Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=5&sort=-id
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-id", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1442&sort=-id", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=6&sort=-id", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=4&sort=-id" }, "data": [ { "type": "Grant", "id": "16139", "attributes": { "award_id": "4UH3CA290286-03", "title": "Self-Testing for Cervical Cancer in Priority Populations: the STEP-2 Trial", "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": 44621, "first_name": "PAMELA M", "last_name": "MARCUS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-01", "end_date": "2030-04-30", "award_amount": 965502, "principal_investigator": { "id": 31313, "first_name": "Amanda F.", "last_name": "Petrik", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 24997, "first_name": "Jasmin Anita", "last_name": "Tiro", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 31314, "first_name": "RACHEL L.", "last_name": "WINER", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2645, "ror": "", "name": "UNIVERSITY OF WASHINGTON", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "The 29.3 million patients receiving care in US Federally Qualified Health Centers (FQHCs) have much lower cervical cancer screening rates than national averages: Only 53% of eligible patients were up-to-date in 2021 and the COVID-19 pandemic exacerbated these disparities. Self-sampling for human papillomavirus (HPV) is an evidence-based cervical cancer screening method with high potential to reduce screening barriers. Self- sampling kits can be distributed at clinics or mailed to patients' homes. Despite widespread international adoption, HPV self-sampling is nascent in the US. Little data is available to inform implementing this preventive service in low-resource settings such as FQHCs. Our two-phase pilot and pragmatic trial will adapt and evaluate two programs to integrate HPV self-sampling into FQHCs. Our trial accounts for the context, capacity and resources of FQHCs, and leverages FQHC-Medicaid partnerships to promote this preventive care service. Phase 1 will be a milestone-driven planning phase. We will use community-based participatory research and stakeholder input to adapt and pilot-test 2 multilevel interventions in 2 FQHCs for distributing HPV self- sampling kits: in clinics and in clinics plus direct mailing. Phase 2 will be a cluster-randomized pragmatic trial in 42 Oregon and Washington FQHC clinics to evaluate the comparative effectiveness and cost-effectiveness of the interventions. Clinics will be randomized to Usual Care (UC), in-clinic distribution (Clinic Only), or in-clinic plus mailed distribution (Clinic + Mail). For in-clinic distribution, providers will offer self-sampling at in-person or telehealth encounters. The mailed component will be administered by Medicaid health plans. The primary outcome is the proportion of eligible patients (30-64 years, due/overdue for routine screening) who complete screening. Co-primary comparisons are (1) UC vs Clinic Only and (2) Clinic Only vs Clinic + Mail. To minimize bias, each comparison includes distinct but overlapping patient populations. Comparison 1 includes all patients (Medicaid and non-Medicaid) with a clinic encounter during the 12-month study period. Comparison 2 is restricted to Medicaid patients who are enrolled with the clinic, but does not require a clinic encounter during the 12-month study period. Cost-effectiveness will compare the Clinic Only HPV self-sampling intervention relative to UC, and Clinic + Mail relative to Clinic Only. We will use the RE-AIM framework and PRISM to assess provider, clinic and health plan acceptability and evaluate adaptations to the implementation strategies through mixed methods. Our pragmatic trial will be the first in the US to determine the effectiveness and cost- effectiveness of HPV self-sampling for increasing cervical cancer screening in FQHC settings. Results from our comparisons and evaluation of implementation strategies will inform broad-scale implementation of HPV self- sampling across FQHCs and other safety-net clinics in the US to reduce cervical cancer screening disparities.", "keywords": [ "Adherence", "Adopted", "Adoption", "COVID-19 pandemic", "Caring", "Cervical Cancer Screening", "Characteristics", "Clinic", "Clinical", "Cost Analysis", "Data", "Diagnosis", "Disparity", "Effectiveness of Interventions", "Eligibility Determination", "Enrollment", "Federally Qualified Health Center", "France", "Health Care Systems", "Home", "Human Papillomavirus", "Hybrids", "Individual", "Instruction", "International", "Intervention", "Intervention Strategies", "Maintenance", "Malignant