Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1404&sort=start_date
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=start_date", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1419&sort=start_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=start_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1403&sort=start_date" }, "data": [ { "type": "Grant", "id": "15767", "attributes": { "award_id": "1R35GM160163-01", "title": "Scalable and Epidemiologically Interpretable Phylodynamics to Recover Heterogeneous Transmission Dynamics", "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": "2025-08-01", "end_date": "2030-06-30", "award_amount": 410000, "principal_investigator": { "id": 32838, "first_name": "Nicola Felix", "last_name": "Mueller", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2635, "ror": "", "name": "UNIVERSITY OF CALIFORNIA, SAN FRANCISCO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "As pathogens are transmitted between individuals, they accumulate mutations, leaving a footprint of the transmission history in the pathogen genomes. Using phylogenetic methods, we can reconstruct the transmission history connecting individual cases from these genomes, by reconstructing the relationships of the pathogens. We can then infer population-level transmission dynamics, from the ancestral relationships of the pathogens, or phylogenies, using phylodynamic methods. Infectious disease transmission and disease burden are highly heterogeneous, differing between neighborhoods, across age, and socioeconomic groups, and racial and ethnic lines. This heterogeneity means that it is crucial to a) be able to illuminate differential disease burdens and b) account for these heterogeneities when modeling or forecasting infectious disease outbreaks. Traditional approaches based on reported caseloads are often insufficient for capturing the full scope of highly heterogeneous transmission dynamics. Phylodynamics offers a potential solution, as it infers transmission dynamics from the connectivity of cases, providing an opportunity to disentangle these complex patterns. However, limitations in our available toolbox prevent us from fully utilizing the vast availability of pathogen genomes to study these complex transmission dynamics, as current phylodynamic approaches suffer from multiple challenges. With the advent of widely available sequencing, phylodynamic tools are not computationally efficient enough to analyze the amounts of data generated at the granular scales crucial to understanding transmission dynamics. Additionally, the model parameters need to be epidemiologically interpretable to be actionable. In this project, we seek to address these two points by developing novel approaches to reconstruct transmission dynamics from pathogen sequence data. We will develop novel phylodynamic tools to reconstruct transmission dynamics at a granular scale by integrating neural networks into phylodynamic likelihood calculations that we show in preliminary results to dramatically improve computational efficiency and scalability. Phylodynamic methods are parameterized by more or less abstract parameters that either have no direct epidemiological meaning or are contingent on idealized assumptions about disease spread. We will establish how and when current approaches return biased results when reconstructing city-scale transmission dynamics, describe how they can be used to estimate actual disease burden, and test them using SARS-CoV-2 sequence data collected by Kaiser Permanente Southern California (KPSC) and in the UK over the pandemic. Finally, we will develop ways to quantify the factors influencing disease burden, such as geography, age, and socioeconomics. We will apply these tools to KPSC SARS-CoV-2 data, where we can access rich patient metadata to study these patterns. Our overarching goal is to utilize phylodynamic inference of heterogeneous transmission dynamics to parameterize complex infectious disease dynamic models and improve prediction accuracy.", "keywords": [ "2019-nCoV", "Address", "Age", "California", "Cities", "Communicable Diseases", "Complex", "Data", "Disease", "Disease Outbreaks", "Epidemiology", "Ethnic Origin", "Genome", "Geography", "Goals", "Guidelines", "Heterogeneity", "Individual", "Metadata", "Methods", "Modeling", "Mutation", "Neighborhoods", "Patients", "Pattern", "Phylogenetic Analysis", "Phylogeny", "Population", "Race", "Recording of previous events", "Reporting", "Testing", "Viral", "burden of illness", "disease transmission", "genome sequencing", "improved", "neural network", "novel", "novel strategies", "pandemic disease", "pathogen", "pathogen genome", "prevent", "socioeconomics", "tool", "transmission process" ], "approved": true } }, { "type": "Grant", "id": "15769", "attributes": { "award_id": "1K23HL181397-01", "title": "Optimal Ventilator Management in Patients with ARDS on ECMO", "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": 32586, "first_name": "ROYA", "last_name": "KALANTARI", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2030-07-31", "award_amount": 178846, "principal_investigator": { "id": 32840, "first_name": "Mazen Faris", "last_name": "Odish", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2637, "ror": "", "name": "UNIVERSITY OF CALIFORNIA, SAN DIEGO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Research Plan: Acute respiratory distress syndrome (ARDS) is a severe and common condition that affects 10% of patients in the intensive care unit (ICU), and was a major cause of morbidity and mortality during the COVID-19 pandemic. While mechanical ventilation is often necessary for ARDS, it can also induce additional lung injury known as ventilator induced lung injury (VILI). VILI may be minimized by using low tidal volumes/driving pressure and with positive end expiratory pressure (PEEP). Some patients with severe and refractory ARDS require veno-venous extracorporeal membrane oxygenation (V-V ECMO), the highest level of life support which provides oxygen and removes carbon dioxide from the blood using an external device. A major benefit of ECMO is thought to be the ability to minimize VILI; however, the optimal ventilator settings for patients with ARDS on ECMO are not known. Current guidelines use a one-size-fits-all approach. Our central hypothesis is that personalized PEEP adjusted by measuring intrathoracic pressures via esophageal manometry (Pes) will decease VILI as assessed by biomarkers of inflammation (main outcomes IL-6 and sRAGE). To carry out these aims, we plan to prospectively randomize 62 patients with ARDS on V-V ECMO and neuromuscular blockade