Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=3&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=1405&sort=-awardee_organization", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=4&sort=-awardee_organization", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=2&sort=-awardee_organization" }, "data": [ { "type": "Grant", "id": "15772", "attributes": { "award_id": "1R21AI188518-01A1", "title": "Chemical composition-viability relationship of bioaerosols through spatial distribution and size-controlled measurements", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 21312, "first_name": "SONNIE", "last_name": "KIM", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2027-07-31", "award_amount": 429000, "principal_investigator": { "id": 31596, "first_name": "Hui", "last_name": "Ouyang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2640, "ror": "", "name": "UNIVERSITY OF TEXAS DALLAS", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Bioaerosols are small airborne particles that can harbor pathogenic microorganisms leading to serious and challenging-to-control diseases such as respiratory syncytial virus (RSV), SARS-CoV-2, and influenza in humans, and porcine reproductive and respiratory syndrome (PRRS) in animals. RSV is particularly hazardous to young children, causing severe lower respiratory tract infections. Unfortunately, there are no effective therapies or vaccines for RSV in the pediatric population. However, by gaining a better understanding of the transmission dynamics of airborne viruses through bioaerosols, we can improve our ability to predict and control their spread through the implementation of administrative and engineering controls such as optimized ventilation designs. The project’s broad and long-term objectives are to understand how the bioaerosol’s microenvironmental conditions, such as size, chemical composition, and phase status, and environmental conditions, such as temperature, relative humidity (RH), and UV light, can impact the pathogen viability and transmission. Towards this goal, this proposed study aims to develop an innovative method for measuring virus distribution in bioaerosols and understanding their viability decay based on chemical compositions that are more relevant to various respiratory generation locations, specifically for sub-5µm and submicron particles that can transmit long distances. This study will be performed in two aims. First, we will determine the spatial distribution of chemicals and pathogens in bioaerosols. We'll use gold nanoparticles to label RSV and visualize it with advanced electron microscopy and spectroscopy to map the chemical distribution of various components such as salt (Na, K, Cl) and protein. This will help us understand how viruses are distributed in bioaerosols and provide insights into their corresponding survival rate and viability. Second, we will study chemical composition's impact on RSV viability decay for sub-5µm and submicron bioaerosol particles from various generation origins. We will generate monodisperse particles using a unique experimental setup in this size range with various chemical compositions from oral to deep lung, and measure RNA and virus viability to obtain virus decay rates. This aim investigates airborne virus decay rates for submicron and sub-5 m virus-laden particles, critical for long-range airborne transmission, and identifies the relationship between pathogen viability decay rates and chemical compositions from various generation locations. This study proposes a novel gold labeling approach to measure the distribution of viruses within bioaerosol particles. It contributes to our long-term goals by providing insights into the relationship between the chemical composition, virus spatial distribution in bioaerosol particles, and the survival of pathogens. This tool can be applied to various pathogens besides RSV. The proposed work aims to provide a better understanding of how pathogens survive and interact with their microenvironment, going beyond the current state-of-the-art.", "keywords": [ "2019-nCoV", "Aerosols", "Animals", "Area", "Biological", "Chemicals", "Child", "Childhood", "Electron Microscopy", "Energy consumption", "Engineering", "Epidemiology", "Generations", "Goals", "Gold", "Human", "Humidity", "Image", "Infection", "Influenza", "Label", "Lead", "Liquid substance", "Location", "Lower Respiratory Tract Infection", "Lung", "Maps", "Measurement", "Measures", "Methods", "Modeling", "Morphology", "Nucleic Acids", "Oral", "Oral cavity", "Outcome", "Outcome Study", "Particle Size", "Pathogenicity", "Phase", "Population", "Porcine Reproductive and Respiratory Syndrome", "Proteins", "RNA", "Research", "Respiratory Syncytial Virus Vaccines", "Respiratory System", "Respiratory syncytial virus", "Role", "Rotation", "Saliva", "Sampling", "Scanning Electron Microscopy", "Seasons", "Sodium Chloride", "Spatial Distribution", "Spectrum Analysis", "Structure", "Surface", "Survival Rate", "Suspensions", "Technology", "Temperature", "Transmission Electron Microscopy", "Ultraviolet Rays", "Vaccines", "Virus", "Visualization", "Work", "X ray spectroscopy", "cost", "design", "disorder control", "effective therapy", "evaporation", "improved", "influenzavirus", "innovation", "insight", "microorganism", "nanoGold", "novel", "particle", "pathogen", "respiratory", "submicron", "surfactant", "tool", "transmission process", "ventilation", "viral transmission", "virtual" ], "approved": true } }, { "type": "Grant", "id": "15771", "attributes": { "award_id": "1R01AI185685-01A1", "title": "Multi Parametric Total-Body Imaging of Immune Activation in Post Acute Sequelae of SARS-CoV-2 (PASC)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32843, "first_name": "JOSEPH J", "last_name": "BREEN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2029-07-31", "award_amount": 808672, "principal_investigator": { "id": 32844, "first_name": "Negar", "last_name": "Omidvari", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2639, "ror": "", "name": "UNIVERSITY OF CALIFORNIA AT DAVIS", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Post-acute sequelae of SARS-CoV-2 infection (PASC) is a persisting health challenge characterized by a range of symptoms affecting multiple organ systems, which continues to impact approximately 10% of COVID-19 survivors. Multiple, potentially overlapping, mechanisms have been identified that may play a role in PASC. However, with no effective preventative measures or treatments, there is a critical unmet need for understanding the pathophysiology of PASC; as previous