Grant List
Represents Grant table in the DB
GET /v1/grants?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=1424&sort=-awardee_organization", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=2&sort=-awardee_organization", "prev": null }, "data": [ { "type": "Grant", "id": "15995", "attributes": { "award_id": "1IK2HX003695-01A2", "title": "Improving Specialty Care Through Virtual Care Models", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2026-01-01", "end_date": "2030-12-31", "award_amount": null, "principal_investigator": { "id": 44448, "first_name": "Rebecca", "last_name": "Tisdale", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3442, "ror": "", "name": "VETERANS ADMIN PALO ALTO HEALTH CARE SYS", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "1 Background: Specialty care deserts—the absence of specialists in geographic regions—have led to an access 2 crisis for the VA. In addition to increasing wait times and causing delays in care, these access needs drive many 3 Veterans to seek care outside VA, resulting in fragmented care, increased risks for hospitalization and hospital 4 readmission, and higher costs. In response, VA has launched the Clinical Resource Hub (CRH) program, which 5 seeks to deliver virtual care from “hub” to “spoke” sites in VA. VISN 21 has begun implementing this model in 6 cardiology at several spoke sites, but little is known about how care utilization and quality within the program. 7 Significance/Impact: This work seeks to better understand the effects of a virtual model of specialty care, in 8 this case cardiology care, on Veterans’ care access and quality. In addition, it aligns closely with several VA and 9 HSR&D priorities, chiefly access to care, virtual care/telehealth, and advancing the goals of the MISSION Act. 10 Innovation: The CRH program and the virtual care model at its core have yet to be studied in depth, and there 11 is no research in progress regarding specialty CRH despite strong interest at the national VA level in 12 understanding how specialty CRH is used and associated outcomes. Given that virtual cardiology care was very 13 limited prior to the COVID-19 pandemic, cardiology CRH is particularly novel. Hence, this project would add to 14 the limited body of research examining virtual cardiology care in the VA. In addition, the proposed work seeks to 15 evaluate this virtual care model at a time of unprecedented choice for Veterans between in-person and virtual 16 care, and limited data on how best to integrate these modalities. 17 Specific Aims: The proposed CDA will offer mentorship and training for me to pursue the following aims: 18 Aim 1. Evaluate quality of cardiology care associated with CRH implementation with administrative data. 19 I will use adjusted difference-in-difference event studies to compare cardiology quality metric achievement for 20 patients who received cardiology care via CRH versus those who received conventional VA-based cardiology care. 21 Aim 2. Assess Veteran perceptions of quality of cardiology care delivered via CRH. 22 I will interview Veterans participating in the CRH program and their caregivers regarding their experiences and 23 perceptions of quality of CRH cardiology care and elicit suggestions for key metrics to focus on for improvement. 24 Aim 3. Construct intervention to track and improve access to high-quality, equitable care through CRH. 25 Building on finding from Aims 1 and 2, I will interview clinicians and employ a facilitated deliberative process with 26 an expert advisory group to construct and pilot an intervention to improve quality. 27 Methodology: In Aim 1, I will use a difference-in-difference event study design to assess the impact of the program 28 on a battery of validated and/or guideline-based quality of cardiology care metrics. In Aim 2, guided by the Fortney 29 model of care access and quality, I will conduct semi-structured interviews of Veterans and caregivers receiving 30 care through the VISN 21 CRH program to understand their experiences with the CRH program and what outcomes 31 they recommend to include in a quality improvement intervention. In Aim 3, I will interview clinicians (Aim 3.1) and 32 conduct a facilitated deliberation process (Aim 3.2) to inform the construction of an intervention (proactive panel 33 management using a clinical dashboard tool) to track and improve quality of care and pilot the intervention. 34 Next Steps/Implementation: To continue moving this research into practice to improve health outcomes for 35 Veterans, I will extend the analysis of cardiology quality of care to compare cardiology care in the community to 36 CRH care. In addition, I will assess the effect of the intervention constructed in Aim 3 on patient outcomes and 37 clinician satisfaction via a hybrid implementation-effectiveness trial. I will continue to work with operational partners 38 to ensure cardiology CRH is improving access to high-quality cardiology care for Veterans. This project supports 39 my goal of becoming an independent VA health services researcher and leader in optimizing cardiovascular 40 disease care access, value, and equity for Veterans through virtual care innovations and implementation.", "keywords": [ "Achievement", "Address", "Area", "COVID-19 pandemic", "California", "Cardiology", "Cardiovascular Diseases", "Cardiovascular system", "Caregivers", "Caring", "Characteristics", "Cladribine", "Clinical", "Clinical Services", "Communities", "Community Health Care", "Dangerousness", "Data", "Disease", "Ensure", "Equity", "Evaluation", "Event", "Geographic Locations", "Goals", "Guidelines", "Health", "Health Services", "Health Services Accessibility", "Heart failure", "Homogeneously Staining Region", "Hospitalization", "Hospitals", "Improve Access", "Intervention", "Interview", "Medical", "Mentors", "Mentorship", "Methodology", "Methods", "Modality", "Modeling", "Morbidity - disease rate", "Nevada", "Outcome", "Pacific Islands", "Patient-Focused Outcomes", "Patients", "Perception", "Persons", "Physicians", "Policies", "Positioning Attribute", "Process", "Qualitative Methods", "Quality of Care", "Recommendation", "Research", "Research Design", "Research Personnel", "Resources", "Risk", "Rural Health", "Safety", "Site", "Specialist", "Structure", "Suggestion", "Telemedicine", "Telephone", "Testing", "Time", "Training", "Training Activity", "Veterans", "Visit", "Wait