Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=2&sort=-id
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-id", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=-id", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=3&sort=-id", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-id" }, "data": [ { "type": "Grant", "id": "15795", "attributes": { "award_id": "1R21EB037846-01", "title": "Design principles for engineering therapeutic macrophages", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Biomedical Imaging and Bioengineering (NIBIB)" ], "program_reference_codes": [], "program_officials": [ { "id": 32882, "first_name": "TUBA HALISE", "last_name": "FEHR", "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": 621158, "principal_investigator": { "id": 32883, "first_name": "Jason Hung-Ying", "last_name": "Yang", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2655, "ror": "", "name": "RUTGERS BIOMEDICAL AND HEALTH SCIENCES", "address": "", "city": "", "state": "NJ", "zip": "", "country": "United States", "approved": true }, "abstract": "Genetically engineered immune cells are an exciting and promising frontier for treating a wide range of complex diseases. However, hyperinflammatory toxicities such as cytokine release syndrome plague clinical trials, stymieing their widespread clinical adoption. Macrophages are innate immune cells that fulfill many roles in tissue repair, regeneration, and homeostasis and are important regulators of inflammation. However, they are significantly under-utilized as engineered immune cell therapies because significant knowledge gaps exist in understanding how to engineer synthetic gene circuits that work robustly in human macrophages. Tools do not yet exist for determining how macrophages should be biologically manipulated to activate desired effector functions (biological design principles). Tools also do not exist for determining what gene circuit architectures are needed to robustly induce desired gene circuit behaviors (gene circuit design principles). The overall goal for this proposal is to create a human macrophage design toolkit for engineering therapeutic macrophages. Our published and preliminary data demonstrate that we have developed tools that enable us to discover cell signaling interventions that can control macrophage effector functions (biological design principles) and gene circuit architectures that can exert robust behaviors in human macrophages (gene circuit design principles). Here we will apply both these approaches to elucidate biological and gene circuit design principles that can be used to engineer therapeutic macrophages that can suppress inflammatory cytokine secretion or induce anti- inflammatory cytokine secretion in inflamed tissues. We will elucidate biological design principles using an interpretable machine learning approach that we previous developed. This approach combines biochemical screening with predictive network modeling and machine learning to discover network mechanisms causally regulating cell phenotypes. We will elucidate gene circuit design principles using a recently developed ultra-high- throughput genetic screening approach (CLASSIC). This approach synthesizes and screens large, barcoded gene circuit libraries to associate gene circuit architectures with gene circuit behaviors. With these design principles we will engineer gene circuits for controlling IL-1β or IL-10 secretion in inflamed tissue contexts and validate these synthetic gene circuits in human monocyte-derived macrophages and THP-1 cells. In its entirety, this Trailblazer R21 project is a first step towards addressing the unmet need for design principles for engineering therapeutic macrophages. We envision that insights gained by this project will help establish engineered macrophages as a platform technology for treating a wide range of complex human diseases.", "keywords": [ "Address", "Adoption", "Anti-Inflammatory Agents", "Architecture", "Bar Codes", "Behavior", "Biochemical", "Biological", "Cells", "Cellular immunotherapy", "Clinical", "Clinical Trials", "Complex", "Data", "Disease", "Engineered Gene", "Engineering", "Environment", "Future", "Genes", "Genetic", "Genetic Engineering", "Genetic Screening", "Goals", "Homeostasis", "Human", "Immune", "Inflammation", "Inflammatory", "Interleukin-1 beta", "Interleukin-10", "Intervention", "Knowledge", "Libraries", "Machine Learning", "Macrophage", "Natural regeneration", "Phenotype", "Plague", "Process", "Publishing", "Role", "Signal Transduction", "Synthetic Genes", "Therapeutic", "Tissues", "Toxic effect", "Work", "cytokine", "cytokine release syndrome", "design", "explainable machine learning", "frontier", "gene discovery", "human disease", "immunoengineering", "insight", "monocyte", "network models", "prototype", "screening", "simulation", "synthetic biology", "technology platform", "tissue repair", "tool" ], "approved": true } }, { "type": "Grant", "id": "15794", "attributes": { "award_id": "1R21EB037897-01", "title": "Programmable RNA-Based Sensors for In Situ Cell Type Detection and Response", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Biomedical Imaging and Bioengineering (NIBIB)" ], "program_reference_codes": [], "program_officials": [ { "id": 32881, "first_name": "SHAWN PATRICK", "last_name": "MULVANEY", "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": 673600, "principal_investigator": { "id": 30867, "first_name": "Lei", "last_name": "Wang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2654, "ror": "", "name": "NORTHEASTERN UNIVERSITY", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "There is a technology gap in currently developed tools that simultaneously monitor, compute, and respond to both coding and non-coding RNA in real-time within living cells or patients. The continued existence of this gap represents an urgent unmet need because, until it is filled, the accuracy of RNA-based therapeutics