neoplasm of cervix uteri", "Medicaid", "Methods", "Oregon", "Patients", "Persons", "Phase", "Population", "Preventive care", "Preventive service", "Protocols documentation", "Provider", "Randomized", "Reach Effectiveness Adoption Implementation and Maintenance", "Recommendation", "Recording of previous events", "Resource-limited setting", "Resources", "Sampling", "Spanish", "Speed", "Testing", "Underinsured", "Uninsured", "Visit", "Vulnerable Populations", "Washington", "arm", "cancer health disparity", "care systems", "clinical practice", "community based participatory research", "comparative effectiveness", "compare effectiveness", "cost effectiveness", "cost-effectiveness evaluation", "design", "effectiveness evaluation", "ethnic minority", "evidence base", "experience", "flexibility", "follow-up", "health care resources", "health care settings", "health plan", "implementation efforts", "implementation evaluation", "implementation strategy", "minority disparity", "participant enrollment", "patient oriented", "patient population", "pilot test", "pilot trial", "pragmatic randomized trial", "pragmatic trial", "primary outcome", "programs", "racial minority", "routine screening", "safety net", "screening", "screening disparities", "self testing", "sociodemographics", "telehealth", "treatment as usual" ], "approved": true } }, { "type": "Grant", "id": "16138", "attributes": { "award_id": "7R01AI164266-05", "title": "AI-based platform for predicting emerging vaccine-escape variants and designing mutation-proof antibodies", "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": "2026-05-01", "end_date": "2027-04-30", "award_amount": 486436, "principal_investigator": { "id": 7733, "first_name": "Guowei", "last_name": "Wei", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 521, "ror": "https://ror.org/05hs6h993", "name": "Michigan State University", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 7734, "first_name": "YONG-HUI", "last_name": "ZHENG", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 3498, "ror": "", "name": "UNIVERSITY OF GEORGIA", "address": "", "city": "", "state": "GA", "zip": "", "country": "United States", "approved": true }, "abstract": "Due to massive vaccination, coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been partially under control. However, emerging contagious variants such as Delta are still fueling new waves of infections around the world. Vaccine-escape (or vaccine-breakthrough) variants pose renewed threats to our battle against COVID-19. Understanding viral mutagenesis and evolution is of preeminent importance. By integrating genomic analysis, artificial intelligence (AI), computational biophysics, advanced mathematics, and experimental data, the PIs have built a comprehensive program with the experimental level of accuracy and population-level of reliability for predicting SARS-CoV-2 variant infectivity and antibody disruption. It remains challenging to forecast future emerging vaccine-escape variants, to develop the next-generation of vaccines, and to design mutation- proof antibody therapeutics. These challenges are tackled in the proposed project. New mathematical tools and AI algorithms will be developed to further improve the current state-of- the-art in predicting mutation-induced viral infectivity changes, vaccine breakthroughs, and antibody disruptions. Vital mutations in future emerging variants will be forecasted based on molecular mechanisms, natural selection, and evolutionary effects. New mutation-proof antibody drugs will be designed and tested based on those antibodies that had gone through earlier clinical trials. The predictive models will be implemented into a user-friendly platform with online servers for researchers to design mutation-proof new vaccines and antibody therapies. The proposed methods will be applied to forecast emerging variants in the flu and improve the efficacy of seasonal flu vaccines.", "keywords": [ "2019-nCoV", "ACE2", "Affinity", "Antibodies", "Antibody Therapy", "Antigens", "Artificial Intelligence", "Artificial Intelligence enhanced", "Artificial Intelligence platform", "Binding", "Biophysical Process", "Biophysics", "COVID-19", "COVID-19 pandemic", "COVID-19 patient", "COVID-19 vaccination", "Categories", "Cells", "Cessation of life", "Clinical Trials", "Computer Assisted", "Country", "Data", "Databases", "Deposition", "Development", "Elements", "Emergency Situation", "Evolution", "Future", "Generations", "Genes", "Genome", "Genomics", "Genotype", "Goals", "Graph", "Induced Mutation", "Infection", "Libraries", "Life", "Literature", "Mathematics", "Methodology", "Methods", "Modeling", "Molecular", "Mutagenesis", "Mutate", "Mutation", "Natural