and perform serial biomarker measurements with PEEP of 10 cmH2O (ECMO guidelines) vs. PEEP guided by esophageal manometry. In addition to biomarkers of VILI, we will assess differences in other physiological outcomes including pulmonary mechanics and gas exchange. Although this proposal focuses on patients on ECMO, we believe the knowledge gained will have relevance for all patients with ARDS. Career Development Plan: The goal of the PI, Dr. Mazen Odish, is to personalize ARDS and ventilator strategies for those on ECMO based on physiology and biomarkers. The PI has an interest in applied physiology and critical care, this award will help him refine these skills and develop new skills in clinical trials, statistics, and patient-oriented research, to test rigorously methods to care for critically ill patients with ARDS with or without ECMO. To obtain these new skills Dr. Odish and his excellent and multi-disciplinary mentoring/advisory team (led by Drs. Owens and Malhotra, plus outstanding statistical and methodologic support) has three main training goals. 1) Pulmonary mechanics and biomarkers during ARDS, 2) control of breathing and measurement of work of breathing during ARDS/mechanical ventilation, and 3) clinical trial design and statistical training. These training activities are tailored for the PI to achieve his goals and maximize career development towards becoming an independent physician scientist. Furthermore, his structured course work will lead to a Masters of Advanced Studies in Clinical Research. Dr. Odish is at the right place and time in his career to align his clinical expertise in ECMO and ARDS with his research goals to understand optimal ventilator settings and therapies. Eventually his work and new skill set may improve the lives of all people suffering from respiratory illness.", "keywords": [ "Acute Respiratory Distress Syndrome", "Advisory Committees", "Affect", "Arteries", "Atelectasis", "Automobile Driving", "Award", "Biological Markers", "Blood", "Body Weight", "Breathing", "COVID-19 pandemic", "Carbon Dioxide", "Clinical", "Clinical Research", "Clinical Trials", "Clinical Trials Design", "Critical Care", "Critical Illness", "Development Plans", "Devices", "Esophagus", "Extracorporeal Membrane Oxygenation", "Functional disorder", "Gases", "Goals", "Guidelines", "Heart and Lung machine", "Heterogeneity", "Hour", "Hypoxemia", "Induction of neuromuscular blockade", "Inflammation", "Injury", "Intensive Care Units", "Interleukin-6", "Knowledge", "Life", "Lung", "Lung Compliance", "Manometry", "Measurement", "Measures", "Mechanical ventilation", "Mechanics", "Mediator", "Mentors", "Meta-Analysis", "Methodology", "Methods", "Morbidity - disease rate", "Multiple Organ Failure", "Organ", "Outcome", "Oxygen", "Patient Care", "Patients", "Persons", "Physicians", "Physiological", "Physiology", "Positive-Pressure Respiration", "Process", "Prone Position", "Pulmonary Gas Exchange", "Randomized", "Recommendation", "Recording of previous events", "Refractory", "Research", "Research Design", "Resolution", "Respiratory Failure", "Respiratory System", "Respiratory physiology", "Rest", "Risk", "Scientist", "Stress", "Structure", "Testing", "Tidal Volume", "Time", "Training", "Training Activity", "Venous", "Ventilator", "Ventilator-induced lung injury", "Vision", "Work", "Work of Breathing", "career", "career development", "esophagus pressure", "healing", "improved", "improved outcome", "individual patient", "interest", "lung injury", "mortality", "multidisciplinary", "patient oriented research", "personalized approach", "pressure", "prevent", "primary outcome", "prospective", "pulmonary", "radiological imaging", "respiratory", "skills", "soluble RAGE", "statistics", "theories", "ventilation" ], "approved": true } }, { "type": "Grant", "id": "15771", "attributes": { "award_id": "1R01AI185685-01A1", "title": "Multi Parametric Total-Body Imaging of Immune Activation in Post Acute Sequelae of SARS-CoV-2 (PASC)", "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": 32843, "first_name": "JOSEPH J", "last_name": "BREEN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2029-07-31", "award_amount": 808672, "principal_investigator": { "id": 32844, "first_name": "Negar", "last_name": "Omidvari", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2639, "ror": "", "name": "UNIVERSITY OF CALIFORNIA AT DAVIS", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Post-acute sequelae of SARS-CoV-2 infection (PASC) is a persisting health challenge characterized by a range of symptoms affecting multiple organ systems, which continues to impact approximately 10% of COVID-19 survivors. Multiple, potentially overlapping, mechanisms have been identified that may play a role in PASC. However, with no effective preventative measures or treatments, there is a critical unmet need for understanding the pathophysiology of PASC; as previous studies, often limited by focus on peripheral blood biomarkers only or confined to single organ systems, have not sufficiently and quantitatively investigated the multisystemic and immune-related complexities of this condition in non-blood tissue. The long-term objective of this project is to bridge this knowledge gap by providing insight into the immune and systemic manifestations of PASC, through the innovative use of total-body dynamic positron emission tomography (PET) with the 18F-AraG radiotracer, which particularly offers selectivity towards activated T cells. To achieve this, we will use the dynamic PET images obtained from a high-sensitivity total-body PET scanner to develop, optimize, and validate a kinetic model for 18F-AraG in different anatomical sites and tissue types for multi parametric quantification of uptake. We expect that this will not only improve the quantification accuracy compared to standard static imaging, but also can shed light on the underlying mechanisms of uptake. The multi parametric imaging will be firstly used to identify sites of immunological perturbation in PASC patients, offering a total-body view of tissue-level manifestations of PASC. For this, we will compare the kinetic parameters of different tissues between symptomatic PASC participants and a control group consisting of individuals with a complete COVID-19 recovery. Second, we will integrate the multiparametric imaging data with peripheral blood assays, aiming to assess the correlations between certain 18F-AraG kinetic parameters and biomarkers of inflammation, immune dysregulation, and endothelial dysfunction in peripheral blood. Particularly, to identify vascular alterations in tissue and their association with endothelial