Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=5&sort=-awardee_organization
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-awardee_organization", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1442&sort=-awardee_organization", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=6&sort=-awardee_organization", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=4&sort=-awardee_organization" }, "data": [ { "type": "Grant", "id": "16104", "attributes": { "award_id": "1K23AI199607-01", "title": "Epidemiological assessment of Strongyloides stercoralis in at-risk populations in Texas", "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": 44582, "first_name": "JOHN T", "last_name": "PESCE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-06-02", "end_date": "2031-05-31", "award_amount": 191219, "principal_investigator": { "id": 44583, "first_name": "Megan", "last_name": "Duffey", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3506, "ror": "", "name": "BAYLOR COLLEGE OF MEDICINE", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Strongyloidiasis (causative agent Strongyloides stercoralis) is a neglected tropical disease that is often asymptomatic but causes severe morbidity and mortality when the infection becomes disseminated in periods of host immunosuppression. Due to the auto-infective portion of the S. stercoralis lifecycle, infections can persist for decades, long after a person has left an endemic area. Although strongyloidiasis is not considered endemic across the United States, places in the southern US with subtropical climates, such as Texas, can support the S. stercoralis lifecycle; therefore, continued transmission can occur. Adequate screening and prompt treatment of asymptomatic chronic strongyloidiasis will prevent the morbidity that disseminated strongyloidiasis carries. Still, cases are likely missed due to a lack of symptoms and suboptimal screening. Wastewater-based epidemiology has recently been leveraged during the COVID-19 pandemic for disease surveillance independent of health- seeking behavior, making it a powerful tool to assess strongyloidiasis, which is often asymptomatic and likely underdiagnosed. The long-term objective of this project is to understand the epidemiology and risk factors of strongyloidiasis in the greater Houston metropolitan area so that public health efforts may be directed towards the timely detection and treatment of at-risk populations. We will achieve this objective by completing the following aims: 1) Determine chronic strongyloidiasis prevalence and associated risk factors in a population seeking healthcare at a safety-net hospital system in Houston, TX, and 2) Identify areas in the greater Houston area with S. stercoralis presence using wastewater-based epidemiology. The innovation of wastewater-based epidemiology in the novel area of strongyloidiasis will be bolstered by a rigorous epidemiological study and risk-factor analysis. Additionally, this project will be innovative in its combination of improved diagnostic testing compared to standard of care. In aim 1, patients seeking healthcare at two primary care clinics in a safety net hospital system in Houston, Texas, will be approached for enrollment. Participants will answer a risk factor questionnaire and undergo blood and stool testing for strongyloidiasis. A risk map will be generated from neighborhood-level variables. In aim 2, wastewater samples from 16 wastewater treatment plants in Houston will be tested for S. stercoralis, and a spatial analysis will be conducted to determine if strongyloidiasis positivity coincides with high-risk areas on the risk map. By completing this project, the candidate, Dr. Megan Duffey, will develop essential skills in advanced epidemiological study design, statistical modeling, geospatial analysis, and science communication and advocacy. With these skills, she will create an R01-funded laboratory studying emerging neglected tropical diseases across the southern US. This work will be completed in the supportive research environment at Texas Children’s Hospital Division of Pediatric Tropical Medicine and Baylor College of Medicine’s National School of Tropical Medicine under the mentorship of Dr. Sarah Gunter and Dr. Peter Hotez.", "keywords": [ "Address", "Advocacy", "Affect", "Agriculture", "Area", "Biological Assay", "Blood", "Blood specimen", "COVID-19 pandemic", "Characteristics", "Childhood", "Chronic", "Climate", "Communication", "Communities", "County", "Coupled", "Data", "Demographic Factors", "Detection", "Diagnosis", "Diagnostic", "Diagnostic tests", "Dideoxy Chain Termination DNA Sequencing", "Disease", "Disease Surveillance", "Enrollment", "Environment", "Environmental Risk Factor", "Epidemiologic Factors", "Epidemiologic Methods", "Epidemiologic Research Design", "Epidemiologic analysis", "Event", "Factor Analysis", "Feces", "Frequencies", "Funding", "Goals", "Growth", "Health Care", "Health system", "Home", "Hospitals", "Immunosuppression", "Immunosuppressive Agents", "Individual", "Infection", "Infrastructure", "Investigation", "Laboratory Study", "Larva", "Left", "Life Cycle Stages", "Low income", "Maps", "Medicine", "Mentorship", "Mexico", "Modeling", "Molecular", "Monitor", "Morbidity", "Nature", "Neighborhoods", "Occupations", "Parasitic nematode", "Participant", "Patients", "Pediatric Hospitals", "Penetration", "Persons", "Plants", "Population", "Populations at Risk", "Poverty", "Prevalence", "Public Health", "Questionnaires", "Recording of previous events", "Research", "Risk", "Risk Factors", "Schools", "Science", "Serology", "Seroprevalences", "Sewage", "Skin", "Soil", "Statistical Data Interpretation", "Statistical Models", "Strongyloides", "Strongyloides stercoralis", "Strongyloidiasis", "Symptoms", "System", "Techniques", "Testing", "Texas", "Time", "Tropical Disease", "Tropical Medicine", "United States", "Urban Developments", "Work", "built environment", "burden of illness", "chronic infection", "college", "deprivation", "disorder risk", "epidemiology study", "experience", "extreme weather", "geospatial analysis", "health seeking