Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=3&sort=-start_date
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-start_date", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=-start_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=4&sort=-start_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=2&sort=-start_date" }, "data": [ { "type": "Grant", "id": "15758", "attributes": { "award_id": "1R01HL180743-01", "title": "Putting Implementation into context to advance the management of mechanically ventilated patients.", "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": 32823, "first_name": "SHAHNAZ", "last_name": "KHAN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-15", "end_date": "2029-05-31", "award_amount": 748970, "principal_investigator": { "id": 32824, "first_name": "Meeta Prasad", "last_name": "Kerlin", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2627, "ror": "", "name": "UNIVERSITY OF PENNSYLVANIA", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "Over one million Americans undergo invasive mechanical ventilation (IMV) annually in intensive care units (ICUs). A few interventions have improved patient-centered outcomes in IMV patients, including sedation minimization, corticosteroid administration in selected patients, and low tidal volume ventilation and prone positioning in the subgroup patients with acute respiratory distress syndrome (ARDS). However, variability exists across ICUs in processes of care, clinical outcomes, and resource utilization. ICUs are highly complex interprofessional environments, and knowledge gaps remain regarding how contextual elements influence implementation determinants in different ICUs. The coronavirus disease 2019 (COVID-19) pandemic created unprecedented surges of patients requiring IMV and catalyzed rapid and dynamic changes in critical care delivery, facilitating some evidence-based practices after many years of persistently low penetration, and impeding others. Furthermore, new evidence, such as corticosteroids for COVID-19 and pneumonia, may have later influenced practice changes for IMV patients more broadly. Thus, this major disruption in critical care delivery is a unique opportunity to gain new knowledge about implementation in the ICU context. The overall objective of this proposal is to better understand the interplay between contextual factors and intervention features in care delivery for IMV patients. Guided by implementation frameworks, we will employ state-of-the-art causal inference methods and innovative qualitative approaches to conduct three specific aims: (1) Quantify penetration of four evidence-based treatments – sedation minimization, corticosteroid administration, low tidal volume ventilation, and prone positioning – over time among IMV patients and specific subgroups; (2) Develop a novel conceptual model of ICU implementation incorporating relationships between determinants and contextual elements; and (3) Apply implementation mapping to create adaptable menus to facilitate evidence-based practices. We will apply state-of-the-art causal inference methods to analyze a diverse, multicenter retrospective cohort of IMV patients admitted to more than 30 ICUs in 16 hospitals before, during, and after the height of the COVID-19 pandemic. In addition, we will use cutting-edge qualitative techniques and implementation research frameworks and will engage an array of stakeholders to develop implementation menus for each treatment that not only provide strategies to promote utilization of evidence- based treatments but also guidance for tailoring those strategies to different contexts. This project will advance the science of care delivery in a high-stakes setting by increasing the evidence regarding how contextual elements interact with treatment characteristics in critical care delivery. It will generate direct preliminary data for future implementation studies to test strategies to promote evidence-based care of IMV patients. Finally, it will create a conceptual model with potential application to delivery of critical care interventions in different ICU contexts more broadly.", "keywords": [ "Acute Respiratory Distress Syndrome", "Adherence", "Adrenal Cortex Hormones", "Advocate", "American", "COVID-19", "COVID-19 pandemic", "Caring", "Characteristics", "Clinical", "Communities", "Complex", "Consolidated Framework for Implementation Research", "Critical Care", "Data", "Effectiveness", "Elements", "Environment", "Evidence based intervention", "Evidence based practice", "Evidence based treatment", "Familiarity", "Focus Groups", "Height", "Hospitals", "Intensive Care Units", "Interruption", "Intervention", "Interview", "Knowledge", "Life", "Literature", "Maps", "Mechanical ventilation", "Methodology", "Methods", "Modeling", "Morbidity - disease rate", "Natural experiment", "Nurses", "Outcome", "Patient Admission", "Patient Care", "Patient Selection", "Patient-Focused Outcomes", "Patients", "Pattern", "Penetration", "Phase", "Physicians", "Pneumonia", "Process", "Prone Position", "Publications", "Qualitative Methods", "Resources", "Respiratory Failure", "Retrospective cohort", "Role", "Safety", "Science", "Sedation procedure", "Sepsis", "Service