remains limited in complex and evolving biological systems like differentiation or cancer. The long-term goal of this proposal is to develop safe, universal, and programmable synthetic biology tools that using both coding and non- coding RNAs as disease marker inputs and program outputs to trigger therapeutic responses in patients. The objective of this particular application is to develop an RNA-based sensor (using mRNA as the delivery modality) that detects integrated changes in both mRNA and miRNA for in situ therapeutic responses within living cells and mouse models, given the crucial role of ncRNAs, especially microRNAs (miRNAs), as key regulators of post- transcriptional gene regulation, which allow only the correct set of genes to be active in each cell type. The central hypothesis is that an RNA-based sensor integrating both mRNA and miRNA inputs, using Boolean logic gate computation, can improve the specificity of cell type identification in complex biological systems. This proposed work builds on our and other’s recent works on sensing individual RNA species like mRNA in live cells. The rationale for the proposed research is that a deeper understanding of disease progression, derived from the vast RNA sequencing resources now available in user-friendly databases, creates a timely and unique opportunity for synthetic biologists to develop tools that can precisely identify diseased cells based on their RNA species and levels in living cells or even in patients. This allows for the development of treatments that specifically target diseased cells while minimizing off-target effects on healthy cells. Additionally, the success of COVID-19 mRNA vaccines using lipid nanoparticle delivery systems highlights the potential to translate RNA-based genetic circuits into practical medical applications. Given these advances, we plan to develop two independent and complementary aims for in situ cell state sensing using endogenous mRNA and miRNA as inputs: AND logic gates (requiring both inputs for an output) in Aim 1 and NOR logic gates (requiring neither input for an output) in Aim 2. This platform has broad biomedical potentials. As a proof of concept, we will demonstrate its ability to distinguish breast cancer cells from normal breast epithelial cells, evaluating its translational potential using a syngeneic mouse model of triple-negative breast cancer, which lacks key cell surface targets in current therapies. The proposed platform is innovative because it develops new platform by integration of existing miRNA sensing and RNA detecting approaches in a previously unproven combinatorial logic computation format to address a significant unmet need for accurate cell type identification for basic and translational applications. The proposed research is significant, because in situ monitoring and intervening based on endogenous RNAs will be key to addressing this unmet need, transforming disease detection and treatment.", "keywords": [ "4T1", "Address", "Animal Model", "Award", "Biological", "Biomedical Engineering", "Breast Cancer Cell", "Breast Cancer therapy", "Breast Epithelial Cells", "COVID-19", "Cell Line", "Cell Physiology", "Cell model", "Cell surface", "Cells", "Clinical", "Code", "Complex", "Data", "Databases", "Detection", "Disease", "Disease Marker", "Disease Progression", "Double-Stranded RNA", "Elements", "Engineering", "Ensure", "Gene Expression", "Genes", "Genetic", "Goals", "Human", "Immune System Diseases", "In Situ", "Individual", "Logic", "MCF10A cells", "MDA MB 231", "Malignant Neoplasms", "Medical", "Messenger RNA", "MicroRNAs", "Mission", "Modality", "Modeling", "Monitor", "National Institute of Biomedical Imaging and Bioengineering", "Nature", "Nerve Degeneration", "Output", "Patients", "Performance", "Play", "Post-Transcriptional Regulation", "Proteins", "Publishing", "RNA", "RNA vaccine", "Regulation", "Regulator Genes", "Repression", "Research", "Resources", "Role", "Sampling", "Specificity", "Survival Rate", "System", "Technology", "Testing", "Time", "Tissues", "Translating", "United States National Institutes of Health", "Untranslated RNA", "Work", "biological systems", "cell type", "combinatorial", "complex biological systems", "design", "design and construction", "differential expression", "improved", "in vitro Model", "innovation", "lipid nanoparticle", "mRNA delivery", "mammary", "model design", "model organism", "molecular sequence database", "mouse model", "nanoparticle delivery", "novel", "novel strategies", "programs", "prototype", "response", "risk mitigation", "scaffold", "sensor", "single-cell RNA sequencing", "success", "synthetic biology", "targeted treatment", "therapeutic RNA", "therapy development", "tool", "transcriptome sequencing", "transcriptomics", "translational applications", "translational potential", "treatment response", "triple-negative invasive breast carcinoma", "user-friendly" ], "approved": true } }, { "type": "Grant", "id": "15793", "attributes": { "award_id": "1R03AI188484-01A1", "title": "Establishing Human 2D and 3D Testicular Models to Elucidate Monkeypox Virus Tropism and Pathogenic Mechanisms in the Testes", "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": 32841, "first_name": "JANE M", "last_name": "KNISELY", "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": 156500, "principal_investigator": { "id": 32880, "first_name": "SAGUNA", "last_name": "VERMA", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2653, "ror": "", "name": "UNIVERSITY OF HAWAII AT MANOA", "address": "", "city": "", "state": "HI", "zip": "", "country": "United States", "approved": true }, "abstract": "One of the most important lessons learned from the recent global outbreak of the monkeypox virus, now called Mpox virus (MPXV, clade II), is the recognition that males are at a much higher risk for infection and higher occurrence of genital rash. Transmission via sexual contact is one of the main routes of virus