Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=2&sort=-principal_investigator
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-principal_investigator", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1442&sort=-principal_investigator", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=3&sort=-principal_investigator", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-principal_investigator" }, "data": [ { "type": "Grant", "id": "16131", "attributes": { "award_id": "1K08DK143346-01A1", "title": "Renal endothelial cell signaling following viral priming in sepsis-associated acute kidney injury", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)" ], "program_reference_codes": [], "program_officials": [ { "id": 7449, "first_name": "TRACY L", "last_name": "RANKIN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-15", "end_date": "2031-02-28", "award_amount": 173232, "principal_investigator": { "id": 44613, "first_name": "James D", "last_name": "Odum", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3397, "ror": "", "name": "UNIVERSITY OF ALABAMA AT BIRMINGHAM", "address": "", "city": "", "state": "AL", "zip": "", "country": "United States", "approved": true }, "abstract": "ABSTRACT: Sepsis is a heterogeneous syndrome consisting of overlapping phenotypes that cause a broad range of organ injuries. Sepsis-associated acute kidney injury (SA-AKI) is among the most consequential, with high mortality and poor functional outcomes. No direct disease-modifying therapies currently exist. A major barrier to therapeutic progress is the diversity of sepsis phenotypes, which leads to heterogeneity of treatment effect. A prominent, yet understudied SA-AKI phenotype involves viral priming preceding bacterial sepsis. First recognized in pediatrics due to the high prevalence of viral infections, interest in this phenotype grew during the COVID-19 pandemic. Viral-primed SA-AKI is marked by thrombotic microangiopathy, impaired renal microperfusion, and injury to renal tubular epithelial cells. Firmly rooted in this proposed pathophysiology is the interaction between renal endothelial cells and tubular epithelial cells. The objectives of this study are to understand the renal endothelial cell response to a synthetic analog of viral double-stranded RNA, polyinosinic- polycytidylic (poly(I:C)) acid, and to determine whether poly(I:C) mediated renal endothelial cell activation directly leads to downstream tubular epithelial injury. Preliminary data suggests poly(I:C) induces renal endothelial cells to produce type 1 interferons, which act in a paracrine manner to alert nearby cells to the presence of a viral infection. In isolation, poly(I:C) does not cause kidney injury. However, when poly(I:C) is given prior to low-dose lipopolysaccharide (LPS), a significant and disproportionate systemic inflammatory response with early, severe SA-AKI ensues. Together, these data support the novel hypothesis that systemic exposure to viral dsRNA activates renal endothelial cells and initiates a type 1 IFN response, thereby priming the kidney for exaggerated injury following a secondary bacterial challenge. To test this hypothesis, we will leverage in vitro and in vivo techniques to accomplish two specific aims. AIM 1 will focus on the renal endothelial cell response to poly(I:C) with and without LPS to establish type 1 IFNs as essential mediators in the development of viral primed SA-AKI. AIM 2 will examine the heterogeneity of viral responses among renal endothelial cell subpopulations using CITEseq, and will computationally define microenvironmental signaling networks between endothelial cells and renal tubular epithelial cells using single-cell RNA sequencing of whole kidney. This research training program will expand upon the candidate’s translational science background elucidating the role of chemokines involved in murine models of SA-AKI to gain new expertise in kidney physiology and vascular endothelial biology. The candidate will hone skills in cell culture, flow cytometry, single-cell RNA sequencing analysis, and laboratory management. Altogether, this career development award will facilitate the successful transition to scientific independence and the establishment of a reputable SA-AKI translational research program.", "keywords": [ "Acids", "Acute Kidney Failure", "Address", "Area", "Bacterial Model", "Bioinformatics", "Biology", "COVID-19 pandemic", "Cell Culture Techniques", "Cell surface", "Cells", "Cellular Indexing of Transcriptomes and Epitopes by Sequencing", "Communication", "Data", "Development", "Disease", "Dose", "Double-Stranded RNA", "Endothelial Cells", "Endothelium", "Environment", "Epithelial Cells", "Epithelium", "Exposure to", "Flow Cytometry", "Functional disorder", "Funding", "Future", "Glomerular Filtration Rate", "Goals", "Health Priorities", "Heterogeneity", "High Prevalence", "Homeostasis", "Human", "Immune", "Impairment", "In Vitro", "Infection", "Inflammation", "Inflammatory", "Injury", "Injury to Kidney", "Interferon-α", "Interferons", "Investigation", "Investments", "K-Series Research Career Programs", "Kidney", "Laboratories", "Link", "Lipopolysaccharides", "Mediating", "Mediator", "Mentorship", "Modeling", "Molecular Profiling", "Morbidity", "Mus", "Nature", "Outcome", "Pathogenesis", "Pathogenicity", "Pathway interactions", "Patients", "Pediatrics", "Perfusion", "Phenotype", "Physicians", "Physiology", "Play", "Poly I-C", "Pre-Clinical Model", "Production", "Productivity", "Public Health", "Renal function", "Renal tubule structure", "Research", "Research Training", "Role", "Scientist", "Sepsis", "Shapes", "Signal Transduction", "Site", "Syndrome", "Technical Expertise", "Techniques", "Testing", "Therapeutic", "Tissue-Specific Gene Expression", "Training Programs", "Translational Research", "Tubular formation", "United States National Institutes of Health", "Vascular Endothelial Cell", "Vascular Endothelium", "Viral", "Virus Diseases", "Virus Replication", "Work", "analog", "bacterial sepsis", "career", "cell injury", "chemokine", "cytokine", "cytokine release syndrome", "early onset sepsis", "epithelial injury", "functional outcomes", "global health", "in vivo", "interest", "kidney vascular structure", "mortality", "mortality risk", "mouse model", "neglect", "novel", "novel therapeutics", "organ injury", "paracrine", "pathogen", "receptor", "recruit", "response", "severe sepsis", "single-cell RNA sequencing", "skills", "systemic inflammatory response", "thrombotic", "translational research program", "treatment effect" ], "approved": true } }, { "type": "Grant", "id": "16129", "attributes": { "award_id": "1R35GM162331-01", "title": "Advancing Low-Cost Synthetic Biosensor Arrays for Rapid Multiplex Biomarker Detection", "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": 44611, "first_name": "CAROLINA", "last_name": "SALVADOR MORALES", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-01", "end_date": "2031-02-28", "award_amount": 