Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1405&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=1419&sort=principal_investigator", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1406&sort=principal_investigator", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1404&sort=principal_investigator" }, "data": [ { "type": "Grant", "id": "15743", "attributes": { "award_id": "1R34HL173375-01A1", "title": "Democratizing Access to Cleaner Residential Air (DACRA)", "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": 32796, "first_name": "MICHELLE M", "last_name": "FREEMER", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-15", "end_date": "2028-07-31", "award_amount": 293395, "principal_investigator": { "id": 32797, "first_name": "Doug", "last_name": "Brugge", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2614, "ror": "", "name": "UNIVERSITY OF CONNECTICUT SCH OF MED/DNT", "address": "", "city": "", "state": "CT", "zip": "", "country": "United States", "approved": true }, "abstract": "Particulate air pollution (PM2.5) is the 4th leading cause of morbidity and mortality. Attention from leading health organizations has recently turned to interventions to reduce exposure and prevent adverse health outcomes. As evidence has begun to mount for the efficacy of these machines, and will likely grow further in the coming years, it has, however, become apparent that for most people, including low-income populations in the US, cannot afford effective commercially available units. Low-cost commercial air purifiers are of low efficacy and often introduce new pollutants into the air. To our knowledge, there are no published intervention studies of Corsi-Rosenthal Boxes (C-R Boxes), the devices we propose to use in this study. We have a study team that is ideally suited for the proposed research. Ms. Creed has extensive experience building and deploying the C-R Boxes which became popular during the Covid pandemic. Dr. Brugge has three published RCTs of high-quality commercial air purifiers and another, full trial, nearing completion. Thus, he has knowledge and experience which qualifies him to lead this proposed study. Drs. Levy Zamora has extensive air monitoring expertise, will direct measurement of indoor and outdoor air pollution concentrations at each home. Dr. Eliasziw is a biostatistician with extensive experience analyzing randomized trials. We have three aims: 1)Conduct focus groups/interviews and BP measurements with participants who meet study inclusion criteria to refine our protocol; 2) Conduct a randomized crossover pilot trial with 65 participants to calculate preliminary effect size estimates to inform a larger crossover efficacy trial; and 3) Determine the feasibility of conducting a larger crossover efficacy multisite trial in the US. We will conduct our randomized cross over trial in three settings with low, medium, and high air pollution. Our low and medium air pollution locations will be in Hartford CT and our high pollution setting will be in Boston Chinatown, where we can reliably expect high pollution levels. Participants (N=65) will have dried blood spots collected and blood pressure measured at the start and end of each 4-week intervention session. Our randomized cross over design controls for time invariant confounding. Interviews and standardized questionnaires with study participants will provide feedback that will inform the decision as to whether to proceed with a full trial. We seek to meet targets for 80% recruitment and retention as well as 80% satisfaction as benchmarks for moving to a full trial. The findings for health end points will provide preliminary data to justify the potential future R01 proposal for a fully powered clinical trial. An expert elicitation process conducted with the research team in the final year will make the final decision about a future, full trial. The significance of this work is that showing efficacy of C-R Boxes for reducing exposure would lead to their widespread use and contribute to improving public health", "keywords": [ "Africa", "Air", "Air Movements", "Air Pollutants", "Air Pollution", "Allergens", "American Heart Association", "Asia", "Attention", "Benchmarking", "Biological Markers", "Blood", "Blood Glucose", "Blood Pressure", "Boston", "COVID-19 pandemic", "Cardiopulmonary", "Cardiovascular Diseases", "Cardiovascular system", "Centers for Disease Control and Prevention (U.S.)", "Cessation of life", "Childhood Asthma", "Clinical Trials", "Consensus", "Country", "Cross-Over Trials", "Crossover Design", "Data", "Developed Countries", "Devices", "Diet", "Dryness", "Educational workshop", "Exposure to", "Fasting", "Feedback", "Filtration", "Focus Groups", "Future", "Goals", "Health", "Health Benefit", "Home", "Hour", "Household", "Income", "Indoor Air Pollution", "Inflammation", "Interleukin-6", "Intervention", "Intervention Studies", "Interview", "Knowledge", "Lead", "Link", "Location", "Low Income Population", "Measurement", "Measures", "Meta-Analysis", "Morbidity - disease rate", "Outcome", "Participant", "Particulate", "Particulate Matter", "Persons", "Pollution", "Power Sources", "Predisposition", "Process", "Protocols documentation", "Public Health", "Publishing", "Qualifying", "Questionnaires", "Randomized", "Research", "Risk", "Sampling", "Spottings", "Standardization", "Time", "Tobacco", "Translating", "United States Environmental Protection Agency", "United States National Institutes of Health", "Vulnerable Populations", "Whole Blood", "Work", "acceptability and feasibility", "air filter", "air monitoring", "ambient air pollution", "cost", "efficacy trial", "epidemiology study", "experience", "feasibility testing", "feasibility trial", "fine particles", "health assessment", "health organization", "health related quality of life", "high risk population", "improved", "inclusion criteria", "indoor concentrations", "inflammatory marker", "innovation", "meter", "mortality", "multi-site trial", "noise perception", "particle", "peripheral blood", "pilot trial", "pollutant", "portability", "prevent", "randomized trial", "randomized clinical trials", "recruit", "respiratory", "satisfaction", "systematic review", "systemic inflammatory response" ], "approved": true } }, { "type": "Grant", "id": "15745", "attributes": { "award_id": "7R01HL163881-04", "title": "Targeting Estrogenic pathways in Tregs to promote ARDS resolution - 5R01HL163881", "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": 