Selections", "Patients", "Pattern", "Pharmaceutical Preparations", "Phase", "Physics", "Play", "Population", "Prevention Measures", "Probability", "Property", "Proteins", "Race", "Research Personnel", "SARS-CoV-2 antibody", "SARS-CoV-2 genome", "SARS-CoV-2 spike protein", "SARS-CoV-2 variant", "Series", "Structure", "Testing", "Therapeutic antibodies", "Training", "Vaccine Therapy", "Vaccines", "Validation", "Variant", "Viral", "Viral Vaccines", "Virus", "Work", "algebraic topology", "antibody libraries", "artificial intelligence algorithm", "artificial intelligence based", "artificial intelligence model", "base", "design", "differential geometry", "drug discovery", "early phase clinical trial", "efficacy validation", "experimental study", "flu", "future pandemic", "improved", "influenza virus vaccine", "innovation", "mathematical algorithm", "next generation", "novel vaccines", "pandemic disease", "predictive modeling", "programs", "receptor", "receptor binding", "seasonal influenza", "software development", "success", "theories", "tool", "user friendly software", "user-friendly" ], "approved": true } }, { "type": "Grant", "id": "16137", "attributes": { "award_id": "1R35GM164072-01", "title": "Generative AI-Powered Exploration of Protein Dynamics and Non-Deterministic Chemical Kinetics", "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": 44592, "first_name": "HAN", "last_name": "NGUYEN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-06-01", "end_date": "2031-02-28", "award_amount": 447174, "principal_investigator": { "id": 44593, "first_name": "Peng", "last_name": "Tao", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3513, "ror": "", "name": "SOUTHERN METHODIST UNIVERSITY", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Overview. The PI’s lab focuses on uncovering the dynamic mechanisms underlying protein functions through advanced computational simulations and theoretical modeling, employing molecular mechanics (MM), quantum mechanics (QM), and their combined approaches (QM/MM). The group's research has concentrated on three major themes. Protein Allostery: Significant advances have been achieved in both methodological development and application studies of key allosteric proteins, including the Light-Oxygen-Voltage-sensing (LOV) domain and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Additionally, the group has created two user- friendly public computational servers to serve the broader research community. Evolution of Enzyme Catalysis: The PI’s lab has pioneered innovative theoretical frameworks that integrate machine learning techniques with catalytic reaction pathways derived from hybrid QM/MM calculations, enhancing our understanding of enzyme evolution and catalytic mechanisms. Fundamental Chemical Mechanism Studies: The PI has a longstanding interest in the mechanisms underlying chemical transitions, particularly focusing on their characterization as rare events. Through extensive computational investigations and innovative methodological advancements, the PI's laboratory has explored a broad spectrum of chemical processes in detail. Goals of Next Five Years. Over the next five years, our research will advance computational modeling across multiple cutting-edge domains, integrating artificial intelligence and advanced theoretical frameworks to address complex biochemical and photochemical phenomena. We aim to establish transformer-based conditional diffusion models to predict protein dynamics, creating an automated, scalable alternative to traditional molecular dynamics simulations. Concurrently, we will expand our generative AI approaches to dissect catalytic mechanisms of β-lactamase enzymes, systematically mapping the catalytic landscapes of serine-based and metallo-β-lactamases. By incorporating protein conformational dynamics into these catalytic models, we aim to elucidate enzyme regulation and evolution, enhancing understanding of antibiotic resistance mechanisms. Additionally, we will develop comprehensive stochastic differential equation (SDE) models using Itô calculus to characterize the stochastic molecular behaviors underlying mechanically activated photochemistry (MAPC). Integrating specialized models for chemiluminescence and mechanochemical activation into a unified MAPC framework, we aim to significantly enhance predictive simulation capabilities in this interdisciplinary area. Collectively, these efforts will produce robust theoretical and computational tools that deepen fundamental understanding and enable innovative applications across biophysics and biochemistry. Overall Vision. Understanding the dynamic behavior of proteins is central to decoding the mechanisms underpinning protein function, enzymatic catalysis, and structure-function