383801, "principal_investigator": { "id": 44612, "first_name": "Yixin", "last_name": "Liu", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3521, "ror": "", "name": "MICHIGAN TECHNOLOGICAL UNIVERSITY", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "The complexity and heterogeneity of diseases such as sepsis and allergy arise from diverse pathophysiological mechanisms and variable patient responses to treatment. Traditional diagnostic approaches relying on clinical phenotypes fail to capture the underlying molecular variability, leading to ineffective therapies and high healthcare costs. Host response-based diagnostics, driven by endotype classification, offer a promising solution by enabling disease stratification and personalized treatment through biomarker-based profiling. However, current biosensing platforms lack the scalability, affordability, and multiplexing capacity necessary for widespread clinical implementation. This research program aims to revolutionize biomarker-based diagnostics by developing a cost-effective, scalable, and multiplexed biosensing platform based on Molecularly Imprinted Polymers (MIPs). MIPs, synthetic receptors mimicking antibody recognition, offer superior stability and lower production costs compared to conventional immunosensors. The PI's lab has already demonstrated MIP-based electrochemical sensors for small molecules and protein targets, including SARS-CoV-2 spike protein and stress biomarkers. Building on this foundation, the next five years will focus on three key objectives: 1) Establishing an adaptable imprinting platform for the rapid synthesis of MIP-based biosensors tailored to amino acids, peptides, and proteins, inspired by nature’s antibody generation system. This approach will integrate computational modeling, machine learning, and experimental validation to predict and optimize imprinting efficiency in physiological environments. 2) Advancing multiplexed biosensing technology by integrating novel transduction mechanisms with scalability, such as redox- integrated MIP sensors and extended-gate field-effect transistors (EG-FETs)-based MIP sensors, coupled with machine learning-driven signal deconvolution for multiplex biomarker detection. 3) Developing a seamless sample-to-answer platform incorporating electrospun nanofiber-based whole blood separation and passive fluidic delivery to facilitate biomarker detection directly from complex biological samples without extensive preprocessing. Our research will initially focus on two key applications: (1) an amino acid biosensor array targeting branched-chain and aromatic amino acids, which are biomarkers for metabolic and neurological disorders; and (2) a multiplexed biosensor for sepsis biomarkers, integrating cytokines, acute-phase proteins, and metabolic indicators for early diagnosis and patient stratification. By integrating expertise in materials science, computational chemistry, electronics, and machine learning, our program will establish a next-generation biosensing framework that is cost-effective, scalable, and adaptable to diverse disease applications. The proposed work will bridge fundamental molecular recognition with real-world clinical translation, accelerating biomarker-based diagnostics, improving patient outcomes, and advancing precision medicine.", "keywords": [ "Acceleration", "Acute-Phase Proteins", "Allergy", "Amino Acids", "Antibodies", "Aromatic Amino Acids", "Biological", "Biological Markers", "Biosensing Techniques", "Biosensor", "Classification", "Complex", "Computer Models", "Coupled", "Detection", "Diagnostic", "Disease", "Disease stratification", "E-learning", "Early Diagnosis", "Enhancement Technology", "Environment", "Foundations", "Generations", "Health Care Costs", "Immune response", "Intervention", "Machine Learning", "Metabolic", "Metabolic Diseases", "Molecular", "Nature", "Nervous System Disorder", "Oxidation-Reduction", "Patient-Focused Outcomes", "Peptides", "Physiological", "Polymers", "Production", "Proteins", "Research", "SARS-CoV-2 spike protein", "Sampling", "Sepsis", "Signal Transduction", "Stress", "System", "Technology", "Transistors", "Validation", "Whole Blood", "Work", "biomarker panel", "clinical implementation", "clinical phenotype", "clinical translation", "computational chemistry", "cost", "cost comparison", "cost effective", "cytokine", "diagnostic platform", "diagnostic strategy", "disease heterogeneity", "imprint", "improved", "ineffective therapies", "materials science", "molecular recognition", "nanofiber", "next generation", "novel", "patient stratification", "patient variability", "personalized diagnostics", "personalized medicine", "precision medicine", "programs", "receptor", "sensor", "small molecule", "treatment response", "treatment strategy" ], "approved": true } }, { "type": "Grant", "id": "16128", "attributes": { "award_id": "1R01AI190919-01A1", "title": "Vectored Immunoprophylaxis of SARS-CoV-2 with receptor decoys", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32536, "first_name": "DIPANWITA", "last_name": "BASU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-19", "end_date": "2031-04-30", "award_amount": 836484, "principal_investigator": { "id": 44610, "first_name": "Nathaniel R.", "last_name": "Landau", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 832, "ror": "", "name": "NEW YORK UNIVERSITY SCHOOL OF MEDICINE", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Monoclonal antibody therapy for severe COVID-19 and for prophylaxis in immunocompromised individuals was initially of great value but was sidelined by the rapid emergence of virus variants with mutations in the spike gene that rendered the antibodies ineffective. Receptor decoys offer a means to overcome this problem. Because the viral spike protein needs to conserve its high affinity for ACE2, there is a high genetic barrier for the virus to escape from neutralization by the decoy. The project will develop vectored immunoprophylaxis (VIP) in which high affinity ACE2 receptor decoys will be expressed by adeno-associated virus (AAV) and lentiviral viral vectors. These will be used to protect against and to treat SARS-CoV-2 infection. The decoys consist of the extracellular domain of ACE-2 fused to a truncated immunoglobulin heavy chain Fc region. The “microbody” neutralizes the virus by binding to the viral spike protein and will be active against all variants. Because the decoys are composed entirely of human-derived protein components, they will be well-tolerated by the human immune system. The decoys will be optimized to increase their affinity for the spike protein and will be produced with Fc regions that alter their tissue localization, half-life, antiviral activity and antibody effector functions. The decoys will be tested as recombinant protein for prophylactic and therapeutic efficacy in ACE2 transgenic mouse and hamster