Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1405&sort=awardee_organization
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=awardee_organization", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1419&sort=awardee_organization", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1406&sort=awardee_organization", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1404&sort=awardee_organization" }, "data": [ { "type": "Grant", "id": "15740", "attributes": { "award_id": "1R43TR005424-01", "title": "A Novel Approach to Eliminate Length Impurities for High-Quality mRNA Production", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Center for Advancing Translational Sciences (NCATS)" ], "program_reference_codes": [], "program_officials": [ { "id": 32559, "first_name": "PJ", "last_name": "BROOKS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2026-07-31", "award_amount": 349746, "principal_investigator": { "id": 32603, "first_name": "Hari", "last_name": "Bhaskaran", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2611, "ror": "", "name": "CISTERNA BIOLOGICS, INC.", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "With the success of mRNA-based Covid vaccines, there is immense interest in leveraging mRNA technology to develop therapeutics for previously untreatable diseases. However, therapeutic applications, such as protein replacement therapy, cardiovascular regeneration, and cancer immunotherapy, require mRNA of exceptional purity to ensure safety and efficacy. Current mRNA production methods often yield mRNA with impurities, such as double-stranded RNA (dsRNA), long RNA (LRNA), and short truncated (stRNA), which can provoke immune responses and compromise therapeutic outcomes. Cisterna has developed an innovative platform capable of synthesizing high-quality, purified mRNA, devoid of product-related contaminants, making it ideal for therapeutic use while ensuring consistency and reproducibility across batches. In this Phase I SBIR, our goal is to demonstrate the efficacy of our technology in eliminating dsRNA, LRNA, and stRNA compared to conventional methods. We will employ sensitive fluorescence-based methods and assays to quantify and eliminate these impurities, enabling the production of highly pure therapeutic mRNA. Furthermore, we will validate our technology by assessing its impact on immunogenic response and protein expression in mice, aiming for minimal to no immune activation while maintaining or enhancing therapeutic efficacy. Successful completion of this project will provide a validated production platform for contaminant-free mRNA synthesis, paving the way for Phase II studies focused on target identification, construct design, and scale-up manufacturing. The mRNA therapeutics market is poised for significant growth, with biotech and pharmaceutical companies actively developing mRNA-based therapeutics. We aim to leverage potential partnerships to position ourselves as a key player in this dynamic field.", "keywords": [ "Address", "Advanced Development", "Affect", "Antibodies", "Biological Assay", "Biological Products", "Biotechnology", "COVID-19 vaccine", "Cardiovascular system", "Catalytic RNA", "Cellulose", "Consumption", "Detection", "Development", "Disease", "Dose", "Dot Immunoblotting", "Double-Stranded RNA", "Engineering", "Ensure", "Enzymes", "Event", "Excision", "Fluorescence", "Gel", "Goals", "Growth", "Hela Cells", "High Pressure Liquid Chromatography", "Immune", "Immune response", "Innate Immune Response", "Legal patent", "Length", "Longevity", "Luciferases", "Malignant Neoplasms", "Marketing", "Measures", "Messenger RNA", "Metabolic", "Methods", "Modeling", "Mus", "Natural regeneration", "Pharmacologic Substance", "Phase", "Positioning Attribute", "Process", "Production", "RNA", "Rare Diseases", "Recovery", "Reference Standards", "Regimen", "Reproducibility", "Safety", "Sepharose", "Small Business Innovation Research Grant", "Technology", "Technology Assessment", "Testing", "Therapeutic", "Therapeutic Uses", "Time", "Treatment Efficacy", "Validation", "Variant", "Work", "cancer immunotherapy", "commercial application", "cost", "cytokine", "design", "design and construction", "detection limit", "dosage", "drug development", "effective therapy", "enzyme replacement therapy", "high standard", "immune activation", "immunogenic", "immunogenicity", "in vivo", "innovation", "interest", "manufacturing scale-up", "mouse model", "multiplex assay", "novel strategies", "oligo (dT)", "phase 2 study", "prophylactic", "protein expression", "research and development", "response", "success", "therapy development", "therapy outcome", "tool", "transcriptome sequencing" ], "approved": true } }, { "type": "Grant", "id": "15741", "attributes": { "award_id": "1R35GM160071-01", "title": "Viral Biosensors of Host Post-Translational Modifications", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 22244, "first_name": "MICHAEL", "last_name": "SAKALIAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2030-07-31", "award_amount": 420984, "principal_investigator": { "id": 26190, "first_name": "Mehdi", "last_name": "Bouhaddou", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2612, "ror": "", "name": "UNIVERSITY