delivery model", "Structure", "Subgroup", "Surveys", "Syndrome", "Techniques", "Testing", "Tidal Volume", "Time", "Time Series Analysis", "Trauma", "Treatment outcome", "Vulnerable Populations", "acceptability and feasibility", "alternative treatment", "aspirate", "care delivery", "community acquired pneumonia", "comparative", "contextual factors", "evidence base", "future implementation", "high risk", "implementation determinants", "implementation framework", "implementation process", "implementation protocol", "implementation science", "implementation strategy", "implementation study", "improved", "improved outcome", "innovation", "mortality", "novel", "pandemic disease", "patient subsets", "respiratory", "rural area", "suburb", "ventilation" ], "approved": true } }, { "type": "Grant", "id": "15728", "attributes": { "award_id": "2537245", "title": "Collaborative Research: Belmont Forum Collaborative Research: BIOrepositories build Adaptive and Resilient Capacity (BioARC)", "funder": { "id": 3, "ror": "https://ror.org/021nxhr62", "name": "National Science Foundation", "approved": true }, "funder_divisions": [ "Unknown", "Intl Global Change Res & Coord" ], "program_reference_codes": [], "program_officials": [ { "id": 7800, "first_name": "Maria", "last_name": "Uhle", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-15", "end_date": null, "award_amount": 125998, "principal_investigator": { "id": 32778, "first_name": "John", "last_name": "Grieco", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 171, "ror": "https://ror.org/00mkhxb43", "name": "University of Notre Dame", "address": "", "city": "", "state": "IN", "zip": "", "country": "United States", "approved": true }, "abstract": "This award provides support to U.S. researchers participating in a project competitively selected by a 55-country initiative on global change research through the Belmont Forum. The Belmont Forum is a consortium of research funding organizations focused on support for transdisciplinary approaches to global environmental change challenges and opportunities. It aims to accelerate delivery of the international research most urgently needed to remove critical barriers to sustainability by aligning and mobilizing international resources. Each partner country provides funding for their researchers within a consortium to alleviate the need for funds to cross international borders. This approach facilitates effective leveraging of national resources to support excellent research on topics of global relevance best tackled through a multinational approach, recognizing that global challenges need global solutions. Working together in this Collaborative Research Action, the partner agencies have provided support to foster global transdisciplinary research teams of natural, health and social scientists and stakeholders from across the globe to improve understanding of climate, environment and health pathways to protect and promote health. The projects will provide crucial new understanding into the health implications arising from the impacts of climate change and variability on; 1) decision-science approaches to adaptation and implementation, 2) food, environment, and biological security and 3) risks to ecosystems and populations. This award provides support for the U.S. researchers to cooperate in consortia that consist of partners from at least three of the participating countries to increase our knowledge of the complex linkages and pathways between the climate, environment and health to help solve complex challenges that face societies. The BioARC project seeks to develop an interdisciplinary network of scientists, health professionals, and stakeholders to build the missing physical, human, and material infrastructure to stop pandemics at their source. These various forms of infrastructure will be centered on the development of multiple in-country biorepositories spread throughout The Americas, where pathogens with pandemic potential (e.g., Zika, Andes Virus) and neglected tropical diseases (e.g., Dengue, Chagas, and hookworm infection) have previously emerged and spread. This new infrastructure will provide the critical spatial, temporal, and taxonomic sampling and associated informatics necessary to understand the role of environmental drivers in host-pathogen dynamics, enabling a more proactive and predictive approach to pathogen emergence. This project directly addresses a critical challenge to pandemic preparedness. COVID-19 directly illustrated the high costs of pandemics to human wellbeing and the persistent gaps in our approach to preventing pathogen emergence. As humans and wildlife increasingly share space, opportunities for spillovers grow. Additionally, environmental stresses can cause wildlife to shed pathogens more readily as stress induced by things like habitat loss, heat exposure, or food scarcity decreases immune functionality that would typically keep pathogen shedding low. The project will focus on improving biorepository infrastructure including equipment and databases. The project team will develop training modules on museum science, fieldwork, molecular genetics, informatics, geospatial data analysis, science communication, and interdisciplinary