Time", "Work", "adverse outcome", "care fragmentation", "care seeking", "care utilization", "clinical implementation", "connected care", "cost", "dashboard", "design", "effectiveness/implementation trial", "experience", "follow-up", "health economics", "hospital readmission", "hospitalization rates", "implementation efforts", "implementation science", "improved", "innovation", "insight", "interest", "intervention effect", "medical specialties", "mortality", "novel", "operation", "patient subsets", "pilot test", "preference", "programs", "rapid growth", "research to practice", "response", "rural counties", "satisfaction", "sociodemographics", "southern nevada", "telehealth", "therapy design", "tool", "virtual", "virtual delivery", "virtual health care", "virtual model" ], "approved": true } }, { "type": "Grant", "id": "15994", "attributes": { "award_id": "1F31AI181508-01A1", "title": "Investigating the Role of Epstein-Barr Virus in Long COVID Pathogenesis", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32795, "first_name": "EUN-CHUNG", "last_name": "PARK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-01-16", "end_date": "2028-01-15", "award_amount": 33538, "principal_investigator": { "id": 44447, "first_name": "Alexandra", "last_name": "Tabachnikova", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3441, "ror": "", "name": "YALE UNIVERSITY", "address": "", "city": "", "state": "CT", "zip": "", "country": "United States", "approved": true }, "abstract": "SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease, which is known as Long COVID. Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions; however, the basic biological mechanisms responsible for these debilitating symptoms are unclear. Previously, this research group profiled 177 individuals in an exploratory, cross-sectional study encompassing multi-dimensional immune phenotyping in conjunction with machine learning. Key immunological features distinguishing Long COVID were identified and described in the Mount Sinai Yale –Long COVID (MY-LC) study. A striking finding was an elevation in antibodies to lytic antigens of Epstein-Barr Virus (EBV) in Long COVID participants, which may be indicative of more recent reactivation of EBV in these patients. In addition, levels of these antibodies correlated with IL-4, IL-6 cytokine double-producing CD4+ T- cells, which suggests that EBV reactivation is not merely incidental but reflects, mediates or aggravates immune perturbations in these patients. The overarching goal of this proposal is to provide a thorough insight into whether EBV reactivation contributes to LC disease pathogenesis and symptomatology, building on current literature. The research plan proposed will utilize the Iwasaki lab’s expertise in in vitro and in vivo modeling to assess whether SARS-CoV-2 infection can reactivate EBV and contribute to lasting sequelae, as described in Aim 1. Aim 2 will leverage large patient cohorts previously recruited through the MY-LC study and robust sample and data availability to test whether patients with Long COVID characterized by recent EBV reactivation experience unique immune alterations. Aim 2 will also test whether these responses correlate to unique symptoms. The findings uncovered by these studies have the potential to deepen understanding of one cause of Long COVID, and to inform future treatment of a growing, currently largely-untreated patient population. Mentorship from an interdisciplinary group of collaborators, who are experts in the proposed techniques, will facilitate this applicant’s training as an independent immunologist.", "keywords": [ "2019-nCoV", "Acute", "Acute Disease", "Antibodies", "Antigens", "Autoimmunity", "Autonomic Dysfunction", "B-Lymphocytes", "Biological", "Biological Assay", "Blood specimen", "CD4 Positive T Lymphocytes", "COVID-19", "COVID-19 impact", "COVID-19 pathogenesis", "COVID-19 patient", "Cell Culture Techniques", "Cells", "Communication", "Computational Technique", "Cross-Sectional Studies", "DNA Viruses", "Data", "Development", "Diagnosis", "Dimensions", "Disease", "Disease Marker", "EBV reactivation from latency", "Elements", "Epstein-Barr Virus latency", "Exertion", "Exhibits", "Fatigue", "Functional disorder", "Future", "Glycoproteins", "Goals", "Herpesviridae", "Hospitalization", "Human", "Human Herpesvirus 4", "Immune", "Immune response", "Immunologics", "Immunologist", "Impaired cognition", "Impairment", "In Vitro", "Individual", "Infection", "Inflammatory", "Influenza", "Influenza A Virus H1N1 Subtype", "Interleukin-4", "Interleukin-6", "Laboratories", "Literature", "Long COVID", "Lymphopenia", "Lytic", "Lytic Virus", "Machine Learning", "Malaise", "Mediating", "Memory", "Mentorship", "Methods", "Multiple Sclerosis", "Muridae", "Mus", "Neurocognitive", "Participant", "Pathogenesis", "Pathology", "Patients", "Phenotype", "Plasma", "Production", "Quality of life", "Recovery", "Reporting", "Research", "Rheumatoid Arthritis", "Risk", "Role", "SARS-CoV-2 infection", "Sampling", "Serology", "Serum", "Severity of illness", "Study Subject", "Symptoms", "Systemic Lupus Erythematosus", "T cell response", "T-Lymphocyte", "Techniques", "Testing", "Training", "Viral Antigens", "Viremia", "Virus Diseases", "Virus Latency", "Writing", "acute COVID-19", "autoimmune pathogenesis", "brain fog", "chronic infection", "cohort", "comparison control", "cytokine", "daily functioning", "debilitating symptom", "experience", "experimental study", "in vivo", "in vivo Model", "insight", "mortality", "mouse model", "patient population", "persistent symptom", "recruit", "response", "skills", "symptomatology", "virus envelope" ], "approved": true } }, { "type": "Grant", "id": "15993", "attributes": { "award_id": "1F30AI194459-01", "title": "Testing the role of microbial infections in the development of auto-antibodies to type I interferons", "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": 32556, "first_name": "TIMOTHY A", "last_name": "GONDRE-LEWIS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-01-27", "end_date": "2029-01-26", "award_amount": 43914, "principal_investigator": { "id": 44446, "first_name": "Adrianna M.", "last_name": "Rivera-León", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3440, "ror": "", "name": "UNIVERSITY OF MINNESOTA", "address": "", "city": "", "state": "MN", "zip": "", "country": "United States", "approved": true }, "abstract": "Type I interferons (IFN) are crucial to anti-viral immunity. Neutralizing autoantibodies (AAb) to IFN are found in the general population, increase in prevalence with age, and are linked to worse, often fatal, outcomes in some of the most lethal acute respiratory viral diseases known to date, including fulminant influenza and COVID-19 pneumonia. Despite this, the mechanisms behind the formation of IFN AAb remain unknown. Human data suggest that impairments in thymic tolerance—due to dysfunction of autoimmune regulator (AIRE) and medullary thymic epithelial cells (mTEC)—may be required for the development of IFN AAb. AIRE is a transcription factor expressed by mTEC that is essential for establishing T cell tolerance in the thymus. In mTEC, AIRE promotes the expression and presentation of antigens from extrathymic tissues to developing T cells (thymocytes). This allows for the elimination of auto-reactive thymocyte clones, thereby preventing autoimmunity. Interestingly, AIRE+ mTEC have been shown to express IFN at steady-state conditions in the thymus suggesting that, in this context, AIRE+ mTEC act as antigen-presenting cells to thymocytes to mediate T cell tolerance to IFN. Supporting this idea, individuals with Autoimmune Polyglandular Syndrome 1 (APS1), who lack AIRE and experience T cell tolerance loss, consistently develop IFN AAb. These AAb are isotype- switched and somatically hypermutated, supporting the notion that a failure of T cell tolerance, rather than solely B cell tolerance, is necessary for their generation. However, additional findings suggest that loss of thymic T cell tolerance alone is insufficient for IFN AAb to develop. First, APS1 patients do not typically present IFN AAb at birth or infancy; instead, they develop these AAb later in life after exposure to pathogens is likely to have occurred. Second, IFN AAb have not been observed in specific pathogen-free, Aire-deficient mice. Combined, these observations suggest that pathogen exposure, in addition to AIRE and mTEC dysfunction, may be required for IFN AAb to develop. This proposal aims to understand how infections, combined with AIRE deficiency, contribute to the loss of thymic tolerance to IFN. My central hypothesis is that in individuals with predisposing AIRE deficiency, infections that induce IFN expression act as a double hit, promoting the development of neutralizing IFN AAb. Until now, methods to detect neutralizing IFN AAb in mice have been lacking, which has hindered the field's ability to test this hypothesis. I have developed a novel, sensitive, reproducible, and high-throughput assay for detecting murine neutralizing IFN AAb. This new tool will serve as the basis for this proposal and will facilitate exploration of how microbial infections and thymic defects contribute to the development of IFN AAb in an animal model. The findings from this work will deepen our understanding of how tolerance to IFN is mediated and may inform strategies to prevent IFN AAb development in affected individuals.", "keywords": [ "Academia", "Acute", "Affect", "Affinity", "Age", "Animal Model", "Antibody Affinity", "Antigen Presentation", "Antigen-Presenting Cells", "Antigens", "Autoantibodies", "Autoimmune Polyendocrinopathies", "Autoimmune Regulator", "Autoimmunity", "B-Lymphocytes", "Binding", "Biological Assay", "Birth", "CD4 Positive T Lymphocytes", "COVID-19 pandemic", "COVID-19 pneumonia", "Cells", "Cerebrum", "Chronic", "Clinical", "Clonal Deletion", "Clone Cells", "Competence", "Data", "Defect", "Development", "Epitopes", "Event", "Exposure to", "Failure", "Flow Cytometry", "Frequencies", "Functional disorder", "General Population", "Generations", "Human", "Immune system", "Immunoglobulin Class Switching", "Immunologics", "Impairment", "Individual", "Infection", "Interferon Type I", "Interferons", "Knockout Mice", "Life", "Life Experience", "Link", "Luciferases", "Lymphocytic choriomeningitis virus", "Measures", "Mediating", "Methods", "Microbe", "Modeling", "Mus", "Mutation", "Organ", "Outcome", "Patients", "Peptides", "Play", "Prevalence", "Process", "Regulatory T-Lymphocyte", "Reporting", "Reproducibility", "Research", "Risk Factors", "Role", "Severity of illness", "T-Lymphocyte", "Testing", "Thymic Tissue", "Thymic epithelial cell", "Thymus Gland", "Tissues", "Training", "Virus Diseases", "Wild Type Mouse", "Work", "age related", "aged", "aging population", "antiviral immunity", "autoreactive T cell", "autoreactivity", "career", "comparative", "cytokine", "detection assay", "experience", "experimental study", "germ free condition", "high throughput screening", "human data", "infancy", "influenza pneumonia", "interest", "later life", "loss of function mutation", "microbial", "novel", "pathogen", "pathogen exposure", "peptide vaccination", "prevent", "public health relevance", "respiratory", "response", "severe COVID-19", "thymocyte", "tool", "transcription factor" ], "approved": true } }, { "type": "Grant", "id": "15989", "attributes": { "award_id": "1R21AI191169-01A1", "title": "Intelligent biosensing system for automated real-time monitoring of airborne pathogens for safe indoor environments", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32597, "first_name": "BROOKE ALLISON", "last_name": "BOZICK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-05", "end_date": "2028-01-31", "award_amount": 396448, "principal_investigator": { "id": 28438, "first_name": "Vishal", "last_name": "Verma", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 31634, "first_name": "Na", "last_name": "Wei", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 3439, "ror": "", "name": "UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "The increasing frequency of respiratory infectious diseases, such as influenza and COVID-19, which can spread rapidly and lead to severe outbreaks, necessitates that we re-envision our approaches to monitor pathogen exposures in the indoor environments. Current surveillance methods mostly depend on syndromic data from hospital admissions, clinic visits, and school absenteeism rates. However, these approaches can lead to underestimation and delay in disease surveillance due to no reporting of mild or asymptomatic cases, lack of access to healthcare, and time-consuming lab and diagnostic processes. A proactive approach in combating airborne diseases requires early detection of target pathogens. Here, we propose to innovate an intelligent system