OF CALIFORNIA LOS ANGELES", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Viruses and their hosts are engaged in a constant, dynamic struggle as part of an ongoing evolutionary arms race. It is well established that viruses continually evolve new offensive strategies, like the production of proteins that disrupt host defenses, while hosts develop countermeasures to detect and neutralize viruses. However, a key question that remains is: how do viruses perceive and respond to host cues in real-time? This ability to sense and adapt to the intracellular environment, akin to real-time \"decision-making,\" which helps them decide when to replicate, assemble, or escape, plays a crucial role in their fitness and ability to spread. To understand how viruses sense and respond to their environment, we will study host-derived post-translational modifications (PTMs) of viral proteins. The overarching hypothesis of this proposal is that viral proteins have evolved as substrates for host enzyme-derived PTMs to equip them with molecular sensors to coordinate viral life cycle transitions. Furthermore, we will study how PTMs enable multifunctionality in viral proteins by creating distinct proteoforms. By understanding the molecular mechanisms of viral biosensors, we expect to pinpoint critical viral dependencies, revealing promising targets for antiviral intervention. PTMs, imposed by the host cell, can dramatically alter the functions of viral proteins, influencing their behavior and ultimately the fate of the virus. Our preliminary mass spectrometry phosphoproteomics analysis of alphavirus infection revealed phosphorylation sites at the capsid-glycoprotein interface, likely regulated by plasma membrane-localized kinases, suggesting a functional switch in glycoproteins at the membrane. We similarly identified phosphorylation sites on herpesvirus latency proteins, which we believe may play a role in allowing the viral genome to replicate alongside the host genome during latency. Lastly, we discovered phosphorylation of a SARS-CoV-2 accessory protein by innate immune kinases, suggesting a feedback mechanism that may modify viral protein function in response to immune activation. Our data have led us to three specific areas of inquiry, each forming a distinct research project being conducted by PhD students, a project scientist, and undergraduate trainees: (1) How do viruses navigate through distinct host subcellular locations during their life cycle? (2) How do viruses coordinate their life cycle with the host cell cycle? (3) How do viruses sense, respond to, and exploit the host innate immune system? The projects and questions outlined in this proposal will serve as the foundation for the primary research in my laboratory over the next five years. Our questions seek to establish a new research area centered on the biochemical mechanisms through which viruses act as biosensors of the host signaling environment, how these biosensors adjust their functionality in response to PTMs, and how targeting these sensors may result in innovative antiviral therapies.", "keywords": [ "2019-nCoV", "Alphavirus Infections", "Anti-viral Therapy", "Area", "Behavior", "Biochemical", "Biosensor", "Capsid", "Cell Cycle", "Cell membrane", "Cells", "Cues", "Data", "Decision Making", "Dependence", "Development", "Disease", "Environment", "Enzymes", "Feedback", "Foundations", "Genome", "Glycoproteins", "Herpesviridae", "Host Defense", "Immune", "Innate Immune System", "Intervention", "Knowledge", "Laboratories", "Life Cycle Stages", "Location", "Mass Spectrum Analysis", "Membrane", "Mission", "Molecular", "Phosphorylation", "Phosphorylation Site", "Phosphotransferases", "Play", "Post-Translational Protein Processing", "Production", "Proteins", "Public Health", "Research", "Research Project Grants", "Role", "Scientist", "Signal Transduction", "Time", "United States National Institutes of Health", "Viral", "Viral Genome", "Viral Physiology", "Viral Proteins", "Virus", "Virus Diseases", "arms race", "doctoral student", "fitness", "immune activation", "innovation", "insight", "novel therapeutic intervention", "phosphoproteomics", "protein function", "response", "sensor", "undergraduate student" ], "approved": true } }, { "type": "Grant", "id": "15742", "attributes": { "award_id": "1R21AI188400-01A1", "title": "Uncovering mechanisms that underpin bat virus virulence", "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": 32795, "first_name": "EUN-CHUNG", "last_name": "PARK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-04", "end_date": "2027-07-31", "award_amount": 455692, "principal_investigator": { "id": 26531, "first_name": "Cara", "last_name": "Brook", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2613, "ror": "", "name": "UNIVERSITY OF CALIFORNIA BERKELEY", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Bats are reservoir hosts for zoonoses that cause the highest case fatality rates documented in humans, including rabies and related lyssaviruses, Hendra and Nipah henipaviruses, Ebola and Marburg filoviruses, and SARS and MERS coronaviruses. Bats exhibit