relationships. It remains computationally prohibitive for simulating biophysical and biochemical processes at functionally relevant timescales, which often span seconds to minutes—far beyond the millisecond range achievable by current technologies. Chemical processes at the molecular level are inherently non-deterministic stochastic processes, governed by probabilistic events and random molecular fluctuations rather than fixed, reproducible trajectories. The PI has been developing a long-term vision to advance biomolecular modeling by shifting from traditional MD simulations and reaction pathway calculation for enzyme catalysis mechanism toward AI-driven, predictive models capable of generating protein dynamics, enzyme catalytic mechanisms, and stochastic biochemical behaviors. By combining generative AI, molecular simulations, and stochastic modeling, this research addresses critical limitations in scaling biomolecular dynamics studies. It promises transformative advances in protein engineering, drug discovery, and mechanistic enzymology, while providing computationally efficient tools for simulating molecular behavior at unprecedented scales.", "keywords": [ "2019-nCoV", "Acceleration", "Address", "Antibiotic Resistance", "Area", "Artificial Intelligence enhanced", "Behavior", "Biochemical", "Biochemical Process", "Biochemistry", "Biophysical Process", "Biophysics", "Calculi", "Catalysis", "Chemicals", "Communities", "Complex", "Computer Models", "Computer Simulation", "Development", "Differential Equation", "Diffusion", "Enzymatic Biochemistry", "Enzymes", "Event", "Evolution", "Goals", "Health", "Hybrids", "Investigation", "Laboratories", "Light", "Machine Learning", "Maps", "Mechanics", "Methodology", "Modeling", "Molecular", "Molecular Disease", "Oxygen", "Pathway interactions", "Photochemistry", "Process", "Protein Conformation", "Protein Dynamics", "Protein Engineering", "Proteins", "Public Health Applications Research", "Quantum Mechanics", "Reaction", "Regulation", "Reproducibility", "Research", "Serine", "Stochastic Processes", "Structure-Activity Relationship", "Techniques", "Technology", "Theoretical model", "Therapeutic", "Trajectory", "Translations", "Vision", "beta-Lactamase", "chemical kinetics", "computerized tools", "design", "drug discovery", "empowerment", "generative artificial intelligence", "innovation", "interest", "millisecond", "molecular dynamics", "molecular mechanics", "predictive modeling", "protein function", "protein structure", "resistance mechanism", "simulation", "tool", "user-friendly", "voltage" ], "approved": true } }, { "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": "16135", "attributes": { "award_id": "1P01AI181935-01A1", "title": "Microbiology of Treatment Shortening in Tuberculosis\"", "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": 44618, "first_name": "JIM P", "last_name": "BOYCE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-26", "end_date": "2031-04-30", "award_amount": 3589323, "principal_investigator": { "id": 24121, "first_name": "Kyu Y", "last_name": "Rhee", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 44619, "first_name": "Dirk", "last_name": "Schnappinger", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 825, "ror": "", "name": "WEILL MEDICAL COLL OF CORNELL UNIV", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "- OVERALL Efforts to establish control of the tuberculosis (TB) pandemic face historically unprecedented challenges. In the wake of COVID-19-induced disruptions in TB healthcare-related services, TB has re-emerged as the leading cause of deaths due to an infectious disease with 2 consecutive years of the first increases in TB mortality seen in over a decade. Lacking more effective and scalable transmission blocking interventions, control of the TB pandemic will continue to rest on the clinical efficacy of chemotherapy. Unfortunately, while still therapeutically effective against 95% of newly diagnosed cases, existing chemotherapies have proven functionally far less effective due to their toxicities and months-long duration. This Program Project proposes to lay a basic-science foundation for developing treatment shortening drugs and regimens. Such studies are motivated by the empirical discovery of the treatment shortening properties of rifampin and pyrazinamide, two frontline agents whose addition enabled a nearly 3-fold reduction in treatment duration, and more recent evidence implicating phenotypically drug-resistant bacterial subpopulations as a biological determinant of treatment duration. This application brings a synergistic combination of investigators and disciplines together for a collaborative attack that mobilizes new concepts, technologies and model