models against a panel of SARS-CoV-2 variants. Tissue localization and half-life of vector-expressed decoy proteins will be determined by live-imaging of decoy–luciferase fusions. Long-term protection against infection will be established with decoy-expressing AAV and lentiviral vectors in mice and hamsters by intranasal instillation and intramuscular injection. The animals will then be challenged with live virus up to a year post- administration. Serum and lung concentrations of the decoy will be measured and the host antibody response to the decoy protein will be tested. An optimized decoy will be designed based on the findings obtained with modified decoy proteins and its effectiveness will be studied in rhesus macaques, a model that closely resembles humans. The decoy approach will be valuable for rapidly establishing long-term protection, and will be of value to immunocompromised individuals for whom vaccination is less effective. The approach offers an off-the-shelf means with which to rapidly protect the population in the event of a novel zoonotic coronavirus pandemic. The lessons learned will be broadly applicable to other viruses for which a decoy receptor can be generated.", "keywords": [ "2019-nCoV", "ACE2", "Acquired Immunodeficiency Syndrome", "Aerosols", "Affect", "Affinity", "Amino Acids", "Animal Model", "Animals", "Antibodies", "Antibody Response", "Binding", "Binding Proteins", "COVID-19 treatment", "COVID-19 vaccination", "Cell Surface Receptors", "Data", "Death Rate", "Dependovirus", "Development", "Disease", "Effectiveness", "Epitopes", "Event", "Evolution", "Exposure to", "Extracellular Domain", "Future", "Gene Transduction Agent", "Generations", "Genes", "Genetic", "Genetic Diseases", "Half-Life", "Hamsters", "Heavy-Chain Immunoglobulins", "Human", "Image", "Immune response", "Immune system", "Immunization Programs", "Immunocompromised Host", "Individual", "Infection", "Intramuscular", "Intramuscular Injections", "Investments", "Length", "Lentivirus Vector", "Luciferases", "Lung", "Macaca", "Macaca mulatta", "Malignant Neoplasms", "Measures", "Modeling", "Monoclonal Antibodies", "Monoclonal Antibody Therapy", "Mus", "Mutation", "Pathogenicity", "Pharmaceutical Preparations", "Physiological", "Population", "Predisposition", "Production", "Prophylactic treatment", "Proteins", "Recombinant Proteins", "Recombinants", "Resistance", "Respiratory System", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "SARS-CoV-2 variant", "Serotyping", "Serum", "Testing", "Therapeutic", "Therapeutic Effect", "Tissues", "Transgenic Mice", "Transplantation", "Treatment Efficacy", "Update", "Vaccination", "Vaccines", "Variant", "Viral", "Viral Antibodies", "Viral Physiology", "Viral Vector", "Viral load measurement", "Virus", "Virus Diseases", "Virus Receptors", "Virus Replication", "acute COVID-19", "acute infection", "adeno-associated viral vector", "compare effectiveness", "coronavirus pandemic", "delivery vehicle", "design", "effectiveness evaluation", "emerging virus", "future pandemic", "hospitalization rates", "immunoprophylaxis", "microbody", "nonhuman primate", "nonhuman primate models", "novel", "pandemic virus", "prevent", "prophylactic", "receptor", "severe COVID-19", "success", "transmission process", "vaccine immunogenicity", "vector", "weapons", "zoonotic coronavirus" ], "approved": true } }, { "type": "Grant", "id": "16127", "attributes": { "award_id": "1R25AI189409-01", "title": "The National Summer Undergraduate Research Project: Virtual Programming and Mentoring in Biomedical Microbiology and Immunology", "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": 44608, "first_name": "CARMEN", "last_name": "MOTEN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-13", "end_date": "2031-04-30", "award_amount": 368681, "principal_investigator": { "id": 44609, "first_name": "Michael David Leslie", "last_name": "Johnson", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3378, "ror": "", "name": "UNIVERSITY OF ARIZONA", "address": "", "city": "", "state": "AZ", "zip": "", "country": "United States", "approved": true }, "abstract": "The National Summer Undergraduate Research Project (NSURP) was created as an eight-week virtual summer research program in the microbial sciences that matches underrepresented minorities in STEM undergraduate students nationwide with faculty mentors worldwide to address the barriers presented by COVID-19 cancelations. NSURP mentees conduct research from any location with an internet connection, allowing students to learn how to conduct impactful research by forming and testing hypotheses. As individuals returned to in-person programs, NSURP found a population unable to travel, independent of COVID-19, due to financial, familial, geography, and health constraints. As we see an increased demand from these individuals, post-pandemic, who can’t travel to in-person opportunities, we seek to expand our ability to serve these undergraduates with research opportunities in our program and provide them with year-long mentoring and professional development. NSURP seeks to apply its virtual research model to human health-related topics, such as the basic and applied disease research conducted within the purview of the NIAID, both in microbiology and immunology. Implementing NSURP within the NIAID infrastructure will create more opportunities for URM scientists and ultimately aid in developing a diverse biomedical research workforce. The central premise of NSURP is to meet undergraduates where they are, facilitate exposure and pursuit of a scientific opportunity, and give them the tools and confidence to continue in their scientific careers. To maximize the contribution of NSURP within the NIAID mission, we will 1) provide virtual biomedical-specific summer research opportunities within the NIAID mission for minoritized undergraduates, 2) facilitate synergistic virtual scientific and career multi-level mentoring relationships, and 3) assess program impact by evaluating educational outcomes of NSURP participants and conducting longitudinal studies on the effects of culturally-responsive virtual mentorship training.", "keywords": [ "Address", "American", "Arizona", "Basic Science", "Biological Sciences", "Biomedical Research", "Black race", "COVID-19", "Caliber", "Collaborations", "Development", "Discipline", "Disease", "Education", "Education Projects", "Enrollment", "Faculty", "Family", "First Generation College Students", "Foundations", "Funding", "Geography", "Health", "Health Professional", "Human", "Immunology", "Indigenous", "Individual", "Infrastructure", "Internet", "Interview", "Latina", "Latino", "Latinx", "Learning", "Location", "Longitudinal Studies", "Low income", "Mentors", "Mentorship", "Microbiology", "Minority Groups", "Mission", "Modeling", "National Institute of Allergy and Infectious Disease", "Outcome", "Participant", "Persons", "Population", "Positioning