network development. The project will develop best practices for biorepositories and relational databases for pathogens, interdisciplinary workflows for wildlife pathogen surveillance, communication across One Health disciplines, and strategies for biorepository decision-maker coordination. The goal of developing best practices is to enable the standardization of procedures for similar efforts locally and globally, and to form the foundation for an early-warning system for zoonotic diseases that will improve U.S. national security and build the U.S. workforce. The project will reduce costs of outbreak response by creating the capacity and data to establish baselines for wildlife pathogen dynamics, detecting deviations from these baselines, informing models, and enabling timely biosecurity decisions. The project will develop a robust, enduring system to safeguard human and animal populations from infectious diseases. 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": "15739", "attributes": { "award_id": "1RF1NS144213-01", "title": "SARS-CoV-2 initiation and acceleration of AD pathology in the setting of endogenous and exogenous risk factors", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Aging (NIA)" ], "program_reference_codes": [], "program_officials": [ { "id": 32579, "first_name": "WILLIAM PATRICK", "last_name": "DALEY", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-15", "end_date": "2029-07-31", "award_amount": 3039032, "principal_investigator": { "id": 8182, "first_name": "Ananth V", "last_name": "Annapragada", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 566, "ror": "https://ror.org/02pttbw34", "name": "Baylor College of Medicine", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 7071, "first_name": "Shannon", "last_name": "Ronca", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 32793, "first_name": "Andrew Arun", "last_name": "Badachhape", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 32794, "first_name": "Parag", "last_name": "Parekh", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2610, "ror": "", "name": "BAYLOR COLLEGE OF MEDICINE", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "The uncertain e,ology of Alzheimer’s disease poses significant obstacles to the development of both therapeu,c and preven,on strategies. At the root of this quandary is the fact that familial disease accounts for a very small frac,on of cases, with the vast majority remaining gene,cally sporadic. The most widely known risk factor, the ApoE4 allele of the gene coding for apolipoprotein E, has been iden,fied, but mechanis,c ,es to disease development are s,ll emerging. Neuroinflamma,on has long been suspected as a contribu,ng factor, and regular exercise documented as a mi,ga,ng factor, with theories to explain their effects being posed, but again with liGle mechanis,c proof. A picture of a very complex process of ini,a,on and progression of Alzheimers disease and related demen,as (AD/RD) including Pick’s disease, fronto-temporal demen,a (FTD) and other tauopathies, is slowly emerging. A key factor in the e,ology of AD/RD that repeatedly crops up is viral infec,on. COVID-19 has brought new aGen,on to this factor, with the observa,on that a frac,on of those infected experience “brain-fog”, a catch-all term that includes cogni,ve dysfunc,on, memory dysfunc,on and mental fa,gue, marked by impaired ability to perform mental tasks compared to before the infec,on. Several factors however, complicate an understanding of the effect of COVID-19 on AD/RD and cons%tute the driving ques%ons for this proposal: These include (1) What are the rela,ve contribu,ons of gene,c risk factors and COVID-19 on ini,a,on and progression of AD/RD? (2) What are the effects of SARS-CoV-2 variants: ex,nct strains e.g. Wuhan, alpha, delta vs. current strains e.g. omicron and its lineage, and their sequen,al infec,on on AD/RD ini,a,on and progression? (3) What are the effects of prior infec,ons with other highly prevalent viruses e.g. HSV-1 on the ini,a,on and progression of AD/RD by SARS-CoV-2? Successful comple,on of this work will probe the rela,onship between COVID-19 and neurodegenera,on, while yielding deep mechanis,c insights into the role of SARS-CoV-2 in combina,on with HSV-1 in triggering/accelera,ng an AD phenotype and focus a search for therapeu,c targets to counteract AD ini,a,on/accelera,on/progression.", "keywords": [ "2019-nCoV", "Acceleration", "Acids", "Alleles", "Alzheimer's Disease", "Alzheimer's disease model", "Alzheimer's disease pathology", "Alzheimer's disease related dementia", "Amyloid", "Amyloid beta-Protein Precursor", "Apolipoprotein E", "Automobile Driving", "COVID-19", "COVID-19 impact", "Code", "Common Cold", "Complex", "Coronavirus", "Coupled", "Development", "Disease", "Exercise", "Familial disease", "Genes", "Herpesvirus 1", "Histopathology", "Image", "Impairment", "Inflammatory", "Interferons", "Interleukin-1", "Interleukin-6", "Link", "MAPT gene", "Magnetic Resonance Imaging", "Measurement", "Measures", "Memory", "Memory Loss", "Metabolism", "Methodology", "Methods", "Modeling", "National Institute of Neurological Disorders and Stroke", "Neurofibrillary Tangles", "Pathology", "Pathway