spread. However, whether MPXV constitutes a sexually transmitted infection and can infect the male reproductive tract is still being debated, thus affecting the strategies to minimize transmission risk. Confirmed reports of MPXV shedding in seminal fluid for long after the clearance of viremia suggest the ability of MPXV to establish a productive infection in genitourinary organs. Poxviruses can also cause testicular complications, including azoospermia and seminiferous tubule atrophy. More recently, MPXV antigens have been detected in the testis of nonhuman primates both during the acute and convalescent stages, and the presence of testicular inflammation and necrosis in these macaques collectively suggests testis-tropism of MPXV, like Zika and Ebola viruses. However, direct evidence of MPXV infection in human testis is currently lacking, including cell targets of the virus and downstream consequences. Relevant human in vitro models are needed to characterize MPXV testicular infection. Human testis immune homeostasis is tightly governed by an elaborate communication network between different cells including testosterone-producing Leydig cells (LC) and Sertoli cells (SC) that form the blood-testis barrier (BTB). We recently established a 3D human testicular organoid (HTO) system comprised of undifferentiated spermatogonia cells, SC, LC, and peritubular myoid cells that closely recapitulates the cell diversity and function of the human testis to study Zika virus and SARS-CoV-2 infection. We have also established 2D cultures of primary SC, LC, and mixed seminiferous tubule cells and an in vitro BTB model to delineate cell-specific responses to viruses. Therefore, the goal of this study is to utilize our 2D and 3D testicular culture systems as an effective in vitro surrogate to model testicular infection of MPXV and understand downstream consequences. In Aim 1, we will assess MPXV infection in the 2D and 3D HTOs, identify cell targets, and characterize key infection pathologies, including cytopathic effects, antiviral response, and effect on BTB integrity. Aim 2 will utilize single-cell RNA sequencing to determine relative infectivity in each cell type and key pathways, including antiviral and inflammatory response, cell death, and spermatogenesis. Collective data will provide much-needed evidence of the testis as one of the target organs of MPXV replication after it is cleared from blood and skin lesions and lay the foundation for future in vivo studies of transmission via the sexual route. The knowledge of whether MPXV is a sexually transmitted infection is critical in providing clinical management and transmission guidelines, especially in men who have sex with men (MSM), an underrepresented group in biomedical research.", "keywords": [ "2019-nCoV", "3-Dimensional", "Acute", "Affect", "Androgens", "Anti-viral Response", "Antigens", "Area", "Atrophic", "Basic Science", "Biological Assay", "Biomedical Research", "Biomimetics", "Blood", "Blood-Testis Barrier", "CASP3 gene", "Cell Death", "Cell Differentiation process", "Cell Survival", "Cells", "Clinical", "Clinical Management", "Communication", "Data", "Development", "Discipline of Nursing", "Disease", "Disease Outbreaks", "Dissociation", "Ebola virus", "Electrical Resistance", "Environment", "Exanthema", "Foundations", "Future", "Genitalia", "Genitourinary system", "Germ Cells", "Goals", "Guidelines", "Homeostasis", "Human", "Immune", "Impairment", "In Situ Nick-End Labeling", "In Vitro", "Individual", "Infection", "Inflammation", "Inflammatory Response", "Injury", "Interferons", "International", "Investigation", "Kinetics", "Knowledge", "Macaca", "Measures", "Modeling", "Monkeypox", "Monkeypox virus", "Necrosis", "Organ", "Organoids", "Pathogenesis", "Pathogenicity", "Pathology", "Pathway interactions", "Plaque Assay", "Poxviridae", "Productivity", "Public Health", "Reporting", "Research Personnel", "Risk", "Route", "SARS-CoV-2 infection", "Seminal fluid", "Seminiferous tubule structure", "Sexual Transmission", "Sexually Transmitted Diseases", "Skin", "Spermatogenesis", "Supporting Cell", "Surface", "Suspensions", "System", "Testing", "Testis", "Testosterone", "Time", "Tropism", "Tubular formation", "Underrepresented Populations", "Undifferentiated", "United States National Institutes of Health", "Viral", "Viral Pathogenesis", "Viremia", "Virus", "Virus Diseases", "Virus Replication", "ZIKA", "Zika Virus", "cell type", "effective therapy", "high risk", "high risk population", "human model", "in vitro Model", "in vivo", "infection risk", "insight", "leydig interstitial cell", "male", "men", "men who have sex with men", "migration", "multidisciplinary", "nonhuman primate", "novel", "novel therapeutics", "public health emergency", "receptor", "reproductive tract", "response", "sertoli cell", "single-cell RNA sequencing", "skin lesion", "spermatogonial stem cells", "therapeutic development", "three-dimensional modeling", "transmission process", "viral transmission", "virus tropism" ], "approved": true } }, { "type": "Grant", "id": "15792", "attributes": { "award_id": "1R21AI193885-01", "title": "UTS-1401 as a Medical Countermeasure to H-ARS Consequent to a Radiation Mass Casualty", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "NIH Office of the Director" ], "program_reference_codes": [], "program_officials": [ { "id": 32879, "first_name": "LANYN P", "last_name": "TALIAFERRO", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-18", "end_date": "2027-07-31", "award_amount": 157000, "principal_investigator": { "id": 32877, "first_name": "Stephen L", "last_name": "Brown", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32878, "first_name": "FREDERICK Augustus", "last_name": "VALERIOTE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2633, "ror": "", "name": "HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Abstract: Our long term objective is to develop a new class of radiation mitigating agents with attractive chemical, physical and biological characteristics required to be an effective drug that can be distributed widely. We have identified a small molecule, UTS-1401 [5-(methylthiomethyl) isoxazole-3-carboxylic acid] which demonstrates mitigation of hematopoietic stem cell death when administered at either 24h or 48h following whole body irradiation (WBI). Using the endogenous spleen colony assay, we demonstrated a mitigating effect in that the colony number with and without UTS-1401 was 3.5 ± 0.4 for a 24h interval and 2.3 ± 0.5 for a 48h interval. We have recently demonstrated a significant radioprotection for both mouse survival and hematopoietic stem cells for this compound when administered up to 72h before irradiation (Valeriote et al, Radiation Research, 202:16- 25, 2024). In this application, we propose to further examine solely the mitigating effect on the hematopoietic acute radiation syndrome (H-ARS) using survival as the endpoint in specific aim 1. Groups of Swiss mice will receive a series of graded doses of WBI (in 0.5 Gy increments) around the LD50 for this syndrome (approximately 7.5 Gy in females and 8.5 Gy in males) with and without the administration of 150 mg/kg UTS-1401. The single dose of UTS-1401 being used in all studies is the highest dose administrable due to its aqueous solubility (in tartrate buffered saline). The radiation mitigation factors will be calculated as the ratio of the LD50 for radiation plus UTS-1401 versus that for radiation alone. The degree of mitigation will be examined at 24, 48 and 72 h following WBI to determine the radiation mitigation fraction as a function of time after radiation exposure. Three routes of drug delivery, intravenous (iv), oral, and subcutaneous (sc), will be examined and compared. Radiation will be delivered by 16 MeV electrons from a Linac. In specific aim 2, we will examine the pharmacokinetics (PK) for 150 mg/kg UTS-1401 comparing the iv, oral, and sc routes to obtain a determination of both the drug kinetics and bioavailability. The AUC values will be correlated with the extent of mitigation. For both specific aims, both male and female mice will be separately studied. The results from these studies are expected to demonstrate an effective first-in-class compound, UTS-1401, which has a small molecular weight, is chemically stable, nontoxic, aqueous soluble and inexpensive with H-ARS radiation mitigating properties which extend for a number of days following WBI. The mechanism studies (not proposed here) are expected to demonstrate UTS- 1401 as a new class of agents for mitigating the cytokine storm consequent to the irradiation.", "keywords": [ "Accidents", "Acute", "Address", "Animal Model", "Animals", "Biologic Characteristic", "Biological", "Biological Assay", "Biological Availability", "Biotechnology", "Blood", "Bone Marrow", "Buffers", "Carboxylic Acids", "Cell Death", "Cells", "Chemicals", "Chernobyl Nuclear Accident", "China", "Clinical", "Conflict (Psychology)", "Cyclic GMP", "Data", "Development", "Dose", "Drug Delivery Systems", "Drug Kinetics", "Drug Stability", "Electromagnetics", "Electrons", "Employee", "Equipment and supply inventories", "Exposure to", "FDA approved", "Federal Government", "Female", "Fibrosis", "Follow-Up Studies", "Formulation", "Fukushima", "Geographic Distribution", "Goals", "Growth Factor", "Hematopoietic", "Hematopoietic System", "Hematopoietic stem cells", "Hospitals", "Individual", "Industry", "Inflammation", "Inflammatory", "Injury", "International", "Intervention", "Intravenous", "Ionizing radiation", "Iran", "Isoxazoles", "Israel", "Korea", "Lethal Dose 50", "Location", "Molecular Weight", "Mus", "North Korea", "Nuclear", "Nuclear Accidents", "Nuclear Weapon", "Oral", "Oral Administration", "Organ", "Pharmaceutical Preparations", "Pharmacologic Substance", "Pharmacology and Toxicology", "Phase", "Phase I Clinical Trials", "Physiologic pulse", "Procedures", "Process", "Property", "Radiation", "Radiation Accidents", "Radiation Protection", "Radiation Toxicity", "Radiation exposure", "Refrigeration", "Research", "Rotation", "Route", "Russia", "Saline", "Schedule", "Series", "Solubility", "South Korea", "Spleen", "Swiss Mice", "Syndrome", "System", "Taiwan", "Tartrates", "Temperature", "Terrorism", "Time", "Tissues", "Ukraine", "United States National Aeronautics and Space Administration", "Vomiting", "War", "Whole-Body Irradiation", "Work", "aqueous", "chemical stability", "cost effective", "cytokine", "cytokine release syndrome", "design", "drug development", "efficacy study", "expiration", "irradiation", "male", "manufacture", "mass casualty", "medical countermeasure", "novel", "product development", "radiation countermeasure", "radiation mitigation", "radiation response", "radioprotected", "research study", "safety study", "scale up", "small molecule", "subcutaneous", "success" ], "approved": true } }, { "type": "Grant", "id": "15791", "attributes": { "award_id": "1R21AI186055-01A1", "title": "UTS-1401: A Novel Mitigator of Radiation Injury", "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": 32876, "first_name": "ANDREA L", "last_name": "DICARLO-COHEN", "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": 431750, "principal_investigator": { "id": 32877, "first_name": "Stephen L", "last_name": "Brown", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32878, "first_name": "FREDERICK Augustus", "last_name": "VALERIOTE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2633, "ror": "", "name": "HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Abstract: Our long term objective is to develop a new class of radiation mitigating agents with attractive chemical, physical and biological characteristics required to be an effective drug that can be distributed widely. We have identified a small molecule, UTS-1401 [5-(methylthiomethyl) isoxazole-3-carboxylic acid] which demonstrates mitigation of hematopoietic stem cell death when administered