behavior", "high risk", "high risk population", "improved", "indexing", "innovation", "metropolitan", "mortality", "neglect", "neglected tropical diseases", "neighborhood characteristics", "novel", "prevent", "primary care clinic", "public health intervention", "recruit", "safety net", "screening", "screening guidelines", "skills", "socioeconomic disadvantage", "standard of care", "stool sample", "tool", "transmission process", "viral pandemic", "wastewater epidemiology", "wastewater samples", "wastewater screening", "wastewater testing" ], "approved": true } }, { "type": "Grant", "id": "16103", "attributes": { "award_id": "1R15GM165000-01", "title": "Mechanisms of Mpro autocleavage", "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": "2026-06-01", "end_date": "2029-05-31", "award_amount": 583503, "principal_investigator": { "id": 44581, "first_name": "John Sing", "last_name": "Choy", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3505, "ror": "", "name": "CATHOLIC UNIVERSITY OF AMERICA", "address": "", "city": "", "state": "DC", "zip": "", "country": "United States", "approved": true }, "abstract": "SARS-CoV-2, the virus that causes COVID-19, relies on a critical enzyme called Mpro (main protease) to reproduce inside infected cells. This enzyme must first \"cut itself free\" from a larger protein before it can function properly. This process is called autocleavage. However, we don't fully understand how this self- activation is controlled, which limits our ability to develop new antiviral treatments. Our research will investigate two key questions about Mpro activation. First, we will determine how small changes in the protein sequences surrounding Mpro affect how efficiently it cuts itself free. We suspect that certain sequence changes could make this process work better, suggesting that the virus hasn't yet evolved to be perfectly efficient. If we can identify these \"better\" sequences, we might discover new ways to disrupt the virus. Second, we will explore how the virus's association with cell membranes influences Mpro activation. The proteins that flank Mpro attach to cellular membranes, and we believe this placement helps coordinate the timing of enzyme activation. Understanding this spatial control could reveal new targets for antiviral drugs. We will use baker's yeast as our experimental system because it allows us to study these processes in a controlled, safe environment without working directly with the live virus. This approach lets us systematically test different protein variants and membrane interactions that would be difficult to study in other systems. We will then validate our most promising yeast findings using safe SARS-CoV-2 replicon systems that mimic viral replication without producing infectious particles. This two-step approach ensures our mechanistic results in yeast are relevant in the viral system. Our research has a strong educational component that will train the next generation of scientists. We will involve undergraduate students, graduate students, and high school students in hands-on research experiences. This work could lead to new therapeutic strategies by identifying previously unknown vulnerabilities in the virus's replication process. The principles we discover may also apply to other similar viruses, potentially informing future pandemic preparedness efforts. The findings will advance our fundamental understanding of how viruses control these essential enzymes while providing authentic research experiences that prepare students for careers in science and medicine.", "keywords": [ "2019-nCoV", "Address", "Affect", "Amino Acid Sequence", "Anti-viral Agents", "Area", "Biological Assay", "Biological Models", "Biology", "COVID-19", "COVID-19 therapeutics", "Cell membrane", "Cells", "Cellular Membrane", "Complex", "Coronavirus", "Data", "Development", "Education", "Educational Status", "Ensure", "Environment", "Enzyme Activation", "Enzymes", "Event", "Evolution", "Future", "Goals", "High School Student", "Hydrophobic Interactions", "Hydrophobic Surfaces", "Knowledge", "Laboratories", "Length", "Mediating", "Medicine", "Membrane", "Membrane Proteins", "Methods", "Modeling", "Molecular", "Papain", "Peptide Hydrolases", "Polyproteins", "Positioning Attribute", "Process", "Productivity", "Protease Inhibitor", "Proteins", "Public Health", "RNA Viruses", "Readiness", "Replication-Associated Process", "Replicon", "Research", "Research Personnel", "Role", "SH2D3A gene", "SH2D3C gene", "Saccharomyces cerevisiae", "Science", "Science Technology Engineering and Mathematics Education", "Scientist", "Site", "Structure", "Students", "System", "Testing", "Therapeutic", "Training", "Variant", "Viral", "Viral Proteins", "Virus", "Virus Replication", "Work", "Yeasts", "anti-viral efficacy", "career", "dimer", "experience", "experimental study", "fitness", "future pandemic", "graduate student", "hands on research", "human disease", "improved", "inhibitor", "insight", "new therapeutic target", "next generation", "novel", "novel therapeutic intervention", "pandemic preparedness", "particle", "premature", "prevent", "programs", "undergraduate research experience", "undergraduate student", "viral fitness", "viral pandemic" ], "approved": true } }, { "type": "Grant", "id": "16101", "attributes": { "award_id": "1R01HL182777-01", "title": "Disordered mitochondrial proteostasis and alveolar epithelial repair in the aging lung", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 44231, "first_name": "INGRID CECILIA", "last_name": "ESPINOZA GRANDON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-06-25", "end_date": "2028-05-31", "award_amount": 1589058, "principal_investigator": { "id": 27544, "first_name": "GR Scott", "last_name": "Budinger", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 31773, "first_name": "Seunghye", "last_name": "Han", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 44579, "first_name": "NAVDEEP S", "last_name": "CHANDEL", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 3504, "ror": "", "name": "NORTHWESTERN UNIVERSITY", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "Pneumonia, the