capable of real-time, efficient, and cost-effective monitoring of airborne pathogens in the environment. We will build upon our preliminary success in automated bioaerosol sampling and pathogen detection, to create an Airborne Pathogen Sensing (APS) system. This goal will be achieved by focusing on two specific aims. First, we will create a novel class of modular whole-cell biosensors for sensitive, rapid, and robust detection of multiple critical airborne pathogens. The pathogen detection will be achieved by creating quenchbody (Q-body) display biosensors, where target specific quenchbody is expressed and displayed on the surface of microbial host cells. When the Q-body binds to its antigen (target pathogen), the fluorescence intensity substantially increases via the antigen-dependent removal of the quenching effect on the fluorophore. Second, we will design and build a portable and automated bioaerosol sampling device that can be coupled to the biosensing and signal detection systems. To this end, we will evaluate and optimize two sampling devices: mist chamber and biosampler, and choose the device with the highest bioaerosol capture efficiency. Finally, we will integrate the biosensing component with the bioaerosol sampling device and an automated flow-through fluorescence detection system to achieve automated real-time monitoring of airborne pathogens.", "keywords": [ "Absenteeism", "Address", "Antibodies", "Antigens", "Binding", "Biosensing Techniques", "Biosensor", "COVID-19", "COVID-19 pandemic", "Cell membrane", "Cell surface", "Cells", "Cessation of life", "Characteristics", "Clinic Visits", "Communicable Diseases", "Consumption", "Coupled", "Coupling", "Data", "Detection", "Development", "Devices", "Diagnostic", "Disease", "Disease Outbreaks", "Disease Surveillance", "Early Diagnosis", "Economic Burden", "Education", "Engineering", "Environment", "Environmental Monitoring", "Enzyme-Linked Immunosorbent Assay", "Epidemic", "Equipment", "Excision", "Exhibits", "Expert Systems", "Exposure to", "Fluorescence", "Fostering", "Frequencies", "Future", "Goals", "Health", "Health Care Costs", "Health protection", "Hospitalization", "Human Resources", "Incidence", "Indoor environment", "Influenza", "Laboratories", "Lead", "Machine Learning", "Measurement", "Methods", "Monitor", "Mutate", "Output", "Pathogen detection", "Play", "Polymerase Chain Reaction", "Prevention", "Procedures", "Process", "Public Health", "Reaction", "Readiness", "Reagent", "Reporting", "Research Personnel", "Resources", "Respiratory syncytial virus", "Risk Assessment", "Risk Reduction", "Sampling", "Schools", "Seasons", "Signal Transduction", "Social Well-Being", "Societies", "Streptococcus pyogenes", "Surface", "Surveillance Methods", "System", "Technology", "Time", "Work", "air sampling", "clinical diagnostics", "cost", "cost effective", "design", "detection limit", "detection method", "detection platform", "fluorophore", "health care availability", "improved", "indoor air", "influenzavirus", "innovation", "microbial", "microbial host", "novel", "novel strategies", "pandemic disease", "pathogen", "pathogen exposure", "pathogenic virus", "portability", "real time monitoring", "respiratory", "respiratory aerosol", "response", "seasonal influenza", "skills", "success", "syndromic surveillance", "synthetic biology", "transmission process", "virology" ], "approved": true } }, { "type": "Grant", "id": "15988", "attributes": { "award_id": "1R01AI189680-01A1", "title": "Mechanisms of simian arterivirus entry, immune evasion, and zoonotic potential", "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": 32795, "first_name": "EUN-CHUNG", "last_name": "PARK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-09", "end_date": "2031-01-31", "award_amount": 790507, "principal_investigator": { "id": 24434, "first_name": "Cody Jay", "last_name": "Warren", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1583, "ror": "", "name": "UNIVERSITY OF COLORADO", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 3438, "ror": "", "name": "OHIO STATE UNIVERSITY", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "Many emerging zoonotic viruses (animal viruses that transmit to humans) are highly pathogenic, having the potential to cause deadly epidemics or even global pandemics. The risks zoonotic viruses pose are highlighted by the emergence of the SARS/MERS coronaviruses, Ebola virus, and HIV-1, all of which are related to animal viruses that were unknown before they caused substantial cases of disease in humans. Given the risk animal viruses pose to humans, many researchers have turned to viral discovery—using genome sequencing tools and metagenomic analyses, researchers hope to identify novel animal viruses before they emerge in humans. We've developed a pipeline that integrates viral surveillance with molecular investigations in the laboratory to identify pre-emergent viruses with epidemic potential. Using this approach, we've provided compelling evidence suggesting that simian arteriviruses (SAVs)—understudied and neglected pathogens of African monkeys—are poised for spillover, posing a threat to human health. We demonstrate key biological features that poise SAVs for zoonosis, including: (1) compatibility with human receptors; (2) high titer propagation in human cells; and (3) potential for evasion of human innate immunity. Further interrogation of the biology of SAV infection is crucial for future epidemic preparedness efforts. The objective of this proposal is to uncover mechanisms of cell entry, immune evasion, and zoonotic potential for these highly concerning viral pathogens. In Aim 1, we employ a series of molecular, biochemical, structural, and functional approaches to define SAV-receptor interactions and establish proof-of-concept strategies for future therapeutics—an essential step in outbreak preparedness. In Aim 2, we will identify SAV proteins that antagonize the human innate immune response, with the goal of revealing vulnerabilities that may help develop safe and effective antiviral approaches. In Aim 3, we will thoroughly evaluate the zoonotic potential of diverse SAVs. This includes: (1) identifying novel SAVs through whole virome sequencing of wild African primate biomaterials; (2) the development and application of non-human primate induced-pluripotent stem cell (iPSC)-derived macrophages to isolate novel SAVs in cell targets from natural