markers in blood, we will use vascular permeability modeling to estimate the blood flow in different tissues from the early frames of the kinetic data. Third, we will employ a longitudinal design to quantify changes in 18F-AraG kinetic parameters and correlate them with evolving PASC symptom profiles over time. We will include two follow-up scans of the PASC participants at 4 months and 8 months after the baseline scans with systematic symptom assessments, focusing on individual patient trajectories. Through this, we expect to establish a direct and meaningful connection between molecular imaging data and clinical manifestations. In summary, the incorporation of cutting-edge imaging technology with quantitative modeling techniques for non- invasive evaluation of total-body immune response, combined with the longitudinal design of the study promises to provide unprecedented insights into this complex condition and would extend well beyond the confines of the PASC condition, offering frameworks and tools that could as well be used for other post-viral conditions.", "keywords": [ "2019-nCoV", "Affect", "Anatomy", "Autoimmunity", "Autopsy", "Biological Assay", "Biological Markers", "Biopsy", "Blood", "Blood Vessels", "Blood coagulation", "Blood flow", "Blood specimen", "Body System", "COVID-19", "COVID-19 patient", "COVID-19 survivors", "Cardiovascular system", "Cells", "Clinical", "Complex", "Control Groups", "Controlled Study", "Data", "Endocrine", "Endothelium", "Evaluation", "Functional disorder", "Guanine", "Health", "Image", "Imaging Techniques", "Imaging technology", "Immune", "Immune response", "Immunologic Markers", "Immunologics", "Individual", "Inflammation", "Kinetics", "Knowledge", "Latent virus infection phase", "Link", "Long COVID", "Masks", "Measures", "Modeling", "Monitor", "Organ", "Outcome", "Participant", "Patients", "Persons", "Phenotype", "Positron-Emission Tomography", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Preventive measure", "Preventive treatment", "Quality of life", "Questionnaires", "Radiopharmaceuticals", "Recovery", "Regional Anatomy", "SARS-CoV-2 infection history", "Sampling", "Scanning", "Site", "Symptoms", "System", "T-Cell Activation", "Techniques", "Technology", "Time", "Tissues", "Tracer", "Vascular Permeabilities", "Viral", "Virus Diseases", "acute COVID-19", "blood-based biomarker", "endothelial dysfunction", "follow-up", "forging", "gastrointestinal", "health care burden", "healthy volunteer", "imaging agent", "imaging approach", "imaging biomarker", "imaging study", "immune activation", "immune imaging", "improved", "individual patient", "innovation", "insight", "kinetic model", "longitudinal design", "molecular imaging", "multiparametric imaging", "neuropsychiatry", "pandemic response", "peripheral blood", "personalized diagnostics", "personalized intervention", "personalized medicine", "pre-pandemic", "predictive marker", "pulmonary", "quantitative imaging", "radiotracer", "reactivation from latency", "sample collection", "tool", "treatment strategy", "uptake" ], "approved": true } }, { "type": "Grant", "id": "15772", "attributes": { "award_id": "1R21AI188518-01A1", "title": "Chemical composition-viability relationship of bioaerosols through spatial distribution and size-controlled measurements", "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": 21312, "first_name": "SONNIE", "last_name": "KIM", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2027-07-31", "award_amount": 429000, "principal_investigator": { "id": 31596, "first_name": "Hui", "last_name": "Ouyang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2640, "ror": "", "name": "UNIVERSITY OF TEXAS DALLAS", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Bioaerosols are small airborne particles that can harbor pathogenic microorganisms leading to serious and challenging-to-control diseases such as respiratory syncytial virus (RSV), SARS-CoV-2, and influenza in humans, and porcine reproductive and respiratory syndrome (PRRS) in animals. RSV is particularly hazardous to young children, causing severe lower respiratory tract infections. Unfortunately, there are no effective therapies or vaccines for RSV in the pediatric population. However, by gaining a better understanding of the transmission dynamics of airborne viruses through bioaerosols, we can improve our ability to predict and control their spread through the implementation of administrative and engineering controls such as optimized ventilation designs. The project’s broad and long-term objectives are to understand how the bioaerosol’s microenvironmental conditions, such as size, chemical composition, and phase status, and environmental conditions, such as temperature, relative humidity (RH), and UV light, can impact the pathogen viability and transmission. Towards this goal, this proposed study aims to develop an innovative method for measuring virus distribution in bioaerosols and understanding their viability decay based on chemical compositions that are more relevant to various respiratory generation locations, specifically for sub-5µm and submicron particles that can transmit long distances. This study will be performed in two aims. First, we will determine the spatial distribution of chemicals and pathogens in bioaerosols. We'll use gold nanoparticles to label RSV and visualize it with advanced electron microscopy and spectroscopy to map the chemical distribution of various components such as salt (Na, K, Cl) and protein. This will help us understand how viruses are distributed in bioaerosols and provide insights into their corresponding survival rate and viability. Second, we will study chemical composition's impact on RSV viability decay for sub-5µm and submicron bioaerosol particles from various generation origins. We will generate monodisperse particles using a unique experimental setup in this size range with various chemical compositions from oral to deep lung, and measure RNA and virus viability to obtain virus decay rates. This aim investigates airborne virus decay rates for submicron and sub-5 m virus-laden particles, critical for long-range airborne transmission, and identifies the relationship between pathogen viability decay rates and chemical compositions from various generation locations. This study proposes a novel gold labeling approach to measure the distribution of viruses within bioaerosol particles. It contributes to our long-term goals by providing insights into the relationship between the chemical composition, virus spatial distribution in bioaerosol particles, and the survival of pathogens. This tool can be applied to various pathogens