systems to discover and test new treatment shortening targets and strategies. Project 1 focuses on mechanisms that allow these populations to persist in patients undergoing chemotherapy. Project 2 focuses on reverse translating the treatment shortening activities of rifampin and pyrazinamide into in vitro biomarkers, mechanisms and targets. Project 3 will use innovative CRISPRi-based genetic-genetic interaction mapping to identify highly efficacious Mtb drug-target combinations. Project 4 exploits genetic approaches to define the Mtb gene products whose inactivation has the greatest potential to shorten TB chemotherapy. Core A ensures the efficient flow of information and material among these projects. Core B will combine technical advances in single-cell measurement with data integration approaches to enable single cell studies of how different subpopulations respond to treatment and/or gene inactivation. Core C will provide access to a novel paucibacillary and a drug treatment mouse model of TB relapse.", "keywords": [ "Animals", "Back", "Basic Science", "Biological", "Biological Markers", "Biological Models", "Biology", "COVID-19", "CRISPR interference", "Cause of Death", "Cells", "Clinical", "Clinical Research", "Clinical Treatment", "Communicable Diseases", "Communication", "Communities", "Discipline", "Drug Targeting", "Drug Tolerance", "Drug resistance", "Drug toxicity", "Ensure", "Face", "Fatigue", "Foundations", "Gene Silencing", "Genes", "Genetic", "Goals", "Health Care", "In Vitro", "Intervention", "Knowledge", "Maps", "Measurement", "Mediating", "Methodology", "Methods", "Microbiology", "Modeling", "Mycobacterium tuberculosis", "Newly Diagnosed", "Patients", "Performance", "Pharmaceutical Preparations", "Pharmacotherapy", "Phenotype", "Population", "Predisposition", "Property", "Pyrazinamide", "Recurrent disease", "Regimen", "Relapse", "Research", "Research Design", "Research Personnel", "Resources", "Rest", "Rifampin", "Services", "Shapes", "Technology", "Testing", "Therapeutic", "Toxic effect", "Translating", "Tuberculosis", "antimicrobial", "bacterial resistance", "chemotherapy", "clinical efficacy", "data integration", "drug development", "drug relapse", "experimental study", "gene product", "genetic approach", "in vivo", "innovation", "mortality", "mouse model", "novel", "pandemic disease", "pandemic response", "pre-clinical", "premature", "programs", "technology platform", "therapeutically effective", "transmission blocking", "treatment duration", "tuberculosis chemotherapy", "tuberculosis drugs", "tuberculosis treatment" ], "approved": true } }, { "type": "Grant", "id": "16134", "attributes": { "award_id": "1R21AI195434-01A1", "title": "Isolation and functional analyses of monoclonal antibodies against the HIV-1 antisense protein ASP from people living with HIV-1", "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": 44616, "first_name": "JESUS FIDEL", "last_name": "SALAZAR-GONZALEZ", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-21", "end_date": "2028-04-30", "award_amount": 247125, "principal_investigator": { "id": 44617, "first_name": "Fabio", "last_name": "Romerio", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 24795, "first_name": "Mohammad Mohseni", "last_name": "Sajadi", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1532, "ror": "https://ror.org/036a0e562", "name": "Baltimore VA Medical Center", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 2615, "ror": "", "name": "JOHNS HOPKINS UNIVERSITY", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "The antisense gene asp maps in the HIV-1 genomic region overlapping env at the SU/TM boundary. Asp is found in pandemic strains of group M, but not in other primate lentiviruses including non-pandemic HIV-1 groups N, O, and P. We showed that asp is highly conserved despite constraining the evolution of env. We also reported that the asp gene is found at a higher frequency in people living with HIV-1 (PLWH) who progress to AIDS in <3 years (rapid progressors) compared to those who progress to AIDS in >12 years (long term non-progressors). The asp gene encodes the 189-aa hydrophobic protein, ASP. We reported that ASP shows high sequence iden- tity across HIV-1 isolates from all group-M subtypes. Work from our lab described the presence of ASP on the plasma membrane of infected cells, and on the envelope of infectious HIV-1 particles. Our unpublished studies demonstrate that the presence of ASP on the surface of HIV-1 particles facilitates viral entry. Several studies have shown the presence of cellular and humoral immune responses to ASP in PLWH, which proves its expression in vivo. A recent report reported that antibodies against ASP were specific for epitopes in the