32514, "first_name": "EMMANUEL FRANCK", "last_name": "MONGODIN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-15", "end_date": "2026-05-31", "award_amount": 684280, "principal_investigator": { "id": 32799, "first_name": "Franco Rafael", "last_name": "D'Alessio", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 22591, "first_name": "RACHEL L", "last_name": "DAMICO", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 22592, "first_name": "Srinivasan", "last_name": "Yegnasubramanian", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2616, "ror": "", "name": "UNIVERSITY OF MIAMI SCHOOL OF MEDICINE", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true }, "abstract": "Pneumonia (PNA) is one of the leading causes of death worldwide. PNA can result in devastating acute inflammatory injury in the lung manifesting in acute respiratory distress syndrome (ARDS). Current treatments for PNA have focused on the pathogens, but do not target excessive lung inflammation elicited by the host immune response. Both the emergence of new infections, typified by COVID-19, and the expanding impact of antimicrobial resistant pathogens, highlight the limitations of our current armamentarium and underscore the need to identify additional therapeutic targets in PNA-induced ARDS. With the understanding that resolution of PNA is an actively regulated program to promote return to homeostasis, our work has focused on identifying cellular and molecular mediators of this resolution phase. Others and we have demonstrated that regulatory T cells (Tregs) promote resolution of infectious-ARDS. Our strong preliminary data has identified lung-derived Treg DHX58, which encodes an RNA helicase protein essential for antiviral responses, as a candidate gene upregulated during the resolution phase of ARDS. DHX58- deficient animals fail to resolve lung inflammation after Streptococcus pneumoniae-ARDS with significantly diminished lung Treg numbers during injury resolution, implicating DHX58 in optimal Treg function in vivo. Further, we observed significantly increased 30-day mortality among carriers of a putative loss-of-function variant of DHX58 with infectious ARDS (71% vs. 47%, p=0.01), underscoring the potential clinical impact of DHX58 in ARDS outcomes. Our in-silico analysis of the DHX58 promoter identified numerous estrogen responsive elements (ERE). Indeed, DHX58 expression was induced in Tregs by estradiol (E2). Importantly, our published work showed that therapeutic E2 promotes resolution of preclinical PNA-ARDS in a Treg-dependent manner. Estrogen receptor beta (ER) was necessary for both Treg-dependent rescue of lymphopenic hosts and Treg-mediated suppression of pro-inflammatory cytokine production in macrophages in vitro. Preliminary gene expression analysis and high- dimensional flow cytometry implicate E2 and its downstream-target, DHX58, in the regulation of critical Treg transcription factors (TFs), notably Foxp3 and GATA3. Thus, we hypothesize that E2, in part via ER-dependent upregulation of DHX58, orchestrates critical Treg pro-resolution functions, through regulating expression of key TFs in Tregs. The goals of this proposal are to determine the cellular, molecular and transcriptional determinants of E2-ER-DHX58 in Treg-mediated resolution of PNA-ARDS to provide the mechanistic underpinnings of the regulation and functional role of ER in Tregs.", "keywords": [ "Acute", "Acute Pneumonia", "Acute Respiratory Distress Syndrome", "Agonist", "Alveolar", "Animals", "Anti-viral Response", "COVID-19", "Candidate Disease Gene", "Cause of Death", "Cell Count", "Cell Physiology", "Cells", "Cellular biology", "Clinical", "Clinical Trials", "Critical Pathways", "Data", "Development", "Elements", "Estradiol", "Estrogen Receptor 2", "Estrogens", "FOXP3 gene", "Flow Cytometry", "GATA3 gene", "Gene Expression", "Gene Expression Profiling", "Genetic Transcription", "Goals", "Homeostasis", "Human", "Immune", "Immune response", "In Vitro", "Infection", "Inflammatory", "Inflammatory Response", "Injury", "Lung", "Macrophage", "Mediating", "Mediator", "Modeling", "Molecular", "Mus", "Outcome", "Pathway interactions", "Phase", "Pilot Projects", "Play", "Pneumonia", "Pre-Clinical Model", "Production", "Proteins", "Publishing", "Pulmonary Inflammation", "RNA Helicase", "Regulation", "Regulatory T-Lymphocyte", "Resolution", "Role", "Signal Pathway", "Signal Transduction", "Streptococcus pneumoniae", "Testing", "Therapeutic", "Therapeutic Effect", "Upregulation", "Variant", "Work", "acute infection", "alveolar epithelium", "antimicrobial resistant pathogen", "cytokine", "disease model", "disease-causing mutation", "drug resistant pathogen", "estrogenic", "high dimensionality", "in silico", "in vitro activity", "in vivo", "inflammatory lung disease", "loss of function", "lung injury", "mortality", "neutrophil", "novel therapeutics", "pathogen", "pneumonia model", "pneumonia treatment", "pre-clinical", "programs", "promoter", "repaired", "response", "therapeutic evaluation", "therapeutic target", "transcription factor" ], "approved": true } }, { "type": "Grant", "id": "15746", "attributes": { "award_id": "1R21AI188180-01A1", "title": "Determining the role of PARP14 in restricting HSV-1 replication", "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": 32800, "first_name": "LESLEY CONRAD", "last_name": "DUPUY", "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": 411499, "principal_investigator": { "id": 32801, "first_name": "David J", "last_name": "Davido", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 24962, "first_name": "Anthony R", "last_name": "Fehr", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1496, "ror": "", "name": "UNIVERSITY OF KANSAS LAWRENCE", "address": "", "city": "", "state": "KS", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 2617, "ror": "", "name": "UNIVERSITY OF KANSAS LAWRENCE", "address": "", "city": "", "state": "KS", "zip": "", "country": "United States", "approved": true }, "abstract": "Herpes simplex virus 1 (HSV-1) infects 70-90% of the human population and causes significant diseases such as blindness and life-threatening encephalitis, most notably in immunocompromised individuals. In contrast, most infections of immunocompetent hosts are asymptomatic and result in viral latency. Limited disease in most human hosts is likely the result of millions of years of co-evolution between HSV-1 and humans, due, in part, to