limited disease upon infection with these viruses that cause extreme pathology in other mammals, likely due to robust and rapid innate and cell-mediated immune defenses, coupled with hyper-efficient mechanisms of DNA damage repair and dampened inflammatory pathways. Recent theoretical work in our lab demonstrates how these unique features of bat immunology and physiology—chiefly, constitutive antiviral immunity and resilience to inflammation that confers tolerance to immunopathology—should select for the evolution of high virus growth rates that, while avirulent to bats, are likely to cause pathology following spillover to non-bat, including human, hosts. Here, we seek to explicitly test the predictions of our theoretical model by carrying out experimental evolution of vesicular stomatitis virus (VSV) in bat cell cultures that span a range of both (Aim 1) constitutive antiviral and (Aim 2) inflammation tolerant phenotypes. Under Aim 1, we examine variation in VSV growth rate evolution and the rate of molecular evolution following serial passage of virus across a suite of Pteropus alecto bat cell lines that exhibit both intact (wildtype) and deficient (CRISPR knock-outs) antiviral immune functions. Under Aim 2, we leverage our lab’s unique system of primary bat fibroblast cell lines derived from related species spanning a range of longevities to evaluate whether cells derived from longer-lived species that demonstrate resilience to aging-related stressors also exhibit heightened tolerance of virus infection. We then compare VSV evolution following serial passage across cell lines that demonstrate variable resilience to aging-related stressors in vitro. We hypothesize that antiinflammatory properties in bat cells which confer resilience to aging stressors may also facilitate virus tolerance by limiting immunopathology and—by extension—drive the evolution of high growth rate viruses likely to generate pathology in non-bat hosts. Ultimately, we offer an explicit empirical test of the hypothesized mechanisms underpinning the extreme virulence of bat virus zoonoses.", "keywords": [ "Acceleration", "Aging", "Anti-Inflammatory Agents", "Anti-viral Response", "Automobile Driving", "Birds", "Body Size", "Case Fatality Rates", "Cell Culture Techniques", "Cell Line", "Cells", "Chiroptera", "Clustered Regularly Interspaced Short Palindromic Repeats", "Coupled", "DNA Repair", "Data", "Disease", "Ebola", "Evolution", "Exhibits", "Fibroblasts", "Filovirus", "Genes", "Genome", "Genus Pteropus", "Growth", "Harvest", "Hendra Virus", "Human", "IFNAR2 gene", "IRF1 gene", "IRF3 gene", "Immune", "Immune response", "Immunity", "Immunologics", "Immunology", "In Vitro", "Indiana", "Infection", "Inflammation", "Inflammatory", "Interferons", "Knock-out", "Link", "Literature", "Locomotion", "Longevity", "Lyssavirus", "Mammals", "Marburgvirus", "Mediating", "Metabolic", "Metabolic stress", "Middle East Respiratory Syndrome Coronavirus", "Molecular", "Molecular Evolution", "Nipah Virus", "Paper", "Pathology", "Pathway interactions", "Phenotype", "Physiological", "Physiology", "Plaque Assay", "Process", "Property", "Public Health", "RNA", "Rabies", "Regulator Genes", "Research", "Residual state", "Resistance", "SARS coronavirus", "Secondary to", "Serial Passage", "Serotyping", "Signal Transduction", "System", "Testing", "Theoretical model", "Variant", "Vesicular stomatitis Indiana virus", "Viral", "Viral Load result", "Virulence", "Virulent", "Virus", "Virus Diseases", "Work", "Zoonoses", "aging related", "anti aging", "antiviral immunity", "burden of illness", "cellular resilience", "comparative", "cost", "experience", "experimental study", "extend lifespan", "immune function", "immunopathology", "life span", "oxidative damage", "predictive modeling", "rapid growth", "resilience", "resilience in aging", "response", "stressor", "theories", "trait", "transcriptome sequencing", "transcriptomics", "transmission process", "viral resistance" ], "approved": true } }, { "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": "15744", "attributes": { "award_id": "1U19AI189183-01", "title": "Accelerator for the rapid development of countermeasures targeting drug resistant fungal pathogens", "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": 32798, "first_name": "PING", "last_name": "CHEN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2030-06-30", "award_amount": 6977446, "principal_investigator": { "id": 8841, "first_name": "Arturo", "last_name": "Casadevall", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [ { "id": 344, "ror": "https://ror.org/00za53h95", "name": "Johns Hopkins University", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 23143, "first_name": "David S", "last_name": "Perlin", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1487, "ror": "https://ror.org/008zj0x80", "name": "Hackensack University Medical Center", "address": "", "city": "", "state": "NJ", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 2615, "ror": "", "name": "JOHNS HOPKINS UNIVERSITY", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Invasive fungal infections pose a significant medical challenge, particularly