predicted ectodomain of ASP. Our preliminary studies confirmed the presence of antibodies against the ASP ectodomain in Elite Controllers (EC). Yet, none of the studies published so far endeavored to isolate ASP anti- bodies from PLWH and to test their functional activity as a way to investigate the role of ASP in HIV-1 infection. The overall aim of this application is to isolate monoclonal antibodies (mAbs) against the ectodomain of ASP from EC, Viremic Controllers, and PLWH both on and off ART. We will test their activity in in vitro and ex vivo assays. These studies will be performed in collaboration with Dr. Mohammad Sajadi (Institute of Human Virology, University of Maryland School of Medicine), who has established a cohort of >200 PLWH from whom he has already obtained paired serum and PBMC samples that are immediately available for the studies proposed here. Dr. Sajadi has developed a method for the identification, isolation, and cloning of mAbs that led to the discovery of best-in-class mAbs against HIV-1, SARS-CoV2, and CCHFV. Here, we propose the following specific aims: In Specific Aim 1, we will generate pools of overlapping peptides that span the ectodomain of ASP, and we will use these peptide pools to screen serum samples from PLWH in Dr. Sajadi’s cohort to identify those with strong- est binding to each of the five ASP peptide pools, and to determine their peptide sequence specificity. Next, we will use single-cell PCR and mass spectrometry to isolate and clone high affinity anti-ASP mAbs from the paired PBMC samples of the same donors. We will then validate the ASP specificity of these mAbs in ELISA and virion capture assays. In Specific Aim 2, we will test the activity of the ASP mAbs in mediating antibody dependent cellular toxicity (ADCC), reducing viral entry in single-round infection and viral replication in multiple rounds of infection, and detecting ASP on the cell surface, in the cytosol, and within nuclei.", "keywords": [ "2019-nCoV", "Acquired Immunodeficiency Syndrome", "Affinity", "Amino Acids", "Antibodies", "Binding", "Biological Assay", "CD4 Positive T Lymphocytes", "Cell Nucleus", "Cell membrane", "Cell surface", "Cells", "Cloning", "Collaborations", "Confocal Microscopy", "Cytosol", "Data Set", "Enzyme-Linked Immunosorbent Assay", "Epitopes", "Evolution", "Flow Cytometry", "Frequencies", "Genes", "Genome", "Genomic Segment", "HIV", "HIV Infections", "HIV Nonprogressors", "HIV-1", "High Prevalence", "Human", "Hydrophobicity", "Immune response", "In Vitro", "Individual", "Infection", "Maps", "Maryland", "Mass Spectrum Analysis", "Mediating", "Methods", "Monoclonal Antibodies", "Peptides", "Peripheral Blood Mononuclear Cell", "Persons", "Plasma", "Play", "Primate Lentiviruses", "Property", "Proteins", "Publishing", "Reporting", "Role", "Sampling", "Scheme", "Serum", "Specificity", "Surface", "Testing", "Toxic effect", "Transmembrane Domain", "Universities", "Viral", "Virion", "Virus Replication", "Work", "cohort", "ex vivo", "in vivo", "large datasets", "lonely individuals", "medical schools", "nef Protein", "new therapeutic target", "pandemic disease", "particle", "protein aminoacid sequence", "virology" ], "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": "16131", "attributes": { "award_id": "1K08DK143346-01A1", "title": "Renal endothelial cell signaling following viral priming in sepsis-associated acute kidney injury", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)" ], "program_reference_codes": [], "program_officials": [ { "id": 7449, "first_name": "TRACY L", "last_name": "RANKIN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-15", "end_date": "2031-02-28", "award_amount": 173232, "principal_investigator": { "id": 44613, "first_name": "James D", "last_name": "Odum", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3397, "ror": "", "name": "UNIVERSITY OF ALABAMA AT BIRMINGHAM", "address": "", "city": "", "state": "AL", "zip": "", "country": "United States", "approved": true }, "abstract": "ABSTRACT: Sepsis is a heterogeneous syndrome consisting of overlapping phenotypes that cause a broad range of organ injuries. Sepsis-associated acute kidney injury (SA-AKI) is among the most consequential, with high mortality and poor functional outcomes. No direct disease-modifying therapies currently exist. A major barrier to therapeutic progress is the diversity of sepsis phenotypes, which leads to heterogeneity of treatment effect. A prominent, yet understudied SA-AKI phenotype involves viral priming preceding bacterial sepsis. First recognized in pediatrics due to the high prevalence of viral infections, interest in this phenotype grew during the COVID-19 pandemic. Viral-primed SA-AKI is marked by thrombotic microangiopathy, impaired