a wide variety of host restriction factors that limit early stages of HSV-1 replication. Understanding the mechanisms used by humans to repress HSV-1 replication will help identify treatments that can mitigate severe HSV-1 diseases, especially in immunocompromised hosts. In a screen designed to identify novel host proteins that interact with the HSV-1 genome, 3 poly(ADP-ribose) polymerase (PARP) proteins were identified that bound to HSV-1 DNA with high confidence: PARP1, PARP9, and PARP14. Interestingly, prior studies had also found that these three PARP proteins were bound to HSV-1 genomic DNA, providing strong evidence that these PARP proteins could impact the replication of HSV-1, even though there have been very few reports of PARPs associated with HSV-1 replication. In addition, PARP14 has been evolving under positive selection, suggesting that it is involved in host-virus conflict, and we recently demonstrated that it can restrict coronavirus replication. Thus, the ability of HSV-1 to replicate in PARP14 knockout (KO) A549 cells was tested, and surprisingly PARP14 KO cells produced 1-2 logs more in viral yield assays and increased the plaquing efficiency ~2-logs higher compared to WT A549 cells. These results support the central hypothesis that PARP14 binds to the HSV-1 genome early in infection, leading to significant repression of HSV-1 replication. The overall objective of this application is to establish PARP14 as a novel host restriction factor and determine how it binds to the viral genome and inhibits virus replication. These objectives will be achieved through the following specific aims: 1) Establish PARP14 as a potent restriction factor for HSV-1 in cell culture and in mice; and 2) Determine how PARP14 represses the HSV-1 replication cycle and define how it binds to the viral genome. In Aim 1 a set of PARP14 knockdown/overexpressing cells and knockout mice will be used to determine if PARP14 restricts HSV- 1 replication in multiple cell culture models and in mice. In Aim 2 the stage of the viral lifecycle that is repressed by PARP14 will be determined using classical virological techniques, then ChIP-seq and several PARP14 truncation mutants will be utilized to define how it interacts with the viral genome. This research is innovative because PARP14 has not previously been described as an HSV-1 restriction factor. The proposed research is significant because it will provide a potential mechanism by which PARP14 restricts HSV-1 replication. Results from this study will lead to a greater understanding of how PARPs interact with DNA-containing viruses, which can ultimately lead to the rational development of novel therapies to prevent or treat HSV-1 diseases.", "keywords": [ "A549", "ADP Ribose Transferases", "Animal Model", "Binding", "Binding Proteins", "Biological Assay", "Blindness", "Cell Culture Techniques", "Cells", "ChIP-seq", "Conflict (Psychology)", "Coronavirus", "DNA", "DNA Damage", "DNA Viruses", "DNA biosynthesis", "Data", "Development", "Disease", "Double Stranded DNA Virus", "Encephalitis", "Epithelial Cells", "Face", "Funding", "Gene Expression", "Genetic Transcription", "Genome", "Genomic DNA", "Health", "Herpes Simplex Infections", "Herpesviridae", "Herpesvirus 1", "Host Defense", "Human", "Immunocompetent", "Immunocompromised Host", "Individual", "Infection", "Integration Host Factors", "KH Domain", "Knock-out", "Knockout Mice", "Life", "Life Cycle Stages", "Measures", "Mediating", "Mission", "Modeling", "Mus", "Nucleic Acids", "Outcome", "PARP9 gene", "Poly(ADP-ribose) Polymerases", "Population", "Proteins", "RNA", "Reporting", "Repression", "Research", "Role", "Sequence Analysis", "Techniques", "Testing", "United States National Institutes of Health", "Viral", "Viral Genome", "Viral Physiology", "Virus", "Virus Latency", "Virus Replication", "alveolar epithelium", "cell type", "design", "experimental study", "in vivo", "innovation", "insight", "interest", "knock-down", "lytic replication", "mutant", "novel", "novel therapeutics", "overexpression", "pathogen", "prevent", "response", "viral DNA", "virus host interaction" ], "approved": true } }, { "type": "Grant", "id": "15747", "attributes": { "award_id": "1R13CA301746-01", "title": "2025 Hormone-Dependent Cancers Gordon Research Conference and Gordon Research Seminar", "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": 32802, "first_name": "CHRISTINA DAWN", "last_name": "GEORGE", "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": 8000, "principal_investigator": { "id": 32803, "first_name": "Scott M.", "last_name": "Dehm", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2618, "ror": "", "name": "GORDON RESEARCH CONFERENCES", "address": "", "city": "", "state": "RI", "zip": "", "country": "United States", "approved": true }, "abstract": "The Gordon Research Conference (GRC) and the associated Gordon Research Seminar (GRS) on “Hormone-Dependent Cancers” build on the success of five prior GRC conferences on this topic in 2013, 2015, 2017, 2019, and 2023. No meeting was held 2021 due to COVID-19 restrictions. The 2025 GRC “Hormone-Dependent Cancers: A Place in Time, from the Global to the Cellular, the Significance of Environment and Tumor Dynamics on Disease Progression” will provide the stimulating and engaging format for interaction and fruitful exchange of knowledge to allow new ideas, collaborations, and projects to develop, with the ultimate goal to decrease suffering and casualties from the disease. We will cover varied perspectives on hormone-dependent cancers through the voices of early stage and experienced investigators, as well as investigators from academia and industry. The GRS entitled “Next-Generation Approaches in Basic Science and Clinical Data Integration” will precede the GRC, and is specifically geared towards early-career scientists (ECS) including graduate students, postdoctoral fellows, and clinical fellows. Leading national and international speakers will present research that represents the entire spectrum, from basic biology to clinical application of their biological findings. The focus of the meeting is hormone-dependent cancers, with an emphasis on breast and prostate cancers, since 75% of all breast cancers and all prostate cancers are deemed hormone-dependent. The presentations will be divided among a total of 9 sessions: Keynote Session 1: Advances in Therapeutic Targeting; Session 2: Breast and Prostate Metastasis; Session 