studies, often limited by focus on peripheral blood biomarkers only or confined to single organ systems, have not sufficiently and quantitatively investigated the multisystemic and immune-related complexities of this condition in non-blood tissue. The long-term objective of this project is to bridge this knowledge gap by providing insight into the immune and systemic manifestations of PASC, through the innovative use of total-body dynamic positron emission tomography (PET) with the 18F-AraG radiotracer, which particularly offers selectivity towards activated T cells. To achieve this, we will use the dynamic PET images obtained from a high-sensitivity total-body PET scanner to develop, optimize, and validate a kinetic model for 18F-AraG in different anatomical sites and tissue types for multi parametric quantification of uptake. We expect that this will not only improve the quantification accuracy compared to standard static imaging, but also can shed light on the underlying mechanisms of uptake. The multi parametric imaging will be firstly used to identify sites of immunological perturbation in PASC patients, offering a total-body view of tissue-level manifestations of PASC. For this, we will compare the kinetic parameters of different tissues between symptomatic PASC participants and a control group consisting of individuals with a complete COVID-19 recovery. Second, we will integrate the multiparametric imaging data with peripheral blood assays, aiming to assess the correlations between certain 18F-AraG kinetic parameters and biomarkers of inflammation, immune dysregulation, and endothelial dysfunction in peripheral blood. Particularly, to identify vascular alterations in tissue and their association with endothelial markers in blood, we will use vascular permeability modeling to estimate the blood flow in different tissues from the early frames of the kinetic data. Third, we will employ a longitudinal design to quantify changes in 18F-AraG kinetic parameters and correlate them with evolving PASC symptom profiles over time. We will include two follow-up scans of the PASC participants at 4 months and 8 months after the baseline scans with systematic symptom assessments, focusing on individual patient trajectories. Through this, we expect to establish a direct and meaningful connection between molecular imaging data and clinical manifestations. In summary, the incorporation of cutting-edge imaging technology with quantitative modeling techniques for non- invasive evaluation of total-body immune response, combined with the longitudinal design of the study promises to provide unprecedented insights into this complex condition and would extend well beyond the confines of the PASC condition, offering frameworks and tools that could as well be used for other post-viral conditions.", "keywords": [ "2019-nCoV", "Affect", "Anatomy", "Autoimmunity", "Autopsy", "Biological Assay", "Biological Markers", "Biopsy", "Blood", "Blood Vessels", "Blood coagulation", "Blood flow", "Blood specimen", "Body System", "COVID-19", "COVID-19 patient", "COVID-19 survivors", "Cardiovascular system", "Cells", "Clinical", "Complex", "Control Groups", "Controlled Study", "Data", "Endocrine", "Endothelium", "Evaluation", "Functional disorder", "Guanine", "Health", "Image", "Imaging Techniques", "Imaging technology", "Immune", "Immune response", "Immunologic Markers", "Immunologics", "Individual", "Inflammation", "Kinetics", "Knowledge", "Latent virus infection phase", "Link", "Long COVID", "Masks", "Measures", "Modeling", "Monitor", "Organ", "Outcome", "Participant", "Patients", "Persons", "Phenotype", "Positron-Emission Tomography", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Preventive measure", "Preventive treatment", "Quality of life", "Questionnaires", "Radiopharmaceuticals", "Recovery", "Regional Anatomy", "SARS-CoV-2 infection history", "Sampling", "Scanning", "Site", "Symptoms", "System", "T-Cell Activation", "Techniques", "Technology", "Time", "Tissues", "Tracer", "Vascular Permeabilities", "Viral", "Virus Diseases", "acute COVID-19", "blood-based biomarker", "endothelial dysfunction", "follow-up", "forging", "gastrointestinal", "health care burden", "healthy volunteer", "imaging agent", "imaging approach", "imaging biomarker", "imaging study", "immune activation", "immune imaging", "improved", "individual patient", "innovation", "insight", "kinetic model", "longitudinal design", "molecular imaging", "multiparametric imaging", "neuropsychiatry", "pandemic response", "peripheral blood", "personalized diagnostics", "personalized intervention", "personalized medicine", "pre-pandemic", "predictive marker", "pulmonary", "quantitative imaging", "radiotracer", "reactivation from latency", "sample collection", "tool", "treatment strategy", "uptake" ], "approved": true } }, { "type": "Grant", "id": "15770", "attributes": { "award_id": "1R21AI194218-01", "title": "Genomic Surveillance of Mpox through the Development of a Wastewater Intelligence Model and Data Analytics Platform", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32841, "first_name": "JANE M", "last_name": "KNISELY", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-07", "end_date": "2027-07-31", "award_amount": 416625, "principal_investigator": { "id": 32842, "first_name": "Edwin C.", "last_name": "Oh", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2638, "ror": "", "name": "UNIVERSITY OF NEVADA LAS VEGAS", "address": "", "city": "", "state": "NV", "zip": "", "country": "United States", "approved": true }, "abstract": "A critical challenge in pandemic preparedness is the rapid identification of viral outbreak sources and tracking mutations that lead to new variants. Current public health surveillance methods, relying on resource-intensive laboratory testing of patient specimens, often yield incomplete data due to underreporting. The recent mpox outbreak in the Democratic Republic of the Congo—with over 22,000 suspected cases since January 2023 and the emergence of a new strain (clade 1b)—underscores the need for more effective surveillance tools. To address these limitations, we and others have developed wastewater approaches to screen municipal sewage for viral levels and variants. This method capitalizes on the shedding of pathogens like SARS-CoV-2 and mpox into sewer systems through bodily fluids, providing a comprehensive, real-time snapshot of community infection levels and viral evolution. Over the last five years, our team has built and implemented a comprehensive wastewater COVID-19 surveillance program that includes a community engagement