Grant List
Represents Grant table in the DB
GET /v1/grants?sort=-program_officials
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-program_officials", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1392&sort=-program_officials", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=2&sort=-program_officials", "prev": null }, "data": [ { "type": "Grant", "id": "15676", "attributes": { "award_id": "1F32HD116425-01A1", "title": "Developing a Biomimetic Lactating Mammary Lobe for Therapeutic Safety", "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": 32520, "first_name": "KATIE MARIE", "last_name": "VANCE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-04-01", "end_date": "2027-07-31", "award_amount": 76756, "principal_investigator": { "id": 32521, "first_name": "Amy H", "last_name": "Lee", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 210, "ror": "https://ror.org/042nb2s44", "name": "Massachusetts Institute of Technology", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "PROJECT SUMMARY. Breast milk is rich with bioactive components that are critical to an infant’s development. It is highly recommended that infants ingest breast milk; but, fluctuating maternal hormones and substandard post-parturition health directly mediate breast milk production. Maternal ingestion of small molecule drugs further compounds decreased breast milk synthesis and secretion, and adversely compromises breast milk quality. Although the majority of actively breastfeeding women consume medication or receive therapeutics, small drug molecule transport from maternal plasma to synthesized breast milk remains largely unknown. Important strides in understanding pharmacokinetics in milk-producing mammary glands have yet to occur because of the lack of engineered bioinspired mammary lobe systems that mimic complex in vivo signatures— topographical lobule microcurves, spiked levels of lactogenic hormones, cellular landscapes, and mechanically-driven lobe expansion and contraction. The objective of this proposal is to determine if our established microengineered mammary lobe system, which integrates key physiological characteristics, i.) faithfully mirrors multifactorial breast milk synthesis processes and ii.) could be employed as a versatile screening testbed for evaluating drug and therapeutic safety during lactation. The project is based on the central hypothesis that exogenous stimuli that reflect in vivo mechanisms, such as hormone levels, dynamic mechanical lobe stimulation, and passive transport of small drug molecules, will potentiate differential cellular landscape phenotypes and lead to unique content differences in engineered breast milk. This could develop a new in vitro preclinical model that promotes the cognizance of drugs or therapeutics that are safe to ingest or receive during lactation. We believe this contributes to improving important women’s health issues. Our hypothesis will be tested through the following two aims. Aim 1 will develop a 3D mammary lobe model and determine how in vivo relevant parameters alter physical and molecular mammary cell phenotypes, and regulate the secretion of important breast milk components. Aim 2 will investigate the pharmacokinetics of small molecule drugs or therapeutics that passively diffuse into the engineered breast milk. Nicotine or mRNA encoding for SARS-CoV-2 will serve as a model drug or therapeutic, respectively. We will pursue these aims using an innovative combination of analytical and adaptable techniques from engineering and biological sciences. These include the development of a scalable lobe model, by which the application of physiologically relevant stimuli and compartments can mimic breast milk synthesis and drug distribution. The engineering approaches that we leverage will develop foundational resources for the ongoing efforts and research revolving lactation and post-parturition health equity. The expected outcome of this work will highlight the importance of engineering new microsystems for in vivo mimicry. These platforms can facilitate clinical translation of rapid drug and therapeutic safety screening. The results will have a significant positive impact to women and will encourage the ongoing efforts to support women during their breastfeeding journey.", "keywords": [ "2019-nCoV", "3-Dimensional", "Affect", "Air", "Apical", "Biological Sciences", "Biomimetics", "Birth", "Breast Feeding", "COVID-19", "COVID-19 vaccine", "Carrier Proteins", "Caseins", "Cell Polarity", "Cell Proliferation", "Cell-Cell Adhesion", "Cells", "Characteristics", "Chemicals", "Circulation", "Complex", "Consumption", "Cultured Cells", "Cytoskeletal Proteins", "Development", "Diffuse", "Diffusion", "Drug Kinetics", "Drug Modelings", "Engineering", "Enzyme-Linked Immunosorbent Assay", "Excretory function", "Exhibits", "Exposure to", "Gland", "Goals", "Harvest", "Health", "High Pressure Liquid Chromatography", "Hormones", "Human Milk", "In Vitro", "Individual", "Infant", "Infant Development", "Ingestion", "Lactation", "Lipids", "Lobe", "Lobule", "Mammary gland", "Maternal health equity", "Mechanical Stimulation", "Mechanical Stress", "Mechanics", "Mediating", "Membrane", "Messenger RNA", "Milk Proteins", "Mission", "Modeling", "Molds", "Molecular", "Mothers", "Motion", "Nicotine", "Nutrient", "Outcome", "Oxytocin", "Perfusion", "Periodicity", "Pharmaceutical Preparations", "Phenotype", "Physiological", "Plasma", "Pre-Clinical Model", "Pregnancy", "Process", "Prolactin", "Protein Biosynthesis", "Protein Secretion", "Proteins", "Proteomics", "Public Health", "Pump", "RNA vaccine", "Recommendation", "Regulation", "Reporting", "Research", "Resources", "Safety", "Side", "Stains", "Stimulus", "Structure", "Surface", "System", "Techniques", "Testing", "Therapeutic", "Tight Junctions", "United States National Institutes of Health", "Variant", "Ventilator", "Woman", "Women&apos", "s Health", "Work", "clinical translation", "drug distribution", "drug testing", "extracellular vesicles", "health equity", "high throughput screening", "improved", "in vivo", "innovation", "interstitial", "lactogenesis", "lipidomics", "mammary", "maternal vaccination", "mechanical drive", "mechanical properties", "mechanical stimulus", "microsystems", "milk expression", "milk production", "milk secretion", "mimicry", "molecular phenotype", "nicotine