3 How Important is Location?; Session 4: Nuclear Receptors, Steroid Sisters, and Orphan Brothers; Session 5: Dynamic Actions, Epi-Genomic and Epi-Transcriptomic Plasticity with Disease Progression; Session 6: Immunology, Metabolism, and Next Generation Approaches to Targeted Treatment Strategies; Session 7: Hormone-Dependent Cancer Global and Population Outcomes; Session 8: Artificial Intelligence (AI), revolutionizing translational research; Keynote Session 2: Key Areas and Questions in Hormones & Cancer. The overall goal of the 2025 GRC/GRS is to encourage the stimulation of new projects and scientific collaborations across multiple disciplines and through informal means. With the discussion of state-of-the-art research and industry perspectives on hormone-dependent cancers, we hope to foster new discoveries, create improved therapies targeting these cancers and ultimately, improve patient outcomes.", "keywords": [ "Academia", "Address", "Area", "Artificial Intelligence", "Awareness", "Basic Science", "Biological", "Biology", "Breast", "Brothers", "COVID-19", "Clinical", "Clinical Data", "Clinical Research", "Collaborations", "Data", "Dedications", "Development", "Discipline", "Disease", "Disease Progression", "Environment", "Fostering", "Goals", "Growth", "Health Care", "Heterogeneity", "Hormones", "Hour", "Immunology", "Industry", "International", "Knowledge", "Laboratory Finding", "Location", "Malignant Breast Neoplasm", "Malignant Neoplasms", "Malignant neoplasm of prostate", "Mentors", "Mentorship", "Metabolism", "Methods", "Neoplasm Metastasis", "Nuclear Receptors", "Orphan", "Outcome", "Patient-Focused Outcomes", "Population", "Postdoctoral Fellow", "Prostate", "Publishing", "Research", "Research Personnel", "Role", "Running", "Scientist", "Senior Scientist", "Sister", "Steroids", "Students", "Time", "Translational Research", "Update", "Voice", "Work", "anti-cancer research", "career", "career development", "clinical application", "clinical development", "clinical practice", "data integration", "design", "epigenomics", "epitranscriptomics", "experience", "global health", "graduate student", "health care disparity", "improved", "innovation", "interdisciplinary collaboration", "meetings", "next generation", "novel strategies", "novel therapeutics", "patient engagement", "patient population", "peer", "posters", "skills", "success", "symposium", "targeted cancer therapy", "targeted treatment", "therapeutic target", "translational pipeline", "treatment strategy", "tumor", "tumor microenvironment" ], "approved": true } }, { "type": "Grant", "id": "15748", "attributes": { "award_id": "1R21AI193903-01", "title": "Identification and characterization of the class I and class II MHC molecules of the Syrian hamster to enable advanced studies of T cell immunity", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32556, "first_name": "TIMOTHY A", "last_name": "GONDRE-LEWIS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-19", "end_date": "2027-07-31", "award_amount": 486200, "principal_investigator": { "id": 32804, "first_name": "Teresa P", "last_name": "DiLorenzo", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2619, "ror": "", "name": "ALBERT EINSTEIN COLLEGE OF MEDICINE", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "The Syrian hamster (Mesocricetus auratus) is a valuable model for the study of many RNA viruses, including SARS-CoV-2, as well as numerous other diseases relevant to human health. T cells are an important component of SARS-CoV-2-specific adaptive immunity, and they represent a key potential correlate of immunity or immunopathology in viral diseases in general. Remarkably, T cell immunity cannot be readily evaluated in Syrian hamsters at present, because their MHC molecules have not yet been identified. The lack of knowledge regarding the identity of the MHC molecules of Syrian hamsters has limited the ability of the model to support advanced investigations of cellular immunity in the response to human pathogens and vaccines. Filling this knowledge gap will be necessary to fully realize the promise of the Syrian hamster as an animal model for human diseases and is the primary objective of our proposed work. As a result of our analysis of gene structure, order, and position in the Syrian hamster genome, coupled with comparison to the mouse genome, we have identified plausible candidates for the genes encoding the classical class I and class II MHC molecules of the research Syrian hamster. We also discovered that select monoclonal antibodies (mAbs) raised to mouse MHC molecules cross-react with splenocytes of Syrian hamsters. In Aim 1, we will generate a group of cell lines, each of which will express a single candidate hamster MHC molecule. These “mono-allelic” cell lines will allow us to characterize the cross-reactivity of the anti-mouse mAbs in terms of which hamster MHC candidates they are recognizing, thus enabling the tentative identification of the candidates as genuine MHC molecules. We will verify that the cell lines can present peptides to stimulate T cells from infected or vaccinated hamsters, using SARS- CoV-2 as a model system. An important practical advance to arise from this work will be the ability to create peptide/MHC tetramers to follow T cell responses in hamsters. In Aim 2, we will define binding motifs for the hamster MHC molecules from the sequences of their natural ligands and create binding matrices to permit the identification of candidate T cell epitopes for pathogens of interest. This will permit the confirmation of the hamster candidates as true MHC molecules capable of presenting diverse arrays of peptides. Primary anchor residues and the most common peptide lengths will also be revealed. The sequences of the eluted peptides will be used to develop binding matrices that will permit prediction of candidate T cell antigens and epitopes for any current or emerging pathogen that can be modeled in the Syrian hamster. Our project will achieve the identification and functional characterization of the class I and class II MHC molecules of the Syrian hamster, enabling advanced studies of T cell immunity and greatly enhancing its utility as a model for diseases relevant to human health.", "keywords": [ "2019-nCoV", "Achievement", "Animal Model", "Animals", "Antigens", "Binding", "Biological Models", "CD4 Positive T Lymphocytes", "CD8-Positive T-Lymphocytes", "COVID-19", "Candidate Disease Gene", "Cause of