host species; and (3) detailed infection studies in human cells to evaluate human compatibility. Further, we will perform the first in-depth serosurvey for SAV exposure history using banked sera from a Ugandan case-control cohort. When taken together, this proposal will lead to a deeper understanding of the molecular biology and pathogenesis of these understudied viruses, as well as a greater appreciation for the zoonotic risk that they pose. It is imperative that we invest in characterizing the biology and pathogenesis of SAVs now so that we may begin to develop platform technologies (i.e., diagnostics, vaccines, therapeutics) in case they do emerge in the future.", "keywords": [ "2019-nCoV", "African", "Animals", "Arterivirus", "Arterivirus Infections", "Binding", "Biochemical", "Biocompatible Materials", "Biological", "Biology", "Blocking Antibodies", "Case/Control Studies", "Cells", "Collection", "Communities", "Complex", "Cryoelectron Microscopy", "Cytokine Signaling", "Dedications", "Development", "Diagnostic", "Disease", "Ebola virus", "Endocytosis", "Epidemic", "Evaluation", "Family", "Frequencies", "Future", "Glycoproteins", "Goals", "HIV-1", "HIV/AIDS", "Health", "Human", "Human Cell Line", "Immune", "Immune Evasion", "Infection", "Influenza A Virus H1N1 Subtype", "Innate Immune Response", "Innate Immune System", "Integration Host Factors", "Interferons", "Investigation", "Investments", "Kinetics", "Knowledge", "Laboratories", "Macrophage", "Membrane Fusion", "Metagenomics", "Middle East Respiratory Syndrome Coronavirus", "Modeling", "Molecular", "Molecular Biology", "Monkey Hemorrhagic Disease Virus", "Monkeys", "Mutation", "Natural Immunity", "Nonstructural Protein", "Pathogenesis", "Pathogenicity", "Population Research", "Primates", "Process", "Proteins", "Recording of previous events", "Research", "Research Personnel", "Resources", "Risk", "Role", "Series", "Severe Acute Respiratory Syndrome", "Structure", "Therapeutic", "Vaccines", "Viral", "Viral Hemorrhagic Fevers", "Virus", "Virus Diseases", "Virus Integration", "Virus Receptors", "Virus Replication", "Zoonoses", "antagonist", "case control", "cohort", "emerging virus", "epidemic potential", "epidemic preparedness", "future epidemic", "genome sequencing", "induced pluripotent stem cell", "influenzavirus", "insight", "neglect", "nonhuman primate", "novel", "outbreak preparedness", "pandemic disease", "pathogen", "pathogenic virus", "receptor", "repeat offender", "response", "serosurvey", "technology platform", "tool", "viral transmission", "virome" ], "approved": true } }, { "type": "Grant", "id": "15987", "attributes": { "award_id": "1R21AI196149-01", "title": "Identification of Novel Targets for Enhancing Targeted RNA Degradation in Antiviral Discovery", "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": "2026-02-05", "end_date": "2028-01-31", "award_amount": 451000, "principal_investigator": { "id": 44441, "first_name": "Jingxin", "last_name": "Wang", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3437, "ror": "", "name": "UNIVERSITY OF CHICAGO", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT The development of targeted RNA degradation (TRD) technologies, such as RNA-degrading chimeras, holds significant promise for antiviral therapies by reducing viral RNA levels to prevent viral replication. Despite their potential, current TRD mechanisms exhibit limited potency. In various literature reports, ribonuclease- targeting chimeras (RIBOTACs) exemplify this problem, achieving only ~75% maximum degradation of distinct RNA targets in cells. For example, our preliminary work optimized a synthetic RNA ligand, C34, which binds robustly to an RNA G bulge in the 5’ untranslated region of SARS-CoV-2’s RNA genome with a low nanomolar dissociation constant. However, the minimum inhibitory concentration (MIC) of the C34-based RIBOTAC remained moderately high at 20 μM in SARS-CoV-2-infected cells, indicating insufficient cellular potency. RIBOTAC is a drug-induced TRD modality utilizing an endogenous ribonuclease, RNase L. Interestingly, this RIBOTAC potency cap in cells was not observed in cell-free assays using purified recombinant RNase L, indicating the possible presence of cellular factors that inhibit the RNase L degradation complex. To address this potency limitation, the proposed project aims to discover novel cellular targets to significantly enhance RNase L activity and brand-new TRD mechanisms for future drug development through two specific aims. Aim 1 focuses on identifying cellular determinants that inhibit RNase L-dependent RIBOTAC activity using a genome-wide CRISPR knockout screen. By targeting these inhibitory genes, we aim to significantly boost the efficacy of existing RIBOTACs. Aim 2 focuses on discovering novel cellular targets for TRD by performing genome-wide screenings in three screening platforms. We will utilize a plasmid library comprising ~14,000 open reading frames from the human genome to identify candidate genes that can effectively induce TRD through drug-induced proximity. Both aims will leverage a SARS-CoV-2 cellular model and our optimized RNA ligand C34 to validate these new mechanisms in antiviral research. Ultimately, this project seeks to expand our chemical genetics toolbox by unveiling new mechanisms and targets for RNA degradation. These advancements will be pivotal in developing new chimeric molecules designed to combat a variety of infectious diseases, significantly enhancing our capacity to address global health challenges. 