use", "passive transport", "pre-clinical", "protein expression", "reconstitution", "screening", "secretory protein", "small molecule", "therapeutic evaluation" ], "approved": true } }, { "type": "Grant", "id": "15675", "attributes": { "award_id": "1R01EB037031-01", "title": "Point-of-care DNA diagnostics from raw samples", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Biomedical Imaging and Bioengineering (NIBIB)" ], "program_reference_codes": [], "program_officials": [ { "id": 32518, "first_name": "KRISTIN HEDGEPATH", "last_name": "GILCHRIST", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-04-05", "end_date": "2029-03-31", "award_amount": 257807, "principal_investigator": { "id": 32519, "first_name": "Robert M", "last_name": "Cooper", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 760, "ror": "https://ror.org/0168r3w48", "name": "University of California, San Diego", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The proposed project will develop living biosensors for detecting and analyzing DNA at the single- base level, without requiring sample purification or any equipment. DNA is the prime information carrier for life, and DNA analysis provides valuable information for, e.g., diagnosing microbial infections or tracking disease outbreaks. Many techniques exist for detecting and analyzing DNA, but these generally require processing steps to extract and purify samples, and most require expensive equipment and significant training and expertise. This proposal will transfer that complexity into the biosensor itself, harnessing functions that evolved into living bacteria over billions of years to pull DNA out of raw samples, analyze it, and produce easily read output. The biosensors will pull in DNA using natural competence, and analyze it with single-base precision using their endogenous CRISPR-Cas system. Upon detecting a target sequence, the living biosensors will release thousands of signal molecules that can be detected using a lateral flow assay, similar to a consumer pregnancy or Covid-19 test. Several target DNA sequences will be used for demonstrations: urinary tract pathogens, E. coli, and Salmonella. The target uropathogens are difficult to diagnose with standard culture tests. Using single-base sequence analysis, the biosensors will subtype E. coli as likely pathogenic or likely commensal. A similar strategy will be employed to detect single-base mutations responsible for the majority of fluoroquinolone-resistant Salmonella isolates. DNA biosensing will be demonstrated in clinically relevant human samples, without the extensive purification required by other methods. The result will be a hybrid living biosensor / lateral flow assay that requires minimal sample preparation, produces rapid results, and can achieve single-base resolution. The biosensors developed in this project could find applications any time DNA monitoring is needed that is inexpensive, requires minimal sample preparation, equipment, and expertise, or takes place at the point of care. Examples include clinical diagnostics, monitoring disease outbreaks for public health, or environmental monitoring, with particular benefits where resources are limited.", "keywords": [ "Antibiotic Resistance", "Architecture", "Bacteria", "Base Sequence", "Binding", "Biological", "Biological Assay", "Biosensing Techniques", "Biosensor", "Blood", "Buffers", "COVID-19 test", "Clinic", "Clinical", "Clustered Regularly Interspaced Short Palindromic Repeats", "Colon", "Colorectal Neoplasms", "Competence", "Complex", "Coupled", "Custom", "DNA", "DNA Sequence", "DNA analysis", "Detection", "Diagnosis", "Diagnostic", "Disease Outbreaks", "Engineering", "Ensure", "Environment", "Environmental Monitoring", "Epitopes", "Equipment", "Escherichia coli", "Genetic", "Genomic DNA", "Goals", "Human", "Hybrids", "In Situ", "In Vitro", "Infection", "Lateral", "Life", "Medical", "Methods", "Monitor", "Mus", "Mutation", "Mutation Detection", "Oncogenic", "Output", "Pathogenicity", "Performance", "Pregnancy Tests", "Preparation", "Proteins", "Public Health", "Publishing", "RNA", "Rapid diagnostics", "Readability", "Reporter", "Resolution", "Resource-limited setting", "Resources", "Salmonella", "Salmonella enterica", "Sampling", "Scheme", "Science", "Sensitivity and Specificity", "Sequence Analysis", "Signal Transduction", "Signaling Molecule", "Source", "Specificity", "Sputum", "Synthetic Genes", "System", "Techniques", "Testing", "Time", "Training", "Urinary tract", "Urinary tract infection", "Urine", "Uropathogen", "Work", "base", "cancer cell", "clinical diagnostics", "clinically relevant", "cost", "diagnostic platform", "fluoroquinolone resistance", "improved", "in vivo", "interest", "lateral flow assay", "microbial", "nanoshell", "pathogen", "point of care", "point-of-care diagnostics", "screening", "tumor" ], "approved": true } }, { "type": "Grant", "id": "15679", "attributes": { "award_id": "1R01HL176493-01", "title": "Pathogenic Mechanism and Therapeutic Approaches for Exercise Intolerance in Post-Acute Sequelae of COVID-19", "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": "2025-04-01", "end_date": "2029-01-31", "award_amount": 633045, "principal_investigator": { "id": 32524, "first_name": "Michael G", "last_name": "Risbano", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32525, "first_name": "Lianghui", "last_name": "Zhang", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 848, "ror": "", "name": "UNIVERSITY OF PITTSBURGH AT PITTSBURGH", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "Post-acute sequelae of COVID-19 (PASC) is an emerging public health priority with up to 18% prevalence. Noteably, almost 30% patients diagnosed with PASC experence exercise intolerance. This activity limitation continues to negatively impact our workforce, and poses a persistent socialeconimic burden on our society. Our Post-Covid Recovery Clinic, a RECOVERY Vital site, has evaluated exercise intolerant PASC for nearly 4 years. We recently discovered pathophysiologic endotypes that contribute to exercise intolerance in PASC via invasive cardiopulmonary exercise testing (iCPET). Yet, the molecular drivers for this population remain elusive. Four- years after the onset of the pandemic we are left without PASC-defining biomarkers, or targeted therapeutics. Thus, it is crucial to