responsive element and serves 2.4 million residents and 50 million annual tourists in Southern Nevada. In Summer 2022, we adapted this program to pilot a study tracking the clade IIb mpox outbreak in Las Vegas. Building on these achievements and developing novel reagents for clades I and II, we have a time-sensitive opportunity to test our central hypothesis: that enhanced wastewater surveillance, coupled with new computational tools, can enable rapid detection of mpox variants from both clades, facilitate assessment of antiviral drug efficacy, and inform strategic prioritization of vaccination sites. This high-risk, high-reward proposal extends our previous successful approaches with SARS-CoV-2, influenza, and drug use in wastewater, potentially breaking new ground in mpox research. Our proposal directly responds to the 2022 and 2024 mpox public health emergency of international concern declarations and aligns with NIAID's 2024 mpox research agenda. The identification of even a single mpox outbreak or treatment-resistant strain through our wastewater studies would significantly advance innovative research in genomic epidemiology and public health surveillance, potentially transforming our approach to managing emerging infectious diseases.", "keywords": [ "2019-nCoV", "Achievement", "Address", "Anti-viral Agents", "Area", "Biological Sciences", "Body Fluids", "COVID-19 surveillance", "Clinical", "Communities", "Coupled", "DNA", "Data", "Data Analytics", "Databases", "Democratic Republic of the Congo", "Detection", "Development", "Disease Outbreaks", "Dose", "Drug usage", "Early Diagnosis", "Effectiveness", "Elements", "Emerging Communicable Diseases", "Ensure", "Evolution", "Genome", "Genomics", "Hour", "Human", "Individual", "Infection", "Influenza", "Intelligence", "International", "Intervention", "Laboratories", "Linear Regressions", "Location", "Methods", "Modeling", "Monitor", "Monkeypox", "Monkeypox virus", "Municipalities", "Mutation", "National Institute of Allergy and Infectious Disease", "Patients", "Pilot Projects", "Plants", "Population Surveillance", "Public Health", "Reagent", "Research", "Resources", "SARS-CoV-2 genome", "SARS-CoV-2 variant", "Sampling", "Sewage", "Site", "Source", "Specimen", "Surveillance Methods", "Surveillance Program", "System", "Testing", "Time", "Vaccination", "Vaccines", "Variant", "Viral", "analysis pipeline", "clinical sequencing", "community engagement", "computational pipelines", "computerized tools", "drug efficacy", "emerging pathogen", "genome sequencing", "genomic data", "genomic epidemiology", "genomic variation", "health equity promotion", "high reward", "high risk", "innovation", "insight", "novel", "pandemic preparedness", "pathogen", "programs", "public health emergency", "rapid detection", "resistant strain", "response", "southern nevada", "tool", "transmission process", "urban area", "viral DNA", "viral detection", "viral outbreak", "wastewater samples", "wastewater surveillance", "whole genome" ], "approved": true } }, { "type": "Grant", "id": "15804", "attributes": { "award_id": "1R01AI187899-01A1", "title": "Optimizing lipid RVn monophosphate prodrugs to maximize RVn-triphosphate delivery", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32536, "first_name": "DIPANWITA", "last_name": "BASU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-18", "end_date": "2029-06-30", "award_amount": 3082513, "principal_investigator": { "id": 32895, "first_name": "Aaron F.", "last_name": "Carlin", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2637, "ror": "", "name": "UNIVERSITY OF CALIFORNIA, SAN DIEGO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Emerging RNA viruses, especially respiratory viruses, are among the leading threats to global health. With few treatments currently available, there is an urgent and ongoing need for the development of safe, effective oral antivirals. The objective of this application is to optimize an innovative lipid prodrug delivery strategy for remdesivir nucleoside monophosphate (RVn-MP), and additional broad-spectrum nucleoside antivirals, to achieve 1) excellent oral bioavailability, 2) efficient intracellular activation across tissue types, and 3) bypass of liver metabolism to enhance tissue delivery. The central hypothesis is that specific modifications to the lipid prodrug scaffold can improve in vivo antiviral efficacy by enhancing prodrug metabolism to the active metabolite and augmenting tissue delivery. The rationale for this project is that a better understanding of how lipid prodrug modifications increase antiviral activity will allow for the rational design and development of novel broad- spectrum oral antivirals for the treatment of clinically important RNA viruses. Strategy: Aim 1 will identify the mechanisms that determine prodrug antiviral potency in vitro to maximize antiviral activity. Quantitation of lipid RVn-MP prodrugs and their metabolites in cell culture using mass spectrometry will determine how scaffold modifications alter uptake, metabolism, and antiviral activity. Genetic knockout studies will identify the specific phospholipase C (PLC) enzyme/s that are necessary for lipid RVn-MP prodrug metabolism across cell types. Finally, PLC enzyme kinetic studies will identify scaffold modifications that maximize metabolism and antiviral activity in vitro. These data will inform lipid prodrug scaffold design that optimizes lipid RVn-MP potency. Aim 2 will determine how lipid prodrug modifications control distribution to maximize tissue delivery. First-pass removal of oral drugs by the liver is a common problem in drug development. We will evaluate how oral lipid nucleoside prodrugs can partition into chylomicrons, move through lymphatics to the thoracic duct, and thereby avoid first-pass liver metabolism while increasing lung delivery. Structure-activity relationship studies using a library of lipid RVn prodrugs will identify scaffold modifications that increase intestinal lymphatic trafficking and improve serum pharmacokinetics and tissue distribution. Scaffolds that maximize in vitro antiviral activity (Aim 1) and in vivo lung delivery (Aim 2) will be selected to rationally design new lipid RVn- MP prodrugs and novel lipid prodrugs containing nucleosides with broad spectrum activity against RNA viruses. New compounds will be evaluated for increased metabolism and antiviral activity in vitro, tissue delivery in vivo, and efficacy against pathogenic coronaviruses and dengue in mice. Collectively, this proposal will optimize the antiviral efficacy of oral lipid RVn-MP prodrugs for the