Attribute", "Productivity", "Readiness", "Research", "Research Project Grants", "Research Training", "Resources", "STEM career", "STEM field", "Scholars Program", "Science", "Science Technology Engineering and Mathematics", "Societies", "Students", "Surveys", "Testing", "Training", "Training Activity", "Trajectory", "Travel", "Underrepresented Minority", "Underrepresented Populations", "United States", "Universities", "career", "design", "experience", "faculty mentor", "improved", "interest", "meetings", "microbial", "minority scientist", "minority undergraduate", "peer", "peer coaching", "post-pandemic", "programs", "skill acquisition", "summer research", "tool", "training opportunity", "undergraduate student", "undergraduate summer research", "underrepresented minority student", "virtual" ], "approved": true } }, { "type": "Grant", "id": "16125", "attributes": { "award_id": "1R21CA301202-01A1", "title": "Innate & Adaptive Determinants of Post-CAR Cytokine Release Syndrome", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Cancer Institute (NCI)" ], "program_reference_codes": [], "program_officials": [ { "id": 44605, "first_name": "YIN", "last_name": "LIU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-01", "end_date": "2028-04-30", "award_amount": 452540, "principal_investigator": { "id": 44606, "first_name": "KATHARINE C", "last_name": "HSU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3519, "ror": "", "name": "SLOAN-KETTERING INST CAN RESEARCH", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Advances in cell therapies have drastically changed treatment algorithms for hematologic malignancies, broadening curative approaches from the previously singular option of allogeneic hematopoietic cell transplantation to now include the highly effective chimeric antigen receptor (CAR) T cell therapies. Despite the promise of CAR T cell therapies, which harness the patient’s own T cell compartment upon the direction of a transduced antigen-specific receptor, they are still accompanied by significant morbidity. Referred to as “cytokine release syndrome” (CRS) due to rapid increases in multiple cytokines, including IL-6, IFN-γ, IL-2, and TNF, the disordered inflammatory response accompanying CAR T-cell therapies manifests clinically as fever, hypotension, hypoxia, and dyspnea. Overall occurrence of CRS is 93% following CAR T-cell administration (23% severe, with potential for fatal outcome), resulting in use of costly antibody therapeutics and intensive monitoring and translating to a financial burden on the healthcare system. Despite its frequency, CRS lacks a widely accepted definition, a clear molecular mechanism, and reliable markers predictive of its occurrence. Most critically, it is known that the CAR itself is not sufficient to elicit CRS. Our central hypothesis is that the origins of CRS are both effector cell- and environment-intrinsic: critical differences between the CAR effector lymphocytes are what elicit CRS from myeloid cells that have become susceptible in certain patients and that absence of either the stimulus or the response mitigates the initiation and propagation of CRS. Natural killer (NK) cells endowed with the same CAR as T cells do not elicit CRS, despite being capable of achieving complete tumor remission. This crucial difference between the two effector lymphocytes is further highlighted by our own findings that NK-like T cells (TKLR), a lymphocyte population demonstrating features of each, also fail to cause CRS in a mouse model for CAR therapy despite robust anti-tumor efficacy. The overlapping spectrum of these three populations with different CRS outcomes permits a more focused dissection in Aim 1 of the features initiating, propagating or suppressing CRS, including differences in response kinetics. Using in vitro models, we will test combinations of cellular components for their ability to elicit cytokine production and transcriptional changes leading to CRS. CRS-associated cytokine and molecular candidates will then be validated in a murine xenograft CRS model. In addition, the toxicity profile of CAR T cell therapy ranges from no CRS to severe CRS, even when treating the same disease with the same CAR T product. Thus, patient-specific factors, particularly the myeloid cell population critical for the pathological feedback loop of CRS, will be analyzed. In Aim 2, we will identify the pre-treatment risk signatures (phenotypic functional, and transcriptional) in the myeloid cell population in matched CAR T recipients who did and did not develop CRS. This comprehensive profiling will reveal novel points of intervention and prevention for CRS and ultimately lead CAR therapies to greater safety.", "keywords": [ "Allogenic", "Antigens", "Binding", "Breathing", "CAR T cell therapy", "Cell Communication", "Cell Compartmentation", "Cell Lineage", "Cell Therapy", "Cells", "Clinical", "Development", "Disease", "Disease remission", "Dissection", "Dyspnea", "Effector Cell", "Endowment", "Environment", "Event", "Evolution", "Fatal Outcome", "Feedback", "Fever", "Financial Hardship", "Frequencies", "Gene Expression Profile", "Genetic Transcription", "Health Care Systems", "Hematologic Neoplasms", "Hematopoietic Neoplasms", "Hematopoietic Stem Cell Transplantation", "Hour", "Hypotension", "Hypoxia", "Immune system", "In Vitro", "Individual", "Inflammatory", "Inflammatory Response", "Interferon Type II", "Interleukin-2", "Interleukin-6", "Intervention", "Kinetics", "Lead", "Lymphocyte", "Macrophage", "Malignant Neoplasms", "Mediating", "Medical", "Modeling", "Molecular", "Monitor", "Morbidity", "Mus", "Myelogenous", "Myeloid Cells", "Natural Killer Cells", "Outcome", "Pathologic", "Patients", "Phenotype", "Population", "Predisposition", "Prevention", "Production", "Proteomics", "Risk", "Role", "Safety", "Sampling", "Stimulus", "Syndrome", "T-Lymphocyte", "TNF gene", "Testing", "Therapeutic antibodies", "Toxic effect", "Translating", "Xenograft procedure", "chimeric antigen receptor", "chimeric antigen receptor T cells", "chimeric antigen receptor natural killer cells", "cost", "cytokine", "cytokine release syndrome", "cytotoxic", "design", "experience", "humanized mouse", "in vitro Model", "in vivo", "insight", "monocyte", "mouse model", "neoplastic cell", "novel", "predictive marker", "receptor", "response", "sample archive", "side effect", "transcriptomic profiling", "transcriptomics", "treatment algorithm", "treatment risk", "tumor" ], "approved": true } }, { "type": "Grant", "id": "16124", "attributes": { "award_id": "1K23DK147585-01", "title": "Harnessing Technology to Develop a Just-in-Time Adaptive Intervention to Promote Physical Activity in Adolescents with Type 2 Diabetes", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)" ], "program_reference_codes": [], "program_officials": [ { "id": 44603, "first_name": "NISHADI", "last_name": "RAJAPAKSE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-01", "end_date": "2031-03-31", "award_amount": 