investigate the interconnected molecular and pathophysiologic links in exercise intolerant PASC, a task uniquely within our team’s expertise. Angiotensin-converting enzyme 2 (ACE2) is not just an entry receptor for SARS-CoV-2 but also an enzyme with a protective function through regulation of the renin- angiotensin system. Studies have shown that a high level of plasma ACE2 is associated with an increased risk of SARS-CoV-2-related mortality. Our preliminary data showed that the catalytic activity of increased plasma ACE2 was significantly impaired in the exercise intolerant PASC patients, and closely correlated with reduced exercise capacity as measured by peak oxygen consumption evaluated during iCPET. Furthermore, to study the pathogenic mechanism of exercise intolerance in PASC, we established a novel PASC mouse model. In this model, we observed the persistence of the SARS-CoV-2 RNAs in lung microvascular ECs, impaired ACE2 activity, chronic pulmonary inflammation, along with a significant reduction in exercise capacity. Thus, we hypothesize that dysfunctional ACE2 shed from pulmonary ECs is a major driver for exercise intolerance in PASC and an engineered solube ACE2 with enhanced ACE2 activity will improve exercise capacity of PASC. To test our hypotheses, we will investigate the predictive value of ACE2 activity as a clinical biomarker and assess its association with exercise capacity over 12 months in PASC patients in Aim 1. We will define an engineered soluble ACE2 with enhanced ACE2 activity as an innovative therapeutic intervention to improve exercise capacity and vascular function in the PASC mouse model in Aim 2. Furthermore, we will explore the mechanism of ACE2 dysfunction shed from the pulmonary vasculature in Aim 3. If successful, we will identify a diagnostic and therapeutic paradigm urgently needed for PASC patients experiencing exercise intolerance, and remediate the deficient response to this global public health threat.", "keywords": [ "2019-nCoV", "ACE2", "Acute Lung Injury", "Adult", "Affect", "Binding", "Biological Markers", "Blood Vessels", "COVID-19", "COVID-19 mortality", "COVID-19 patient", "Cardiopulmonary", "Cell surface", "Characteristics", "Chronic", "Circulation", "Clinic", "Clinical assessments", "Data", "Diagnosis", "Diagnostic", "Disease Progression", "Disintegrins", "Endothelial Cells", "Endothelium", "Engineering", "Enzymes", "Exercise", "Exercise Test", "Fatigue", "Functional disorder", "Health", "Impairment", "Inflammation", "Knock-in", "Knockout Mice", "Left", "Link", "Long COVID", "Lung", "Measures", "Medicine", "Metalloproteases", "Modeling", "Molecular", "Outpatients", "Oxygen Consumption", "Pathogenicity", "Pathology", "Patients", "Peptides", "Plasma", "Population", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Predictive Value", "Prevalence", "Proteins", "Public Health", "Pulmonary Inflammation", "Questionnaires", "RNA", "Recovery", "Regulation", "Renin-Angiotensin System", "Risk", "SARS-CoV-2 infection", "Site", "Societies", "Symptoms", "Testing", "Therapeutic", "Therapeutic Intervention", "clinical biomarkers", "clinical infrastructure", "design", "dosage", "endothelial dysfunction", "exercise capacity", "exercise intolerance", "experience", "improved", "innovation", "knock-down", "lung microvascular endothelial cells", "mortality", "mouse model", "novel", "pandemic disease", "post SARS-CoV-2 infection", "post-COVID-19", "public health priorities", "receptor", "remediation", "research clinical testing", "response", "symptom cluster", "targeted treatment", "treatment optimization" ], "approved": true } }, { "type": "Grant", "id": "15673", "attributes": { "award_id": "1R01HL172872-01A1", "title": "Targeting Angiopoietin-like 4 (ANGPTL4) in Severe Community Acquired Pneumonia", "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": "2025-04-04", "end_date": "2029-01-31", "award_amount": 827909, "principal_investigator": { "id": 32515, "first_name": "William A", "last_name": "Altemeier", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32516, "first_name": "Pavan Kumar", "last_name": "Bhatraju", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "Community-acquired pneumonia (CAP) is a common cause of morbidity and mortality in hospitalized patients but therapeutics are limited. In response, identification of modifiable pathways to alter host response and improve outcomes in patients with severe CAP has been highlighted as a NHLBI research priority. Our research group has identified angiopoietin-like 4 (ANGPTL4) as a potential mediator in adverse outcomes in CAP from viral and bacterial pathogens. We have generated preliminary data in a discovery proteomic analysis of 5000 different plasma proteins. We found that ANGPTL4 was one of the top proteins associated with fewer ventilator free days and worse hospital mortality in severe CAP due to COVID-19. Next, in a multi-center cohort, we replicated these findings in COVID-19 that higher ANGPTL4 concentrations were associated with worse clinical outcomes, and obtained preliminary evidence that ANGPTL4 is also associated with outcomes in severe CAP due to bacteria3. We also have generated data that genetically targeting Angptl4 is protective in mice with severe influenza, a finding that is supported by pre-clinical data that inhibition of ANGPTL4 signaling through a monoclonal antibody is protective in viral pneumonia. In addition, independent research groups have also found that ANGPTL4 is associated with clinical outcomes in severe CAP. Together, these findings support our hypothesis that ANGPTL4 expression is a significant determinant of outcomes from CAP, independent of pathogen type, and that modulation can lead to improved clinical outcomes. To further examine this hypothesis, we will use complementary clinical and pre-clinical studies in the following aims. In Aim 1, we will determine the relationship between plasma ANGPTL4 levels and outcomes in a hospitalized population with varying severity at enrollment (acute care and ICU) and pathogen type (viral and bacterial). In Aim 2, we will infer causal relationships between ANGPTL4 concentrations and risk for pulmonary and extra- pulmonary organ dysfunction using a non-overlapping 2-sample Mendelian randomization genetic approach. In Aim 3, we will evaluate the role of ANGPTL4 in pre-clinical models of viral