most common cause of death from an infectious disease worldwide, disproportionately affects the elderly. This disproportionate impact of pneumonia in older individuals became evident to all during the COVID-19 pandemic, which caused the death of nearly 7 million mostly elderly people worldwide. Furthermore, older pneumonia survivors are at increased risk for age-related disorders including persistent lung injury, skeletal muscle dysfunction leading to immobility, cognitive impairment, and dementia, highlighting pneumonia as a gateway for the compounding morbidity that limits healthspan at the end of life. We published a mechanistic model to explain the worsened lung injury and impaired lung recovery after viral pneumonia in old compared with young mice and humans. Respiratory viruses infect alveolar epithelial cells damaging the alveolar membrane. The loss of alveolar epithelial cells activates a process of repair, which is primarily mediated by alveolar epithelial type 2 (AT2) cells, the major progenitor cell population in the alveolus. AT2 cells proliferate and differentiate into alveolar epithelial type 1 (AT1) cells to restore the alveolar epithelium. Using single-cell RNA-sequencing, we and others identified a “transitional epithelial cell” population that accumulates during AT2 to AT1 differentiation. During postnatal development, we causally linked an increase in the NADH/NAD+ ratio resulting from dysfunction in complex I of the mitochondrial electron transport chain to pathologic activation of the integrated stress response (ISR) that led to the accumulation of transitional cells and death of the animal during alveologenesis. Our preliminary data reveal that loss of mitochondrial complex I function in AT2 cells of young adult mice leads to progressive fatal lung fibrosis. These findings support our hypothesis that age-related dysfunction in complex I of the mitochondrial electron transport chain increases NADH/NAD+ to induce pathologic activation of the ISR that acts via ATF4 and ATF5 to prevent alveolar epithelial repair after viral pneumonia. We will test this hypothesis in three interrelated Specific Aims. Aim 1: To determine whether age-related changes in mitochondrial complex I function or the mitochondrial NADH/NAD+ ratio in alveolar epithelial cells is necessary for the failure of alveolar epithelial repair after viral pneumonia. Aim 2. To determine whether activation of the ISR is necessary for alveolar epithelial repair after viral pneumonia. Aim 3: To determine whether activation of ATF4 alone or in combination with ATF5 in AT2 cells is necessary for the age-related failure of alveolar epithelial repair after viral pneumonia. Completion of these Aims will credential therapies targeting the NADH/NAD+, ISR, ATF4, and ATF5 to reduce the morbidity and mortality associated with viral pneumonia in the elderly.", "keywords": [ "2019-nCoV", "Adult", "Affect", "Aging", "Alveolar", "Alveolus", "Animals", "COVID-19 pandemic", "Caenorhabditis elegans", "Cause of Death", "Cell Aging", "Cell Differentiation process", "Cell Proliferation", "Cells", "Cellular Stress", "Cessation of life", "Communicable Diseases", "Complex", "Credentialing", "Data", "Dementia", "Development", "Drug Targeting", "EIF-2alpha", "Elderly", "Electron Transport", "Epithelial Cells", "Epithelium", "Exhibits", "Failure", "Functional disorder", "Gases", "Gene Expression", "Gene Targeting", "Genetic", "Human", "Immobilization", "Impaired cognition", "Impairment", "Inflammatory", "Influenza A virus", "Injury", "Link", "Lung", "Mammals", "Measures", "Mediating", "Membrane", "Mitochondria", "Mitochondrial Diseases", "Mitochondrial Electron Transport Complex I", "Modeling", "Morbidity", "Mus", "Mutation", "NADH", "NADH oxidase", "Nature", "Older Population", "Open Reading Frames", "Outcome", "Pathologic", "Pathway interactions", "Patients", "Persons", "Phosphorylation", "Phosphotransferases", "Physiological", "Pneumonia", "Population", "Predisposition", "Process", "Proliferating", "Protein Inhibition", "Proteins", "Publishing", "Pulmonary Fibrosis", "Recovery", "Risk", "Skeletal Muscle", "Survivors", "Testing", "Transitional Cell", "Transitional Epithelium", "Translational Repression", "Translations", "Viral Pneumonia", "Virus", "Yeasts", "Youth", "age related", "age related changes", "age-related disease", "alveolar epithelium", "biological adaptation to stress", "cell injury", "end of life", "epithelial repair", "functional decline", "healthspan", "influenza A pneumonia", "influenza infection", "inhibitor", "lung injury", "lung repair", "mRNA Translation", "mortality", "mouse model", "novel", "old mice", "pharmacologic", "postnatal", "postnatal development", "prevent", "protective pathway", "proteostasis", "recruit", "repaired", "respiratory virus", "response", "single-cell RNA sequencing", "stem cell population", "targeted treatment", "young adult", "young population" ], "approved": true } }, { "type": "Grant", "id": "16099", "attributes": { "award_id": "1R01HL184418-01", "title": "The role of tPA in reducing Lp(a) assembly", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 44576, "first_name": "LIJUAN", "last_name": "LIU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-07-01", "end_date": "2030-03-31", "award_amount": 812747, "principal_investigator": { "id": 44577, "first_name": "Gissette", "last_name": "Reyes-Soffer", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 44578, "first_name": "Ze", "last_name": "Zheng", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 3503, "ror": "", "name": "MEDICAL COLLEGE OF WISCONSIN", "address": "", "city": "", "state": "WI", "zip": "", "country": "United States", "approved": true }, "abstract": "Epidemiological, genome-wide association, and mendelian randomization studies have demonstrated that lipoprotein (a) is an independent causal risk factor for cardiovascular disease. High Lp(a) levels are associated with up to 8 times higher risk of myocardial infarction and ischemic stroke, which are thrombotic events that can occur in atherosclerotic vessels. Lp(a) consists of two main protein