1", "keywords": [ "2019-nCoV", "5' Untranslated Regions", "Address", "Anti-viral Therapy", "Autophagocytosis", "Bar Codes", "Binding", "Biochemical", "Biological Assay", "Candidate Disease Gene", "Cell model", "Cells", "Chimera organism", "Clinical", "Clustered Regularly Interspaced Short Palindromic Repeats", "Communicable Diseases", "Complex", "DNA", "Data", "Degradation Pathway", "Development", "Dissociation", "Exhibits", "Exposure to", "Flow Cytometry", "Future", "Gene Targeting", "Genes", "Genome", "Guide RNA", "Human", "Human Genome", "Individual", "Infection", "Infection Control", "Integration Host Factors", "Knock-out", "Libraries", "Life Cycle Stages", "Ligands", "Literature", "Luciferases", "Minimum Inhibitory Concentration measurement", "Minor Groove", "Modality", "Modeling", "Open Reading Frames", "Pancreatic ribonuclease", "Pathway interactions", "Pharmaceutical Preparations", "Plasmids", "Protac", "Proteins", "Protocols documentation", "RNA", "RNA Binding", "RNA Degradation", "Recombinants", "Reporting", "Research", "Ribonucleases", "Structure", "Tacrolimus Binding Proteins", "Technology", "Therapeutic", "Untranslated RNA", "Untranslated Regions", "Viral", "Virus", "Virus Replication", "Work", "antiviral drug development", "arm", "candidate identification", "candidate validation", "cellular targeting", "chemical genetics", "combat", "cytotoxicity", "design", "drug development", "drug discovery", "druggable target", "genome wide screen", "genome-wide", "global health", "human disease", "improved", "inhibitor", "interest", "nanomolar", "novel", "novel therapeutics", "pharmacologic", "prevent", "protein degradation", "recruit", "screening", "success", "transcriptome sequencing", "viral RNA", "virulence gene", "whole genome" ], "approved": true } }, { "type": "Grant", "id": "15986", "attributes": { "award_id": "1R21AI185790-01A1", "title": "Lymphotoxin-dependent control of long COVID", "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": "2026-02-13", "end_date": "2028-01-31", "award_amount": 234715, "principal_investigator": { "id": 7654, "first_name": "Alexei V", "last_name": "Tumanov", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3436, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH SCIENCE CENTER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "SARS-CoV-2 infection causes acute lung pathology and can lead to long-term complications, collectively known as long COVID. These complications include persistent pain, headaches, myalgia, and post-exertional malaise. However, the mechanisms behind these neurological symptoms remain poorly understood. In particular, the role of sensory neurons in the pathogenesis of long COVID is largely unexplored. This knowledge gap hinders the development of novel therapeutic strategies for managing neurological complications associated with long COVID. Animal models are essential for investigating the role of sensory neurons in SARS-CoV-2 infection and testing preclinical interventions. Unfortunately, existing mouse models that allow for the study of SARS-CoV-2 specific effects on sensory neurons in vivo are lacking. In our research, we found that wild-type mice infected with a mouse- adapted SARS-CoV-2 strain develop long-term pain. To further explore the role of sensory neurons in long COVID, we developed a mouse model with selective SARS-CoV-2 infection of sensory neurons through hACE2 expression in Nav1.8+ neurons. Additionally, we identified lymphotoxin beta receptor (LTβR) as a novel immune regulator of chronic pain following SARS-CoV-2 infection. The objective of this proposal is to investigate the role of LTβR signaling in sensory neurons in the pathogenesis of long COVID and to test the potential of LTβR antagonist to mitigate neurological complications of long COVID. Our central hypothesis is that LTβR signaling in sensory neurons promotes long COVID neurological symptoms which can be ameliorated by administration of LTβR antagonist. This hypothesis will be tested through two specific aims. In Aim 1, we will define the impact of LTβR signaling in sensory neurons on long COVID neurological symptoms, viral replication, and immune cell changes in sensory ganglia, using mice with selective LTβR inactivation in Nav1.8+ sensory neurons. In Aim 2, we will assess the therapeutic effects of LTβR antagonist in alleviating long COVID neurological symptoms and identify critical LTβR-dependent pathways in sensory ganglia using single-cell RNA sequencing. This proposal is innovative, significant and impactful, as it will elucidate the role of sensory neurons in long COVID pain, establish new animal models for studying long COVID, and evaluate the therapeutic potential of LTβR antagonists for treating SARS-CoV-2-induced neurological complications.", "keywords": [ "2019-nCoV", "ACE2", "Acute", "Address", "Affect", "Afferent Neurons", "Angiotensinogen", "Animal Model", "Automobile Driving", "COVID-19", "COVID-19 complications", "COVID-19 impact", "COVID-19 patient", "COVID-19 treatment", "CRISPR/Cas technology", "Cells", "Chimeric Proteins", "Data", "Development", "Disease", "Enzymes", "Exertion", "Exhibits", "Filament", "Genetic", "Goals", "Hand Strength", "Headache", "Human", "Hypersensitivity", "Immune", "Immunohistochemistry", "Immunomodulators", "Impairment", "Individual", "Infection", "Intervention", "Kinetics", "Knowledge", "Ligands", "Light", "Long COVID", "Malaise", "Measures", "Modeling", "Mus", "Myalgia", "Neuroglia", "Neuroimmunomodulation", "Neurologic", "Neurologic Dysfunctions", "Neurologic Symptoms", "Neuronal Plasticity", "Neurons", "Nociceptors", "Pain", "Pain management", "Pathogenesis", "Pathway interactions", "Peripheral", "Peripheral Nervous System Diseases", "Persistent pain", "Play", "Preclinical Testing", "Public Health", "Pulmonary Pathology", "Quality of life", "Receptor Inhibition", "Receptor Signaling", "Recombinants", "Research", "Role", "SARS-CoV-2 infection", "SCN2A protein", "Sensory Ganglia", "Signal Transduction", "Spinal Ganglia", "Structure of trigeminal ganglion", "Study models", "Symptoms", "Testing", "Therapeutic", "Therapeutic Effect", "Therapeutic Intervention", "Time", "Tumor Necrosis Factor Receptor", "Tumor Necrosis Factor-Beta", "Venus", "Virus", "Virus Replication", "Wild Type Mouse", "antagonist", "behavior change", "behavior test", "brain fog", "chemotherapy", "chronic pain", "efficacy testing", "immune activation", "in vivo", "innovation", "insight", "lymphotoxin beta receptor", "mechanical allodynia", "member", "mouse model", "new therapeutic target", "novel", "novel therapeutic intervention", "pain reduction", "painful neuropathy", "post SARS-CoV-2 infection", "pre-clinical", "response", "single-cell RNA sequencing", "transcriptomics", "transmission process" ], "approved": true } }, { "type": "Grant", "id": "15985", "attributes": { "award_id": "1R21AI197441-01", "title": "Sphingolipids and Innate Immunity", "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": 44439, "first_name": "RAJEEV", "last_name": "GAUTAM", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-06", "end_date": "2028-01-31", "award_amount": 195000, "principal_investigator": { "id": 44440, "first_name": "Fikadu G.", "last_name": "Tafesse", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3435, "ror": "", "name": "OREGON