besides RSV. The proposed work aims to provide a better understanding of how pathogens survive and interact with their microenvironment, going beyond the current state-of-the-art.", "keywords": [ "2019-nCoV", "Aerosols", "Animals", "Area", "Biological", "Chemicals", "Child", "Childhood", "Electron Microscopy", "Energy consumption", "Engineering", "Epidemiology", "Generations", "Goals", "Gold", "Human", "Humidity", "Image", "Infection", "Influenza", "Label", "Lead", "Liquid substance", "Location", "Lower Respiratory Tract Infection", "Lung", "Maps", "Measurement", "Measures", "Methods", "Modeling", "Morphology", "Nucleic Acids", "Oral", "Oral cavity", "Outcome", "Outcome Study", "Particle Size", "Pathogenicity", "Phase", "Population", "Porcine Reproductive and Respiratory Syndrome", "Proteins", "RNA", "Research", "Respiratory Syncytial Virus Vaccines", "Respiratory System", "Respiratory syncytial virus", "Role", "Rotation", "Saliva", "Sampling", "Scanning Electron Microscopy", "Seasons", "Sodium Chloride", "Spatial Distribution", "Spectrum Analysis", "Structure", "Surface", "Survival Rate", "Suspensions", "Technology", "Temperature", "Transmission Electron Microscopy", "Ultraviolet Rays", "Vaccines", "Virus", "Visualization", "Work", "X ray spectroscopy", "cost", "design", "disorder control", "effective therapy", "evaporation", "improved", "influenzavirus", "innovation", "insight", "microorganism", "nanoGold", "novel", "particle", "pathogen", "respiratory", "submicron", "surfactant", "tool", "transmission process", "ventilation", "viral transmission", "virtual" ], "approved": true } }, { "type": "Grant", "id": "15773", "attributes": { "award_id": "1K99AI187316-01A1", "title": "Leveraging the sensitivity of antigen-specific T cells to interrogate disease mechanisms and identify therapeutic targets for 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": 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": "2025-08-01", "end_date": "2027-07-31", "award_amount": 175428, "principal_investigator": { "id": 31273, "first_name": "Mark M", "last_name": "Painter", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2627, "ror": "", "name": "UNIVERSITY OF PENNSYLVANIA", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "Project Summary/Abstract: An estimated 400 million people worldwide have experienced persisting and sometimes debilitating symptoms for months and years after SARS-CoV-2 infection, known as Long COVID (LC). No proven therapies exist to treat LC, and the underlying mechanisms driving disease remain poorly understood. Reactivation of herpesviruses such as Epstein-Barr virus (EBV) and varicella zoster virus (VZV) has been linked to LC, but it is unclear how SARS-CoV-2 infection alters immune responses to these common viruses. Recent studies have also provided emerging evidence for persistence of SARS-CoV-2 in some individuals with LC, but key questions remain unanswered, including how viral reservoirs persist, why the immune system fails to clear virus, whether persisting virus drives ongoing immune stimulation, and how therapies to treat LC will affect immune responses to SARS-CoV-2. Efforts to identify effective treatments for LC depend on answering these questions. Our preliminary data demonstrate elevated activation of SARS-CoV-2-, EBV-, or VZV-specific T cells in 40% of LC patients, providing one of the most sensitive measures of immunopathology in LC to date. Thus, there is an urgent need to investigate virus-specific T cell activation in LC to define underlying mechanisms of disease and identify promising therapeutic targets. The proposed research will respond to this need by testing three working hypotheses: first, that SARS-CoV-2-specific CD8 T cells survey tissue reservoirs of SARS-CoV-2 and sense viral antigens, but fail to clear the virus due to impaired functionality in LC; second, that therapies suppressing SARS-CoV-2 replication will reduce T cell stimulation in LC but may not achieve a durable cure; and third, that immune stimulation by common herpesviruses is associated with disease pathology in LC. These hypotheses will be tested by leveraging custom HLA-I/peptide tetramers to identify and sort rare virus-specific CD8 T cells from hundreds of longitudinal blood and tissue samples from people with LC and people who fully recovered after SARS-CoV-2 infection. Cells will be analyzed using spectral flow cytometry and single-cell sequencing approaches to elucidate the mechanisms driving LC pathology, identify promising therapeutic targets for LC, and investigate how immune stimulation by herpesviruses shapes human disease. This research will be integrated with a comprehensive training plan to develop skills in tissue immunology, single-cell sequencing, and bioinformatics, which will be reinforced with targeted coursework and professional development activities in scientific writing, responsible conduct of research, laboratory management, and mentorship of junior personnel. The research and training plan will take full advantage of the outstanding environment at the University of Pennsylvania and the wealth of expertise in Dr. John Wherry’s lab. Completing the proposed research and training will substantially advance the human immunology field and form the foundation of my research program as I open my independent laboratory, creating a pathway to my goal of being an impactful independent researcher in human infectious disease immunology.", "keywords": [ "2019-nCoV", "Adult", "Affect", "American", "Anti-viral Agents", "Anti-viral Therapy", "Antigens", "Automobile Driving", "Binding", "Bioinformatics", "Biological Assay", "Biosensor", "Blood", "Blood specimen", "CD8-Positive T-Lymphocytes", "COVID-19 pathogenesis", "COVID-19 patient", "Cells", "Chronic", "Custom", "Data", "Defect", "Development", "Disease", "Environment", "Epigenetic Process", "Failure", "Flow Cytometry", "Foundations", "Functional disorder", "Functional impairment", "Genetic Transcription", "Goals", "Herpesviridae", "Herpesviridae Infections", "Herpesvirus Type 3", "Human", "Human Herpesvirus 4", "Human Resources", "Immune", "Immune Targeting", "Immune response", "Immune system", "Immunologic Stimulation", "Immunology", "Immunotherapeutic agent", "Immunotherapy", "Individual", "Infectious Disease Immunology", "Inflammatory", "Intervention", "Knowledge", "Laboratories", "Light", "Link", "Long COVID", "Longitudinal Studies", "Measures", "Mediating", "Mentorship", "Monoclonal Antibodies", "Nature", "Pathology", "Pathway interactions", "Pennsylvania", "Peptides", "Persons", "Production", "Reporting", "Research", "Research Personnel", "Research