treatment of many clinically important RNA viruses. Additionally, a better understanding of how to maximize the efficacy of lipid nucleoside prodrug design may be the key to unlocking a whole new generation of broad-spectrum antivirals.", "keywords": [ "2019-nCoV", "Affect", "Anti-viral Agents", "Biological Availability", "Bypass", "COVID-19 treatment", "Cell Culture Techniques", "Chylomicrons", "Clinical", "Clinical Treatment", "Coronavirus", "Data", "Dengue", "Dengue Virus", "Development", "Drug Kinetics", "Drug or chemical Tissue Distribution", "Ebola", "Enzyme Kinetics", "Enzymes", "Esters", "Excision", "Filovirus", "Flavivirus", "GS-441524", "Generations", "Genetic", "Glycerol", "In Vitro", "Intestines", "Knock-out", "Libraries", "Lipids", "Liver", "Lung", "Lymphatic", "Lysophospholipids", "Marburgvirus", "Mass Spectrum Analysis", "Metabolic", "Metabolism", "Methods", "Mission", "Modification", "Mus", "National Institute of Allergy and Infectious Disease", "Nipah", "Nucleosides", "Oral", "Oral Administration", "Paramyxovirus", "Pathogenicity", "Pharmaceutical Preparations", "Phospholipase C", "Plasma", "Positioning Attribute", "Prodrugs", "Public Health", "Publishing", "RNA Virus Infections", "RNA Viruses", "RNA-Directed RNA Polymerase", "Series", "Serum", "Site", "Small Intestines", "Structure-Activity Relationship", "Synthesis Chemistry", "Therapeutic", "Thoracic Duct", "Tissues", "Viral", "Viral Physiology", "Virus", "Virus Replication", "absorption", "analog", "anti-viral efficacy", "cell type", "design", "drug development", "esterase", "global health", "improved", "in vitro activity", "in vivo", "innovation", "lipophilicity", "liver metabolism", "mouse model", "novel", "nucleoside monophosphate", "pandemic potential", "preclinical efficacy", "rational design", "remdesivir", "respiratory virus", "scaffold", "targeted delivery", "trafficking", "tripolyphosphate", "uptake" ], "approved": true } }, { "type": "Grant", "id": "15769", "attributes": { "award_id": "1K23HL181397-01", "title": "Optimal Ventilator Management in Patients with ARDS on ECMO", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 32586, "first_name": "ROYA", "last_name": "KALANTARI", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2030-07-31", "award_amount": 178846, "principal_investigator": { "id": 32840, "first_name": "Mazen Faris", "last_name": "Odish", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2637, "ror": "", "name": "UNIVERSITY OF CALIFORNIA, SAN DIEGO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Research Plan: Acute respiratory distress syndrome (ARDS) is a severe and common condition that affects 10% of patients in the intensive care unit (ICU), and was a major cause of morbidity and mortality during the COVID-19 pandemic. While mechanical ventilation is often necessary for ARDS, it can also induce additional lung injury known as ventilator induced lung injury (VILI). VILI may be minimized by using low tidal volumes/driving pressure and with positive end expiratory pressure (PEEP). Some patients with severe and refractory ARDS require veno-venous extracorporeal membrane oxygenation (V-V ECMO), the highest level of life support which provides oxygen and removes carbon dioxide from the blood using an external device. A major benefit of ECMO is thought to be the ability to minimize VILI; however, the optimal ventilator settings for patients with ARDS on ECMO are not known. Current guidelines use a one-size-fits-all approach. Our central hypothesis is that personalized PEEP adjusted by measuring intrathoracic pressures via esophageal manometry (Pes) will decease VILI as assessed by biomarkers of inflammation (main outcomes IL-6 and sRAGE). To carry out these aims, we plan to prospectively randomize 62 patients with ARDS on V-V ECMO and neuromuscular blockade and perform serial biomarker measurements with PEEP of 10 cmH2O (ECMO guidelines) vs. PEEP guided by esophageal manometry. In addition to biomarkers of VILI, we will assess differences in other physiological outcomes including pulmonary mechanics and gas exchange. Although this proposal focuses on patients on ECMO, we believe the knowledge gained will have relevance for all patients with ARDS. Career Development Plan: The goal of the PI, Dr. Mazen Odish, is to personalize ARDS and ventilator strategies for those on ECMO based on physiology and biomarkers. The PI has an interest in applied physiology and critical care, this award will help him refine these skills and develop new skills in clinical trials, statistics, and patient-oriented research, to test rigorously methods to care for critically ill patients with ARDS with or without ECMO. To obtain these new skills Dr. Odish and his excellent and multi-disciplinary mentoring/advisory team (led by Drs. Owens and Malhotra, plus outstanding statistical and methodologic support) has three main training goals. 1) Pulmonary mechanics and biomarkers during ARDS, 2) control of breathing and measurement of work of breathing during ARDS/mechanical ventilation, and 3) clinical trial design and statistical training. These training activities are tailored for the PI to achieve his goals and maximize career development towards becoming an independent physician scientist. Furthermore, his structured course work will lead to a Masters of Advanced Studies in Clinical Research. Dr. Odish is at the right place and time in his career to align his clinical expertise in ECMO and ARDS with his research goals to understand optimal ventilator settings and therapies. Eventually his work and new skill set may improve the lives of all people suffering from respiratory illness.", "keywords": [ "Acute Respiratory Distress Syndrome", "Advisory Committees", "Affect", "Arteries", "Atelectasis", "Automobile Driving", "Award", "Biological Markers", "Blood", "Body Weight", "Breathing", "COVID-19 pandemic", "Carbon Dioxide", "Clinical", "Clinical Research", "Clinical Trials", "Clinical Trials Design", "Critical Care", "Critical Illness", "Development Plans", "Devices", "Esophagus", "Extracorporeal Membrane Oxygenation", "Functional disorder", "Gases", "Goals", "Guidelines", "Heart and Lung machine", "Heterogeneity", "Hour", "Hypoxemia", "Induction of neuromuscular blockade", "Inflammation", "Injury", "Intensive Care Units", "Interleukin-6", "Knowledge", "Life", "Lung", "Lung Compliance", "Manometry", "Measurement", "Measures", "Mechanical ventilation", "Mechanics", "Mediator", "Mentors", "Meta-Analysis", "Methodology", "Methods", "Morbidity - disease rate", "Multiple Organ Failure", "Organ", "Outcome", "Oxygen", "Patient