Death", "Cavia", "Cell Line", "Cell surface", "Cells", "Cellular Immunity", "Characteristics", "Complex", "Cotton Rats", "Coupled", "Cross Reactions", "Disease", "Elements", "Epitopes", "Evaluation", "Ferrets", "Flow Cytometry", "Gene Structure", "Genes", "Genetic Transcription", "Genome", "Goals", "Hamsters", "Health", "Histocompatibility Antigens Class II", "Human", "Immune system", "Immunity", "Infection", "Investigation", "Knowledge", "Length", "Ligands", "Literature", "Major Histocompatibility Complex", "Mass Spectrum Analysis", "Mesocricetus auratus", "Modeling", "Monoclonal Antibodies", "Mus", "Pattern", "Peptides", "Phenotype", "Positioning Attribute", "RNA Viruses", "Reagent", "Research", "Splenocyte", "Study models", "Syria", "T cell response", "T-Cell Receptor", "T-Lymphocyte", "T-Lymphocyte Epitopes", "Time", "Transplantation", "Vaccinated", "Vaccination", "Vaccines", "Viral", "Virus", "Virus Diseases", "Work", "adaptive immunity", "beta-2 Microglobulin", "candidate identification", "cross reactivity", "disease model", "emerging pathogen", "fighting", "human disease", "human pathogen", "immunoaffinity chromatography", "immunopathology", "interest", "mouse genome", "pathogen", "protein complex", "response", "vaccine development", "vaccine-induced immunity" ], "approved": true } }, { "type": "Grant", "id": "15749", "attributes": { "award_id": "1R21AI188683-01A1", "title": "Contribution of adipose tissue immune cells to Influenza pathogenesis", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32599, "first_name": "MICHELLE MARIE", "last_name": "ARNOLD", "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": 240750, "principal_investigator": { "id": 32805, "first_name": "Senad", "last_name": "Divanovic", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2620, "ror": "", "name": "CINCINNATI CHILDRENS HOSP MED CTR", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "Epidemiological evidence establishes obesity as an independent risk factor for increased severity of viral respiratory pneumonias including influenza virus infection. Dysregulated systemic and tissue inflammation is critical to the pathogenesis of both influenza- and obesity-comorbidities. However, the critical processes that govern increased influenza severity in obesity remain undefined. The expansion of white adipose tissue (WAT) along with activation of WAT-residing immune cells inflammation promotes tissue/organ damage severity in obesity. Of note, WAT depots differ in their anatomical location and function—characteristics that are directly linked with the pathogenesis of disease-impacted organs. Using a model that combines obesity and influenza A virus (IAV) infection we reported that obese mice exhibit in greater mortality and worsened lung inflammation and tissue pathology compared to lean controls. Focusing on immune cells, we showed that IAV infection changes epididymal WAT (eWAT; a depot distal to the lungs) and lung immune cell composition and function, and favors accrual of a macrophage (MØ) subset in the lungs that shares a transcriptomic signature with eWAT residing inflammatory MØs. However, although transfer of eWAT MØ from obese into lean IAV infected mice amplified host immune cell infiltration to the lungs, it was not sufficient to increase influenza severity. Thus, eWAT MØ, although important, either do not possess the full extent of pathogenic traits or other WAT-residing immune cells are dominant contributors to influenza severity in obesity. Importantly, the presence of thoracic WAT (tWAT; a depot that is proximal to the lungs) was reported in individuals living with obesity and in obese mice. Notably, adipocytes and MØ within tWAT support IAV replication and produce proinflammatory factors during IAV infection. However, whether the character and function of tWAT and eWAT immune cells, including MØ, differs during IAV infection has not been studied. Our preliminary studies comparing tWAT and eWAT immune cells show that: (i) transfer of tWAT immune cells from obese mice into IAV infected lean mice induces mortality; (ii) tWAT is highly enriched in phenotypically distinct immune cell types; and (iii) tWAT MØ exhibit greater ability to produce proinflammatory cytokines relevant in influenza pathogenesis. Together, our novel data and existing literature support the overarching hypothesis that tWAT MØ become progressively more proinflammatory during obesity and IAV infection, and that activation of tWAT MØ unique pathogenic traits is sufficient to increases influenza severity. To test this hypothesis, we will: (1) Determine cellular traits of tWAT immune cells in obesity and influenza severity; and (2) Determine pathological processes whereby tWAT macrophages exacerbate influenza severity. Given the global increase in the incidence of obesity and viral pneumonias (e.g., Influenza, SARS-CoV-2) our high-risk/high-reward proposal will provide keen insights into previously unexplored processes that govern inflammation-associated disease severity in obesity.", "keywords": [ "2019-nCoV", "Adipocytes", "Adipose tissue", "Adoptive Transfer", "Adult", "Affect", "Anatomy", "Blood", "Cardiovascular Diseases", "Cell Physiology", "Cells", "Cessation of life", "Characteristics", "Chest", "Chronic Kidney Failure", "Communicable Diseases", "Crohn's disease", "Data", "Development", "Disease", "Distal", "Enzyme-Linked Immunosorbent Assay", "Epidemiology", "Evolution", "Exhibits", "Exploratory/Developmental Grant", "Flow Cytometry", "Future", "Gene Modified", "Goals", "Heart", "Histopathology", "Hospitalization", "Immune", "Incidence", "Individual", "Infection", "Inflammation", "Inflammatory", "Influenza", "Influenza A virus", "Kidney", "Link", "Literature", "Location", "Lung", "Lung Diseases", "Macrophage", "Modeling", "Mus", "Obese Mice", "Obesity", "Organ", "PTPRC gene", "Pathogenesis", "Pathogenicity", "Pathologic Processes", "Pathology", "Persons", "Phenotype", "Pneumonia", "Preventive", "Process", "Production", "Public Health", "Pulmonary Inflammation", "Pulmonary Pathology", "Reporting", "Risk", "Risk Factors", "Severities", "Severity of illness", "Shapes", "Source", "Structure of parenchyma of lung", "Testing", "Therapeutic", "Thinness", "Thoracic cavity structure", "Tissues", "Viral", "Viral Load result", "Viral Pneumonia", "Virus Diseases", "Virus Replication", "Visceral", "Wild Type Mouse", "Youth", "cell type", "clinically significant", "comorbidity", "cytokine", "experimental