Proposals", "SARS-CoV-2 antigen", "SARS-CoV-2 infection", "Sampling", "Shapes", "Sorting", "Specimen", "Surveys", "Symptoms", "T cell response", "T-Cell Activation", "T-Lymphocyte", "Testing", "Therapeutic Intervention", "Tissue Sample", "Tissues", "Training", "Universities", "Viral Antigens", "Viral reservoir", "Virus", "Virus Replication", "Writing", "antigen-specific T cells", "cohort", "cytokine", "cytotoxicity", "debilitating symptom", "design", "effective therapy", "exhaust", "experience", "human disease", "immunopathology", "innovation", "multiple omics", "new therapeutic target", "post SARS-CoV-2 infection", "programs", "proliferation potential", "reduce symptoms", "response", "responsible research conduct", "single cell analysis", "single cell sequencing", "skills", "success", "systemic inflammatory response", "therapeutic target" ], "approved": true } }, { "type": "Grant", "id": "15776", "attributes": { "award_id": "1R35GM160065-01", "title": "Statistical Approaches to Unlock Protein Function from Deep Mutational Scans", "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": "2025-08-01", "end_date": "2030-07-31", "award_amount": 420984, "principal_investigator": { "id": 32849, "first_name": "Harold", "last_name": "Pimentel", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 818, "ror": "", "name": "UNIVERSITY OF CALIFORNIA LOS ANGELES", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Understanding how genetic variants impact protein function is essential for unraveling the mechanisms underlying both basic biology and disease, particularly for rare genetic variants. Of the 4.6 million missense variants found in large population studies, only about 2% have clinical interpretations. Due to their rarity, these variants are exceptionally challenging to study through observational methods. However, Deep Mutational Scanning (DMS) offers a high-throughput method for testing thousands of protein variants by generating a mutant library and obtaining a phenotypic readout for each mutation in one sequencing assay. Initially focused on fitness-based readouts, DMS has expanded to include fluorescence-based methods for protein profiling, binding assays, and more. It has been crucial for studying proteins like SARS-CoV-2, BRCA1, and drug-metabolism transporters like OCT1. With over 1,000 protein datasets publicly available, a recent study highlights technical advances by independently assaying over 500 additional proteins in one study. Unfortunately, the development of statistical methods to interpret and analyze these technologies has not kept pace. For example, DMS with fluorescence-activated cell sorting (DMS-FACS), which has been used for nearly a decade to measure protein abundance and other functional phenotypes, still lacks dedicated analysis methods. As a result, analyses are often ad hoc, and small sample sizes (typically three replicates) make standard statistical methods unsuitable. Our recent work demonstrates that naive approaches miss many real effects and lead to many false discoveries. We propose three statistical areas to improve DMS analysis and interpretation through accurate sample comparisons, epistasis analysis, and causal inference. First, we will develop methods to analyze DMS-FACS for assessing how genetic variants affect molecular phenotype targeted by FACS, and enabling precise comparisons between experimental conditions. Second, we will develop methods to improve genetic interaction (epistasis) analysis and interpretation within proteins, and thus ask which protein regions are acting in concert. Third, we open a new area of research for DMS, aiming to identify the causal impact of variants through measured pathways, including complex traits. In summary, we will solve the analysis gap for DMS-FACS, epistasis DMS, and causally link DMS data through structural causal models by leveraging our expertise in DMS data and small sample statistics. Leveraging our expertise in DMS data and small sample statistics, we will create reliable, robust tools for common workflows while also enabling new types of analyses that improve the interpretation of DMS, epistasis, and phenotypic relationships. With strong collaborations with assay developers and DMS experts, along with a proven track record in developing tools for high-throughput sequencing in small sample contexts, we are well-positioned to lead this effort.", "keywords": [ "2019-nCoV", "Affect", "Area", "BRCA1 gene", "Binding", "Biological Assay", "Biology", "Clinical", "Collaborations", "Complex", "Data", "Data Analyses", "Data Set", "Dedications", "Development", "Disease", "Fluorescence", "Fluorescence-Activated Cell Sorting", "Genetic", "Genetic Epistasis", "High-Throughput Nucleotide Sequencing", "Lead", "Libraries", "Link", "Measures", "Methods", "Missense Mutation", "Molecular", "Mutation", "Pathway interactions", "Phenotype", "Population Study", "Positioning Attribute", "Protein Region", "Proteins", "Research", "Sample Size", "Sampling", "Statistical Methods", "Statistical Models", "Technology", "Testing", "Variant", "Work", "causal model", "drug metabolism", "fitness", "genetic variant", "improved", "molecular phenotype", "mutant", "mutation screening", "protein function", "protein profiling", "statistics", "tool", "trait" ], "approved": true } }, { "type": "Grant", "id": "15782", "attributes": { "award_id": "1R01AI189398-01", "title": "Structural and mechanistic study of bat NLRP6 inflammasome in detecting RNA viruses", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32860, "first_name": "KENTNER L", "last_name": "SINGLETON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2030-07-31", "award_amount": 451836, "principal_investigator": { "id": 32861, "first_name": "Chen", "last_name": "Shen", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2646, "ror": "", "name": "WASHINGTON UNIVERSITY", "address": "", "city": "", "state": "MO", "zip": "", "country": "United States", "approved": true }, "abstract": "Bats harbor the unique ability to host a wide array of emerging viruses, such as Ebola virus, Nipah virus, Hendra virus, and severe acute respiratory syndrome coronavirus (SARS-CoV). These RNA viruses are highly pathogenic and often lethal to humans and animals. Intriguingly, bats develop no/minimal signs of diseases in both natural and experimental infections. Significant progress has been made to suggest the altered immunological networks and dampened inflammatory signaling in bats. However, the direct viral sensing mechanisms in bats and the unique immunological features that distinguish bats from other mammals remain poorly studied. Inflammasomes are multi-protein