at either 24h or 48h following whole body irradiation (WBI). Using the endogenous spleen colony assay we demonstrated a significant mitigating effect (ratio of colony number with and without UTS-1401) when drug was given 24h or 48h after radiation. We have also recently demonstrated a significant radioprotection for both mouse survival and hematopoietic stem cells for this compound for up to 72h before irradiation (Valeriote et al, Radiation Research, 202:16-25, 2024). In this application, we propose to examine solely the mitigating effect to both the hematopoietic acute radiation syndrome (H-ARS) in specific aim 1 and the gastrointestinal acute radiation syndrome (GI-ARS) in specific aim 2 following WBI (with 5% bone marrow protection for specific aim 2). Swiss mice will receive a series of graded doses of WBI around the LD50 for both syndromes with and without the administration of 150 mg/kg UTS- 1401. The single dose of UTS-1401 being used in all studies is the highest dose administrable due to its aqueous solubility (in tartrate buffered saline). The radiation mitigation factors will be calculated as the ratio of the LD50 for radiation plus UTS-1401 versus radiation alone. The degree of mitigation will be examined at 24, 48 and 72 h following WBI to determine the timeframe of mitigation after radiation exposure. Three routes of drug delivery, intravenous (iv), oral, and subcutaneous (sc), will be examined and compared. For all specific aims, both male and female mice will be separately studied. Radiation will be delivered by electrons from a Linac. In specific aim 3, we will examine the pharmacokinetics (PK) for 150 mg/kg UTS-1401 comparing the iv, oral, and sc routes to obtain a determination of both the drug kinetics and bioavailability. The AUC values will be correlated with the extent of mitigation. Finally, in specific aim 4, we will address the mechanism of action with studies focused on the role of specific cytokines induced by radiation in the so-called “cytokine storm”. We will assess the time course changes of TNF-α, IL-1β, IL-6, CSF and TGF-β in blood as well as bone marrow and intestinal mucosa over 20 days following: UTS-1401 alone, 10 Gy irradiation, and the combination of UTS-1401 and radiation at a 24h interval. The results from these studies are expected to demonstrate an effective first-in-class compound, UTS-1401, which has a small molecular weight, is chemically stable, nontoxic, aqueous soluble and inexpensive with radiation mitigating properties which extend for a number of days following irradiation. The mechanism studies are expected to demonstrate UTS-1401 as a new class of agents for mitigating the cytokine storm consequent to the irradiation.", "keywords": [ "Animals", "Biologic Characteristic", "Biological", "Biological Assay", "Biological Availability", "Blood", "Bone Marrow", "Buffers", "Carboxylic Acids", "Cell Death", "Characteristics", "Chemicals", "Complex", "Data", "Development", "Dose", "Drug Delivery Systems", "Drug Kinetics", "Effectiveness", "Electrons", "Exposure to", "FDA approved", "Female", "Femur", "Formulation", "Gender", "Goals", "Hematopoietic", "Hematopoietic System", "Hematopoietic stem cells", "Hour", "Individual", "Inflammatory", "Interleukin-1 beta", "Interleukin-6", "Intestinal Mucosa", "Intestines", "Intravenous", "Ionizing radiation", "Isoxazoles", "Lethal Dose 50", "Measures", "Methods", "Molecular Weight", "Mus", "Nuclear", "Nuclear Accidents", "Nuclear Weapon", "Oral", "Pharmaceutical Preparations", "Plasma", "Property", "Radiation", "Radiation Accidents", "Radiation Dose Unit", "Radiation Injuries", "Radiation Protection", "Radiation Toxicity", "Radiation exposure", "Refrigeration", "Research", "Role", "Route", "Saline", "Sampling", "Series", "Solubility", "Spleen", "Swiss Mice", "Syndrome", "TNF gene", "Tartrates", "Technology", "Terrorism", "Testing", "Time", "Tissues", "Transforming Growth Factor beta", "United States National Institutes of Health", "War", "Weight", "Whole-Body Irradiation", "aqueous", "chemical stability", "cost effective", "cytokine", "cytokine release syndrome", "flexibility", "gastrointestinal", "gender difference", "intravenous administration", "irradiation", "male", "medical countermeasure", "mouse model", "novel", "radiation countermeasure", "radiation mitigation", "radiation mitigator", "radioprotected", "small molecule", "stem cells", "subcutaneous", "success" ], "approved": true } }, { "type": "Grant", "id": "15790", "attributes": { "award_id": "1R21AI193738-01", "title": "Combined pathogen and host-based diagnostic to identify etiology of lower respiratory tract infection", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32875, "first_name": "INKA I", "last_name": "SASTALLA", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-05", "end_date": "2027-07-31", "award_amount": 244044, "principal_investigator": { "id": 7629, "first_name": "GAYANI", "last_name": "TILLEKERATNE", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 246, "ror": "https://ror.org/00py81415", "name": "Duke University", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 2652, "ror": "", "name": "DUKE UNIVERSITY", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "Lower respiratory tract infection (LRTI) is the leading infectious cause of death globally. Despite its prevalence, the exact etiology of LRTI is unknown in the vast majority of cases. Even when identified, bacteria or viruses in nasopharyngeal (NP) or sputum samples may be colonizers in the upper tract rather than the cause of infection in the lower tract. Unclear LRTI etiology results in the overprescription of antibacterials, which in turn drives the global crisis in antibacterial resistance. Antibacterial overprescription and resistance are greater in low- or middle-income countries (LMICs), where basic diagnostic capacity is limited. Host-based diagnostics, which assess the host immune response to infection, have recently