components that may both contribute to atherosclerosis and thrombosis: a full-length apolipoprotein B100 (apoB) moiety and an apolipoprotein (a) [apo(a)] moiety. The apoB moiety is pro-atherogenic because it is a low-density lipoprotein (LDL)-like particle with a scaffolding protein apoB. The apo(a) moiety is pro-thrombotic because it is a structural homolog to plasminogen and inhibits plasminogen activation which is the primary mechanism breaking down blood clots, a process called fibrinolysis. The plasma level of Lp(a) was thought to be mostly determined by the genetic variants of LPA gene, and therefore, its level theoretically should be stable, leading to the numerous clinical recommendations for measuring Lp(a) once in lifetime. However, recent evidence shows changes in Lp(a) levels in the same individual. These changes highlight the presence of regulatory mechanisms, beyond genetics, that regulate plasma Lp(a) levels. Fibrinolysis is initiated by a serine protease tissue-type plasminogen activator (tPA) by converting plasminogen to its active form, plasmin, which cleaves cross-linked fibrin clots. Recently we have made several observations that suggest a potential role of tPA in lowering Lp(a) levels. We have shown that: 1) hepatocytes synthesize tPA and hepatocyte-derived tPA contributes to circulating tPA concentration and fibrinolysis. 2) In patients with severe COVID-19, tPA activity decreases while Lp(a) increasing during hospitalization. Among those who survived, Lp(a) decreased and tPA enzymatic activity increased after recovering from COVID-19 symptoms. 3) The Kringle 2 domain of tPA directly binds apoB’s the N-terminus, where the Kringle IV types 5-8 domains of apo(a) also interacts with, suggesting a potential role of tPA in competing with apo(a) for its interaction with apoB. Our new preliminary data showed that 1) tPA forms complexes with apoB’s N-terminal fragments apoB9, apoB15, or apoB18 where apo(a) interacts with apoB through lysine-mediated mechanisms. 2) A lysine analog, tranexamic acid, partially blocks the interaction between tPA and apoB. 3) Silencing tPA in human primary hepatocytes increased Lp(a) in serum-free culture medium. 4) Silencing PAI1 in human primary hepatocytes increases Lp(a) levels. Based on these compelling data, in this proposal, we will test the central hypothesis that tPA inhibits Lp(a) assembly by blocking apoB binding to apo(a) using Lp(a) transgenic mice, human primary hepatocytes and human plasma samples in the following specific aims: Aim 1. To test the hypothesis that tPA blocks apoB-apo(a) interaction. Aim 2. To test the hypothesis that tPA reduces the available apoB and apo(a). Aim 3. To test the hypothesis that reducing Lp(a) by increasing hepatocyte tPA lowers atherosclerosis and improves fibrinolysis.", "keywords": [ "Affect", "Age", "Alteplase", "Antisense Oligonucleotides", "Apolipoproteins", "Aspartic Acid", "Atherogenicity", "Atherosclerosis", "Automobile Driving", "Autophagocytosis", "Autophagosome", "Binding", "Binding Sites", "Blood coagulation", "Body mass index", "COVID-19", "Cardiovascular Diseases", "Charge", "Circulation", "Clinical", "Coagulation Process", "Communities", "Complex", "Culture Media", "Cytolysis", "Data", "Endoplasmic Reticulum", "Epidemiology", "Event", "Fibrin", "Fibrinolysis", "Genes", "Genetic", "Golgi Apparatus", "Hepatocyte", "Homologous Gene", "Hospitalization", "Human", "In Vitro", "Individual", "Ischemic Stroke", "Kringles", "Length", "Lipoprotein (a)", "Low-Density Lipoproteins", "Lysine", "Lysosomes", "Measures", "Mediating", "Mendelian randomization", "Messenger RNA", "Myocardial Infarction", "Myocardial Ischemia", "N-terminal", "Patients", "Plasma", "Plasmin", "Plasminogen", "Plasminogen Activator", "Plasminogen Activator Inhibitor 1", "Process", "Proteins", "Reagent", "Recommendation", "Role", "Sampling", "Scaffolding Protein", "Serine Protease", "Serum", "Sorting", "Symptoms", "Testing", "Thrombosis", "Tranexamic Acid", "Transgenic Mice", "apolipoprotein Lp(a+)", "cardiovascular risk factor", "crosslink", "genetic variant", "genome wide association study", "high risk", "improved", "in vivo Model", "inhibitor", "lysine analog", "multicatalytic endopeptidase complex", "particle", "receptor", "severe COVID-19", "sortilin", "thrombotic" ], "approved": true } }, { "type": "Grant", "id": "16098", "attributes": { "award_id": "1K08AG098035-01", "title": "Identification of molecular-neuropathological signatures in AD, FTLD and Long COVID", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Aging (NIA)" ], "program_reference_codes": [], "program_officials": [ { "id": 44574, "first_name": "CHELSEA MARIE", "last_name": "HAAKENSON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-07-01", "end_date": "2031-04-30", "award_amount": 146750, "principal_investigator": { "id": 44575, "first_name": "Ting", "last_name": "Zhang", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3502, "ror": "", "name": "UNIVERSITY OF CALIFORNIA LOS ANGELES", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Neurodegenerative diseases, including Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), exhibit neuropathological features (e.g., amyloid and p-tau accumulation) that disproportionately affect certain brain regions and subsets of cells. This selective vulnerability to neuropathological features has been recognized for decades, yet its underlying molecular mechanisms remain unclear. Long COVID, a prevalent post-pandemic condition with largely unknown disease mechanisms, is reported to exhibit p-tau pathology, linking it to neurodegeneration. Current methods, including single-nucleus RNA sequencing, are unable to integrate spatial and pathological contexts with transcriptomic profiles, limiting direct molecular characterization of disease pathology at the single cell level. Here, I propose to leverage single-cell spatial multi-omics on postmortem brain tissues to in-situ capture molecular and cellular alterations that directly linked to selective vulnerability to neuropathological features across AD, FTLD, and Long COVID at single-cell resolution—insights