interactions", "Phenotype", "Pick Disease of the Brain", "Process", "Psyche structure", "Recording of previous events", "Reporting", "Risk", "Risk Factors", "Role", "SARS-CoV-2 B.1.617.2", "SARS-CoV-2 variant", "Severity of illness", "Signal Transduction", "Study models", "Tauopathies", "Testing", "Transgenic Mice", "Viral", "Virus", "Work", "apolipoprotein E-4", "brain fog", "cytokine", "disease model", "experience", "human coronavirus", "hyperphosphorylated tau", "in vivo imaging", "insight", "mouse model", "neuropathology", "novel", "post-COVID-19", "presenilin-1", "response", "tau Proteins", "theories", "transcriptomics" ], "approved": true } }, { "type": "Grant", "id": "15760", "attributes": { "award_id": "1U54HL170290-01A1", "title": "Project II: Adaptive Immunity and AT1-AA in Mediating the PE Phenotype and Long-term Effects on Offspring", "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": 32827, "first_name": "MARRAH ELIZABETH", "last_name": "LACHOWICZ-SCROGGINS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-15", "end_date": "2030-07-31", "award_amount": 210490, "principal_investigator": { "id": 31496, "first_name": "Babbette", "last_name": "LaMarca", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2629, "ror": "", "name": "UNIVERSITY OF MISSISSIPPI MED CTR", "address": "", "city": "", "state": "MS", "zip": "", "country": "United States", "approved": true }, "abstract": "Preeclampsia (PE) affects 12% of deliveries in Mississippi and this incidence of PE increased significantly due to the COVID-19 pandemic rising to 24% in December of 2020. PE is characterized by placental ischemia, inflammation, vascular dysfunction, cognitive decline, hypertension (HTN), IUGR and developmental origins of disease in the offspring. We have shown that agonistic autoantibodies to the angiotensin II type I receptor (AT1- AA) cause placental and cerebral dysfunction contributing to HTN in pregnant rats which is attenuated by blockade of the AT1-AA with the peptide ‘n7AAc’. Moreover, we have shown that the inflammatory cytokine TNF- α stimulates the AT1-AA and causes HTN and cerebral dysfunction during pregnancy. One important unanswered question in PE research is the relative importance of immune mediators to cause HTN and cerebral dysfunction in the pregnant mom or to cause adult HTN in her offspring. Moreover, we don’t know the role of immune mediators as mechanisms of a PE phenotype in pregnant patients with a history (Hx) of COVID 19 infection. Preliminary data in support of AIM 1 are that placental CD4+ T cells cause HTN and cerebrovascular dysfunction in pregnant rats and lead to cognitive dysfunction at 4 months postpartum (PP). Our preliminary data supporting AIM 2 are that Etanercept reduces blood pressure in adoptive transfer recipients of PE T cells. Preliminary data supporting AIM 3 is that HTN, AT1-AA and TNF-α are produced in pregnant women with HTN and a history (Hx) of COVID during pregnancy and in adoptive transfer recipients of T cells from PE women with a COVID 19 Hx during pregnancy compared to recipients of T cells from normotensive women with a Hx of COVID during pregnancy. Based on our findings, we hypothesize that PE stimulated T cells, in the presence or absence of a past COVID infection during pregnancy, secrete TNF-α stimulating B cell secretion of AT1-AA, both of which cause cerebral dysfunction and HTN during pregnancy and programming of cerebral dysfunction and cognitive decline in adult male and female offspring which could be attenuated by either TNF-α or AT1-AA blockade. Specific Aim 1. Does perinatal administration of CD4+T cells from PE women cause HTN and cerebrovascular dysfunction during pregnancy or PP in recipient dams or lead to HTN or cognitive decline in IUGR offspring? Specific Aim 2. Does blockade of AT1-AA or TNF-α in response to perinatal administration of PE CD4+T cells improve HTN and cerebrovascular dysfunction during pregnancy or PP in recipient dams and HTN and cognitive decline in IUGR offspring? Specific Aim 3. Do CD4+T cell mediated inflammatory responses from prior COVID-19 infection lead to PE-like HTN and neurovascular dysfunction in pregnant rats and PP that could be improved with blockade of TNF-α or AT1-AA? Does blockade of AT1-AA or TNF-α in response to perinatal administration of PE CD4+T cells improve HTN and cerebrovascular dysfunction in IUGR offspring?", "keywords": [ "Address", "Adoptive Transfer", "Adult", "Adult Children", "Affect", "Animals", "Attenuated", "Autoantibodies", "Autoimmune Diseases", "B-Lymphocytes", "Biological Response Modifiers", "Body System", "CD4 Positive T Lymphocytes", "COVID-19", "COVID-19 pandemic", "COVID-19 patient", "Cardiovascular Diseases", "Cell Culture Techniques", "Cell secretion", "Cells", "Cerebrovascular Disorders", "Cerebrum", "Cessation of life", "Child", "Chronic", "Cognition", "Cognitive", "Data", "Development", "Diagnosis", "Disease", "Endothelin", "Etanercept", "Exhibits", "Exposure to", "Female", "Fetal Growth", "Fetal Growth Retardation", "Functional disorder", "Genetic Complementation Test", "Headache", "Hypertension", "Immunologics", "Impaired cognition", "In Vitro", "Incidence", "Infection", "Inflammation", "Inflammatory", "Inflammatory