Care", "Patients", "Persons", "Physicians", "Physiological", "Physiology", "Positive-Pressure Respiration", "Process", "Prone Position", "Pulmonary Gas Exchange", "Randomized", "Recommendation", "Recording of previous events", "Refractory", "Research", "Research Design", "Resolution", "Respiratory Failure", "Respiratory System", "Respiratory physiology", "Rest", "Risk", "Scientist", "Stress", "Structure", "Testing", "Tidal Volume", "Time", "Training", "Training Activity", "Venous", "Ventilator", "Ventilator-induced lung injury", "Vision", "Work", "Work of Breathing", "career", "career development", "esophagus pressure", "healing", "improved", "improved outcome", "individual patient", "interest", "lung injury", "mortality", "multidisciplinary", "patient oriented research", "personalized approach", "pressure", "prevent", "primary outcome", "prospective", "pulmonary", "radiological imaging", "respiratory", "skills", "soluble RAGE", "statistics", "theories", "ventilation" ], "approved": true } }, { "type": "Grant", "id": "15768", "attributes": { "award_id": "75N92023D00011-0-759202500001-1", "title": "COPD GENE - GENETIC EPIDEMIOLOGY OF COPD - TASK AREA A: YEAR 3 - AUGUST 10, 2025 - AUGUST 9, 2026", "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": [], "start_date": "2025-08-10", "end_date": "2026-08-09", "award_amount": 9292344, "principal_investigator": { "id": 32839, "first_name": "LEE S", "last_name": "NEWMAN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2636, "ror": "", "name": "NATIONAL JEWISH HEALTH", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true }, "abstract": "Genetic Epidemiology of COPD (COPDGene) is a multi-site longitudinal cohort study of current and former smokers to better understand risk factors, natural history, and genetic contributions of chronic obstructive pulmonary disease (COPD) as well as other smoking-related diseases. The purpose of this acquisition is to fund a 15-year follow-up in-person clinical visit (Visit 4) of this cohort, to be re-enrolled from approximately 19 active Clinical Study Centers. A Visit 4 of COPDGene subjects is needed to identify clinical, physiological, imaging, and Omics determinants of COPD and other disease progression in elderly subjects, to assess the impact of COVID-19 on COPD and other disease progression, and to discover determinants of severe COPD development in subjects with preserved ratio, impaired spirometry (PRISm). The acquisition will also support the maintenance of previously collected data and biospecimens, regulatory oversight of the study, and analysis of study data and study biospecimens. The goal of COPDGene is to use extensive longitudinal imaging, physiology, and Omics molecular data in combination with genetics in the COPDGene cohort to identify high-risk subgroups with distinct diagnostic, prognostic, and therapeutic implications. COPDGene has been funded for 15 years through grants and cooperative agreements awarded by NHLBI to National Jewish Health and Brigham and Women’s Hospital. Grant applications for the three Phases of COPDGene [Phase 1: baseline visit (“Visit 1”); Phase 2: five year follow-up (“Visit 2”); Phase 3: ten year follow-up (“Visit 3”)] were all submitted to the parent NIH R01 Funding Opportunity Announcement. Study investigators originally recruited 10,198 current or former smokers in Phase 1. Including nonsmoking controls from both Phase 1 and Phase 2, COPDGene has recruited a total 10,718 subjects all of whom have been extensively phenotyped clinically and radiologically. Additional data collected on these participants include whole genome sequencing as well as RNA sequencing, proteomics, metabolomics, and DNA methylation data from collected blood samples. Investigators have published more than 450 publications, the vast majority of which were peer-reviewed, using COPDGene data. COPDGene also serves as a parent study for many ancillary studies, using public or private funding, a subset of which have collected additional data on all or a subset of participants. COPDGene is overseen by an NHLBI-convened Observational Study Monitoring Board (OSMB). The Visit 4 (15-year follow-up) evaluations will include, where possible, lung function tests (spirometry), questionnaires (including COVID-19 assessment), chest computerized tomography (CT), other functional assessments (e.g., six minute walk distance), and collection and storage of biospecimens from 3,500 of the original 10,718 COPDGene subjects. In addition, this acquisition will support continuation of semi-annual long-term follow-up of the COPDGene cohort and other contact with the cohort as needed, oversight of clinical sites and human subjects protection, maintenance of the database and biobank, continued coordination with NIH and NHLBI data resources, activities relevant to the data management and sharing plan, analysis of data, travel to meetings, and publication costs.", "keywords": [ "Address", "Adverse event", "Ancillary Study", "Annual Reports", "Applications Grants", "Archives", "Area", "Award", "Bioinformatics", "Biological Markers", "Biological Specimen Banks", "Blood specimen", "Bronchodilator Agents", "COVID-19", "COVID-19 impact", "Cause of Death", "Certification", "Cessation of life", "Characteristics", "Chest", "Chronic Obstructive Pulmonary Disease", "Clinical", "Clinical Data", "Clinical Research", "Clinical/Radiologic", "Collaborations", "Collection", "Communication", "Communities", "Compensation", "Computer Security", "Contractor", "Contracts", "DNA Methylation", "Data", "Data Analyses", "Data Coordinating Center", "Data Science", "Data Security", "Data Set", "Databases", "Development", "Diagnostic", "Diffusion", "Disease Progression", "Documentation", "Educational workshop", "Elderly", "Electronics", "Enrollment", "Ensure", "Epidemiology", "Evaluation", "Event", "Funding", "Funding Opportunities", "Future", "Genes", "Genetic", "Genomics", "Goals", "Grant", "Health", "Hospitals", "Image", "Impairment", "Information Systems", "Institutional Review Boards", "International", "Internet", "Jews", "Journals", "Laboratories", "Link", "Long-term Follow-up", "Longitudinal cohort study", "Maintenance", "Manuscripts", "Measures", "Medical History", "Metadata", "Methods", "Molecular", "Monitor", "Names", "National Heart Lung and Blood Institute", "Natural History", "Observational Study", "Outcome", "Oxygen", "Parents", "Participant", "Peer Review", "Persons", "Phase", "Physical Performance", "Physiological", "Physiology", "Policies", "Privatization", "Procedures", "Proteomics", "Protocols documentation", "PubMed", "Publications", "Publishing", "Pulmonary