previously unattainable. I will also identify potential pathological modulators using functional genomics in human induced pluripotent stem cell (iPSC)-derived neurons. In this proposal, Aim1 will characterize neuropathological and transcriptomic alterations in Long COVID and compare findings to AD and FTLD. Aim2 will leverage same- slide single-cell spatial multi-omics with neuropathology phenotyping (Xenium 5K + Phenocycler-Fusion) and define the molecular-neuropathological signatures specific to amyloid, neuronal p-tau, and glial p-tau pathology in AD, FTLD and Long COVID. Aim3 will employ CRISPRi/a screening in iPSC-derived neurons to identify neuronal p-tau modifiers from signatures uncovered in Aim2. By integrating single-cell spatial multi-omics with functional genomics, this project will bridge the gap between neuropathology and molecular profiling, provide novel insights into selective vulnerability to neuropathological features and identify pathological modulators. My long-term goal is to become a physician(neuropathologist)-scientist leading a NIH-funded research laboratory focused on neurodegenerative diseases and COVID-19. This five-year mentored career development plan will provide the necessary training for my transition to independence, emphasizing expertise in single-cell spatial transcriptomics and proteomics, bioinformatics, imaging analysis, iPSC technology and CRISPR-based functional genomics. Additionally, I will deepen my knowledge of neuropathology, molecular genetics, and clinical aspects of AD, FTLD, and Long COVID. I have assembled a multidisciplinary mentorship team of distinguished physician-scientists that includes Dr. Daniel Geschwind (primary mentor), Drs. Harry Vinters and Shino Magaki (co-mentors), and advisory members Drs. Inma Cobos, Vivek Swarup, and Edward Lee. With UCLA's cutting- edge facilities, exceptional research environment, and strong clinical resources, this award will prepare me to become a competitive neuropathologist-scientist, advancing our understanding of neurodegenerative diseases and COVID-19 while informing therapeutic strategies.", "keywords": [ "Address", "Affect", "Aging", "Alzheimer's Disease", "Alzheimer's disease brain", "Amyloid", "Astrocytes", "Autopsy", "Award", "Bioinformatics", "Brain", "Brain region", "COVID-19", "CRISPR interference", "Cell Communication", "Cell Death", "Cell model", "Cells", "Clinical", "Clustered Regularly Interspaced Short Palindromic Repeats", "Code", "Coiled Bodies", "Couples", "Data", "Dementia", "Development Plans", "Diagnosis", "Diffuse", "Disease", "Disease Progression", "Environment", "Etiology", "Exhibits", "Flow Cytometry", "Frontotemporal Lobar Degenerations", "Functional disorder", "Funding", "Genes", "Goals", "Image", "Immunofluorescence Immunologic", "In Situ", "Individual", "Induced pluripotent stem cell derived human neuron", "Induced pluripotent stem cell derived neurons", "Knowledge", "Laboratory Research", "Link", "Long COVID", "Mentors", "Mentorship", "Methods", "Molecular", "Molecular Genetics", "Molecular Profiling", "Nature", "Nerve Degeneration", "Neurodegenerative Disorders", "Neurofibrillary Tangles", "Neurons", "Onset of illness", "Pathologic", "Pathology", "Patients", "Phenotype", "Physicians", "Pick Disease of the Brain", "Pick body", "Progressive Supranuclear Palsy", "Proteins", "Proteomics", "Reporting", "Research", "Resolution", "Resources", "Scientist", "Senile Plaques", "Slide", "Stimulus", "Tauopathies", "Technology", "Therapeutic", "Tissues", "Training", "United States National Institutes of Health", "Work", "acute COVID-19", "amyloid pathology", "brain cell", "brain tissue", "career development", "cell type", "cohort", "four repeats tau", "functional genomics", "human induced pluripotent stem cells", "hyperphosphorylated tau", "induced pluripotent stem cell", "induced pluripotent stem cell technology", "insight", "member", "multidisciplinary", "neuropathology", "novel", "post-pandemic", "resilience", "response", "screening", "single nucleus RNA-sequencing", "spatial integration", "spatial omics", "spatial transcriptomics", "tau Proteins", "tau aggregation", "tau-1", "transcriptome sequencing", "transcriptomics" ], "approved": true } }, { "type": "Grant", "id": "16097", "attributes": { "award_id": "1R21AI195374-01", "title": "Antifolates with Broad Spectrum Antifungal Activity", "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": 44573, "first_name": "BAOYING", "last_name": "LIU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-07-01", "end_date": "2028-06-30", "award_amount": 251062, "principal_investigator": { "id": 24307, "first_name": "Dennis L.", "last_name": "Wright", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3501, "ror": "", "name": "UNIVERSITY OF CONNECTICUT STORRS", "address": "", "city": "", "state": "CT", "zip": "", "country": "United States", "approved": true }, "abstract": "The effective treatment of invasive fungal infections represents a growing, unmet clinic need that is exacerbated by the development of antimicrobial resistance by major pathogenic strains and the emergence of new species. These infections are often associated with immunocompromised patient populations, such as chemotherapy patients or patients being treated with immunosuppressive therapies for autoimmune or inflammatory disease. These infections also present as secondary infections following illnesses such as infection by SARS-CoV-2, tuberculosis or unmanaged HIV. Although most of these pathogens occur as opportunistic infections in vulnerable patient populations, the recently emerging Candida auris has shown a more infective profile and has been responsible for several outbreaks among immunocompetent patients in the healthcare setting. C. auris, a saprophytic fungus, has emerged only recently as a human pathogen. Other saprophytic fungi, like Aspergillus spp. and Coccidioides spp., are also ubiquitous where inhalation of spores lead to colonization of the respiratory track can lead to serious disease. New therapeutics are desperately needed to address these pathogens. Our lab has been interested using