and bacterial pneumonia and determine the relative contributions of the proteolytically processed cANGPTL4 and nANGPTL4 peptides. The outstanding qualifications of our team in the fields of sepsis, community acquired pneumonia, molecular epidemiology, and pre-clinical models uniquely position us to deliver an integrated molecular view of host response in CAP that is not only responsive to the challenges in severe CAP care identified by global leaders, but could fundamentally alter paradigms of patient care in severe CAP. The long-term goals are to delineate the role of ANGPTL4 in severe CAP through understanding which clinical outcomes are most closely linked with ANGPTL4 levels through epidemiological and genetic causal inference analyses and to understand the cell of origin and relative contributions of different cleavage products of ANGPTL4 through pre-clinical studies.", "keywords": [ "ANGPTL4 gene", "Acute Renal Failure with Renal Papillary Necrosis", "American", "Bacteria", "Bacterial Pneumonia", "Biometry", "C-terminal", "COVID-19", "COVID-19 pandemic", "COVID-19 pneumonia", "Caring", "Cells", "Cessation of life", "Chest", "Clinical", "Clinical Research", "Clinical Trials", "Data", "Development", "Enrollment", "Epidemiology", "Follow-Up Studies", "Functional disorder", "Genetic", "Genetic Models", "Genotype", "Goals", "Health Care Costs", "Hospital Mortality", "Hospitalization", "Hour", "Human Genetics", "Immune response", "Infection", "Influenza", "Link", "Lung", "Measures", "Mechanical ventilation", "Mediator", "Mendelian randomization", "Metabolic Diseases", "Molecular", "Monoclonal Antibodies", "Morbidity - disease rate", "Mus", "N-terminal", "National Heart Lung and Blood Institute", "Organ", "Outcome", "Pathway interactions", "Patient Care", "Patients", "Peptides", "Permeability", "Plasma", "Plasma Proteins", "Pneumonia", "Population", "Positioning Attribute", "Pre-Clinical Model", "Preclinical data", "Process", "Protein Secretion", "Proteins", "Proteomics", "Pulmonary Inflammation", "Pulmonology", "Qualifying", "Research", "Research Priority", "Resolution", "Risk", "Role", "SARS-CoV-2 infection", "Sample Size", "Sampling", "Sepsis", "Severities", "Severity of illness", "Shock", "Signal Transduction", "Societies", "Source", "Streptococcus pneumoniae", "Testing", "Therapeutic", "Translational Research", "Variant", "Vascular Permeabilities", "Ventilator", "Viral", "Viral Pneumonia", "Virus", "acute care", "adverse outcome", "antimicrobial", "bacterial community", "biobank", "biological heterogeneity", "clinical heterogeneity", "clinical phenotype", "clinical translation", "cohort", "community acquired pneumonia", "epidemiological model", "experimental study", "genetic approach", "genetic epidemiology", "improved", "improved outcome", "influenza infection", "insight", "lipoprotein lipase", "molecular modeling", "mortality", "mouse model", "multidisciplinary", "pathogen", "pathogenic bacteria", "pathogenic virus", "patient population", "patient response", "pneumonia model", "pre-clinical", "preclinical study", "protein expression", "response" ], "approved": true } }, { "type": "Grant", "id": "15671", "attributes": { "award_id": "2517733", "title": "Collaborative Research: RI: Medium: Transparent Fair Division of Indivisible Items", "funder": { "id": 3, "ror": "https://ror.org/021nxhr62", "name": "National Science Foundation", "approved": true }, "funder_divisions": [ "Unknown", "Robust Intelligence" ], "program_reference_codes": [], "program_officials": [ { "id": 32177, "first_name": "Andy", "last_name": "Duan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-10-01", "end_date": null, "award_amount": 621874, "principal_investigator": { "id": 2616, "first_name": "Lirong", "last_name": "Xia", "orcid": null, "emails": "[email protected]", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 148, "ror": "https://ror.org/01rtyzb94", "name": "Rensselaer Polytechnic Institute", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 218, "ror": "", "name": "Rutgers University New Brunswick", "address": "", "city": "", "state": "NJ", "zip": "", "country": "United States", "approved": true }, "abstract": "Fair division deals with the distribution of resources and tasks among different parties, e.g., individuals, firms, nations, or autonomous agents, with the goal of achieving fairness and economic efficiency. Fairness has increasingly become crucial in distributing precious and scarce medical equipment, and its absence has exacerbated healthcare issues during the COVID-19 global pandemic. A wide variety of real-world applications such as scheduling, dispute resolution, healthcare management, and refugee settlement assume complete knowledge about allocation decisions, which gives rise to negative computational and impossibility results. The existing approaches to mitigate these challenges, in turn, impose a high cost on transparency. The broad goal of this project is to provide theoretical and algorithmic solutions for fair allocation of indivisible items in practical, large-scale settings, as a broad contribution to the grand scheme of artificial intelligence (AI) and economics for social good. This research will offer a novel and promising perspective for developing practical and transparent fair solutions while providing a systematic investigation on the perceived fairness of allocation mechanisms that are applicable to societies at large. This project will integrate and develop algorithmic solutions for transparent fair division in a publicly available software system with the goal of extending its reach--and in general promoting fairness and transparency--to a broad national and international audience. This project will develop a new framework for achieving fairness and efficiency in the allocation of indivisible resources with minimum cost on transparency. Specifically, it will make progress in four interconnected dimensions: 1) Tradeoffs between transparency, fairness, and efficiency, that aim at analyzing the compatibility of the properties and devising algorithmic solutions when allocating indivisible items, 2) Strategic aspects of fair division, that investigates agents' behavior and strategies under transparency requirements, 3) Domain restriction, that focuses on developing tractable solutions by circumventing the impossibility results in achieving compatible solutions, and 4) Bads and mixtures, that extend the transparency and fairness framework to include desirable (goods) and undesirable items (bads). Furthermore, this research plans to close the current gap between theoretical foundations of fairness and the perception of fairness through a series of comprehensive empirical evaluations. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15651", "attributes": { "award_id": "2501232", "title": "Advantaging the National Artificial Intelligence Research Resource (NAIRR) Pilot: Leveraging the COVID-19 HPC Consortium Experience", "funder": { "id": 3, "ror": "https://ror.org/021nxhr62", "name": "National Science Foundation", "approved": true }, "funder_divisions": [ "Unknown", "NAIRR-Nat AI Research Resource" ], "program_reference_codes": [], "program_officials": [ { "id": 32154, "first_name": "Sharon", "last_name": "Geva", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-02-15", "end_date": null, "award_amount": 896755, "principal_investigator": { "id": 32155, "first_name": "John", "last_name": "Towns", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 15575, "first_name": "Christine R", "last_name": "Kirkpatrick", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 281, "ror": "", "name": "University of Illinois at Urbana-Champaign", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "This project supports the broader efforts of the National Artificial Intelligence Research Resource (NAIRR) Pilot to address how powerful Artificial Intelligence (AI) resources can be used to accelerate scientific understanding and discovery and further the capabilities of AI models. It also develops efficient processes for providing these resources to researchers. This project builds on the successful model of, and lessons learned from, the COVID-19 HPC Consortium (C19HPCC), which demonstrated the power of public-private partnerships in addressing global challenges. By applying these lessons to the NAIRR Pilot, the project creates a robust framework for future government-academia-industry collaborations. This not only enhances the NAIRR Pilot but also paves the way for the full NAIRR program, ultimately supporting a broader range of research efforts and fostering innovation in artificial intelligence. The project leverages lessons learned from the C19HPCC to enhance the National Artificial Intelligence (NAIRR) Pilot. The C19HPCC was a collaborative effort that brought together high-performance computing (HPC) resources from government, academia, and industry to accelerate research and discovery in the fight against COVID-19. The primary goals are to develop efficient processes for allocating AI resources, improve proposal review mechanisms, establish effective reporting methods, foster partnerships across government, academia, and industry, and establish and evolve governance structures and coordination mechanisms to manage the diverse set of resources and stakeholders involved. The scope includes leveraging prior policies, procedures, and tools from the C19HPCC to support the NAIRR Pilot and ultimately the full NAIRR program. By applying these methods, the project aims to create a robust framework for future AI research and innovation. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15639", "attributes": { "award_id": "1F31HL178200-01", "title": "Myocarditis is necessary for the development of arrhythmogenic cardiomyopathy", "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": 32142, "first_name": "Stephanie Johnson", "last_name": "Webb", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-01-06", "end_date": "2027-01-05", "award_amount": 37045, "principal_investigator": { "id": 32143, "first_name": "Steven Elias", "last_name": "Valdez", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 202, "ror": "https://ror.org/03r0ha626", "name": "University of Utah", "address": "", "city": "", "state": "UT", "zip": "", "country": "United States", "approved": true }, "abstract": "Arrhythmogenic cardiomyopathy (ACM) is a devastating inherited disease that causes sudden cardiac death in young people, accounting for up to 22% of sudden cardiac deaths in adults under 35. Despite the identification of causative mutations, the mechanisms triggering ACM remain elusive, and there are no preventative therapies for individuals carrying pathogenic allele variants. This project aims to elucidate the role of early immune cell infiltration in the development of ACM using a mouse model with a mutation in the desmosomal protein desmoglein-2 (DSG2). The central hypothesis is that early myocardial immune cell populations and inflammation determine ACM phenotype severity. Aim 1 will test whether increased neonatal immune cell recruitment accelerates arrhythmias, scar formation, and death in DSG2 mice using an adeno-associated viral vector expressing a modified COVID-19 spike protein. Aim 2 will investigate if neonatal treatment with gene therapy expressing the connexin-43 isoform GJA1-20k reduces immune cell burden, inflammation, arrhythmias, and death. Aim 3 will examine whether neonatal inhibition of NFκB signaling using AAV9-A20 can prevent immune cell recruitment, inflammation, arrhythmias, and scarring. This research is significant because it explores a novel preventative treatment strategy for ACM, focusing on early immune-mediated events that precede overt cardiac dysfunction. The approach is innovative in its examination of the early stages of ACM pathophysiology and the use of gene therapies targeting different pathways involved in disease development. The expected outcomes include identifying the role of immune cell infiltration in ACM, demonstrating the efficacy of two gene therapies, and offering a new treatment paradigm focusing on early intervention to prevent disease onset in genetically susceptible individuals. If successful, this work could transform the clinical management of ACM and potentially other genetic cardiomyopathies.", "keywords": [ "Acceleration", "Accounting", "Adult", "Age", "Anti-Inflammatory Agents", "Arrhythmia", "Benign", "Birth", "CCL2 gene", "CMV promoter", "Cardiac Myocytes", "Cd68", "Cells", "Cessation of life", "Childhood", "Cicatrix", "Clinical", "Clinical Management", "Connexin 43", "Coupling", "Data", "Desmosomes", "Development", "Devices", "Disease", "Dose", "Early