emerged as a complementary method to pathogen-based diagnostics for identifying the class of respiratory infection. Our team has developed host- based gene expression classifiers using peripheral blood samples to differentiate viral versus bacterial respiratory infection. The goal of the current application is to develop an integrated diagnostic that uses a single, non-invasive NP sample to detect both pathogen and host response to identify LRTI etiology. The following specific aims will be conducted at a collaborative research site in Sri Lanka: 1) Develop a novel NP- based gene expression classifier to identify viral versus non-viral LRTI, and 2) Design and validate an integrated pathogen and host gene expression test to identify viral versus non-viral LRTI using a quantitative real-time polymerase chain reaction (qRT-PCR) assay. For aim 1, we will use previously collected NP samples from clinically adjudicated viral and non-viral LRTI patients in Sri Lanka and conduct low-input RNA sequencing. Machine-learning approaches will identify host gene expression classifiers that discriminate viral versus non-viral LRTI. For aim 2, the genes identified in the NP-based classifier, as well as nucleic acid targets for two respiratory viruses that are frequently implicated in true infection as well as asymptomatic colonization (SARS-COV-2 and human rhinovirus [HRV]), will be migrated onto TaqMan Low-Density Array (TLDA) cards. A prospective cohort of patients will be enrolled in Sri Lanka, and etiological testing and clinical adjudications will be performed as the reference standard to identify viral (including SARS-CoV-2 and HRV) and non-viral LRTI. Using an optimally retrained and parsimonious viral versus non-viral classifier, we will perform a feasibility analysis of incorporating pathogen detection and host-response classifier. Among samples with TLDA-based pathogen detection for SARS-CoV-2 or HRV, performance of the host- response classifier to distinguish viral versus non-viral LRTI will be assessed. Successful completion of these aims will result in the development of a novel diagnostic that integrates host and pathogen detection using a single, non-invasive NP sample to identify the etiology of LRTI. Translation of this assay to a rapid platform will help shift the current diagnostic paradigm for LRTI.", "keywords": [ "2019-nCoV", "Anti-Bacterial Agents", "Bacteria", "Bacterial Drug Resistance", "Bacterial Infections", "Biological", "Biological Assay", "Blood Tests", "Blood specimen", "Bronchoscopy", "COVID-19 detection", "Cause of Death", "Clinical", "Country", "Data", "Development", "Diagnostic", "Diagnostic Procedure", "Enrollment", "Etiology", "Fever", "Future", "Gene Expression", "Gene Targeting", "Genes", "Goals", "Hour", "Human", "Immune response", "Income", "Infection", "Influenza", "Lower Respiratory Tract Infection", "Machine Learning", "Manuscripts", "Methods", "Nasopharynx", "Nucleic Acids", "Pathogen detection", "Patients", "Performance", "Pilot Projects", "Polymerase Chain Reaction", "Prevalence", "Procedures", "Prospective cohort", "Reference Standards", "Research", "Resistance", "Respiratory Signs and Symptoms", "Respiratory Tract Infections", "Respiratory syncytial virus", "Rhinovirus", "Sampling", "Site", "Sputum", "Sri Lanka", "Testing", "Time", "Training", "Translating", "Upper respiratory tract", "Viral", "Virus", "Work", "adjudication", "biobank", "density", "design", "differential expression", "experience", "migration", "novel", "novel diagnostics", "pathogen", "peripheral blood", "prospective", "respiratory virus", "transcriptome sequencing", "translation assay" ], "approved": true } }, { "type": "Grant", "id": "15789", "attributes": { "award_id": "1R56AI191526-01", "title": "Novel Statistical Methods for Confounded and Incomplete Network Data", "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": 32873, "first_name": "MISRAK", "last_name": "GEZMU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-06", "end_date": "2026-07-31", "award_amount": 822015, "principal_investigator": { "id": 9648, "first_name": "Ilya", "last_name": "Shpitser", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 344, "ror": "https://ror.org/00za53h95", "name": "Johns Hopkins University", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 32874, "first_name": "Eric Joel", "last_name": "Tchetgen Tchetgen", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2627, "ror": "", "name": "UNIVERSITY OF PENNSYLVANIA", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "Studies of public health interventions aimed at controlling the spread of infectious diseases such as HIV/AIDS or COVID19 often face important methodological challenges due to pervasive network dependence, confounding and widespread missing data. Each of these complications has separately received considerable attention, however, methods to tackle them when they coexist are currently lacking. We will develop new statistical methodology, specifically causal identification theory and robust estimation theory which we plan to apply to address pressing scientific questions in infectious disease research using data from two randomized trials and two observational studies with data at hand, where both missing data, and network structure occur including the HAALSA South African Study, the Networks, Norms, and HIV/STI Risk Among Youth (NNAHRAY) study, and the Botswana Combination Prevention Study (BCPP) and the Home-based Interventionto Test and Start (HITS) cluster randomized trial. Success in the proposed research will not only allow for robust conclusions to be drawn from data in the above studies, despite the presence of missing data, the potential for confounding bias, and complex social network structure; it will also provide a methodological template for addressing similar questions beyond these four studies as confounded, missing and dependent data are routinely co-occurring complications in