structure-based design to aid the development of novel agents targeting one-carbon metabolism in both prokaryotic and eukaryotic pathogens. In prior work, we developed inhibitors of the fungal dihydrofolate reductase (DHFR) enzymes from opportunistic fungi such as Candida albicans, Candida glabrata and Cryptococcus neoformans. DHFR catalyzes the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate, a key carrier of one carbon units required for the synthesis of deoxythymidine monophosphate and purines need for genome replication, as well as methionine needed for the recycling of SAM cofactors. These efforts have resulted in the preparation of a library of over 200 antifolates, representing a variety of chemotypes with respect to shape, charge and polarity – parameters we have shown to be important determinants for fungal cell permeation and efflux. Our compound collection can be leveraged to identify leads against other priority pathogens, having already identified compounds with activity against C. auris, Coccidioides immitis (causative agent of Valley fever) and moderate activity against Aspergillus fumigatus. Recently, we were able to obtain high resolution crystal structures of several lead antifolates in complex with C. auris DHFR. In this proposal, we will expand our in-house library and evaluate it against these three pathogens at both the target and organism level to identify important structure activity relationships related to potency, selectivity and spectrum of coverage. Subsequent structure-based design approaches will be directed at the identification of promising candidates for one or more priority fungal pathogens. These compounds will be further developed in the R33 phase through optimization of pharmacokinetics properties and evaluation in animal efficacy models.", "keywords": [ "2'-Deoxythymidine", "Address", "Adverse event", "Antimicrobial Resistance", "Aspergillus", "Aspergillus fumigatus", "Autoimmune Diseases", "Azoles", "Binding Proteins", "Candida", "Candida albicans", "Candida auris", "Candida glabrata", "Carbon", "Cells", "Charge", "Clinic", "Coccidioides", "Coccidioides immitis", "Collaborations", "Collection", "Complex", "Cryptococcus neoformans", "Crystallization", "Data", "Development", "Dihydrofolate Reductase", "Dihydrofolate Reductase Inhibitor", "Disease", "Disease Outbreaks", "Dose", "Drug Kinetics", "Drug or chemical Tissue Distribution", "Drug resistance", "Ensure", "Enzyme Inhibition", "Enzymes", "Evaluation", "Folic Acid Antagonists", "Fungal Proteins", "Fungal Spores", "Genome", "Grant", "HIV", "Half-Life", "Homologous Gene", "Human", "Immunocompetent", "Immunocompromised Host", "In Vitro", "Incidence", "Infection", "Inflammatory", "Inhalation", "Lead", "Libraries", "Mammalian Cell", "Measures", "Metabolic", "Metabolism", "Methionine", "Modeling", "Moderate Activity", "Mus", "Mycoses", "NADP", "Opportunistic Infections", "Organism", "Oxidoreductase", "Pathogenicity", "Patients", "Permeability", "Persons", "Phase", "Population", "Positioning Attribute", "Preparation", "Property", "Purines", "Qualifying", "Recycling", "Reproduction spores", "Resistance", "Resources", "Respiratory Disease", "Respiratory System", "Role", "SARS-CoV-2 infection", "Series", "Serum", "Shapes", "Solubility", "Structure", "Structure-Activity Relationship", "Tetrahydrofolates", "Therapeutic", "Therapeutic immunosuppression", "Time", "Toxic effect", "Tuberculosis", "Vulnerable Populations", "Work", "animal efficacy", "anti-fungal agents", "appropriate dose", "chemotherapy", "cofactor", "desert fever", "dihydrofolate", "effective therapy", "efficacy evaluation", "efflux pump", "emerging pathogen", "experience", "falls", "fungus", "health care settings", "high-resolution", "human pathogen", "in vivo", "in vivo evaluation", "inhibitor", "interest", "lead series", "medication safety", "mouse model", "mutant", "novel", "novel therapeutics", "pathogen", "pathogenic fungus", "patient population", "priority pathogen", "residence", "respiratory colonization", "secondary infection", "structure-based drug design", "structure-guided design", "targeted agent", "transmission process" ], "approved": true } }, { "type": "Grant", "id": "16095", "attributes": { "award_id": "1P60AA032166-01", "title": "ARCH REACH Telephone Delivered Brief Alcohol Interventions for People with HIV", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Alcohol Abuse and Alcoholism (NIAAA)" ], "program_reference_codes": [], "program_officials": [], "start_date": "2026-07-20", "end_date": "2031-06-30", "award_amount": 283186, "principal_investigator": { "id": 25058, "first_name": "Judith", "last_name": "Tsui", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3500, "ror": "", "name": "UNIVERSITY OF WASHINGTON", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "Unhealthy alcohol use (UAU) among people with HIV (PWH) is a modifiable barrier to HIV treatment as prevention and widespread efforts to end the HIV epidemic. Despite effective evidence-based interventions (EBI) that reduce UAU and improve viral suppression among PWH, there are substantial gaps in their uptake and receipt. As we emerge from the COVID-19 pandemic there is a need to “step-up” efforts to address UAU in HIV clinics. Our prior work has demonstrated the effectiveness of person and computer-delivered brief alcohol intervention in HIV care settings, yet a major limitation of these interventions is that they require either an in- clinic visit, or a computer or device with reliable internet connection and a level of comfort with computers or devices that many individuals do not possess. We propose to adapt and pilot test a telephone-based model to deliver EBI for UAU for PWH using a Type1 Hybrid Implementation-Effectiveness design to inform and increase efficiency of future implementation if the intervention shows promise. If successful, this research will provide evidence for a clinical intervention that can easily adopted by other HIV clinics, and thus have widespread effects on reducing UAU and contributes toward ending the HIV epidemic. Co-led by Dr. Tsui and Dr. Kim, the research will occur