Intervention", "Electrocardiogram", "Environmental Risk Factor", "Event", "Exercise", "Fibrosis", "Flow Cytometry", "Functional disorder", "Genes", "Genetic Carriers", "Heart", "Heart Transplantation", "Heart failure", "Hereditary Disease", "Immune", "Immunohistochemistry", "Implant", "Individual", "Infection", "Infiltration", "Inflammation", "Inflammatory", "Injections", "Interleukin-6", "Intervention", "Limb structure", "Macrophage", "Measures", "Mechanics", "Mediating", "Mus", "Mutant Strains Mice", "Mutation", "Myocardial", "Myocardial dysfunction", "Myocarditis", "Myocardium", "Neonatal", "Onset of illness", "Other Genetics", "Outcome", "Outcome Study", "PTPRC gene", "Pathogenicity", "Pathway interactions", "Patients", "Persons", "Phase", "Phenotype", "Population", "Predisposition", "Preventive therapy", "Preventive treatment", "Protein Isoforms", "Proteins", "Reporting", "Research", "Role", "SARS-CoV-2 spike protein", "Saline", "Serotyping", "Severities", "Signal Transduction", "Structure", "Sudden Death", "TNF gene", "Telemetry", "Testing", "Transgenic Mice", "Translating", "Trichrome stain", "Ventricular Arrhythmia", "Viral Vector", "Western Blotting", "Work", "adeno-associated viral vector", "arrhythmogenic cardiomyopathy", "causal variant", "cytokine", "desmoglein 2", "disease phenotype", "disease-causing mutation", "emerging adult", "gene therapy", "gene-targeted therapy", "genetic variant", "immune activation", "immune cell infiltrate", "inherited cardiomyopathy", "innovation", "mortality", "mouse model", "mutant mouse model", "mutation carrier", "novel", "novel therapeutic intervention", "osteopontin", "prevent", "recruit", "sudden cardiac death", "treatment strategy" ], "approved": true } }, { "type": "Grant", "id": "15636", "attributes": { "award_id": "1R21AI190589-01", "title": "Unravelling the mechanisms of virus host species jump", "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": 32138, "first_name": "Susan Soo", "last_name": "Park ochsner", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-01-16", "end_date": "2026-12-31", "award_amount": 228435, "principal_investigator": { "id": 32139, "first_name": "Masmudur Mohammed", "last_name": "Rahman", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 912, "ror": "", "name": "ARIZONA STATE UNIVERSITY-TEMPE CAMPUS", "address": "", "city": "", "state": "AZ", "zip": "", "country": "United States", "approved": true }, "abstract": "Uncovering the mechanisms enabling the cross-species jumps of viruses that happen in nature is essential for our understanding of viral spillovers, most notably those that can result in severe disease outbreaks, for example, the coronavirus SARS-CoV-2 pandemic and Mpox (monkeypox) epidemic. Therefore, studying the evolution of viruses that cause species jumps is essential. Myxoma virus (MYXV), a leporipoxvirus, is nonpathogenic in its evolutionary host (Sylvilagus sp.) but was highly lethal (causing myxomatosis) immediately after it leaped into European rabbits (Oryctolagus cuniculus) in the late 19th century. The introduction of MYXV to control feral European rabbit populations in Australia and Europe in the early 1950s presents the best-documented field example of host-virus co-evolution. In 2018, a new natural MYXV variant was identified in Iberian hares (Lepus granatensis) in Spain, causing a myxomatosis-like disease in hares and wild European rabbits. Between 2018 and 2020, the disease became endemic, with an estimated mean mortality rate of 55% in hares. This newly emerged MYXV variant, named MYXV Toledo (MYXV-Tol) or hare MYXV (ha-MYXV), has acquired a novel insertion of four viral genes “cassette” of ~ 2,800 bp within the M009L gene. The MYXV-Tol genome also includes three disrupted genes (M009L, M152R, and M036L). We recently reported that the C7-like host range gene M159-Tol present in the MYXV-Tol recombination cassette is essential for infection and replication in hare cells, suggesting that M159-Tol may be required for the extreme pathogenicity in hares. Since MYXV-Tol is also isolated from wild European rabbits, we studied the pathogenicity of MYXV-Tol in European rabbits and compared it with MYXV-Lau and the C7-like host range mutant vMyxTol-M159KO. Our results, for the first time, demonstrate that the natural MYXV variant MYXV-Tol has adapted to cause a uniquely different lethal disease and pathogenicity in European rabbits compared to typical myxomatosis caused by MYXV-Lau. Surprisingly, the deletion of M159-Tol had minimal or no effect on the disease progression and pathogenicity of MYXV-Tol in rabbits. Thus, M159-Tol may have adapted hare-specific host tropism functions, and we hypothesize that the additional newly acquired viral genes or the disruptions in some of the ORFs have enabled MYXV-Tol to cause a novel lethal disease in Iberian hares and European rabbits. In this application, we propose investigating the biological mechanisms and genetic changes in the MYXV-Tol that facilitate species leaping and cause novel pathogenicity and disease in European rabbits. Aim 1: Elucidate the biological mechanisms of how MYXV-Tol is causing a novel lethal disease in European rabbits. Aim 2: Define the genetic changes in MYXV causing the novel disease in European rabbits. This information will be essential for future identification of the unique cellular targets for MYXV-Tol. This R21 proposal will enable us to understand how natural genetic changes in poxviruses allow species leaping and sometimes cause a new lethal disease in a new host.", "keywords": [ "Animals", "Attenuated", "Australia", "Automobile Driving", "Biological", "Biological Models", "Body part", "COVID-19 pandemic", "Cell Line", "Cells", "Cellular Tropism", "Climate", "Collaborations", "Cowpox virus", "Cutaneous", "DNA cassette", "Death Rate", "Disease", "Disease Outbreaks", "Disease Progression", "Edema", "Epidemic", "Europe", "European", "Event", "Evolution", "Farm", "Future", "Genes", "Genetic Recombination", "Genome", "Genomics", "Global Change", "Hares", "Horizontal Gene Transfer", "Human", "In Vitro", "Infection", "Kinetics", "Knock-out", "Lagomorpha", "Leporipoxvirus", "Lesion", "Lymphocyte", "Monkeypox", "Monkeypox virus", "Mutation", "Myxoma virus", "Names", "Nature", "Open Reading Frames", "Oryctolagus cuniculus", "Pathogenicity", "Peripheral Blood Mononuclear Cell", "Polynucleotide