Emphysema", "Pulmonary function tests", "Quality Control", "Quality of life", "Questionnaires", "Recommendation", "Reporting", "Research", "Research Personnel", "Resolution", "Resources", "Risk Factors", "SARS-CoV-2 infection", "Scanning", "Schedule", "Scientist", "Site", "Specific qualifier value", "Spirometry", "Standardization", "Subgroup", "Support Contracts", "System", "Teleconferences", "Telephone", "Testing", "Therapeutic", "Time", "Tobacco use", "Training", "Trans-Omics for Precision Medicine", "Travel", "U-Series Cooperative Agreements", "United States National Institutes of Health", "Update", "Vaccination", "Visit", "Walking", "Woman", "Work", "X-Ray Computed Tomography", "adjudication", "biobank", "catalyst", "clinical ce" ], "approved": true } }, { "type": "Grant", "id": "15767", "attributes": { "award_id": "1R35GM160163-01", "title": "Scalable and Epidemiologically Interpretable Phylodynamics to Recover Heterogeneous Transmission Dynamics", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 32565, "first_name": "GUOQIN", "last_name": "YU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2030-06-30", "award_amount": 410000, "principal_investigator": { "id": 32838, "first_name": "Nicola Felix", "last_name": "Mueller", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2635, "ror": "", "name": "UNIVERSITY OF CALIFORNIA, SAN FRANCISCO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "As pathogens are transmitted between individuals, they accumulate mutations, leaving a footprint of the transmission history in the pathogen genomes. Using phylogenetic methods, we can reconstruct the transmission history connecting individual cases from these genomes, by reconstructing the relationships of the pathogens. We can then infer population-level transmission dynamics, from the ancestral relationships of the pathogens, or phylogenies, using phylodynamic methods. Infectious disease transmission and disease burden are highly heterogeneous, differing between neighborhoods, across age, and socioeconomic groups, and racial and ethnic lines. This heterogeneity means that it is crucial to a) be able to illuminate differential disease burdens and b) account for these heterogeneities when modeling or forecasting infectious disease outbreaks. Traditional approaches based on reported caseloads are often insufficient for capturing the full scope of highly heterogeneous transmission dynamics. Phylodynamics offers a potential solution, as it infers transmission dynamics from the connectivity of cases, providing an opportunity to disentangle these complex patterns. However, limitations in our available toolbox prevent us from fully utilizing the vast availability of pathogen genomes to study these complex transmission dynamics, as current phylodynamic approaches suffer from multiple challenges. With the advent of widely available sequencing, phylodynamic tools are not computationally efficient enough to analyze the amounts of data generated at the granular scales crucial to understanding transmission dynamics. Additionally, the model parameters need to be epidemiologically interpretable to be actionable. In this project, we seek to address these two points by developing novel approaches to reconstruct transmission dynamics from pathogen sequence data. We will develop novel phylodynamic tools to reconstruct transmission dynamics at a granular scale by integrating neural networks into phylodynamic likelihood calculations that we show in preliminary results to dramatically improve computational efficiency and scalability. Phylodynamic methods are parameterized by more or less abstract parameters that either have no direct epidemiological meaning or are contingent on idealized assumptions about disease spread. We will establish how and when current approaches return biased results when reconstructing city-scale transmission dynamics, describe how they can be used to estimate actual disease burden, and test them using SARS-CoV-2 sequence data collected by Kaiser Permanente Southern California (KPSC) and in the UK over the pandemic. Finally, we will develop ways to quantify the factors influencing disease burden, such as geography, age, and socioeconomics. We will apply these tools to KPSC SARS-CoV-2 data, where we can access rich patient metadata to study these patterns. Our overarching goal is to utilize phylodynamic inference of heterogeneous transmission dynamics to parameterize complex infectious disease dynamic models and improve prediction accuracy.", "keywords": [ "2019-nCoV", "Address", "Age", "California", "Cities", "Communicable Diseases", "Complex", "Data", "Disease", "Disease Outbreaks", "Epidemiology", "Ethnic Origin", "Genome", "Geography", "Goals", "Guidelines", "Heterogeneity", "Individual", "Metadata", "Methods", "Modeling", "Mutation", "Neighborhoods", "Patients", "Pattern", "Phylogenetic Analysis", "Phylogeny", "Population", "Race", "Recording of previous events", "Reporting", "Testing", "Viral", "burden of illness", "disease transmission", "genome sequencing", "improved", "neural network", "novel", "novel strategies", "pandemic disease", "pathogen", "pathogen genome", "prevent", "socioeconomics", "tool", "transmission process" ], "approved": true } }, { "type": "Grant", "id": "15775", "attributes": { "award_id": "1R01AI193318-01", "title": "Assessing the mechanisms underlying female sex-predominance in Long COVID", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32597, "first_name": "BROOKE ALLISON", "last_name": "BOZICK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-22", "end_date": "2030-07-31", "award_amount": 913012, "principal_investigator": { "id": 31372, "first_name": "Michael Joseph", "last_name": "Peluso", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32848, "first_name": "Nadia R", "last_name": "Roan", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2635, "ror": "", "name": "UNIVERSITY OF CALIFORNIA, SAN FRANCISCO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Long COVID, or post-acute sequelae of COVID-19 (PASC), is estimated to occur after ~10% of COVID-19 cases and affects tens of millions of people worldwide. The mechanisms underlying Long COVID remain poorly understood, which hinders the ability to establish effective evidence-based treatments for the condition. One of the most striking observations in the epidemiology of Long COVID is its female sex predominance: women, particularly pre-menopausal women, are much more likely than men to have the condition. In this proposal, we leverage the Long-term Impact of Infection with Novel Coronavirus (LIINC) cohort (NCT04362150) – which since April 2020 has recruited >1,000 participants with and without Long COVID – to interrogate the mechanistic basis underlying the increased prevalence of Long COVID in women. Our central hypothesis is that in women with Long COVID, there is an elevated and sustained immune type I IFN (T1IFN) response to SARS-CoV-2 (SCV2) gene products, which in turn diminishes the quality of adaptive immune responses against chronic herpesviruses (EBV, CMV) and SCV2 itself, increases the risk of pathogenic autoantibody responses, and results in overall systemic inflammation and immune dysregulation that is characteristic of Long COVID. We further postulate that both incomplete X chromosome inactivation and sex hormones drive the elevated T1IFN responses in women with Long COVID. In Aim 1, we will subject banked longitudinal blood specimens from women and men from LIINC (including both those with and without Long COVID) to assays that will measure the extent of persistent SCV2, T1IFN responses, the features of adaptive immune responses to persistent viruses associated with Long COVID (SCV2, EBV, CMV), autoantibody responses, and the overall state of inflammation. In Aim 2, we will leverage the LIINC Tissue Biopsy program to obtain paired endometrial and gut biopsies from women with Long COVID, to test the hypothesis that the endometrium is a key site of SCV2 persistence and immune dysregulation during Long COVID. This analysis will be compared to a parallel set of studies using gut specimens from matched men with Long COVID. Finally, Aim 3 will analyze specimens from two clinical trials designed to eliminate SCV2 gene products as treatment for Long COVID. The first of these, performed by Resolve Therapeutics, found that administration of RSLV-132, a catalytically active RNase1 intended to degrade SCV2 RNA, improved Long COVID symptoms in women but not men (NCT04944121). The second, occurring within LIINC, is ongoing (enrollment is complete) and testing the effects of AER002, a monoclonal antibody that directly targets and clears SCV2 protein (NCT05877508). Using specimens from both trials, we will test the notion that SCV2 gene products drive sustained T1IFN responses in women that contribute to Long COVID symptoms. Collectively, our aims will improve our understanding of the mechanisms underlying the female-predominance of Long COVID and improve our overall understanding of the disease. This will be a key step in the identification of evidence-based treatments for both women and men who continue to develop and live with this disabling condition.", "keywords": [ "2019-nCoV", "Acute", "Affect", "Age", "Antibodies", "Antibody Response", "Antigens", "Autoantibodies", "Autoimmunity", "Biological", "Biological Assay", "Biology", "Biopsy", "Biopsy Specimen", "Blood", "Blood specimen", "Body System", "COVID-19", "COVID-19 impact", "COVID-19 prevalence", "Characteristics", "Chronic", "Clinical Trials", "Clinical Trials Design", "Cytomegalovirus", "Data", "Disabling condition", "Disease", "Disproportionately impacts women", "Endometrial", "Endometrium", "Enrollment", "Epidemiology", "Estradiol", "Evidence based treatment", "Exhibits", "Fatigue", "Female", "Functional impairment", "Genes", "Genitourinary system", "Gonadal Steroid Hormones", "Health", "Herpesviridae", "High Prevalence", "Human Herpesvirus 4", "Immune", "Immune System Diseases", "Immune response", "Immunity", "Individual", "Infection", "Inflammation", "Inflammatory", "Inflammatory Response", "Interferons", "Intervention", "Intervention Trial", "Link", "Long COVID", "Longitudinal Studies", "Measurement", "Measures", "Monoclonal Antibodies", "Nature", "Observational epidemiology", "Organ", "Outpatients", "Paper", "Participant", "Pathway interactions", "Persons", "Phenotype", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Premenopause", "Prevalence", "Progesterone", "Proteins", "Publishing", "RNA", "Research Infrastructure", "Risk", "SARS-CoV-2 infection", "SARS-CoV-2 inhibitor", "Sex Differences", "Signal Transduction", "Site", "Specimen", "Symptoms", "T cell response", "TLR7 gene", "Testing", "Testosterone", "Therapeutic", "Tissues", "Vaccination", "Viral", "Virus", "Virus Diseases", "Woman", "Women's prevalence", "X Inactivation", "acute COVID-19", "adaptive immune response", "brain fog", "cohort", "common symptom", "design", "experience", "female reproductive tract", "gene product", "improved", "interest", "longitudinal analysis", "men", "mucosal site", "novel coronavirus", "pathogenic autoantibodies", "programs", "prospective", "randomized trial", "recruit", "repository", "response", "sex", "single-cell RNA sequencing", "systemic inflammatory response", "therapy design", "transcriptome", "women's outcomes" ], "approved": true } }, { "type": "Grant", "id": "15800", "attributes": { "award_id": "1F31AI191669-01", "title": "Uncovering the mechanisms and implications of BST2 antagonism by SARS-CoV-2", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32891, "first_name": "MARY KATHERINE BRADFORD", "last_name": "PLIMACK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-01", "end_date": "2028-06-30", "award_amount": 49538, "principal_investigator": { "id": 32892, "first_name": "Haley", "last_name": "Aull", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2634, "ror": "", "name": "UNIVERSITY OF ROCHESTER", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "BST2/Tetherin is a key factor of the cellular intrinsic immune response that broadly restricts enveloped viruses. BST2 tethers nascent virions to the cell surface by embedding itself into cellular and viral membranes. Tethering not only limits viral release, but also facilitates adaptive immune recognition of the infecting virus. Tethered virions are opsonized by antibodies, which can be recognized by Fc receptors on both natural killer cells and macrophages, activating their ability to kill or phagocytose the infected cell. We have recently reported that SARS-CoV-2 is susceptible to BST2 restriction. However, the virus has evolved to use its Spike to downregulate BST2. Downregulation is achieved by an interaction between Spike and the extracellular domains of BST2, routing BST2 for lysosomal degradation in a Clathrin- and Ubiquitin-dependent manner. Remarkably, newly emerged variants of concern (VOC) have enhanced their ability to counteract BST2, suggesting that BST2 antagonism is a contributing factor to the host adaptation of SARS-CoV-2. Therefore, my long-term goal is to block the ability of SARS-CoV-2 to evade BST2 restriction. My overall objective is to