study", "high reward", "high risk", "immune cell infiltrate", "immune function", "improved", "influenza infection", "insight", "mortality", "novel", "pandemic disease", "pulmonary function", "respiratory", "systemic inflammatory response", "trait", "transcriptome", "transcriptomics" ], "approved": true } }, { "type": "Grant", "id": "15750", "attributes": { "award_id": "1R15AI191143-01A1", "title": "RNA homodimerization strand displacement pathways to extended duplexes: Atomistic details for a mechanistic paradigm to identify unique antiviral targets for current and emerging viral pandemics", "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": 32806, "first_name": "DAVID JOSEPH", "last_name": "MCDONALD", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-21", "end_date": "2028-07-31", "award_amount": 507121, "principal_investigator": { "id": 32807, "first_name": "JEFFREY D", "last_name": "EVANSECK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2621, "ror": "", "name": "DUQUESNE UNIVERSITY", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "Kissing complexes (KC) and extended duplexes (ED) represent dynamic RNA structures whose interconversion is an example of strand displacement reactions that has been implicated in playing vital roles in several viruses, influencing a broad spectrum of biochemical processes including genome packaging, viral recombination, and host-pathogen interactions. However, the structural, dynamic, and energetic details on how these interconversions occur are virtually unknown yet are vital in our novel approach of identifying and characterizing previously unconsidered meta-stable pathway states to inspire future antiviral and drug resistance development. Overcoming significant challenges that hamper meaningful modelling of RNA and dimers, and associated interconversion pathways necessitate judicious choice of computational techniques and integration with experimental data across physiologically relevant timescales. Our overarching hypothesis is that by leveraging the limited kinetic and thermodynamic data reported on RNA transition pathway systems, including the human immunodeficiency virus 1 (HIV-1) dimer initiation site (DIS) and model complexes based on the bacterial E. coli DsrA-rpoS RNA-mRNA regulatory complex, a general paradigm will be developed for other known RNA dimerization systems, such as SARS-CoV, SARS-CoV-2, HCV, and future emerging RNA viruses requiring novel antiviral therapies. To address our hypothesis, we first employ a unique approach to establish the unbiased structure and dynamics of RNA structures representing both pathway endpoints of each strand displacement reaction, such as KC to ED (Aim I). Confidence in structural predictions for systems without experimental structures is engendered by comparing computations against HIV-1 DIS crystallographic structures. We next apply a minimum energy pathway technique with and without protein chaperones to identify meta-stable states (Aim II). Reliability of the method is evaluated against the kinetic and thermodynamic data reported for the KC to ED interconversion for the E. coli DsrA-rpoS RNA-mRNA regulatory complex. Finally, as a proof of concept, we will screen RNA-binding molecules and antisense oligonucleotides against identified meta-stable intermediates along the pathways (Aim III). Aligned with NIH/R15 goals, we will train undergraduates to understand the capabilities, limitations, and errors of experimental and computational chemistry to craft ultimately a seamless research approach. Our training objective is to deliver a quality research experience that motivates undergraduates to achieve their highest potential and best prepare them for scientific research and discovery. The intent is to attract and retain the nation’s diverse student talent pool, having the consequence of enriching and diversifying the U.S. workforce by adding experts in the field of biomedical chemistry. The expected scientific outcomes are to unlock novel physical insights into strand displacement reactions and provide a foundation for targeted drug design and therapeutic interventions for drug resistance of HIV-1, SARS-CoV2, and HCV viruses of current", "keywords": [ "2019-nCoV", "Address", "Anti-viral Agents", "Anti-viral Therapy", "Anti-viral resistance", "Antisense Oligonucleotides", "Bacteria sigma factor KatF protein", "Benchmarking", "Binding", "Biochemical", "Biochemical Process", "Biological", "Biophysics", "Chemistry", "Complex", "Computational Technique", "Computer software", "Computing Methodologies", "Conserved Sequence", "Coronavirus", "Crystallography", "Data", "Data Reporting", "Dimerization", "Docking", "Drug Combinations", "Drug Design", "Drug Targeting", "Drug resistance", "Elasticity", "Elements", "Escherichia coli", "Foundations", "Free Energy", "Future", "Generations", "Genetic Recombination", "Genome", "Geometry", "Goals", "HIV-1", "Health", "Hepatitis C", "Hepatitis C virus", "Homodimerization", "Immune response", "Investments", "Kinetics", "Knowledge", "Life", "Life Cycle Stages", "Messenger RNA", "Methodology", "Methods", "Modeling", "Molecular Chaperones", "Nucleocapsid", "Oligonucleotides", "Outcome", "Pathway interactions", "Pharmaceutical Preparations", "Pharmacologic Substance", "Physiological", "Play", "Process", "Proteins", "Publications", "RNA", "RNA Binding", "RNA Viruses", "RNA-targeting therapy", "Reaction", "Reporting", "Research", "Research Personnel", "Resistance", "Role", "SARS coronavirus", "Sampling", "Signal Transduction", "Site", "Small RNA", "Structure", "Students", "System", "Talents", "Techniques", "Testing", "Therapeutic Intervention", "Thermodynamics", "Training", "United States National Institutes of Health", "Validation", "Viral", "Viral Drug Resistance", "Virus", "Work", "X-Ray Crystallography", "antiviral drug development", "comparative", "computational chemistry", "dimer", "drug resistance development", "experience", "experimental study", "genomic RNA", "graduate student", "insight", "interest", "novel", "novel strategies", "pathogen", "public health relevance", "simulation", "small molecule", "student training", "trustworthiness", "undergraduate student", "viral RNA", "viral pandemic", "virtual" ], "approved": true } }, { "type": "Grant", "id": "15751", "attributes": { "award_id": "1R01AI184716-01A1", "title": "Explore a key nucleotide synthesis enzyme to develop a broad-spectrum antiviral