Adenylyltransferase", "Population", "Poxviridae", "Primary Lesion", "Proteins", "Reporting", "Site", "Spain", "Testing", "Thymidine Kinase", "Time", "Tissues", "Tropism", "Variant", "Viral", "Viral Genes", "Viral Proteins", "Virion", "Virus", "Weight Gain", "Zoonoses", "anthropogenesis", "cellular targeting", "cross-species transmission", "experimental study", "in vivo", "mutant", "neutralizing antibody", "novel", "programs", "seroconversion" ], "approved": true } }, { "type": "Grant", "id": "15629", "attributes": { "award_id": "1F31NR021624-01", "title": "An epidemiological study to investigate the multifactoral nature of diabetes risk among adults with COVID-19 with a genetic and social determinants of health lens", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Nursing Research (NINR)" ], "program_reference_codes": [], "program_officials": [ { "id": 32130, "first_name": "Nadra", "last_name": "Tyus", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-01-01", "end_date": "2026-12-31", "award_amount": 32974, "principal_investigator": { "id": 32131, "first_name": "Jordan", "last_name": "Keels", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 425, "ror": "https://ror.org/02n2fzt79", "name": "Boston College", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "This proposal seeks to enhance our understanding of new-onset diabetes in individuals with COVID-19 by exploring social determinants of health and underlying biology. Both diabetes and COVID-19 disproportionately affect individuals from racial and ethnic minority groups. Further, these individuals experience worse clinical outcomes, including higher rates of mortality compared to non-Hispanic Whites. Some have suggested these observations may be due to differences in comorbidities, home/work environment, or access to care. This study will investigate the 1) prevalence of new-onset diabetes in COVID-19; 2) how social determinants of health influence health outcomes; and 3) the genetic likelihood of developing diabetes. Study results will not only help identify high risk populations, but will also contribute to enhancing health equity, reducing disparities, and promoting better health outcomes. The proposed work will use quantitative methods to address the question. We will conduct a systematic review and meta-analysis to determine the true prevalence of new-onset diabetes in individuals diagnosed with COVID-19. Additionally, we will use prospective survey data from the All of Us database to determine salient factors related to social determinants of health and health outcomes. Last, we will use the All of Us database to conduct genome-wide-association studies and calculate the risk score for diabetes and COVID-19 to examine underlying biologic risk of developing new-onset diabetes. The training plan for this fellowship includes a variety of opportunities to develop and apply knowledge in social determinants of health and analytic skills as well as professional development activities aimed at nurturing a well-rounded nurse scientist. Training opportunities include structured and experiential learning activities to develop substantive and methodological knowledge. Interdisciplinary team-based research experiences and mentorship will complement formal and experiential learning opportunities. A strong mentoring team has been assembled with complementary experts in endocrinology/diabetes, social determinants of health, and statistical analysis. The proposed study and study sponsors are supported by the institutional environment of Boston College Connell School of Nursing which has significant resources to support the proposed project. The mentoring team and institutional environment are well-suited for the successful completion of the proposed project and training plan for this fellowship. This study addresses the NINR’s research lens of advancing health equity and social determinants of health research. The proposed work will elucidate the intersection of social and environmental factors with biologic risk factors and their impact on health outcomes. Findings will inform a holistic approach to understanding health disparities and advancing health equity among racial and ethnic minorities affected by diabetes and COVID-19", "keywords": [ "2019-nCoV", "Active Learning", "Acute", "Acute Respiratory Distress Syndrome", "Address", "Admission activity", "Adrenal Cortex Hormones", "Adult", "Affect", "Beta Cell", "Big Data Methods", "Biological", "Biological Factors", "Biology", "Blood Vessels", "Boston", "COVID-19", "COVID-19 diagnosis", "COVID-19 impact", "Cessation of life", "Clinical", "Communities", "Community Health", "Complement", "Containment", "Data", "Databases", "Death Rate", "Detection", "Development", "Diabetes Mellitus", "Discipline of Nursing", "Early Diagnosis", "Economics", "Endocrine system", "Endocrinology", "Environment", "Environmental Risk Factor", "Event", "Fellowship", "Genetic", "Genetic Determinism", "Health", "Health Care Costs", "Health Services Accessibility", "Health Surveys", "Healthcare", "Heart failure", "Home", "Hormonal Change", "Hyperglycemia", "Iatrogenesis", "Individual", "Inflammation", "Injury", "Institution", "Insulin Resistance", "Insulin-Dependent Diabetes Mellitus", "Intensive Care", "Intervention", "Kidney Diseases", "Knowledge", "Link", "Long COVID", "Low income", "Measures", "Mental Depression", "Mentors", "Mentorship", "Meta-Analysis", "Metabolic dysfunction", "Methodology", "Methods", "Minority Groups", "Mission", "Morbidity - disease rate", "Myocardial Infarction", "Nature", "Neuropathy", "Non-Insulin-Dependent Diabetes Mellitus", "Not Hispanic or Latino", "Nurses", "Obesity", "Outcome", "Pancreas", "Patient-Focused Outcomes", "Peripheral Vascular Diseases", "Persons", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Prediabetes syndrome", "Prevalence", "Public Health", "Publishing", "Reporting", "Research", "Resolution", "Resources", "Respiratory Failure", "Respiratory Tract Infections", "Retinal Diseases", "Risk", "Risk Factors", "SARS-CoV-2 infection", "School Nursing", "Science", "Scientist", "Societal Factors", "Statistical Data Interpretation", "Stress", "Structure", "Structure of beta Cell of islet", "Surveys", "Symptoms", "System", "Training", "Underserved Population", "United States", "United States National Institutes of Health", "Variant", "Virus