understand the mechanism and implications of BST2 evasion by SARS-CoV-2. My central hypothesis is that mutations accumulated in the Spike of SARS-CoV-2 allow for more efficient counteraction of BST2, increasing virion release and reducing the susceptibility of SARS-CoV-2 to BST2-dependent antibody-mediated cellular responses. I will achieve my overall objective by exploring these two specific aims: (1) elucidate the mechanism of enhancement of BST2 antagonism across VOC, and (2) identify the driving pressures of BST2 antagonism. This work is significant as it will (1) fill the critical gap in knowledge of how SARS-CoV-2 evades BST2 restriction, and how VOC enhance this activity; (2) define the extent to which evasion of BST2 allows for evasion of antibody-mediated responses, and how this translates to vaccine efficacy; and (3) provide proof-of-concept for the design of antivirals to disable SARS-CoV- 2 antagonism of BST2 with the goal of both blocking viral replication and enhancing clearance of infected cells. The support provided by this F31 award will enhance my education by (1) facilitating my training in Surface Plasmon Resonance by Dr. Jermaine Jenkins and the URMC Structural Biology Core Facility (see letter of support), (2) allowing me to travel to the University of Wisconsin-Madison to gain hands-on training from my co- sponsor, Dr. David Evans (see co-sponsor statement), who developed assays to measure Fc receptor-mediated killing of infected cells, which we are proposing to use here, and (3) expanding my experience in scientific writing and communication as I publish my findings and present at both national and international conferences.", "keywords": [ "2019-nCoV", "Affinity", "Anti-viral Agents", "Antibodies", "Antibody-Dependent Enhancement", "Automobile Driving", "Award", "Binding", "Biological Assay", "COVID-19 susceptibility", "COVID-19 vaccine", "Cell surface", "Cells", "Clathrin", "Collaborations", "Communication", "Core Facility", "Coronavirus", "Defect", "Down-Regulation", "Education", "Extracellular Domain", "Fc Receptor", "Future", "Goals", "Immune", "Immune response", "Immunoprecipitation", "International", "Knowledge", "Letters", "Macrophage", "Maps", "Measures", "Mediating", "Membrane", "Mutation", "Natural Killer Cells", "Predisposition", "Process", "Proteins", "Publications", "Publishing", "Reporting", "Resistance", "Role", "Route", "SARS-CoV-2 B.1.1.529", "SARS-CoV-2 antibody", "Surface Plasmon Resonance", "Susceptibility Gene", "Testing", "Training", "Translating", "Travel", "Ubiquitin", "Universities", "Vaccine Design", "Viral", "Virion", "Virus", "Virus Replication", "Wisconsin", "Work", "Writing", "antagonist", "antibody-dependent cell cytotoxicity", "antibody-dependent cellular phagocytosis", "base", "design", "experience", "improved", "pressure", "response", "skills", "structural biology", "symposium", "vaccine efficacy", "variants of concern" ], "approved": true } }, { "type": "Grant", "id": "15766", "attributes": { "award_id": "1R01HL176697-01A1", "title": "Platelet Regulation of Monocyte Responses in Vascular Inflammation", "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": 32837, "first_name": "ILANA GRACE", "last_name": "GOLDBERG", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2029-04-30", "award_amount": 573261, "principal_investigator": { "id": 23693, "first_name": "CRAIG N", "last_name": "MORRELL", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 464, "ror": "https://ror.org/022kthw22", "name": "University of Rochester", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 2634, "ror": "", "name": "UNIVERSITY OF ROCHESTER", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Trained immunity is a biologic process in which prior immune stimuli durably ‘trains’ innate immune cell responses to future stimulation. Trained immunity is driven by changes in glycolysis and its metabolites, leading to histone modifications, DNA methylation, or changes in non-coding RNA (ncRNA) that immune programs subsequent monocyte/macrophage responses to either be greater or lessened. Trained immunity research has largely focused on how pathogen derived molecules immune train monocytes and macrophages (mono/macs), but there are also indications of cell based trained immunity. We recently made the novel discovery that resting platelet interactions with mono/macs via platelet CD47 increased glycolysis and durably programmed mono/macs through changes in histone methylation to limit TLR responses. This was the first demonstration of endogenous cell mediated innate immune training. We now propose the novel idea that in healthy conditions, resting platelet-monocyte interactions limits monocyte TLR responses, that are overcome by platelet activation. Because platelets are small, they circulate at the interface between endothelial cells and leukocytes, ideally positioning platelets as sensors of both vascular health and tissue injury/infection. How activated platelets induce and amplify immune responses has received an increasing amount of attention, including significant work from our group. However, studies have also shown that normal platelet counts maintain immune homeostasis and our recent manuscript provides a mechanistic framework for how resting platelets immune train monocytes to a tolerant phenotype. We found that circulating monocytes from thrombocytopenic (low platelet count) mice produced more inflammatory cytokines in response to TLR ligands. Resting platelets express CD47 that interacts with circulating monocytes to induce glycolysis dependent changes in histone methylation, epigenetically modifying mono/macs to a more immune tolerant phenotype. Thrombocytopenia (clinically defined as a platelet count less than 150,000/µL) independently associates with dysregulated monocyte responses, increased plasma cytokines, prolonged morbidity, and increased mortality. A decline in platelets may also independently lead to long-term changes in mono/mac responses, for example, some COVID-19 patients have persistent/recurrent thrombocytopenia beyond the infection, and with it, prolonged inflammation. However, little is known about the mechanisms and the long-term implications of thrombocytopenia on immune responses. Hypothesis: Resting platelet-monocyte interactions immune trains monocytes to a quiescent phenotype. Aim #1. To determine the platelet-mediated signaling that leads to monocyte immune programming. Aim #2. To determine the functional outcomes of resting platelet-mediated monocyte immune programming. Aim #3. 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