183540, "principal_investigator": { "id": 44604, "first_name": "Ana Maria", "last_name": "Gutierrez Colina", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3372, "ror": "", "name": "COLORADO STATE UNIVERSITY", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true }, "abstract": "The incidence of youth-onset type 2 diabetes (T2D) is on the rise, with a 95% escalation rate since 2001, and a staggering 77% increase during the COVID-19 pandemic. Regular physical activity is a cornerstone of T2D treatment. Yet, physical activity engagement is alarmingly low among youth with T2D, and effective interventions are lacking. Dr. Gutierrez-Colina’s long-term career objective is to improve health outcomes for youth with T2D by developing state-of-the-art mobile health (mHealth) interventions that provide personalized support for T2D self-management. The goal of this K23 proposal is to develop a novel just-in-time adaptive intervention (JITAI) that integrates dissemination and implementation science with real-time assessments of physical activity barriers and facilitators to deliver tailored strategies for promoting physical activity in adolescents with T2D. In Aim 1, a sequential exploratory design will be used to identify time-varying factors (e.g., motivation, fatigue, self- regulation) that influence physical activity engagement in adolescents with T2D. Qualitative interviews with N=18 T2D stakeholders will be conducted to gather in-depth feedback about physical activity barriers and facilitators. Qualitative findings will be integrated into the development of a 2-week ecological momentary assessment protocol designed to examine daily temporal associations between real-world barriers/facilitators and physical activity in the daily lives of N=25 adolescents with T2D. In Aim 2, the intervention components of a physical activity JITAI (e.g., personalized text messages, tailoring variables) will be co-developed with an advisory board of adolescents and caregivers. Intervention development will draw from dissemination and implementation science frameworks, as well as the “Capability, Opportunity, and Motivation (COM-B) Model,” a well-established theory of health behavior change. The JITAI will target activity barriers/facilitators related to Capability, Opportunity, and Motivation and deliver tailored support at the right time, in the right dose, and only when needed. In Aim 3, a sequential factorial experimental design will be used to pilot a 28-day micro-randomized trial of the physical activity JITAI with N=30 adolescents. Study feasibility and acceptability will be evaluated through usability surveys and post-intervention end-user interviews. Findings will generate critical data to inform an R01 application focused on a full-scale micro-randomized trial to optimize the physical activity JITAI. The proposed K23 research and career development plan will be supported by an outstanding mentorship team and a rich research environment at Colorado State University and the University of Colorado/Children's Hospital Colorado. Completion of the K23 training goals in (1) qualitative/mixed methods, (2) JITAI intervention development with an emphasis on dissemination and implementation science, and (3) the design and evaluation of micro- randomized clinical trials will equip Dr. Gutierrez-Colina with essential expertise in digital interventions and the rigorous methods involved in their evaluation. This training will directly support her successful transition to an independent research career focused on advancing personalized digital interventions for youth with T2D.", "keywords": [ "Address", "Adherence", "Adolescent", "Adult", "Behavioral", "COVID-19 pandemic", "Caregivers", "Cellular Phone", "Childhood", "Clinical", "Colorado", "Data", "Data Analyses", "Deterioration", "Development", "Development Plans", "Diabetes Mellitus", "Dissemination and Implementation", "Dose", "Ecological momentary assessment", "Effectiveness", "Enrollment", "Environment", "Evaluation", "Experimental Designs", "Face", "Fatigue", "Feasibility Studies", "Feedback", "Funding", "Future", "Glycosylated hemoglobin A", "Goals", "Guidelines", "Health", "Health Benefit", "Health Technology", "Health behavior", "Health behavior change", "Incidence", "Individual", "Informal Social Control", "Intervention", "Interview", "Just-in-Time Adaptive Intervention", "Life", "Link", "Measures", "Mentored Patient-Oriented Research Career Development Award", "Mentors", "Mentorship", "Methodology", "Methods", "Modeling", "Motivation", "Nature", "Non-Insulin-Dependent Diabetes Mellitus", "Obesity", "Outcome", "Overweight", "Pediatric Hospitals", "Persons", "Pharmacotherapy", "Physical activity", "Physical assessment", "Positioning Attribute", "Protocols documentation", "Randomized", "Recommendation", "Research", "Resources", "Scientist", "Self Management", "Specific qualifier value", "Structure", "Surveys", "Technology", "Text Messaging", "Time", "Training", "Universities", "Work", "Youth", "acceptability and feasibility", "actigraphy", "adolescent health outcomes", "cardiometabolic risk", "cardiovascular health", "career", "career development", "course of disease", "design", "diabetes management", "diabetes self-management", "digital intervention", "digital technology", "digital tool", "dissemination science", "effective intervention", "exercise intervention", "glycemic control", "implementation framework", "implementation science", "improved", "interest", "lifestyle intervention", "mHealth", "meetings", "mhealth interventions", "novel", "post intervention", "precision medicine", "randomized trial", "randomized clinical trials", "research and development", "tailored text messaging", "theories", "therapy development", "usability" ], "approved": true } }, { "type": "Grant", "id": "16123", "attributes": { "award_id": "1R01HL184145-01", "title": "ENHANCE-O2: ENsuring High Accuracy in Non-invasive Clinical Evaluation of Oxygenation", "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": 44601, "first_name": "CATHERINE", "last_name": "BURKE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-01", "end_date": "2031-01-31", "award_amount": 753721, "principal_investigator": { "id": 44602, "first_name": "Ashraf", "last_name": "Fawzy", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2615, "ror": "", "name": "JOHNS HOPKINS UNIVERSITY", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Pulse oximeters are used extensively in medical settings to monitor acutely ill patients, but testing is only required on healthy volunteers in laboratory settings to attain Food and Drug Administration (FDA) clearance for clinical use. This project’s investigators have led the contemporary re-evaluation of pulse oximeter accuracy, showing that pulse oximeters overestimated true oxygen saturation three-fold more frequently among critically ill Black patients and that these