Diseases", "Work", "autoimmune pathogenesis", "cerebrovascular", "college", "comorbidity", "diabetes risk", "disparity reduction", "epidemiology study", "ethnic minority", "ethnic minority population", "experience", "experimental analysis", "formal learning", "genetic architecture", "genome wide ass" ], "approved": true } }, { "type": "Grant", "id": "15625", "attributes": { "award_id": "1K08HL177422-01", "title": "Using novel RNA therapy to understand the role of fibrinogen in thromboinflammation in acute and chronic venous thrombosis", "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": 32124, "first_name": "CRYSTAL DARLEANE-ROBIN", "last_name": "Hill-Pryor", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-01-01", "end_date": "2029-12-31", "award_amount": 151523, "principal_investigator": { "id": 32125, "first_name": "Mitchell R", "last_name": "Dyer", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 700, "ror": "https://ror.org/00qqv6244", "name": "Medical College of Wisconsin", "address": "", "city": "", "state": "WI", "zip": "", "country": "United States", "approved": true }, "abstract": "Deep venous thrombosis (DVT) is a major cause of short and long-term morbidity and mortality. Despite the use of gold-standard anticoagulation therapies for the prevention and treatment of DVT, such as heparins and direct oral anticoagulants (DOACs), the incidence of DVT remains high in certain at-risk populations such as trauma patients and patients who suffer from chronic inflammatory diseases. Furthermore, current therapies have increased risks of bleeding. 40-70% of patients develop Post Thrombotic Syndrome (PTS) due to the extensive nature of the clot or poor clot resolution resulting in chronic thrombosis and vein wall scarring. Clinically, there are few treatments for PTS, which is characterized by pain, leg swelling, and ulcer formation. At the cellular level, the development and subsequent resolution of thrombus occurs through a complex interplay between the coagulation system and inflammation. Fibrinogen is the most abundant protein in circulation that is involved in the process of thrombus formation and resolution. The fibrin matrix serves as a platform for cellular infiltration, thrombus growth, and can result in dense clots resistant to lysis. Inadequate clot resolution and vein wall scarring, processes that are in part regulated by matrix metalloproteases (MMPs), lead to chronic DVT. The proposed aims of this project will investigate the role of fibrinogen in thromboinflammation in post-traumatic and acute DVT and the interplay between fibrinogen and MMPs in thrombus resolution and vein wall remodeling/fibrosis. To address these aims we will use novel RNA therapy to reduce circulating levels of fibrinogen. We have developed small interfering RNA (siRNA) directed against fibrinogen messenger RNA (mRNA) that can be delivered into cells using lipid nanoparticles (LNPs). Within the cell, the siRNA is released from the LNP and induces degradation of the target mRNA, preventing translation of the protein product. I will use LNPs similar to those used in the COVID-19 mRNA vaccines as a delivery platform, which naturally accumulate in the liver after intravenous injection, where fibrinogen is synthesized. We will use the LNP-RNA therapy in models of rodent and swine thrombosis to provide rigorous pre-clinical data. We hypothesize that fibrinogen plays a central role in regulating inflammatory cell infiltration in the developing thrombus and in regulating the activity of MMPs to promote thrombus resolution and vein wall healing. Through selective control of fibrinogen levels using a highly specific approach, targeting fibrinogen is not expected to increase the risk of bleeding. These studies will provide mechanistic insights into the role of fibrinogen in regulating thromboinflammation in settings of acute and chronic venous thrombosis. I have assembled a mentorship team with expertise in RNA therapy, LNP biochemistry, and coagulation biology that will oversee my successful completion of the proposed studies and development of the professional and scientific skills to transition to independence.", "keywords": [ "Acute", "Address", "Age", "Animal Model", "Anticoagulants", "Anticoagulation", "Automobile Driving", "Biochemistry", "Biological", "Biology", "Blood Coagulation Factor", "Blood Platelets", "COVID-19", "Cell Physiology", "Cells", "Cellular Infiltration", "Chronic", "Cicatrix", "Circulation", "Clinical", "Coagulation Process", "Complex", "Cytolysis", "Deep Vein Thrombosis", "Deposition", "Development", "Encapsulated", "Endothelium", "Environmental Risk Factor", "Event", "Family suidae", "Fibrin", "Fibrinogen", "Fibrinolysis", "Fibrosis", "Goals", "Grant", "Growth", "Health Care Costs", "Hemorrhage", "Hemostatic Agents", "Hemostatic function", "Heparin", "Hospitalization", "Incidence", "Individual", "Inferior vena cava structure", "Infiltration", "Inflammation", "Inflammatory", "Injury", "Innate Immune System", "Knowledge", "Lead", "Leg", "Leukocytes", "Liver", "Mediating", "Mentors", "Mentorship", "Messenger RNA", "Metalloproteases", "Modeling", "Morbidity - disease rate", "Multiple Trauma", "Mus", "Nature", "Operative Surgical Procedures", "Oral", "Pain", "Patients", "Plasma", "Play", "Populations at Risk", "Postphlebitic Syndrome", "Preclinical data", "Pregnancy", "Prevention", "Prevention therapy", "Process", "Prophylactic treatment", "Proteins", "Pulmonary Embolism", "Quality of life", "RNA", "RNA vaccine", "Recurrence", "Research Personnel", "Resistance", "Resolution", "Risk", "Rodent Model", "Role", "Small Interfering RNA", "Smoking", "Swelling", "System", "Tail", "Technology", "Thrombosis", "Thrombus", "Training", "Translations", "Trauma", "Trauma patient", "Ulcer", "Veins", "Venous Thrombosis", "Work", "chronic inflammatory disease", "efficacy evaluation", "extracellular", "healing", "immune activation", "improved", "insight", "intravenous injection", "lipid nanoparticle", "mortality", "mouse model", "neutrophil", "novel", "patient population", "porcine model", "preservation", "prevent", "release factor", "scaffold", "skills", "therapeutic RNA", "thromboinflammation", "thrombotic", "tool", "venous thromboembolism", "von Willebrand Factor" ], "approved": true } } ], "meta": { "pagination": { "page": 1, "pages": 1392, "count": 13920 } } }