therapy.", "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": 32808, "first_name": "MINDY I", "last_name": "DAVIS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-21", "end_date": "2030-07-31", "award_amount": 831235, "principal_investigator": { "id": 32809, "first_name": "Pinghui", "last_name": "Feng", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 25475, "first_name": "Chao", "last_name": "Zhang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2622, "ror": "", "name": "UNIVERSITY OF SOUTHERN CALIFORNIA", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Title: Explore a key nucleotide synthesis enzyme to develop a broad-spectrum antiviral therapy Co-PI: Pinghui Feng (contact) and Chao Zhang With highly infectious viruses rapidly emerging and re-emerging (such as SARS-Coronavirus, influenza virus and drug-resistant herpes simplex viruses), the human society is challenged with limited options to treat diseases associated with these human viruses. In fact, antiviral therapies that effectively thwart the infection of a broad spectrum of viral pathogens are long sought in the antiviral community. In studying viral immune evasion, we have discovered that diverse viruses, including SARS- CoV-2, herpes simplex virus 1 (HSV-1) and influenza A virus (IAV), activate a key nucleotide synthesis enzyme not only to fuel nucleotide supply, but also block antiviral inflammatory cytokine production, thus efficiently promoting viral replication. We aim to target the key nucleotide synthesis enzyme for inhibition, which will deplete nucleotide supply and restore antiviral immune response to impede their replication. To achieve this goal, we have engineered conditional knockout and knockin mouse strains that will enable the genetic interrogation of the enzyme- mediated evasion of inflammatory response and metabolic reprogramming during the infection of SARS-CoV-2, IAV and HSV-1. Teaming up with a chemical biologist (Dr. Chao Zhang, University of Southern California), we have synthesized a library of small molecules and characterized specific inhibitors of the nucleotide enzyme. Furthermore, we will collaborate with a structural biologist (Dr. Santiago Ramon-Maiques, Instituto de Biomedicina de Valencia, Spain) to perform structure-activity relationship (SAR) analysis to further improve the lead small-molecule inhibitors. This study will provide a proof-of-concept to target a nucleotide synthesis enzyme in an effort to combat the infection of key human viral pathogens.", "keywords": [ "2019-nCoV", "Amino Acids", "Anti-viral Therapy", "Aspartate", "COVID-19 pandemic", "California", "Carbamoyl Transferases", "Carbamyl Phosphate", "Cell Line", "Cells", "Chemicals", "Coenzymes", "Collaborations", "Communities", "DNA Virus Infections", "DNA Viruses", "Data", "Dihydroorotase", "Disease", "Drug Kinetics", "Drug resistance", "Engineering", "Enzyme Inhibition", "Enzymes", "Gene Expression", "Genes", "Genetic", "Glutamine", "Glycoproteins", "Goals", "Herpesviridae", "Herpesvirus 1", "Homeostasis", "Host Defense", "Human", "Immune Evasion", "Immune response", "In Vitro", "Infection", "Infectious Agent", "Inflammatory", "Inflammatory Response", "Influenza A virus", "Knock-in Mouse", "Knockout Mice", "Laboratories", "Lead", "Libraries", "Ligase", "Lung", "Mediating", "Medical", "Medicine", "Metabolic", "Metabolism", "Modernization", "Mouse Strains", "Mus", "NF-kappa B", "Normal Cell", "Nucleotides", "Production", "Proliferating", "Property", "Proteins", "Pyrimidine", "RNA Viruses", "Role", "SARS coronavirus", "SARS-CoV-2 infection", "Shunt Device", "Signaling Protein", "Simplexvirus", "Societies", "Spain", "Structural Biologist", "Structure-Activity Relationship", "Tissues", "Translating", "Universities", "Viral", "Virus", "Virus Diseases", "Virus Replication", "Work", "aerobic glycolysis", "antiviral drug development", "cancer cell", "cellular targeting", "combat", "conditional knockout", "cytokine", "cytotoxicity", "deamidation", "design", "genetically modified cells", "glutamine analog", "improved", "influenzavirus", "inhibitor", "insight", "interest", "nucleotide metabolism", "pathogen", "pathogenic virus", "pharmacologic", "programs", "prototype", "recruit", "small molecule", "small molecule inhibitor", "small molecule libraries", "transcription factor" ], "approved": true } }, { "type": "Grant", "id": "15752", "attributes": { "award_id": "1DP2CA311214-01", "title": "Harnessing natural killer cells for cellular immunotherapy against solid tumors", "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": 32810, "first_name": "LILLIAN S", "last_name": "KUO", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-06", "end_date": "2028-07-31", "award_amount": 1457050, "principal_investigator": { "id": 32811, "first_name": "Wilfredo F", "last_name": "Garcia-Beltran", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2623, "ror": "", "name": "MASSACHUSETTS GENERAL HOSPITAL", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Despite recent advances in cancer therapy, cancer remains the second leading cause of death in the United States. The field of cancer immunotherapy has evolved to meet this challenge, but there is an ongoing need for treating metastatic and treatment-resistant solid tumors, particularly those of lung, breast, prostate, and colorectal origin. Cellular immunotherapies, such as chimeric antigen receptor (CAR) T-cell therapy, have shown success in treating blood cancers. However, they remain ineffective against solid tumors, and are often fraught with inherent toxicities such as cytokine release syndrome and attack of healthy tissues. In light of these challenges, this proposal aims to harness natural killer (NK) cells, which have broad anti-tumor activity and a superior safety profile, to generate CAR NK-cell therapy as an effective immunotherapy against solid tumors. CAR NK-cell therapy has recently shown remarkable success against blood cancers but remains challenging for use in solid tumors. The tumor microenvironment employs immune-evasive mechanisms to subvert NK-cell killing and limits their infiltration and survival. Our research proposal will address these obstacles by leveraging high-throughput, sequencing-based functional screens and innovative synthetic biology approaches that will shed light on fundamental NK-cell biology and enhance CAR NK-cell infiltration and killing of solid tumors. We will implement a genome-wide CRISPR screen in primary human NK cells to