in three phases/aims. Aim#1 will adapt an evidence-based brief alcohol intervention currently delivered in-person and by computer to PWH, for telephone delivery using human- centered design methods. In Aim#2, we will conduct a pilot RCT (N=60) of this telephone-based brief alcohol intervention (T-BAI) among PWH with unhealthy alcohol use. PWH will be recruited from HIV clinics at the UW/Harborview Medical Center and randomized to T-BAI or wait-list control and outcomes will include alcohol risk scores, alcohol treatment engagement, and antiretroviral therapy adherence, retention in care, and viral suppression. In the third phase, using mixed methods and guided by the Consolidated Framework for Implementation Research, we will explore the potential for future implementation of T-BAI in other HIV clinical settings.", "keywords": [ "ARHGEF5 gene", "Acceleration", "Address", "Adherence", "Adopted", "Alcohol consumption", "Alcohols", "COVID-19 pandemic", "Caring", "Clinic Visits", "Clinical", "Clinical Treatment", "Communities", "Computers", "Consolidated Framework for Implementation Research", "Continuity of Patient Care", "Data Analyses", "Data Collection", "Devices", "Economically Deprived Population", "Effectiveness", "Eligibility Determination", "Equity", "Evidence based intervention", "Funding", "Future", "Goals", "HIV", "HIV Care", "HIV Clinic", "HIV epidemic", "HIV therapy", "HIV transmission", "Health", "Individual", "Internet", "Interruption", "Intervention", "Intervention Studies", "Interview", "Knowledge", "Left", "Medical center", "Methods", "Modeling", "Outcome", "Patients", "Pattern", "Personal Satisfaction", "Persons", "Pharmacotherapy", "Phase", "Population", "Provider", "Randomized", "Research", "Research Activity", "Risk", "Risk Behaviors", "Service delivery model", "Services", "Structure", "Surveys", "Technology", "Time", "Universities", "Viral", "Vulnerable Populations", "Waiting Lists", "Washington", "Work", "alcohol abuse therapy", "alcohol misuse", "alcohol risk", "antiretroviral therapy", "arm", "brief alcohol intervention", "clinical research site", "comorbidity", "comparison control", "digital divide", "effectiveness/implementation design", "effectiveness/implementation hybrid", "evidence base", "future implementation", "health equity", "human centered design", "implementation determinants", "implementation intervention", "improved", "pandemic disease", "patient oriented", "people living with HIV", "pilot test", "pilot trial", "post-COVID-19", "recruit", "remote delivery", "remote health care", "risk score", "social", "socioeconomic disadvantage", "stakeholder perspectives", "substance use", "telephone based", "telephone delivery", "therapy adherence", "treatment as prevention", "uptake" ], "approved": true } }, { "type": "Grant", "id": "16092", "attributes": { "award_id": "1R21AI202573-01", "title": "Targeting Runx3 as a Novel Treatment for Hemophagocytic Lymphohistiocytosis", "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": 44568, "first_name": "MARGARET A", "last_name": "MORRIS FEARS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-07-20", "end_date": "2028-06-30", "award_amount": 223500, "principal_investigator": { "id": 31600, "first_name": "HUA", "last_name": "TANG", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3499, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH CTR AT TYLER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Project Summary: Primary hemophagocytic lymphohistiocytosis (pHLH) is a life-threatening genetic disease (inborn error of immunity) caused by biallelic mutations in genes involved in the cytotoxic machinery of cytotoxic CD8+ T and NK cells. When triggered by a viral infection, the impaired cytotoxic functions result in the exuberant activation and expansion of IFN-producing CD8+ T cells, leading to a self-perpetuating IFN-driven cytokine storm and hemophagocytosis. pHLH commonly occurs in early childhood and is often triggered by viral infection, although pathogens are diverse (viral, bacterial and fungal) and influenced by geographic regions. Despite use of the conventional immunosuppressive and chemotherapeutic regimens and the recently developed anti-IFN therapies, up to 40% of pHLH patients die due to uncontrolled disease and/or the complications of its treatment. Hence, there is a pressing need to develop novel and more effective therapies with less toxicity to ultimately improve outcomes for pHLH patients. This R21 proposal will address this important issue by targeting Runx3 (a critical regulator of CD8+ T cells) for the treatment of pHLH. We and other groups have demonstrated that Runx3 is essential for the activation and expansion of CD8+ cytotoxic T cells and the cell expression of IFN in response to the infections of lymphocytic choriomeningitis virus (LCMV) or influenza A virus (IAV). We also found that an inducible general Runx3 KO did not significantly alter IAV clearance in mice but tended to improve animal survival outcomes following IAV infection, although the numbers of lung CD8+ cytotoxic T cells were markedly reduced. Our new preliminary data show that Runx3 preferentially mediates IFN production from T cells, especially CD8+ T cells by IL-12 plus IL-18 that are two potent inducers of IFN production. Moreover, Runx3 regulates IL-12/IL- 18-mediated production of IFN in mice with endotoxin lipopolysaccharide (LPS) challenge. As a result, Runx3 KO markedly suppressed the IFN-central cytokine storm and mortality in mice challenged with a lethal dose of LPS. These preliminary data prompt us to test the hypothesis that targeting Runx3 could be an effective therapeutic strategy for pHLH. We will test this novel hypothesis with the following two sub-aims. 1) Determine the role of Runx3 in pHLH using a LCMV-infected Prf1−/−;Runx3-KO mouse model; 2) Determine the effect of Runx3 KO after the onset of pHLH on host immune responses. The proposed studies have not been explored previously and will offer proof of concept that targeting Runx3 is a tolerable and effective therapeutic strategy for pHLH, a life-threatening hyperinflammatory disease, thereby