for individuals with compromised immune systems or other conditions due to HIV, cancer, organ transplantation, diabetes, chronic respiratory ailments, tuberculosis, COVID-19, and influenza. Prompt diagnosis and effective antifungal treatment are crucial for positive clinical outcomes. Current antifungal drugs are limited in number and efficacy, and their effectiveness has been compromised by the emergence of drug-resistant strains, notably Candida auris, Candida glabrata, and Aspergillus fumigatus. To combat this growing problem, there is an urgent need to develop new drugs capable of effectively treating invasive infections caused by drug-resistant fungal pathogens. Additionally, actionable point-of-care diagnostics for Candida bloodstream infections are essential for initiating timely and appropriate therapy, ultimately reducing overall mortality rates. While efforts from the biopharmaceutical industry have led to some expansion in the antifungal pipeline, more potent and targeted drugs are urgently required. In response to these pressing challenges, a Center of Excellence in Translational Research (CETR) focused on rapid drug and diagnostic development will be established. This Center harnesses expertise of leading academic and industry professionals, many of whom have a track record of successfully bringing FDA-approved products to market. The Projects selected encompass a wide range of new and established pharmacological drug targets, as well as a state-of-the-art diagnostic platform. Among the projects underway, collaborations with biopharmaceutical partners Prokaryotics and Scynexis are focused on the development of advanced small molecules targeting key enzymes involved in cell wall biogenesis. Additionally, efforts are underway to develop an antibody-based immunotherapy to combat drug-resistant infections. Finally, a Project dedicated to creating a novel point-of-care diagnostic capable of rapidly detecting Candida bloodstream infections in partnership with Cepheid Diagnostics on the GeneXpert platform, holds promise for revolutionizing the diagnosis and management of fungal infections. An integrated network of science cores staffed by experienced directors, facilitate efficient compound optimization and progression through clear ‘go, no-go’ metrics. While all programs prioritize high-threat drug-resistant Candida species, some drug candidates may also demonstrate efficacy against azole-resistant Aspergillus fumigatus. In summary, this CETR-based drug and diagnostic development accelerator represents a concerted effort to address the pressing need for novel treatments and diagnostics for invasive fungal infections. By leveraging the expertise of industry and world class translational academic partners, this initiative aims to rapidly advance innovative solutions to combat antifungal drug resistance and improve clinical outcomes for patients affected by these challenging fungal infections. The anticipated outcome of our successful efforts will be to create two IND-ready small molecule drug candidates, a lead optimized novel immunotherapy, and a 510(k) ready point-of-care diagnostic for bloodstream infections.", "keywords": [ "Academia", "Acceleration", "Address", "Advanced Development", "Affect", "Animal Model", "Antibodies", "Aspergillus fumigatus", "Azole resistance", "Biogenesis", "Biological Products", "Blood", "COVID-19", "Candida", "Candida auris", "Candida glabrata", "Cell Wall", "Chronic", "Clinical", "Collaborations", "Death Rate", "Dedications", "Detection", "Development", "Diabetes Mellitus", "Diagnosis", "Diagnostic", "Disease", "Drug Targeting", "Drug resistance", "Effectiveness", "Ensure", "Enzymes", "FDA approved", "Fungal Drug Resistance", "GPI Membrane Anchors", "Goals", "HIV", "Immune system", "Immunocompromised Host", "Immunotherapy", "Individual", "Industry", "Infection", "Influenza", "Investigational Drugs", "Knowledge", "Lead", "Life", "Malignant Neoplasms", "Marketing", "Medical", "Microbiology", "Mission", "Mycoses", "Organ Transplantation", "Outcome", "Patient-Focused Outcomes", "Pharmaceutical Chemistry", "Pharmaceutical Preparations", "Pharmacology", "Pharmacotherapy", "Process", "Productivity", "Public Health", "Rapid diagnostics", "Records", "Resistance", "Resistant candida", "Resources", "Respiration Disorders", "Science", "Standardization", "The science of Mycology", "Therapeutic", "Time", "Translational Research", "Transplantation", "Tuberculosis", "anti-fungal agents", "biopharmaceutical industry", "bloodstream infection", "combat", "diagnostic development", "diagnostic platform", "diagnostic tool", "diagnostic value", "drug candidate", "drug development", "experience", "formulation optimization", "glucan synthase", "improved", "in vivo", "in vivo Model", "innovation", "lead optimization", "mannoproteins", "mortality", "novel", "novel therapeutics", "pathogen", "pathogenic fungus", "pharmacologic", "point of care", "point-of-care diagnostics", "preclinical development", "prevent", "programs", "rapid detection", "resistant Aspergillus", "resistant strain", "respiratory", "response", "small molecule" ], "approved": true } }, { "type": "Grant", "id": "15756", "attributes": { "award_id": "1R01AI190195-01", "title": "The Impact of Systemic Immunosuppression on RSV Antibody Generation and Effector Functions After Vaccination", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 21312, "first_name": "SONNIE", "last_name": "KIM", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2030-07-31", "award_amount": 775187, "principal_investigator": { "id": 32819, "first_name": "Andrew Hoover", "last_name": "Karaba", "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": "Immunosuppressed persons (ISPs) have a nearly 40% risk of hospitalization if infected with respiratory syncytial virus (RSV). Recently, novel RSV vaccines based on the prefusion F protein of the virus were found to be effective at reducing RSV disease, but these were not tested in high-risk ISPs. Owing to immunosuppression, ISPs often develop attenuated antibody responses to vaccines and require either additional doses or different formulations to achieve protective levels of antibodies. Antibodies against prefusion F are associated with protection from RSV disease and thought to be central to the protection afforded by RSV vaccines. Our preliminary data indicate that, among ISPs, the antibody response to RSV vaccines is heterogeneous, with many ISPs demonstrating minimal or no response. However, the nature of this decreased response (i.e. unrecognized antibody epitopes and impact on neutralizing and non-neutralizing functions) remains unknown. Furthermore, the influence of specific immunosuppressive medications and the type of vaccine received (adjuvanted vs. unadjuvanted) is undetermined. To protect this high-risk group from this common and often devastating infection, a comprehensive understanding of the antibody response to these vaccines by ISPs is necessary and will improve vaccine recommendations, design, and medication management. The proposed research will address these uncertainties by systematically studying the antibody response to novel RSV vaccines in a national observational cohort of ISPs, comparing the responses to those of healthy participants (HPs). This national cohort of highly engaged ISPs was critical in our previous successful efforts to define the effects of immunosuppression on SARS-CoV-2 vaccination, and we will leverage this opportunity to discern the impact of immunosuppression on antibody responses to RSV vaccines. We will accomplish this by quantifying the prefusion F and neutralizing antibody response longitudinally in these groups and determining the impact of vaccine type (adjuvanted vs. unadjuvanted), type of immunosuppressive medication, and demographic factors (Aim 1). Additionally, we will study the entire viral antibody epitope landscape before and after vaccination using innovative DNA barcoded-protein technology to identify key gaps in epitope recognition, measure the impact of pre-existing immunity on vaccine responses, and correlate specific epitope responses with antibody function (Aim 2). Finally, the researchers will measure the effect of immunosuppression and vaccine adjuvant on antibody subtype, subclass, and non-neutralizing functions using a systems serology approach (Aim 3). The investigators’ established productive collaborative relationships, extensive experience studying antibody responses in high-risk and/or immunosuppressed populations, and this cohort of ISPs provide the ideal circumstances to provide critical knowledge that promises to be directly applicable to improving RSV vaccine responses in this high-risk group and inform future vaccine design for immunosuppressed persons.", "keywords": [ "Adjuvant", "Antibodies", "Antibody Formation", "Antibody Response", "Attenuated", "Autoimmune Diseases", "Bar Codes", "COVID-19 vaccination", "COVID-19 vaccine", "Cells", "Clinical", "Clinical Trials", "Complement Activation", "Complex", "DNA", "Data", "Demographic Factors", "Disease", "Dose", "Enzyme-Linked Immunosorbent Assay", "Epitopes", "Formulation", "Future", "Generations", "Goals", "Hospitalization", "Immune response", "Immune signaling", "Immunity", "Immunocompromised Host", "Immunoglobulin A", "Immunoglobulin G", "Immunoglobulin M", "Immunologics", "Immunosuppression", "Individual", "Infection", "Innate Immune System", "Knowledge", "Measures", "Medication Management", "Modeling", "Molecular", "Nature", "Older Population", "Participant", "Peptides", "Persons", "Pharmaceutical Preparations", "Play", "Population", "Process", "Productivity", "Proteins", "Recommendation", "Regimen", "Research", "Research Personnel", "Respiratory Syncytial Virus Infections", "Respiratory Syncytial Virus Vaccines", "Respiratory syncytial virus", "Risk", "Role", "Serology", "Solid", "System", "Technology", "Testing", "Toxic effect", "Uncertainty", "Vaccination", "Vaccine Adjuvant", "Vaccine Design", "Vaccines", "Viral", "Viral Antibodies", "Viral Proteins", "Virus", "Virus Diseases", "antibody-dependent cell cytotoxicity", "attenuation", "cohort", "design", "disorder prevention", "experience", "high risk", "high risk population", "immune activation", "immunogenicity", "immunosuppressed", "improved", "in vitro Model", "indexing", "innovation", "machine