inaccuracies resulted in delayed delivery of care and significantly higher rate of readmissions among patients with COVID-19. As a consequence, the FDA held two advisory committee meetings to re-evaluate regulatory requirements for pulse oximeters, culminating in updated draft guidance released in January 2025 requiring greater diversity of skin pigmentation among pulse oximeter testing subjects but maintains that laboratory testing in healthy volunteers is adequate, which continues to assume – without evidence – that pulse oximeters are accurate in acutely ill patients with common physiologic derangements that cannot be simulated in laboratories. Following up on compelling preliminary studies, this project investigates pulse oximeter accuracy and its impact on clinical outcomes among hospitalized patients with shock (organ hypoperfusion) and acute exacerbation of COPD (AECOPD) in whom severe hypercarbia (elevated blood CO2) is common. Shock will be accurately characterized based on vasopressor dose or low cardiac output in a very large retrospective cohort using a unique high-frequency repository of vital sign and waveform data to precisely match pairs of concurrent pulse oximeter readings (SpO2) with gold-standard arterial oxygen saturation (SaO2) and determine cardiac output by applying an algorithm from an FDA-cleared device to stored arterial catheter waveforms. Pulse oximeter accuracy in shock, its interaction with race, and impact on 3-month mortality and rehospitalization will be investigated. A prospective study will enroll 150 hospitalized patients with AECOPD to obtain arterial blood gases and test whether high levels of partial pressure of CO2 (pCO2) impact accuracy (SpO2- SaO2) of four FDA-cleared pulse oximeters, interact with objectively measured dark skin pigmentation to worsen accuracy, and if pulse oximeter error in AECOPD is associated with clinical outcomes such as hospital length of stay and 3-month rehospitalization for AECOPD. Additionally, we will evaluate and refine the performance of a prototype continuous non-invasive oxygen monitoring device in three sub-cohorts, each of 25 acutely ill patients with either shock, hypercarbia, or pure hypoxemia. This prototype measures partial pressure of diffused oxygen (PtcO2) while forgoing skin heating and harsh adhesives required of traditional PtcO2 devices and uses methods that are hoped to mitigate skin pigmentation-related inaccuracies of pulse oximetry. If our hypotheses that shock and hypercarbia significantly impact pulse oximeter performance are confirmed, clinician approaches to the management of patients will be directly impacted and the need to test existing and new devices in real patients rather than relying on healthy volunteers in laboratory settings will be confirmed.", "keywords": [ "Acute", "Adhesives", "Advisory Committees", "Algorithms", "Arteries", "Black race", "Blood", "Blood Tests", "Blood flow", "Blood gas", "Burn injury", "COVID-19 patient", "Carbon Dioxide", "Cardiac Output", "Caring", "Catheters", "Chronic", "Chronic Obstructive Pulmonary Disease", "Clinical", "Clinical Data", "Consensus", "Critical Illness", "Darkness", "Data", "Devices", "Diagnosis", "Diffusion", "Dose", "Eligibility Determination", "Enrollment", "Ensure", "Evaluation", "Exclusion", "Frequencies", "Funding", "Goals", "Heating", "Hispanic", "Hospitalization", "Hypercapnia", "Hypoxemia", "Impairment", "Intensive Care Units", "Investigation", "Laboratories", "Lead", "Length of Stay", "Life", "Low Cardiac Output", "Marketing", "Measurement", "Measures", "Medical", "Methods", "Monitor", "Organ", "Outcome", "Outpatients", "Oxygen", "Oxygen Therapy Care", "Partial Pressure", "Patients", "Performance", "Perfusion", "Peripheral", "Physiologic pulse", "Physiological", "Prospective Studies", "Proxy", "Pulse Oximetry", "Race", "Regulation", "Reporting", "Research Personnel", "Respiratory Disease", "Retrospective Studies", "Retrospective cohort", "Shock", "Skin", "Skin Pigmentation", "Spectrophotometry", "Testing", "Time", "Tissues", "Triage", "United States Food and Drug Administration", "United States National Institutes of Health", "Update", "Validation", "Vasoconstrictor Agents", "black patient", "care delivery", "clinically relevant", "clinically significant", "cohort", "continuous monitoring", "experience", "healthy volunteer", "hospital readmission", "hypoperfusion", "innovation", "light transmission", "meetings", "monitoring device", "mortality", "multidisciplinary", "new technology", "novel", "peripheral blood", "prospective", "prototype", "readmission rates", "repository", "research clinical testing", "sensor", "supplemental oxygen", "theories", "tool" ], "approved": true } }, { "type": "Grant", "id": "16121", "attributes": { "award_id": "1R21AI194473-01A1", "title": "Multi-scale Computational Analysis of Structure, Dynamics and Function of Protein E from Corona 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": 32891, "first_name": "MARY KATHERINE BRADFORD", "last_name": "PLIMACK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-19", "end_date": "2028-04-30", "award_amount": 204375, "principal_investigator": { "id": 44600, "first_name": "Qiang", "last_name": "Cui", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3517, "ror": "", "name": "BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Project Summary: To help develop effective strategies to battle and prevent future breakouts of corona viruses, it is essential to understand the functions of their proteins. In this proposal, we focus on the envelope protein (E) from SARS-CoV-2 and MERS-CoV, which is involved in virus assembly and budding, and the ion channel activity associated with the transmembrane domain in the endoplasmic reticulum Golgi intermediate compartment (ERGIC) leads to Ca2+ and H+ imbalance, which in turn induces ER stress, NLRP3 inflamma- some activation and excessive secretion of inflammatory cytokines. These functions make the E protein an attractive drug target. There are, however, major questions regarding the underlying molecular mechanism for channel activation and ion permeation, as well as factors that drive the clustering of E proteins and its connection to the generation of local membrane curvature, which is essential to viral particle formation. We have the following specific aims: Aim 1: Conduct atomistic and hybrid QM/MM simulations to define the con- duction mechanism of an individual pentameric channel formed by protein E; this includes elucidating the roles of calcium/proton binding and transient ion-pairing in regulating channel opening and catalyzing ion(s) perme- ation, respectively, and establishing contribution from key polar and aromatic residues to the regulation of pore hydration and ion exit. Aim 2: Conduct atomistic and coarse-grained simulations to probe the mechanism of protein E clustering and the coupling with membrane curvature. In particular, the simulations