project will establish an experimental and computational pipeline for studying how stressors affect bat-borne zoonoses and provide a key baseline for future efforts to mitigate virus spillover risks from migratory bats.", "keywords": [ "Acute-Phase Reaction", "Affect", "Anti-viral Response", "Back", "Bioinformatics", "Biological Assay", "Biological Models", "Birth", "Blood Volume", "Blood specimen", "COVID-19 detection", "COVID-19 susceptibility", "Career Mobility", "Centers of Research Excellence", "Chiroptera", "Chronic", "Clinical", "Coronavirus", "Coronavirus Infections", "Coupling", "DNA", "Data", "Data Science Core", "Demography", "Development", "Disease", "Feces", "Funding", "Future", "Gene Expression", "Gene Proteins", "Genes", "Genetic Markers", "Health", "Human", "Immune", "Immune Tolerance", "Immune response", "Immunologic Markers", "Immunologics", "Impairment", "Infection", "Infrastructure", "Innate Immune System", "Interferons", "Laboratories", "Lactation", "Lymphocyte", "Lyssavirus", "Mentors", "Mexican", "Mexico", "Modeling", "Monitor", "Movement", "North America", "Nucleic Acids", "Oklahoma", "Oral", "Pathogenicity", "Physiological", "Pilot Projects", "Poly C", "Poly I-C", "Predisposition", "Prevalence", "Proteins", "Proteomics", "Protocols documentation", "RNA", "RNA Virus Infections", "RNA Viruses", "Radar", "Receiver Operating Characteristics", "Rectum", "Relapse", "Research Personnel", "Reverse Transcriptase Polymerase Chain Reaction", "Risk", "Route", "Running", "Saline", "Saliva", "Sampling", "Seasonal Variations", "Seasons", "Site", "Stress", "Surgical sutures", "Swab", "System", "Tail", "Technology", "Testing", "Tissue-Specific Gene Expression", "United States National Institutes of Health", "Viral", "Virulent", "Virus", "Virus Diseases", "Virus Replication", "Virus Shedding", "Work", "Workplace", "Zoonoses", "alphacoronavirus", "antigen challenge", "antiviral immunity", "bat coronavirus", "bat-borne", "betacoronavirus", "candidate identification", "candidate marker", "computational pipelines", "data integration", "falls", "field study", "graduate student", "human coronavirus", "immunoengineering", "immunoregulation", "in vivo", "innovation", "insight", "light weight", "machine learning algorithm", "mathematical model", "migration", "neutrophil", "novel", "oral infection", "pathogen", "post-doctoral training", "protein biomarkers", "response", "sample collection", "sex", "sex as a biological variable", "simulation", "spatiotemporal", "stressor", "success", "transcriptomics", "transmission process" ], "approved": true } } ], "meta": { "pagination": { "page": 3, "pages": 1442, "count": 14420 } } }