HEALTH & SCIENCE UNIVERSITY", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true }, "abstract": "Type I interferon (IFN) is the first line of defense in innate antiviral immunity, orchestrating transcriptional and metabolic responses that restrict viral replication. While IFN signaling is known to modulate sterol and glycerolipid pathways, its impact on sphingolipids (SPLs)—a class of bioactive lipids involved in immune signaling and cell stress responses—remains poorly understood. Mounting evidence suggests that infections by RNA viruses, including flaviviruses and coronaviruses, induce the accumulation of ceramide (Cer), but whether this promotes viral replication or enhances antiviral defenses is unclear. Our preliminary studies show that Zika virus (ZIKV) triggers overall changes in SPL composition and relies on Cer biosynthesis for successful infection. However, other studies implicate Cer in restricting viral replication and promoting cell survival, raising the possibility that these lipids are upregulated by the host response rather than the virus. The central goal of this proposal is to uncover how type I IFN affects SPL metabolism and to determine whether these lipids, in turn, control the IFN response and infection outcomes. We hypothesize that SPLs, particularly Cer, play a dual role in infection and immunity. Viruses may induce Cer to suppress innate immune responses, including IFN production, as suggested by the known roles of Cer in modulating host signaling pathways. However, we also propose that IFN itself alters SPL metabolism, as it does with other lipid classes, and that these IFN-induced lipid changes may contribute to antiviral defense. To disentangle these possibilities, we will use a combination of untargeted lipidomics, innovative SPL probes, CRISPR gene editing, and organelle-targeted lipid perturbation to systematically determine the causes and consequences of SPL dysregulation in infection. Aim 1 will define how IFN-β alters SPL content and distribution in infected and uninfected cells. In doing so, we will generate the first comprehensive map of IFN-driven changes in the cellular lipidome—including SPLs—across multiple cell types, providing a foundational resource for the broader virology and immunometabolism communities. Aim 2 will determine whether Cer regulates IFN-β signaling and antiviral defense, and whether the subcellular location of Cer influences its role as a pro- or anti-viral signal. Together, these studies will determine how IFN shapes and is shaped by SPLs, providing fundamental insight into the role of these lipids in the earliest steps of antiviral innate immunity.", "keywords": [ "Acceleration", "Affect", "Anabolism", "Anti-viral Agents", "Anti-viral Response", "Autoimmune Diseases", "Cell Survival", "Cell model", "Cells", "Cellular Stress", "Ceramides", "Clustered Regularly Interspaced Short Palindromic Repeats", "Communities", "Coronavirus", "Data", "Disease", "Double-Stranded RNA", "Drug Targeting", "Enzymes", "Family", "Flavivirus", "Genes", "Genetic", "Genetic Transcription", "Goals", "Host Defense", "Host Defense Mechanism", "Immune response", "Immune signaling", "Immunity", "Infection", "Innate Immune Response", "Interferon Type I", "Interferon-β", "Interferons", "Knock-out", "Lipids", "Location", "Malignant Neoplasms", "Maps", "Membrane", "Metabolic", "Metabolic Pathway", "Metabolism", "Natural Immunity", "Organelles", "Outcome", "Pathway interactions", "Play", "Process", "Production", "RNA Virus Infections", "RNA Viruses", "Resources", "Risk", "Role", "Shapes", "Signal Pathway", "Signal Transduction", "Sphingolipids", "Sterols", "Time", "Viral", "Viral Pathogenesis", "Viral Physiology", "Virus", "Virus Diseases", "Virus Replication", "Visual", "Work", "ZIKV infection", "Zika Virus", "antiviral immunity", "biological adaptation to stress", "cell type", "cytokine", "drug repurposing", "global health", "innovation", "insight", "lipid biosynthesis", "lipid metabolism", "lipidome", "lipidomics", "mosquito-borne pathogen", "novel", "pandemic potential", "pharmacologic", "programs", "response", "therapeutic target", "tool", "virology" ], "approved": true } }, { "type": "Grant", "id": "15984", "attributes": { "award_id": "1R01AI195471-01", "title": "Molecular evolution of entry receptor usage underlying zoonotic human betacoronaviruses", "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": "2026-02-20", "end_date": "2031-01-31", "award_amount": 481520, "principal_investigator": { "id": 7514, "first_name": "Tyler Nelson", "last_name": "Starr", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 757, "ror": "", "name": "FRED HUTCHINSON CANCER RESEARCH CENTER", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 3434, "ror": "", "name": "UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH", "address": "", "city": "", "state": "UT", "zip": "", "country": "United States", "approved": true }, "abstract": "Most human viruses originate from recent zoonotic spillover, but the upstream evolutionary processes in animal reservoirs that drive zoonosis-promoting traits remain poorly understood. Our long-term goal is to elucidate the evolutionary forces enabling animal viruses to acquire traits facilitating human spillover and adaptation, with a focus on viral entry receptor usage as a critical determinant of cross-species transmission. Toward this end, this proposal investigates the evolutionary dynamics underlying changes in receptor-binding specificity in beta-coronaviruses (CoVs) linked to past and potential future zoonoses: SARS-CoV-2, MERS- CoV, and HKU1 alongside their bat, rodent, and other animal relatives. Our central model is that long-term evolutionary arms races between viruses and wildlife hosts drive evolvable mechanisms of receptor- engagement promoting subsequent human spillover and adaptation. This model will be examined through three specific aims: (1) Identify mechanisms driving human receptor binding in bat SARS-related CoVs; (2) Dissect the origins and consequences of receptor-switching in bat MERS-related CoVs; and (3) Identify evolutionary origins of and functional constraints imposed by a newly discovered HKU1 CoV receptor. In each aim, we combine phylogenetic surveys across diverse animal CoVs with high-throughput mutagenesis screens to map the evolutionary, genetic, and structural mechanisms driving receptor-use transitions and their downstream