learning model", "neutralizing antibody", "novel", "organ transplant recipient", "pathogen", "pharmacologic", "response", "self assembly", "vaccine access", "vaccine immunogenicity", "vaccine response" ], "approved": true } }, { "type": "Grant", "id": "15762", "attributes": { "award_id": "1K08AI193077-01", "title": "Impact of Spatial and Social Determinants on Invasive Fungal Infection Risk", "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": 32829, "first_name": "DONA", "last_name": "LOVE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2030-07-31", "award_amount": 197640, "principal_investigator": { "id": 32830, "first_name": "Lucy", "last_name": "Li", "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": ": Invasive fungal infections (IFIs) are a growing public health challenge, leading to over 1.5 million deaths each year worldwide. Contextual factors are believed to be critical components of IFI risk as evidenced by historical fungal outbreaks associated with specific geographic distributions and ecological disruptions. Certain communities are thought to be particularly vulnerable with greater exposure to high-risk contextual factors, leading to higher rates of and worse outcomes from IFIs. In addition, socioeconomic status may impact IFI outcomes, due to delays in diagnosis, access to care, and quality of care. However, prior studies of IFI epidemiology have focused primarily on host factors without adequately considering the uneven distribution of hazards and their spatiotemporal trends related to socioeconomic factors. The objective of this proposal is to assess the impact of social determinants on IFI risk by leveraging a national data source, the National COVID Cohort Collaborative, and a more granular hospital system electronic-health medical records data source. In Aim 1, we will determine neighborhood-level contextual and socioeconomic predictors of IFIs. In Aim 2, we will examine the association between individual socioeconomic status factors and clinical outcomes of IFIs. This work will advance our understanding of the spatial and social determinants of IFI risk and outcomes as well as provide a robust training platform for the award recipient, Dr. Lucy Li. Through both research and career development training, Dr. Li will acquire essential skills in large data analysis, including advanced methods in spatial science and social factors research, time series analyses, and risk prediction modeling. Dr. Li will then be well positioned to be an independent clinical investigator focused on IFIs in at-risk populations with an expertise in integrating spatial and social factors data into population health analyses.", "keywords": [ "Address", "Affect", "Air", "Allergic", "American", "Area", "Asthma", "Award", "COVID-19", "Caring", "Censuses", "Cessation of life", "Clinical", "Clinical Investigator", "Clinical Research", "Communities", "Community Surveys", "Computerized Medical Record", "Data", "Data Analyses", "Data Commons", "Data Sources", "Databases", "Diagnosis", "Dimensions", "Disease", "Disease Outbreaks", "Education", "Electronic Health Record", "Employment Status", "Epidemiology", "Equation", "Ethnic Origin", "Exposure to", "Geographic Distribution", "Geographic Locations", "Health Services Accessibility", "Health system", "Hospitalization", "Hospitals", "Housing", "Immunocompetent", "Immunocompromised Host", "Incidence", "Income", "Individual", "Infection", "Insurance Coverage", "Integration Host Factors", "International Classification of Disease Codes", "Intervention", "Length of Stay", "Logistic Regressions", "Longitudinal trends", "Measures", "Mentors", "Methods", "Molds", "Mycoses", "Neighborhoods", "Organ", "Outcome", "Outcome Assessment", "Patients", "Pattern", "Persons", "Play", "Population", "Populations at Risk", "Positioning Attribute", "Public Health", "Quality of Care", "Race", "Research", "Resolution", "Risk", "Risk Factors", "Science", "Seasons", "Shapes", "Site", "Socioeconomic Factors", "Socioeconomic Status", "Source", "System", "Time Series Analysis", "Training", "United States", "Weather", "Work", "Yeasts", "adjudication", "career", "career development", "clinical care", "clinical risk", "cohort", "contextual factors", "design", "electronic medical record system", "fungus", "hazard", "high risk", "improved", "indexing", "infection risk", "low socioeconomic status", "mortality", "multilevel analysis", "patient screening", "population health", "primary outcome", "research and development", "risk prediction", "risk prediction model", "secondary outcome", "skills", "social determinants", "social factors", "social vulnerability", "socioeconomics", "spatial epidemiology", "spatial integration", "spatial relationship", "spatiotemporal", "statistics", "time use", "trend" ], "approved": true } }, { "type": "Grant", "id": "15857", "attributes": { "award_id": "1R01HD119223-01", "title": "Improving student mental health through a universal trauma-informed intervention: Testing effectiveness and implementation of RAP Club", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 