will advance the field. If successful, this proposal will attract future development of Runx3 selective inhibitors to treat this often-fatal HLH disease.", "keywords": [ "Affect", "Alleles", "Animals", "Antigens", "Birth", "Blood Cells", "CD8-Positive T-Lymphocytes", "CD8B1 gene", "CHS1 gene", "Cells", "Clinical", "Clinical Management", "Complete Blood Count", "Data", "Development", "Disease", "Dose", "Embryonic Development", "Endotoxins", "Ferritin", "Future", "Gene Expression Profile", "Generations", "Genes", "Genetic", "Genetic Diseases", "Geographic Locations", "Hemoglobin", "Hemophagocytic Lymphohistiocytoses", "Histiocytosis haematophagic", "IL18 gene", "Immune response", "Immunosuppression", "Impairment", "Infection", "Inflammation", "Inflammatory", "Influenza A virus", "Injury", "Interferon Inducers", "Interferons", "Interleukin-12", "Knock-out", "Knockout Mice", "Life", "Lipopolysaccharides", "Lung", "Lymphocytic choriomeningitis virus", "Macrophage", "Macrophage Activation", "Mediating", "Mus", "Mutation", "Myeloid Cells", "Natural Killer Cells", "Organ", "Outcome", "Pathogenesis", "Patients", "Production", "RUNX3 gene", "Reaction", "Regimen", "Regulation", "Role", "Seasons", "Serum", "Spleen", "Syndrome", "T-Cell Activation", "T-Lymphocyte", "T-Lymphocyte Subsets", "Testing", "Therapeutic", "Thymus Gland", "Tissues", "Toxic effect", "Triglycerides", "Viral", "Virus Diseases", "Weight", "congenital immunodeficiency", "cytokine", "cytokine release syndrome", "cytotoxic", "cytotoxic CD8 T cells", "early childhood", "effective therapy", "familial hemophagocytic lymphohistiocytosis", "improved", "improved outcome", "inhibitor", "interleukin-12 receptor", "interleukin-18 receptor", "mortality", "mouse model", "novel", "pathogen", "perforin", "response", "survival outcome", "therapeutically effective", "transcription factor", "transcriptome sequencing" ], "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": "16091", "attributes": { "award_id": "1R35GM165843-01", "title": "Modeling the Emergence Cascade: From Wildlife Pathogen Circulation to Human Outbreak Amplification", "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": 32565, "first_name": "GUOQIN", "last_name": "YU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-07-16", "end_date": "2031-05-31", "award_amount": 393673, "principal_investigator": { "id": 44567, "first_name": "Mekala", "last_name": "Sundaram", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3498, "ror": "", "name": "UNIVERSITY OF GEORGIA", "address": "", "city": "", "state": "GA", "zip": "", "country": "United States", "approved": true }, "abstract": "Emerging infectious diseases are among the greatest threats to global health, as shown by recent emergences of Ebola, Zika, avian influenza, and coronaviruses. Although zoonotic outbreaks are recognized as a One Health challenge, most research has focused on single pathogens, retrospective studies of animal hosts, or on human-centered transmission dynamics. This siloed approach neglects how upstream drivers such as wildlife epizootics and hidden host- specific zoonotic burdens influence spillover risk, as well as the ecological and social conditions that transform small spillover events into large epidemics. Without an integrated framework linking animal and human health, pandemic preparedness remains largely reactive rather than preventive. My proposed R35 MIRA program will develop a comprehensive, predictive framework for zoonotic emergence spanning the full cascade from wildlife epizootics to human spillover and outbreak amplification. My hypothesis is that explicitly incorporating animal health measures into models of human disease risk will significantly improve forecasts. To test this, my team and I will integrate large-scale host–virus networks, ecological and demographic data, and advanced statistical and machine learning approaches. We will: (1) identify ecological and environmental drivers of wildlife epizootics, (2) estimate hidden or unsampled viral burdens as well as true total zoonotic burden across animal host taxa, and (3) quantify spillover and amplification risk through a novel standardized epidemic potential parameter that extends beyond R₀. Results will be synthesized into agent-based models, predictive risk maps and early- warning tools validated with influenza and coronavirus datasets. By explicitly linking animal epizootics, host zoonotic burden, spillover dynamics, and amplification risk, this program will generate a multi-stage, data-driven framework for pathogen emergence. Expected outcomes include transformative insights into the upstream drivers of diseases, identification of early warning signals in wildlife health and actionable forecasting tools to strengthen One Health surveillance efforts and pandemic preparedness. Beyond scientific impact, this program will also establish generalizable methodologies and train researchers in advanced modeling, which aligns with the NIGMS MIRA mission to support sustained, flexible, and impactful research with broad relevance to human health.", "keywords": [ "Animals", "Avian Influenza", "Circulation", "Coronavirus", "Data", "Data Set", "Disease", "Disease Outbreaks", "Early identification", "Ebola", "Emerging Communicable Diseases", "Epidemic", "Health", "Human", "Influenza", "Link", "Maps", "Measures", "Methodology", "Mission", "Modeling", "National Institute of General Medical Sciences", "Outcome", "Preventive", "Readiness", "Research", "Research Personnel", "Retrospective Studies", "Risk", "Signal Transduction", "Social Conditions", "Standardization", "Testing", "Training", "Viral Load result", "Virus", "Work", "ZIKA", "Zoonoses", "disorder risk", "epidemic potential", "epizootic", "flexibility", "future pandemic", "global health", "human model", "improved", "insight", "neglect", "novel", "pandemic disease", "pandemic preparedness", "pathogen", "prevent", "programs", "risk prediction", "spillover event", "statistical and machine learning", "tool", "transmission process" ], "approved": true } } ], "meta": { "pagination": { "page": 5, "pages": 1442, "count": 14420 } } }