will help better define the roles of cholesterol and phosphoinositides, and establish the causal relationship between protein E clustering and membrane curvature generation, including the structural features (! strand vs. ↵ helical) of the C-terminal cytoplasmic domain. The proposed computational studies take advantage of our recent methodol- ogy advances and expertise established in related studies, and predictions that emerge from the computational analyses will be readily tested experimentally through collaboration with the Hong group. The mechanistic in- sights and computational strategies established in this work are potentially applicable to the analysis of other envelope proteins in viruses.", "keywords": [ "2019-nCoV", "Anti-viral Agents", "Binding", "C-terminal", "Calcium", "Cations", "Cholesterol", "Collaborations", "Computer Analysis", "Coronavirus", "Coupling", "Cytoplasmic Tail", "Defective Viruses", "Drug Design", "Drug Targeting", "E protein", "Endoplasmic Reticulum", "Future", "Generations", "Genes", "Golgi Apparatus", "Grain", "HIV-1", "Hybrids", "Hydration status", "Hydrophobicity", "Individual", "Infection", "Inflammasome", "Inflammatory", "Ion Channel", "Ions", "Letters", "Life Cycle Stages", "Lipids", "Mediating", "Membrane", "Membrane Proteins", "Methodology", "Middle East Respiratory Syndrome Coronavirus", "Molecular", "Mutation", "Nature", "Pathogenicity", "Phosphatidylinositols", "Process", "Proteins", "Protons", "Recording of previous events", "Regulation", "Role", "SARS coronavirus", "Structural Models", "Structural Protein", "Structure", "System", "Testing", "Transmembrane Domain", "Uncertainty", "Viral", "Viral Physiology", "Viral Proteins", "Virus", "Virus Assembly", "Work", "computer studies", "cytokine", "design", "endoplasmic reticulum stress", "env Gene Products", "high-resolution", "influenza M2", "inhibitor", "insight", "pandemic disease", "particle", "pathogenic virus", "prevent", "protein E", "protein function", "reduce symptoms", "simulation", "solid state nuclear magnetic resonance", "virus envelope" ], "approved": true } }, { "type": "Grant", "id": "16120", "attributes": { "award_id": "2R01HL019278-50", "title": "FcγRIIa-induced Activation of Platelet αIIbβ3 in Thrombosis and Thromboinflammation", "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": 44598, "first_name": "ANDREI L", "last_name": "KINDZELSKI", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-10", "end_date": "2030-02-28", "award_amount": 861102, "principal_investigator": { "id": 44599, "first_name": "Claudia Lorena", "last_name": "Buitrago", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 22562, "first_name": "Barry", "last_name": "Coller", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 763, "ror": "https://ror.org/0420db125", "name": "Rockefeller University", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 3476, "ror": "", "name": "ROCKEFELLER UNIVERSITY", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "There is increasing awareness of the role of thromboinflammation mediated by the activation of αIIbβ3 through the binding of immune complexes to FcγRIIa in the pathogenesis of a variety of serious disorders, among which are heparin-induced thrombocytopenia/thrombosis, viral infections including COVID-19, autoimmune disorders, and chronic inflammatory disorders, including cardiovascular disease. The primary mechanism proposed to underly the thrombotic phenomena is the binding of immune complexes to the FcγIIa receptor (FcγRIIa) on platelets, leading to activation of αIIbβ3 and platelet aggregation. Both infection and autoimmune diseases can generate immune complexes that interact with FcγRIIa. Activated αIIbβ3 interacts with soluble fibrinogen, leading to platelet aggregation, thrombus formation, and thrombin generation. We and others have found that highly-specific BTK inhibitors (BTKi) can inhibit FcγRIIa-mediated αIIbβ3 activation and confirmed that platelets of XLA patients, who lack BTK on a genetic basis but do not have a bleeding disorder, do not aggregate in response to engagement of FcγRIIa. Thus, the central hypothesis of this grant renewal is that the activation of αIIbβ3 by engagement of FcγRIIa plays an important role in the pathophysiology of many immune-mediated disorders. We propose to create better murine models of these disorders by using mice that have had their entire Fc receptor repertoire and their platelet factor 4 (PF4) genes humanized and then test in these models the safety and efficacy of already-approved BTKi and antiplatelet drugs, as well as new agents targeting FcγRIIa directly that are developed under this grant. Our goal is to improve our understanding of these disorders, improve their current therapy, and develop novel, orally active drugs that directly target FcγRIIa for chronic therapy. Specific aim 1: A) To better understand the pathogenesis of the FcγRIIa-mediated disorders of αIIbβ3 activation by developing optimal murine models in which the entire murine repertoire of Fc receptors has been humanized, along with PF4, and both the Arg131 and His131 variants of FcγRIIa are studied. B) To compare the effects of antiplatelet agents (aspirin, P2Y12 inhibitors, αIIbβ3 inhibitors), and inhibitors of immune complex binding to FcγRIIa or signaling through FcγRIIa, initially focusing on BTKi, on the pathogenesis of the disorders in the murine models. Specific aim 2. To develop a rapid functional diagnostic assay that measures the combined effects of platelet FcγRIIa number, FcγRIIa affinity for the Fc domain of immunoglobulins, and the downstream signaling pathways to platelet αIIbβ3 activation for screening compounds, individual risk assessment, and optimizing therapy by monitoring drug effects. Specific aim 3. To use both high-throughput and in silico screening, along with deep learning-based de novo design, to identify novel specific inhibitors of immune complex binding to FcγRIIa or signaling through FcγRIIa as potential human therapeutics.", "keywords": [ "Adhesions", "Affinity", "Agammaglobulinaemia tyrosine kinase", "Antibody Formation", "Antigen-Antibody Complex", "Antiplatelet Drugs", "Aspirin", "Autoimmune Diseases", "Awareness", "B-Lymphocytes", "Binding", "Binding Proteins", "Biology", "Blood Coagulation Disorders", "Blood Platelets", "COVID-19", "Cardiovascular Diseases", "Cell Physiology", "Chronic", "Clot retraction", "Coagulation Process", "Cryoelectron Microscopy", "Defect", "Deposition", "Disease", "Docking", "Drug Monitoring", "Drug Targeting", "FDA approved", "Family", "Fc Receptor", "Fc domain", "Fibrin", "Fibrinogen", "Functional disorder", "Generations", "Genes", "Genetic", "Goals", "Grant", "Hemostatic function", "Human", "Immobilization", "Immune", "Immunoglobulin Domain", "Individual", "Infection", "Inflammation", "Inflammatory", "Integrins", "Mass Spectrum Analysis", "Measures", "Mediating", "Methods", "Modeling", "Molecular", "Molecular