renal microperfusion, and injury to renal tubular epithelial cells. Firmly rooted in this proposed pathophysiology is the interaction between renal endothelial cells and tubular epithelial cells. The objectives of this study are to understand the renal endothelial cell response to a synthetic analog of viral double-stranded RNA, polyinosinic- polycytidylic (poly(I:C)) acid, and to determine whether poly(I:C) mediated renal endothelial cell activation directly leads to downstream tubular epithelial injury. Preliminary data suggests poly(I:C) induces renal endothelial cells to produce type 1 interferons, which act in a paracrine manner to alert nearby cells to the presence of a viral infection. In isolation, poly(I:C) does not cause kidney injury. However, when poly(I:C) is given prior to low-dose lipopolysaccharide (LPS), a significant and disproportionate systemic inflammatory response with early, severe SA-AKI ensues. Together, these data support the novel hypothesis that systemic exposure to viral dsRNA activates renal endothelial cells and initiates a type 1 IFN response, thereby priming the kidney for exaggerated injury following a secondary bacterial challenge. To test this hypothesis, we will leverage in vitro and in vivo techniques to accomplish two specific aims. AIM 1 will focus on the renal endothelial cell response to poly(I:C) with and without LPS to establish type 1 IFNs as essential mediators in the development of viral primed SA-AKI. AIM 2 will examine the heterogeneity of viral responses among renal endothelial cell subpopulations using CITEseq, and will computationally define microenvironmental signaling networks between endothelial cells and renal tubular epithelial cells using single-cell RNA sequencing of whole kidney. This research training program will expand upon the candidate’s translational science background elucidating the role of chemokines involved in murine models of SA-AKI to gain new expertise in kidney physiology and vascular endothelial biology. The candidate will hone skills in cell culture, flow cytometry, single-cell RNA sequencing analysis, and laboratory management. Altogether, this career development award will facilitate the successful transition to scientific independence and the establishment of a reputable SA-AKI translational research program.", "keywords": [ "Acids", "Acute Kidney Failure", "Address", "Area", "Bacterial Model", "Bioinformatics", "Biology", "COVID-19 pandemic", "Cell Culture Techniques", "Cell surface", "Cells", "Cellular Indexing of Transcriptomes and Epitopes by Sequencing", "Communication", "Data", "Development", "Disease", "Dose", "Double-Stranded RNA", "Endothelial Cells", "Endothelium", "Environment", "Epithelial Cells", "Epithelium", "Exposure to", "Flow Cytometry", "Functional disorder", "Funding", "Future", "Glomerular Filtration Rate", "Goals", "Health Priorities", "Heterogeneity", "High Prevalence", "Homeostasis", "Human", "Immune", "Impairment", "In Vitro", "Infection", "Inflammation", "Inflammatory", "Injury", "Injury to Kidney", "Interferon-α", "Interferons", "Investigation", "Investments", "K-Series Research Career Programs", "Kidney", "Laboratories", "Link", "Lipopolysaccharides", "Mediating", "Mediator", "Mentorship", "Modeling", "Molecular Profiling", "Morbidity", "Mus", "Nature", "Outcome", "Pathogenesis", "Pathogenicity", "Pathway interactions", "Patients", "Pediatrics", "Perfusion", "Phenotype", "Physicians", "Physiology", "Play", "Poly I-C", "Pre-Clinical Model", "Production", "Productivity", "Public Health", "Renal function", "Renal tubule structure", "Research", "Research Training", "Role", "Scientist", "Sepsis", "Shapes", "Signal Transduction", "Site", "Syndrome", "Technical Expertise", "Techniques", "Testing", "Therapeutic", "Tissue-Specific Gene Expression", "Training Programs", "Translational Research", "Tubular formation", "United States National Institutes of Health", "Vascular Endothelial Cell", "Vascular Endothelium", "Viral", "Virus Diseases", "Virus Replication", "Work", "analog", "bacterial sepsis", "career", "cell injury", "chemokine", "cytokine", "cytokine release syndrome", "early onset sepsis", "epithelial injury", "functional outcomes", "global health", "in vivo", "interest", "kidney vascular structure", "mortality", "mortality risk", "mouse model", "neglect", "novel", "novel therapeutics", "organ injury", "paracrine", "pathogen", "receptor", "recruit", "response", "severe sepsis", "single-cell RNA sequencing", "skills", "systemic inflammatory response", "thrombotic", "translational research program", "treatment effect" ], "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 } } ], "meta": { "pagination": { "page": 5, "pages": 1442, "count": 14420 } } }