evolutionary consequences. These studies will illuminate how host-virus dynamics shape receptor-binding architectures to enable zoonotic potential and post-spillover antigenic evolution. The resulting large-scale genotype-phenotype maps will inform computational models for assessing viral zoonotic risk and guide the design of broad-spectrum antibody and vaccine therapeutics for pandemic preparedness. Taken together, this work advances understanding of mechanisms of viral evolution while providing actionable insights for proactive ecological, diagnostic, and therapeutic interventions.", "keywords": [ "2019-nCoV", "ACE2", "Animals", "Antibodies", "Architecture", "Automobile Driving", "Binding", "Biological Factors", "Chiroptera", "Communicable Diseases", "Computer Models", "Coronavirus", "Development", "Diagnostic", "Dissection", "Distal", "Epidemic", "Event", "Evolution", "Future", "Genetic", "Genetic Screening", "Genotype", "Glycoproteins", "Goals", "Human", "Immune", "Infection", "Link", "Maps", "Middle East Respiratory Syndrome", "Middle East Respiratory Syndrome Coronavirus", "Modeling", "Molecular", "Molecular Evolution", "Mutagenesis", "Mutation", "Orthologous Gene", "Pathogenicity", "Pathway interactions", "Phenotype", "Phylogenetic Analysis", "Process", "Proteins", "Public Health", "Research", "Risk", "Rodent", "Role", "SARS coronavirus", "Shapes", "Specificity", "Surveys", "TMPRSS2 gene", "Testing", "Therapeutic", "Therapeutic Intervention", "Vaccines", "Viral", "Viral reservoir", "Virus", "Work", "Yeasts", "Zoonoses", "animal coronavirus", "arms race", "betacoronavirus", "biophysical analysis", "coronavirus receptor", "cross-species transmission", "design", "experience", "future pandemic", "human coronavirus", "improved", "insight", "mutation screening", "novel", "pandemic preparedness", "predictive tools", "pressure", "prevent", "receptor", "receptor binding", "respiratory", "tool", "trait", "transmission process", "vaccine development", "viral outbreak", "zoonotic spillover" ], "approved": true } }, { "type": "Grant", "id": "15983", "attributes": { "award_id": "1R35GM162443-01", "title": "Molecular Mechanisms of Antimicrobial Resistance from Machine Learning Augmented Enhanced Sampling", "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": 44257, "first_name": "ANNE", "last_name": "GERSHENSON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-24", "end_date": "2030-12-31", "award_amount": 401285, "principal_investigator": { "id": 44438, "first_name": "Dhiman", "last_name": "Ray", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3433, "ror": "", "name": "UNIVERSITY OF OREGON", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true }, "abstract": "ABSTRACT: Antimicrobial resistance threatens our ability to treat previously curable infectious diseases and may soon become a global public health crisis. The Ray group aims to understand and characterize the molecular mechanisms of antibiotic and antiviral resistance to identify potential avenues to target resistant pathogens. This R35 MIRA pro- gram involves two distinct research projects that utilize advanced machine learning (ML) and enhanced sampling algorithms for molecular dynamics (MD) simulations to gain mechanistic insights into antimicrobial resistance and facilitate the development of future therapeutic applications. In the first project, we will study the process of ligand binding to riboswitches, a class of regulatory RNA segments that are potential targets for next-generation antibi- otics. Our goal is to identify the role of conformational dynamics and distant nucleotide mutations in modulating the binding mechanism of the small molecule inhibitors (e.g., Ribocil) to RNA targets (e.g., Flavin-mononucleotide (FMN) riboswitch). We will design neural network (NN) and explainable artificial intelligence (XAI) based collec- tive variables from system agnostic descriptor space and perform enhanced sampling simulations to compute the free energy landscape of riboswitch conformational transition and ligand binding. This work will provide key mechanistic insights into RNA-small-molecule interactions and pave the way for designing more resilient antibi- otics. In the second project, we will study how resistant mutations in the viral antigens, e.g., SARS-CoV-2 spike protein, affect the binding mechanism of neutralizing antibodies. Previous research in this area primarily focused on the antigen-antibody interface but often overlooked the long-range allosteric effect of antigen mutations on the antibody binding process. We will perform NN and XAI-guided enhanced sampling simulations to elucidate the mechanistic details of antigen-antibody recognition. In addition, we will trace the allosteric communication path- ways using mutual-information-based protein graph connectivity networks constructed for various intermediate configurations sampled from the association pathway. This work will open new avenues for the rational design of broad-spectrum monoclonal antibodies through the judicious strengthening of distant regions of the antibody structure that are less susceptible to epitope mutations.", "keywords": [ "Affect", "Algorithms", "Antibiotics", "Antibodies", "Antigens", "Antimicrobial Resistance", "Area", "Bacterial RNA", "Binding", "Communicable Diseases", "Communication", "Computer Simulation", "Descriptor", "Development", "Distant", "Epitopes", "Flavin Mononucleotide", "Free Energy", "Future", "Goals", "Graph", "Ligand Binding", "Machine Learning", "Molecular", "Molecular Conformation", "Monoclonal Antibodies", "Mutation", "Nucleotides", "Pathway interactions", "Pharmaceutical Preparations", "Predisposition", "Process", "Proteins", "Public Health", "RNA", "Research", "Research Project Grants", "Resistance", "Resistance development", "Role", "SARS-CoV-2 spike protein", "Sampling", "Small RNA", "Structure", "System", "Therapeutic", "Viral Antigens", "Viral Drug Resistance", "Viral Proteins", "Work", "conformational conversion", "design", "drug candidate", "explainable artificial intelligence", "future antibiotics", "insight", "molecular dynamics", "neural network", "neutralizing antibody", "novel therapeutic intervention", "pathogen", "programs", "rational design", "resilience", "resistance mutation", "simulation", "small molecule", "small molecule inhibitor" ], "approved": true } } ], "meta": { "pagination": { "page": 1, "pages": 1424, "count": 14236 } } }