44281, "first_name": "VALERIE", "last_name": "MAHOLMES", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-10", "end_date": "2030-06-30", "award_amount": 661489, "principal_investigator": { "id": 12477, "first_name": "Tamar", "last_name": "Mendelson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 344, "ror": "https://ror.org/00za53h95", "name": "Johns Hopkins University", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 2615, "ror": "", "name": "JOHNS HOPKINS UNIVERSITY", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "ABSTRACT. The COVID-19 pandemic exacerbated adolescent mental health problems and worsened disparities in their prevalence. While universal evidence-based school mental health programs are an effective way to reduce and prevent youth mental health issues, few such programs are, in fact, used in schools. Translation of research into practice averages 17 years, and most evidence-based programs are never sustainably adopted in real-world settings due to implementation barriers. RAP (Relax, Aware, Personal rating) Club is an evidence-based intervention to improve mental health among 8th grade students. Due to its trauma- informed approach and combination of mindfulness and cognitive behavioral skills, RAP Club is appropriate for 8th graders who have been exposed to chronic stress and trauma. Our team’s randomized control trial (RCT) in 29 urban public schools showed that, compared with an active control condition, RAP Club reduced symptoms of post-traumatic stress (PTSD), depression, and anxiety, as well as behavior problems, during the transition into high school. In the RCT, RAP Club sessions were delivered by research staff, which is not a sustainable or scalable delivery model. Thus, the objective of this type II hybrid effectiveness-implementation study is to test RAP Club’s delivery by school personnel, using a randomized factorial experiment to identify the most effective implementation approaches. We will examine the performance of two factors: (1) facilitator expertise (school personnel with versus without mental health expertise) and (2) supervision level (standard versus enhanced). Using a 2x2 factorial design, we will test four conditions that represent all combinations of these two factors. This design will allow us to identify the conditions that improve student mental health, strategically balanced by data on their implementation constraints (e.g., cost). We will test the impact of each of these four conditions on student PTSD symptoms (primary outcome) and anxiety symptoms, depressive symptoms, and behavior problems (secondary outcomes) at post-test and 4- and 12-month follow-ups (Aim 1: Effectiveness outcomes). For each of the four conditions, we will also evaluate cost, cost-effectiveness, and fidelity of implementation, as well as feasibility and acceptability (Aim 2: Implementation outcomes). Potential moderators of the effectiveness and implementation outcomes will be explored for each of the four conditions, including characteristics of schools (size, % low-income students), students (sex, trauma exposure), and facilitators (sex, years in profession) (Exploratory Aim 3: Potential Moderators). Findings will be used to create a toolkit that presents effectiveness and implementation data for each of the four conditions to guide education leaders in selecting strategies that maximize their current resources. Use of a factorial design to test program implementation strategies offers a novel and efficient model for streamlining translation of research into school- based practice. Findings will advance the science on school mental health interventions and will boost RAP Club’s potential for widespread adoption.", "keywords": [ "Address", "Adolescent", "Adopted", "Adoption", "Anxiety", "Attention", "Awareness", "Baltimore", "Behavioral", "COVID-19 pandemic", "Characteristics", "Child Health", "Chronic stress", "Cities", "Clinical", "Cognitive", "Communities", "Cost Analysis", "Data", "Disparity", "Education", "Effectiveness", "Enrollment", "Evidence based intervention", "Evidence based program", "Exposure to", "Future", "Health", "Human Resources", "Hybrids", "Instruction", "Intervention", "Intervention Trial", "Low income", "Mental Depression", "Mental Health", "Methods", "Modeling", "National Institute of Child Health and Human Development", "Perception", "Performance", "Personal Satisfaction", "Persons", "Positioning Attribute", "Post-Traumatic Stress Disorders", "Poverty", "Prevalence", "Problem behavior", "Professional Role", "Public Health", "Randomized", "Randomized Controlled Trials", "Reach Effectiveness Adoption Implementation and Maintenance", "Relaxation", "Research", "Resources", "Schools", "Science", "Strategic Planning", "Students", "Supervision", "Symptoms", "Testing", "Translational Research", "Translations", "Trauma", "Urban Community", "Violence", "Work", "Youth", "acceptability and feasibility", "active control", "adolescent health", "adolescent mental health", "anxiety symptoms", "coping", "cost", "cost effectiveness", "depressive symptoms", "design", "education research", "effectiveness outcome", "effectiveness testing", "effectiveness/implementation study", "eighth grade", "emotion regulation", "evidence