Conformation", "Monitor", "Mus", "Myocardial Infarction", "Natural Immunity", "Neoplasm Metastasis", "New Agents", "Oral", "PF4 Gene", "Pathogenesis", "Pathway interactions", "Patients", "Pharmaceutical Chemistry", "Pharmaceutical Preparations", "Phase", "Platelet Activation", "Platelet aggregation", "Plavix", "Play", "Research", "Risk Assessment", "Role", "Safety", "Signal Pathway", "Signal Transduction", "Stroke", "Structure", "Testing", "Therapeutic", "Thrombin", "Thrombosis", "Thromboxanes", "Thrombus", "Tyrosine Kinase Inhibitor", "Variant", "Virus Diseases", "X-Ray Crystallography", "abciximab", "antagonist", "chronic inflammatory disease", "clopidogrel", "deep learning", "design", "diagnostic assay", "disease model", "heparin-induced thrombocytopenia", "high risk", "high throughput screening", "immunothrombosis", "improved", "in silico", "inhibitor", "interdisciplinary approach", "mortality", "mouse model", "novel", "novel therapeutics", "phase 3 study", "pre-clinical", "receptor", "response", "screening", "simulation", "targeted agent", "thromboinflammation", "thrombotic", "thrombotic complications", "treatment optimization", "von Willebrand Factor", "wound healing" ], "approved": true } }, { "type": "Grant", "id": "16118", "attributes": { "award_id": "1R21AI194202-01A1", "title": "Recovering CD8 T cell memory during chronic infection by JAK-inhibitors", "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": 44596, "first_name": "STACY E", "last_name": "FERGUSON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-05-22", "end_date": "2028-04-30", "award_amount": 234750, "principal_investigator": { "id": 44597, "first_name": "Mohamed", "last_name": "Abdel Hakeem", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3388, "ror": "", "name": "EMORY UNIVERSITY", "address": "", "city": "", "state": "GA", "zip": "", "country": "United States", "approved": true }, "abstract": "Vaccines are the most successful prophylactic measure against pathogens, and their protective capacity depends on the formation of long-lived immunological memory, e.g. memory T lymphocytes (TMEM). Coordination between B and T lymphocytes is required against intracellular pathogens to neutralize pathogens and eradicate infected cells, respectively, as recently highlighted with COVID19 vaccine responses. Individuals living with chronic infections were shown to exhibit inferior responses to subsequent infections and vaccination. Studies in animal models suggested the cause to be the inferior recall responses by the TMEM generated to acute stimuli in hosts with preexisting chronic infection (hereafter termed inflm-TMEM). However, epigenetic imprints of persistent inflammation on inflm-TMEM have not been examined, and interventions to restore efficient protective recall responses by inflm-TMEM are understudied. Previous studies and our preliminary data demonstrated arrested development of inflm-TMEM, especially the central memory subset (TCM). Previous transcriptional profiling and our chromatin-accessibility profiling revealed skewed transcriptional and epigenetic landscapes of antigen-specific inflm-TMEM compared to bona fide TMEM, with enrichment of signatures associated with inflammatory mediators including type I interferon (IFN-I) and interleukin-6 (IL-6), which signal downstream janus kinase 1/2 (JAK1/2). We hypothesize that JAK1/2 inhibition would recover normal TMEM differentiation in hosts with preexisting chronic infection. To investigate this, we will use the same mouse model utilized for our preliminary studies to examine the differentiation of antigen-specific T cells responding to acute infection in the presence of preexisting chronic infection with or without JAK1/2 inhibition (JAKi) treatment. We will dissect the profiles of inflm-TMEM using high- dimensional flowcytometry and combined scRNAseq/scATACseq (MultiOme) profiling. More importantly, we will investigate the functional impact of JAKi-treatment on enhanced pathogen clearance and protection upon rechallenge. Our team has expertise in immunology, mouse models, and MultiOme profiling tools. This puts us in a unique position to address our main objectives which are: (1) to examine the capacity of FDA-approved interventions (JAKi) to recover generation of efficient TMEM in hosts with preexisting chronic infection, and (2) to gain insights into the molecular mechanisms underlying the skewed differentiation of inflm-TMEM., and aspects recovered by JAKi treatment. These studies push the envelope of innovation where we will employ combined state-of-the-art high-dimension flowcytometry, functional assays, and MultiOme profiling, to decipher specific mechanisms associated with lower recall capacity of inflm-TMEM that is understudied to date. We will validate novel therapeutic approaches using FDA-approved medication(s) for enhancing TMEM formation in hosts with preexisting chronic infection. This is of high relevance for enhancing vaccine efficiency in people living with chronic viral infection, and can be extended to benefit other populations living with chronic diseases with underlying inflammation. Summary", "keywords": [ "ATAC-seq", "Acute", "Address", "Adoptive Transfer", "Animal Model", "Antigens", "Binding Sites", "Biological Assay", "CD8-Positive T-Lymphocytes", "CD8B1 gene", "COVID-19 vaccine", "Cell Separation", "Cells", "Chromatin", "Chronic", "Chronic Disease", "Clinical Research", "Cytotoxic T-Lymphocytes", "Data", "Development", "Differentiation Antigens", "Epigenetic Process", "Exhibits", "FDA approved", "FDA-approved drug", "Flow Cytometry", "Gene Expression Profiling", "Generations", "Genetic Transcription", "IRF1 gene", "Immunity", "Immunologic Memory", "Immunology", "Individual", "Infection", "Inferior", "Inflammation", "Inflammation Mediators", "Inflammatory", "Interferon Type I", "Interferons", "Interleukin-6", "Intervention", "JAK1 gene", "Knock-out", "Knowledge", "Listeria", "Listeria monocytogenes", "Lymphocyte", "Lymphocyte Subset", "Lymphocytic choriomeningitis virus", "Measures", "Memory", "Molecular", "Monitor", "Multiomic Data", "Mus", "Ovalbumin", "Persons", "Phenotype", "Population", "Positioning Attribute", "Production", "Signal Transduction", "Sorting", "Stimulus", "T memory cell", "T-Lymphocyte", "TNF gene", "Testing", "Therapeutic Intervention", "Vaccination", "Vaccines", "Virus Diseases", "acute infection", "antigen-specific T cells", "chronic infection", "chronic inflammation", "congenic", "cytokine", "epidemiology study", "high dimensionality", "imprint", "inhibitor", "innovation", "insight", "mouse model", "multiple omics", "novel therapeutic intervention", "pathogen", "prophylactic", "receptor", "response", "single cell ATAC-seq", "single-cell RNA sequencing", "tool", "transcription factor", "vaccine efficacy", "vaccine immunogenicity", "vaccine response" ], "approved": true } } ], "meta": { "pagination": { "page": 2, "pages": 1442, "count": 14420 } } }