Social and Infectious Disease Epidemiology.", "keywords": [ "Accounting", "Address", "Algorithms", "Area", "Attention", "Botswana", "COVID-19", "Caring", "Cluster randomized trial", "Communicable Diseases", "Communities", "Complex", "Complication", "Data", "Dependence", "Development", "Face", "Family", "Family member", "Formulation", "Goals", "HIV", "HIV/AIDS", "HIV/STD", "Hand", "Health", "Hepatitis C", "Home", "Household", "Human immunodeficiency virus test", "Imprisonment", "Incentives", "Incidence", "Individual", "Infection", "Infectious Disease Epidemiology", "Infectious Diseases Research", "Intervention", "Kinship Networks", "Measures", "Methodology", "Methods", "Modeling", "Observational Study", "Outcome", "Participant", "Policies", "Population", "Prevention", "Prevention program", "Process", "Public Health", "Randomized", "Recording of previous events", "Research", "Risk", "Selection Bias", "Social Interaction", "Social Network", "South African", "Statistical Methods", "Structure", "Techniques", "Testing", "Youth", "behavior test", "community transmission", "financial incentive", "high risk sexual behavior", "interest", "mortality", "novel", "participant enrollment", "prevent", "primary endpoint", "public health intervention", "randomized trial", "semiparametric", "simulation", "social", "success", "theories", "uptake", "user friendly software" ], "approved": true } }, { "type": "Grant", "id": "15788", "attributes": { "award_id": "1R16GM159146-01", "title": "Building Reliable Vision-Language Assistant for Dermatology AI through Modeling Uncertainties in Multimodal LLMs", "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": 32871, "first_name": "WUHONG", "last_name": "PEI", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-12", "end_date": "2029-06-30", "award_amount": 175470, "principal_investigator": { "id": 32872, "first_name": "Zhiqiang", "last_name": "Tao", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2651, "ror": "", "name": "ROCHESTER INSTITUTE OF TECHNOLOGY", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Diagnosis delay is one of the key factors that lead to skin cancer death, especially for melanoma diagnosis during the COVID-19 pandemic. The long examination time and limited dermatological access have been the major roadblocks to the preventive treatment of skin cancers to lower the high mortality rate. Developing a clinical AI agent that can analyze digital skin images and provide timely, interactive text responses to patient symptoms and inquiries will significantly mitigate the nationwide dermatologist shortage, thereby improving the early diagnosis chance and teledermatology accessibility for melanoma as well as other skin diseases. Conventional dermatology AI methods mainly focus on medical image recognition to identify skin lesions and malignancies, falling short in visual-language assistance for remote healthcare services. A conversational diagnostic AI model, which is able to answer medical questions by sensing subtle visual patterns of skin disorders/cancers, is still in urgent need. The long-term goal of this research program is to develop a reliable large visual-language (VL) model that enables conversational Dermatology AI to facilitate early melanoma diagnosis and general skin care. The proposed research will generate accurate and interpretable clinical responses by finetuning Large Language Models – LLMs (e.g., the generative AI models deployed in ChatGPT) through answering questions and visual reasoning in multimodal contexts. Specifically, the project will realize three aims: 1) Build a new multimodal LLM specifically for dermatology to discern melanoma and other skin diseases and to automatically answer questions relevant to skin lesions. 2) Study uncertainties stemming from data bias and distribution shifts to enhance the reliability of LLM-powered AI diagnosis in multimodal contexts and teledermatology environments. 3) Determine the visual relevance in LLM decisions based on the rich public dermatological images with clinical text annotations. The proposed research will establish a new multimodal LLM that interweaves visual reasoning and uncertainties to advance Dermatology AI in broad VL assistance tasks, enabling automatic conversational diagnostic in teled- ermatology and providing new insights about how LLM understands skin lesions and dermatological knowledge. A pixelwise visual instruction tuning approach and a novel multi-level uncertainty quantification framework will be developed, providing technical foundations to benefit a wide range of LLM-based healthcare research. This project will be the first large visual-language research study that investigates LLM's intelligence and reliability in coping with multimodal dermatology contexts – visual skin lesions and text clinical annotations/dialogues. The success of this project will provide transformative AI techniques in assisting early melanoma diagnosis and remote skin care, leading to better teledermatology accessibility for patient treatments, reducing mortality from skin cancers through timely detection, and revolutionizing dermatological access in public healthcare systems.", "keywords": [ "Accounting", "Artificial Intelligence enhanced", "Behavior", "Benchmarking", "Benign", "COVID-19 pandemic", "Cellular Phone", "Cessation of life", "ChatGPT", "Clinical", "Cutaneous Melanoma", "Data", "Death Rate", "Dependence", "Dermatologic", "Dermatologist", "Dermatology", "Dermoscopy", "Detection", "Development", "Diagnosis", "Diagnostic", "Disease", "Early Diagnosis", "Environment", "Evaluation", "Foundations", "Generations", "Goals", "Grain", "Hallucinations", "Health Care", "Health Care Research", "Health Care Systems", "Image", "Instruction", "Intelligence", "Knowledge", "Language", "Learning", "Lesion", "Life", "Machine Learning", "Malignant Neoplasms", "Medical", "Medical Imaging", "Melanoma", "Methods", "Modeling", "Morphologic