base", "experimental study", "health disparity", "health economics", "high school", "implementation barriers", "implementation fidelity", "implementation outcomes", "implementation science", "implementation strategy", "improved", "innovation", "marginalization", "mindfulness", "novel", "post-traumatic symptoms", "prevent", "primary outcome", "programs", "psychoeducation", "reduce symptoms", "research to practice", "scale up", "secondary outcome", "sex", "skills", "student participation", "tool", "transition to adulthood", "trauma exposure", "universal prevention", "urban school" ], "approved": true } }, { "type": "Grant", "id": "15920", "attributes": { "award_id": "1R01HD114790-01A1", "title": "Health Outcomes of Youth Who Experience Caregiver Death", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 44281, "first_name": "VALERIE", "last_name": "MAHOLMES", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-24", "end_date": "2030-03-31", "award_amount": 569563, "principal_investigator": { "id": 44365, "first_name": "Dylan B.", "last_name": "Jackson", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 44366, "first_name": "Terrinieka Williams", "last_name": "Powell", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2615, "ror": "", "name": "JOHNS HOPKINS UNIVERSITY", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Each year, over two million US youth experience the death of a caregiver before the age of 18 (hereafter referred to as caregiver death). Given the syndemic of COVID-19, the opioid crisis, and gun violence, rates of caregiver death among US children are likely to remain elevated or increase in the next decade. US non-Hispanic Black children are three times more likely to experience parent death than White children. Bereaved youth (i.e., who experienced a caregiver death) are vulnerable to adverse emotional and behavioral health (EBH) outcomes, such as higher risks of depression, anxiety, substance use, and suicidality. The goal of this research is to identify opportunities for improving EBH outcomes among bereaved youth. Three knowledge gaps must be filled to achieve this goal. First, we need to evaluate caregiver death in the context of other co-occurring adverse experiences. Second, we need to understand how the caregiving context mediates the relationship between caregiver death and EBH outcomes. Third, we need to learn from the lived experiences of bereaved young people. In addition to our multidisciplinary investigative team with relevant content and methodological expertise, an Advisory Board of bereaved young adults and grief professionals will be developed to inform this research. Guided by a Life Course Framework and Multidimensional Grief Theory, we will use a convergent mixed-method design to achieve three aims and fill the identified knowledge gaps: 1) Assess associations between caregiver death and EBH outcomes in the context of adverse childhood expereinces among young adults from the Future of Families and Child Wellbeing Study (N = ~2900); 2) Determine the extent to which the caregiving context (i.e., material hardship and parental monitoring) mediates the relationship between caregiver death and EBH outcomes; 3) Identify diverse strategies to support bereaved youth using longitudinal survey data and lived experiences (i.e., life history interviews with 80 young adults and consensus building with our Advisory Board). Achieving these aims will improve our ability develop tailored, family-centered interventions, practices and policies that support bereaved youth across sociodemographic groups. Ultimately, study findings will inform theory-driven and data-informed recommendations for future research, practice, and policies to improve EBH outcomes for the growing number of bereaved young people.", "keywords": [ "Adverse effects", "Adverse event", "Affect", "Age", "Anxiety", "Bereavement", "Black race", "COVID-19", "Caregivers", "Cessation of life", "Characteristics", "Child", "Child Health", "Child Welfare", "Childhood", "Consensus", "Data", "Development", "Dimensions", "Emotional", "Ethnic Origin", "Exhibits", "Family", "Family member", "Future", "Gender", "Goals", "Grief reaction", "Health", "Intervention", "Interview", "Joints", "Knowledge", "Learning", "Life Cycle Stages", "Lived experience", "Longitudinal Surveys", "Mediating", "Mental Depression", "Mental disorders", "Methodology", "Methods", "Not Hispanic or Latino", "Outcome", "Parents", "Persons", "Policies", "Policy Maker", "Public Health", "Reaction", "Recommendation", "Research", "Research Personnel", "Schools", "Shapes", "Symptoms", "Translating", "Voice", "Youth", "behavioral health", "caregiving", "comparison group", "data centers", "design", "experience", "gun violence", "high risk", "improved", "life history", "multidisciplinary", "opioid epidemic", "parental monitoring", "post-traumatic stress", "prevent", "racial difference", "sociodemographic group", "substance use", "suicidal", "syndemic", "theories", "transition to adulthood", "young adult" ], "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 } } ], "meta": { "pagination": { "page": 1405, "pages": 1419, "count": 14184 } } }