identify negative regulators (‘innate immune checkpoints’) of NK-cell cytotoxicity. Subsequently, we will identify homing and survival signals in tumor- infiltrating immune cells by mining single-cell RNA-sequencing databases. We will then introduce these genes into NK cells to enhance their infiltration and survival in in-vitro and in-vivo models of the tumor microenvironment. Finally, we will perform a high-throughput CARpool screen to simultaneously assess hundreds of NK cell-tailored CARs designed with native NK cell-receptor signaling machinery to maximize CAR NK-cell functioning. In summary, this proposed research introduces several innovative approaches to study fundamental NK-cell biology and engineer NK-cell based immunotherapies against solid tumors. Our project is poised to uncover new targets in NK cells for 'innate immune checkpoint blockade' as well as create the next-generation of CAR NK- cell therapy for treating metastatic and treatment-resistant cancers. Ultimately, we will establish a pipeline of technologies that can be applied to many cancer types in order to broaden the scope of immunotherapies against cancer and transform patient care to mitigate the devastating impact of this disease.", "keywords": [ "Biomedical Engineering", "Breast", "CAR T cell therapy", "CRISPR screen", "Cancer Etiology", "Cause of Death", "Cell Physiology", "Cell Therapy", "Cells", "Cellular biology", "Cellular immunotherapy", "Cessation of life", "Colorectal", "Colorectal Cancer", "Disease", "Effectiveness", "Genes", "Goals", "Hematopoietic Neoplasms", "Homing", "Human", "Immune", "Immune Evasion", "Immunotherapy", "In Vitro", "Infiltration", "Light", "Lung", "Malignant Breast Neoplasm", "Malignant Neoplasms", "Malignant neoplasm of lung", "Malignant neoplasm of prostate", "Methods", "Mining", "Molecular and Cellular Biology", "NK cell therapy", "Natural Killer Cells", "Patient Care", "Patients", "Prostate", "Quality of life", "Receptor Signaling", "Research", "Research Proposals", "Resistance", "Safety", "Signal Transduction", "Solid Neoplasm", "Technology", "Tissues", "Toxic effect", "Tumor-infiltrating immune cells", "United States", "cancer immunotherapy", "cancer therapy", "cancer type", "cell killing", "chimeric antigen receptor", "chimeric antigen receptor natural killer cells", "cytokine release syndrome", "cytotoxicity", "design", "engineered NK cell", "genome-wide", "immune checkpoint blockade", "improved", "in vivo Model", "innate immune checkpoint", "innovation", "molecular sequence database", "next generation", "refractory cancer", "single-cell RNA sequencing", "success", "synthetic biology", "tumor", "tumor microenvironment" ], "approved": true } }, { "type": "Grant", "id": "15753", "attributes": { "award_id": "1R21ES038077-01", "title": "Project Firestorm: Assessing Respiratory and Mental Health Impacts of Wildland-Urban Interface Fires and Long-Term Toxic Exposures", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Environmental Health Sciences (NIEHS)" ], "program_reference_codes": [], "program_officials": [ { "id": 32812, "first_name": "ASHLINN KO", "last_name": "QUINN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-25", "end_date": "2027-08-24", "award_amount": 456500, "principal_investigator": { "id": 32813, "first_name": "FRANK D.", "last_name": "GILLILAND", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32814, "first_name": "Daniel", "last_name": "Soto", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 32815, "first_name": "Jennifer Beth", "last_name": "Unger", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2622, "ror": "", "name": "UNIVERSITY OF SOUTHERN CALIFORNIA", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT The Los Angeles firestorms in January 2025 burned over 50,000 acres, destroyed over 16,000 homes and other structures, and displaced over 150,000 Los Angeles County residents. Most importantly, the fires have significantly impacted air quality across the Los Angeles Basin. The fires released high levels of fine particulate matter, VOCs, CO, NOx, and ozone precursors, exacerbating respiratory and cardiovascular conditions for those throughout Los Angeles. These findings stress the need to study long-term health impacts of wildland- urban interface (WUI) wildfire smoke. The acute and longer-term health effects of exposures from these catastrophic wildfires have yet to be defined. A better understanding of WUI) fire-related exposures and the health impacts is an urgent public health priority for Los Angeles. We will collect biological samples from affected individuals and analyze home dust, surface contaminants and outdoor soil and ash over time. After a wildfire it is critical to assess exposure levels and characterize the composition of toxins before home clean-up and environmental factors, such as wind and rain, alter its distribution or concentrations. We propose to conduct Project Firestorm, a rapid study to quantify the health effects of the wildfires. We will leverage an existing cohort of over 9,000 USC faculty, staff, and students who participated in a longitudinal COVID-19 study in 2021-2022. These participants, most of whom live in or around Los Angeles, have completed surveys about their physical and mental health and sociodemographics, providing an essential baseline assessment. The participants have signed consent forms giving their permission to be recontacted for future studies, enabling us to launch the study quickly without extensive recruitment time. We will recontact these participants and invite them to complete a survey about the effects of the fires on physical, mental, and financial health over the next year. From those who complete the survey (N=approximately 3000), we will recruit and collect more detailed data from a sample of 200 participants--100 who lived near the fires (fire-adjacent) and 100 who live over 15 miles away from the burn site (fire-distant). These participants will provide health outcome data on respiratory and other key outcomes, hair samples, wear silicone bracelets for VOC measurements, and samples of their house dust, surface wipes and yard soil for analysis, in February-March 2025 and again in February-March 2026. We will analyze (1) differences between fire-adjacent and fire-distant participants at baseline, and (2) change over a one-year period among fire-affected households and more distant households. 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