artifacts", "Noise", "Patients", "Pattern", "Preventive treatment", "Prognosis", "Protocols documentation", "Public Health", "Research", "Resolution", "Risk", "Series", "Skin", "Skin Cancer", "Skin Care", "Skin Imaging", "Skin Malignancy", "Symptoms", "Techniques", "Text", "Time", "Training", "Translations", "Uncertainty", "Underserved Population", "United States", "Vision", "Visual", "artificial intelligence model", "chatbot", "clinical imaging", "coping", "data acquisition", "design", "digital", "diverse data", "generative artificial intelligence", "health care service", "improved", "insight", "large language model", "lens", "mortality", "multimodality", "neglect", "novel", "programs", "remote health care", "research study", "response", "skin disorder", "skin lesion", "stem", "success", "teledermatology", "trustworthiness" ], "approved": true } }, { "type": "Grant", "id": "15787", "attributes": { "award_id": "1R13HD118735-01", "title": "Health, Mortality, & Aging Among People with Criminal Legal System Contact in America", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 32868, "first_name": "RANDOLPH CHRISTOPHER", "last_name": "CAPPS", "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": 10000, "principal_investigator": { "id": 32869, "first_name": "Sade", "last_name": "Lindsay", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32870, "first_name": "Bryan Lamont", "last_name": "Sykes", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2650, "ror": "", "name": "CORNELL UNIVERSITY", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "PROJECT SUMMARY/ABSTRACT: Criminal justice contact is an important contributor to population variation in health outcomes, including mortality, morbidity, and aging. During and following the COVID-19 pandemic, people in American jails, prisons, and detention centers experienced elevated health risks that exacerbated their already high morality and aging precariousness. This proposal requests support for a three-year conference program on, “Health, Mortality, and Aging Among People with Criminal Legal System Contact in America,” with each year focusing on critical questions about the health of incarcerated people that have emerged since the COVID-19 crisis. These interdisciplinary conferences will harness the research and expertise of established and emerging scholars conducting research at the intersections of health, mortality, and aging in economics, sociology, demography/population science, law, criminology, public health, medicine, and public policy. The proposed conference programs are innovative by including the participation of people affected by legal system involvement, as well as by investigating population heterogeneity to formulate and to advance a bold new research agenda that will benefit affected communities. The program has four specific aims: (1) to advance scientific knowledge and research recommendations to improve health across the life-course for people involved in the criminal legal system; (2) to amplify the voices of affected people, families, and communities; (3) to train the next generation of criminal legal scholars; and (4) to engage multiple audiences. Deliverables will include: (1) three special issues, each devoted to a unique conference theme over the three years (i.e., mortality, health, and aging), allowing for the discrete and unique treatment of each topic; and (2) research briefs that translate findings into potential interventions and recommendations that broadly engage the individuals, families, and communities subject to criminal justice contact, as well as other stakeholders (government officials, prison and court actors, non-profits, and other advocates). By discussing and documenting how life-course transitions that intersect with the criminal legal system matter for socio-economic, health, and well-being, this conference will engage and advance the conceptual and empirical dialogues that began with several National Academies of Sciences, Engineering, and Medicine workshops in 2013 and 2020, and, more recently, a half-day seminar in 2024. As leaders in the criminal legal field, the investigative team and Cornell University are uniquely positioned to host this program.", "keywords": [ "Acute", "Advocate", "Affect", "Aging", "American", "Area", "Attention", "COVID-19 pandemic", "Cessation of life", "Chronic", "Collaborations", "Collection", "Communities", "Community Health", "Consumption", "Correctional Institutions", "Criminal Justice", "Criminology", "Data", "Dedications", "Demography", "Development", "Economics", "Educational workshop", "Engineering", "Epidemiology", "Event", "Exclusion", "Exposure to", "Family", "Government Officials", "Health", "Imprisonment", "Individual", "Intervention", "Jail", "Journals", "Knowledge", "Laws", "Legal", "Legal system", "Life Cycle Stages", "Life Expectancy", "Lived experience", "Measures", "Medicine", "Mentors", "Methodology", "Methods", "Morality", "Morbidity - disease rate", "Outcome", "Participant", "Personal Satisfaction", "Persons", "Population", "Population Heterogeneity", "Population Sciences", "Positioning Attribute", "Prisons", "Public Health", "Public Policy", "Recommendation", "Reporting", "Request for Proposals", "Research", "Research Personnel", "Risk", "Scientific Advances and Accomplishments", "Scientific Inquiry", "Social Sciences", "Sociology", "Training", "Translating", "Translational Research", "United States National Academy of Sciences", "Universities", "Variant", "Voice", "career", "court", "detention center", "experience", "forging", "health difference", "improved", "improved outcome", "individualized medicine", "innovation", "labor market", "life span", "mortality", "next generation", "population health", "prison population", "programs", "public health relevance", "research and development", "socioeconomics", "symposium", "theories" ], "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": 2, "pages": 1405, "count": 14046 } } }