signaling platforms that form in epithelial cells and myeloid cells upon stimulation by pathogen and damage signals. Their primary function is to active the inflammatory caspases such as caspase-1. Canonical inflammasome sensors consist mainly of nucleotide-binding domain (NBD), leucine-rich repeat (LRR)-containing (NLR) family proteins. Among these NLR proteins, NLRP6 is a unique pattern recognition receptor that is predominantly expressed in intestinal and liver system. The inflammasome function of NLRP6 has been reported to directly detect the RNA viruses (rotavirus and mouse hepatitis virus) that infect the gastrointestinal (GI) tract. On the other hand, the excessive activation of NLRP6 inflammasome may exacerbate the tissue damage and cause the autoinflammatory diseases. In bats, the GI tract represents one major organ for viral infection, while infections rarely cause symptoms. The long-term goal of our project is to understand the specific inflammasome sensing mechanisms in detecting RNA viruses in the intestinal epithelium of bats and gain the insights of how bats protect themselves from the pathogenesis of inflammation-induced intestinal barrier dysfunction. In this application, we propose to pursue the following specific aims: 1) Determine the cryo- EM structures of bat NLRP6 monomer, elucidate the biochemical foundation of bat NLRP6- dsRNA interaction, determine the cryo-EM structures of bat NLRP6 with viral dsRNA and compare the structural mechanisms of dsRNA sensing and inflammasome signaling among bat, mouse and human NLRP6; 2) Elucidate the RNA virus-induced bat NLRP6 inflammasome signaling in reconstituted intestinal epithelial cells (IECs), analyze the bat inflammasome signaling in Eonycteris spelaea (Es) in response to bat-borne RNA viruses, study the genetic role of bat NLRP6 in regulating inflammasome signaling in bat primary IECs/bat intestinal organoids. The proposed studies will guide the development of therapeutics to target GI inflammatory disorders in human based on the molecular details of bat NLRP6 inflammasome.", "keywords": [ "Address", "Affinity", "Animals", "Attention", "Binding", "Biochemical", "Biochemistry", "Biology", "Biophysics", "Blood", "Body Size", "CASP1 gene", "Caspase", "Chiroptera", "Coronavirus", "Cryoelectron Microscopy", "Data", "Development", "Diarrhea", "Disease", "Double-Stranded RNA", "Ebola virus", "Electrophoretic Mobility Shift Assay", "Enteritis", "Epithelial Cells", "Exhibits", "Flying body movement", "Foundations", "Functional disorder", "Gastrointestinal tract structure", "Genetic", "Genetic study", "Goals", "Hendra Virus", "Human", "Immune system", "Immunologics", "Immunology", "In Vitro", "Infection", "Inflammasome", "Inflammation", "Inflammatory", "Inflammatory Bowel Diseases", "Inflammatory Response", "Innate Immune System", "Interdisciplinary Study", "Intestines", "Learning", "Leucine-Rich Repeat", "Liver", "Mammals", "Maps", "Mediating", "Middle East Respiratory Syndrome", "Middle East Respiratory Syndrome Coronavirus", "Molecular", "Murine hepatitis virus", "Mus", "Myeloid Cells", "Nipah Virus", "Nucleotides", "Organ", "Organoids", "Outcome", "Pathogenesis", "Pathogenicity", "Pattern", "Pattern recognition receptor", "Play", "Protein Family", "Proteins", "RNA Virus Infections", "RNA Viruses", "Recombinants", "Reporting", "Resolution", "Role", "Rotavirus", "SARS coronavirus", "Signal Transduction", "Signaling Protein", "Structure", "Symptoms", "Syndrome", "System", "Therapeutic", "Tissues", "Viral", "Viral Load result", "Virus", "Virus Diseases", "Work", "autoinflammatory", "autoinflammatory diseases", "bat-borne", "emerging virus", "experimental study", "gastrointestinal", "gastrointestinal system", "insight", "intestinal barrier", "intestinal epithelium", "life span", "metabolic rate", "monomer", "novel therapeutics", "pathogen", "prevent", "reconstitution", "response", "restraint", "sensor", "therapeutic development", "viral RNA" ], "approved": true } }, { "type": "Grant", "id": "15784", "attributes": { "award_id": "1R34HL177243-01A1", "title": "Empowering Cardiovascular Health in Custodial Grandparents (ECG)", "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": 32863, "first_name": "REBECCA A", "last_name": "CAMPO", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2028-07-31", "award_amount": 197160, "principal_investigator": { "id": 32864, "first_name": "MinKyoung", "last_name": "Song", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2648, "ror": "", "name": "OREGON HEALTH & SCIENCE UNIVERSITY", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true }, "abstract": "There has been a steady increase in grandparent caregiving in the US. This acceleration is due to recent trends in domestic violence, parents’ incarceration, parents’ death due to the COVID-19 pandemic, and opioid overuse that increase familial instability and leave more grandchildren to be cared for by custodial grandparents. These grandparent caregivers face ongoing stressors as they navigate legal custody arrangements, cope with loss of their own child(ren), or face social isolation. A higher prevalence in an array of social determinants of health often put them at higher risk for cardiovascular disease (CVD): belonging to a racial/ethnic minority, living below the poverty line, living in single-caregiver households, and having lower levels of educational attainment. Additionally, custodial grandparents appear to have higher rates of adverse childhood experiences, another known risk for CVD. This unique mixture of stressors manifests in custodial grandparents’ health, where they are at higher risk for CVD compared to their non-caregiving peers. However, there is a dearth of intervention addressing custodial grandparents’ CVD risk. To address this gap and optimize healthy aging and cardiovascular health among this growing at-risk population, we will implement a virtually delivered, evidence-based CVD risk reduction intervention - The Rural Caregiver Heart Health Education [RICHH] Intervention. The RICHH intervention was originally targeted for adult caregivers of adult family members with a chronic illness, and has not been tested in the context of custodial grandparents’ CVD risk. We propose a 3-year planning project to determine the feasibility, acceptability, and initial effect of the RICHH intervention conducted with custodial grandparents. We will employ a mixed method design and conduct a 2-arm randomized controlled trial with 70 custodial grandparents in Oregon. The specific aims are: 1) modify the RICHH intervention to target custodial grandparents from a variety of backgrounds; 2) employ the re-designed intervention and assess its feasibility and acceptability; and 3) evaluate and refine the RICHH protocol among our team members and explore the initial effect of the intervention based on measures of CVD risk, self- management behaviors, and depressive symptoms at 4-months and at 6-months, compared to baseline. Expected outcomes are to complete the sufficient and scientifically necessary groundwork to support a future clinical trial that will test the effectiveness of the RICHH intervention with a longer follow-up and increased inclusivity of participants from marginalized populations, with the objectives of: a) preventing CVD-related morbidity and mortality and overall physical decline, b) improving psychological well-being in these grandparents, and c) fostering a more heart-healthy environment in grandfamilies.", "keywords": [ "2 arm randomized control trial", "Acceleration", "Address", "Adherence", "Adult", "Affect", "Affective", "American", "Attitude", "Behavior", "Blood Pressure", "Body mass index", "COVID-19", "COVID-19 mortality", "COVID-19 pandemic", "Cardiac health", "Cardiovascular Diseases", "Caregivers", "Child", "Child Rearing", "Chronic Disease", "Clinical Trials", "Community Health Aides", "Custodial Care", "Data", "Data Collection", "Development", "Dietary intake", "Domestic Violence", "Educational Intervention", "Educational Status", "Effectiveness", "Environment", "Evaluation", "Face", "Family member", "Focus Groups", "Fostering", "Future", "Glycosylated hemoglobin A", "Goals", "Group Interviews", "Health", "Health education", "Heart", "High Prevalence", "Home", "Household", "Imprisonment", "Intervention", "Knowledge", "Legal", "Link", "Lipids", "Measures", "Mental Depression", "Methods", "Modification", "Morbidity - disease rate", "Oregon", "Outcome", "Parents", "Participant", "Phase III Clinical Trials", "Physical activity", "Planning Theory", "Population", "Populations at Risk", "Poverty", "Preparation", "Prevention", "Procedures", "Protocols documentation", "Public Health", "Research Design", "Research Personnel", "Risk Reduction", "Rural", "Self Care", "Self Efficacy", "Self Management", "Social isolation", "Structure", "Testing", "Trauma", "Well in self", "Work", "Writing", "acceptability and feasibility", "adverse childhood events", "cardiovascular disorder risk", "cardiovascular health", "caregiving", "coping", "data management", "depressive symptoms", "design", "effectiveness testing", "empowerment", "ethnic minority", "evidence base", "experience", "follow-up", "grandchild", "grandparent", "healthy aging", "high risk", "improved", "intervention effect", "marginalized population", "member", "mortality", "nicotine exposure", "older adult", "opioid epidemic", "opioid overuse", "opportunity cost", "peer", "post intervention", "prevent", "primary caregiver", "primary outcome", "racial minority", "recruit", "retention rate", "satisfaction", "secondary outcome", "skills", "social health determinants", "stressor", "therapy design", "treatment as usual", "trend", "virtual delivery" ], "approved": true } }, { "type": "Grant", "id": "15785", "attributes": { "award_id": "1K99HL181185-01", "title": "Investigating Histone Acetylation Modulator Function in Alveolar Regeneration and Disease Pathogenesis", "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": 32586, "first_name": "ROYA", "last_name": "KALANTARI", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2027-07-31", "award_amount": 130593, "principal_investigator": { "id": 32865, "first_name": "Dawei", "last_name": "Sun", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2649, "ror": "", "name": "BROAD INSTITUTE, INC.", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Influenza and COVID-19 remain significant global health concerns, with viral infections in the lungs often leading to alveolar damage and, in severe cases, progressing to acute respiratory distress syndrome (ARDS). ARDS development is closely linked to impaired alveolar regeneration, which relies on the proliferation and differentiation of alveolar type 2 (AT2) stem cells into alveolar type 1 (AT1) cells to restore lung function. The precise molecular mechanisms that govern alveolar regeneration remain poorly understood. Here I have established a high-throughput in vivo genetic screening system in mice to systematically search for essential epigenetic modulators that contribute to alveolar regeneration. Preliminary results have identified numerous histone acetylation pathway related genes, including lysine acetyltransferase 8 (Kat8), are required for AT2 restoration and may contribute to differentiation towards AT1 cells. Kat8 has not previously been linked to alveolar regeneration, however, a key component of its associated protein complex and downstream target genes has been identified in genome-wide association studies as risk genes for idiopathic pulmonary fibrosis, a deadly disease also caused by impaired alveolar regeneration. This proposal aims to clarify the mechanisms by which Kat8 regulates alveolar regeneration, determine the association of Kat8 loss of function with pulmonary fibrosis and further enhance the existing in vivo screen system by integration with single cell techniques to comprehensively map other histone acetylation modulation functions. This study will shed light on epigenetic mechanisms underlying AT2-mediated alveolar regeneration and disease pathology, with the potential to inform the design of novel therapeutic approaches targeting histone acetylation modulators to promote alveolar regeneration and combat fibrosis progression. The proposed research plan will be executed at the Broad Institute of MIT and Harvard, Cambridge, under the mentorship of Dr. Fei Chen and Dr. Jayaraj Rajagopal, with overall complementary expertise in the field of genomics, synthetic biology, and lung stem cell biology. My career objective is to become a tenure-track faculty pioneering and simultaneously training next-generation scientists at the intersection of technology and lung stem cell biology. To accomplish my career goals, I have put together a comprehensive training plan to enhance the overall skill sets required to establish myself as a successful independent investigator. To ensure timely progress toward fulfilling my rigorous research plan and career goals, I have gathered an expert advisory committee comprising Dr. Carla Kim, Dr. Darrell Kotton, Dr. Jason Buenrostro, and Dr. Ruth Franklin, with whom I will regularly discuss my research progress and receive invaluable career development guidance, the key ingredient to my pathway to scientific independence.", "keywords": [ "Acetylation", "Acetyltransferase", "Acute Respiratory Distress Syndrome", "Advisory Committees", "Alveolar", "Automobile Driving", "Biological Assay", "COVID-19", "COVID-19 mortality", "Cancer cell line", "Cell Aging", "Cell Differentiation process", "Cell Proliferation", "Cells", "Cessation of life", "Chemicals", "Complex", "Complication", "Dependovirus", "Development", "Disease", "Disease Progression", "Down-Regulation", "Engineering", "Ensure", "Epigenetic Process", "Faculty", "Fibrosis", "Gene Expression", "Genes", "Genetic", "Genetic Markers", "Genetic Screening", "Genome", "Genomics", "Goals", "Guide RNA", "Histone Acetylation", "Histone Deacetylase", "Histone H4", "Homeostasis", "Impairment", "In Vitro", "Influenza", "Knock-out", "Link", "Lung", "Lysine", "Maps", "Mediating", "Mentors", "Mentorship", "Methods", "Mitochondria", "Molecular", "Mouse Embryonic Stem Cells", "Mus", "Mutation", "Natural regeneration", "Pathogenesis", "Pathology", "Pathway interactions", "Phenotype", "Play", "Population", "Process", "Proliferating", "Pulmonary Fibrosis", "Research", "Research Personnel", "Resolution", "Role", "Satellite Viruses", "Scientist", "Stimulus", "System", "Techniques", "Technology", "Telomere Maintenance Gene", "Training", "Transitional Cell", "Variant", "Vertebral column", "Viral Pneumonia", "Virus Diseases", "career", "career development", "cell behavior", "cell type", "combat", "design", "genome wide association study", "global health", "histone acetyltransferase", "idiopathic pulmonary fibrosis", "improved", "in vivo", "insight", "loss of function", "lung injury", "lung stem cell", "male specific", "mitochondrial dysfunction", "mortality", "new therapeutic target", "next generation", "novel therapeutic intervention", "old mice", "progenitor", "protein complex", "pulmonary function", "restoration", "risk variant", "screening", "skills", "stem cell biology", "stem cells", "synthetic biology", "telomere", "tenure track", "transcriptomics" ], "approved": true } }, { "type": "Grant", "id": "15786", "attributes": { "award_id": "1R01HL173153-01A1", "title": "Statistical Methods for Information Synthesizing Using Multiple Existing Longitudinal Cohort Studies", "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": 32866, "first_name": "MICHAEL", "last_name": "WOLZ", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2029-05-31", "award_amount": 500660, "principal_investigator": { "id": 32867, "first_name": "Yifei", "last_name": "Sun", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 781, "ror": "", "name": "COLUMBIA UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Building on the valuable groundwork laid by the Collaborative Cohort of Cohorts for COVID-19 Research (C4R), this research project aims to advance the statistical methods used in pooled cohort studies. Pooled cohort studies are a powerful tool in clinical and epidemiological research, enabling the detection of subtle effects and interactions and improving the generalizability of findings through increased sample diversity. However, they pose unique challenges, particularly systematic missing data and potential heterogeneity across studies. Our goal is to address these challenges and improve the robustness of pooled cohort studies. To achieve this goal, we have structured four specific aims: Under Aim 1, we propose a novel Generalized Method of Moments (GMM) framework for robust statistical inference across multiple studies dealing with systematically missing data. Our investigation will probe into the missing data mechanism across multiple samples, employing density ratio weight- ing to handle the heterogeneity in covariate and outcome distributions. Under Aim 2, we propose nonparametric predictive models that leverage data from multiple studies with systematically missing data. We will develop a gradient boosting algorithm for versatile prediction model accommodating predictors of varying detail. Addition- ally, we will design algorithms for cohort-specific prediction models that take advantage of information from other cohorts. Aim 3 extends the proposed methods for systematically missing data and cohort heterogeneity to right- censored time-to-event data. Under Aim 4, we perform comprehensive evaluations through simulations and real data analyses, and develop user-friendly analytical pipelines for the proposed methods. Our research design and methods are centered around developing, testing, and refining these new statistical methods. These methods will then be evaluated both via simulation and real-world application to the C4R data. The long-term objective is to establish reliable tools for integrating multiple cohorts and conducting individual participant data meta-analysis. The development of these robust statistical methods and a systematic pipeline for the pooled analysis of system- atically missing data will provide valuable tools for researchers working with pooled cohort data. This project will enhance the validity and reliability of findings from the C4R study, and thereby contribute to a more accurate un- derstanding of risk and resilience factors for COVID-19 severity and outcomes. Our findings will be disseminated widely, including the development of user-friendly software to facilitate the application of our proposed methods.", "keywords": [ "Address", "Adoption", "Algorithm Design", "Algorithms", "Atherosclerosis", "COVID-19", "COVID-19 severity", "Clinical Research", "Cohort Studies", "Complex", "Data", "Data Analyses", "Detection", "Development", "Equation", "Evaluation", "Event", "Exclusion", "Funding", "Goals", "Heterogeneity", "Individual", "Investigation", "Longitudinal cohort study", "Meta-Analysis", "Methods", "Modeling", "National Heart Lung and Blood Institute", "Outcome", "Participant", "Procedures", "Research", "Research Design", "Research Methodology", "Research Personnel", "Research Project Grants", "Risk Factors", "Sampling", "Scheme", "Specific qualifier value", "Statistical Data Interpretation", "Statistical Methods", "Structure", "Target Populations", "Testing", "Time", "United States National Institutes of Health", "Validity and Reliability", "Variant", "cohort", "data harmonization", "data integration", "density", "diverse data", "epidemiology study", "global health", "gradient boosting", "improved", "innovation", "interest", "novel", "post-pandemic", "predictive modeling", "real world application", "research study", "resilience factor", "secondary analysis", "simulation", "tool", "user friendly software", "user-friendly" ], "approved": true } } ], "meta": { "pagination": { "page": 1404, "pages": 1419, "count": 14184 } } }