Response", "Institution", "Ischemia", "Lead", "Link", "Long-Term Effects", "Mediating", "Mediator", "Memory Loss", "Mental disorders", "Mississippi", "Molecular", "Mothers", "Neurodevelopmental Disorder", "Neurologic Dysfunctions", "Nude Rats", "Pathogenesis", "Pathway interactions", "Patients", "Peptides", "Perinatal", "Phenotype", "Physiological", "Placenta", "Postpartum Period", "Pre-Eclampsia", "Pregnancy", "Pregnant Women", "Production", "Publishing", "Rattus", "Receptor Angiotensin Type 1", "Recording of previous events", "Renal function", "Research", "Risk Factors", "Role", "SARS-CoV-2 infection", "SARS-CoV-2 infection history", "SARS-CoV-2 negative", "Schizophrenia", "Sex Differences", "T-Lymphocyte", "TNF gene", "Techniques", "Testing", "Vascular Diseases", "Woman", "adaptive immunity", "autism spectrum disorder", "blood pressure elevation", "blood pressure reduction", "cardiovascular disorder risk", "cerebrovascular", "cytokine", "endothelial dysfunction", "immune activation", "improved", "in vivo", "inflammatory marker", "male", "maternal morbidity", "neurovascular pathology", "normotensive", "offspring", "perinatal morbidity", "pharmacologic", "post SARS-CoV-2 infection", "pregnancy hypertension", "pregnant", "response", "vasoconstriction" ], "approved": true } }, { "type": "Grant", "id": "15743", "attributes": { "award_id": "1R34HL173375-01A1", "title": "Democratizing Access to Cleaner Residential Air (DACRA)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 32796, "first_name": "MICHELLE M", "last_name": "FREEMER", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-15", "end_date": "2028-07-31", "award_amount": 293395, "principal_investigator": { "id": 32797, "first_name": "Doug", "last_name": "Brugge", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2614, "ror": "", "name": "UNIVERSITY OF CONNECTICUT SCH OF MED/DNT", "address": "", "city": "", "state": "CT", "zip": "", "country": "United States", "approved": true }, "abstract": "Particulate air pollution (PM2.5) is the 4th leading cause of morbidity and mortality. Attention from leading health organizations has recently turned to interventions to reduce exposure and prevent adverse health outcomes. As evidence has begun to mount for the efficacy of these machines, and will likely grow further in the coming years, it has, however, become apparent that for most people, including low-income populations in the US, cannot afford effective commercially available units. Low-cost commercial air purifiers are of low efficacy and often introduce new pollutants into the air. To our knowledge, there are no published intervention studies of Corsi-Rosenthal Boxes (C-R Boxes), the devices we propose to use in this study. We have a study team that is ideally suited for the proposed research. Ms. Creed has extensive experience building and deploying the C-R Boxes which became popular during the Covid pandemic. Dr. Brugge has three published RCTs of high-quality commercial air purifiers and another, full trial, nearing completion. Thus, he has knowledge and experience which qualifies him to lead this proposed study. Drs. Levy Zamora has extensive air monitoring expertise, will direct measurement of indoor and outdoor air pollution concentrations at each home. Dr. Eliasziw is a biostatistician with extensive experience analyzing randomized trials. We have three aims: 1)Conduct focus groups/interviews and BP measurements with participants who meet study inclusion criteria to refine our protocol; 2) Conduct a randomized crossover pilot trial with 65 participants to calculate preliminary effect size estimates to inform a larger crossover efficacy trial; and 3) Determine the feasibility of conducting a larger crossover efficacy multisite trial in the US. We will conduct our randomized cross over trial in three settings with low, medium, and high air pollution. Our low and medium air pollution locations will be in Hartford CT and our high pollution setting will be in Boston Chinatown, where we can reliably expect high pollution levels. Participants (N=65) will have dried blood spots collected and blood pressure measured at the start and end of each 4-week intervention session. Our randomized cross over design controls for time invariant confounding. Interviews and standardized questionnaires with study participants will provide feedback that will inform the decision as to whether to proceed with a full trial. We seek to meet targets for 80% recruitment and retention as well as 80% satisfaction as benchmarks for moving to a full trial. The findings for health end points will provide preliminary data to justify the potential future R01 proposal for a fully powered clinical trial. An expert elicitation process conducted with the research team in the final year will make the final decision about a future, full trial. The significance of this work is that showing efficacy of C-R Boxes for reducing exposure would lead to their widespread use and contribute to improving public health", "keywords": [ "Africa", "Air", "Air Movements", "Air Pollutants", "Air Pollution", "Allergens", "American Heart Association", "Asia", "Attention", "Benchmarking", "Biological Markers", "Blood", "Blood Glucose", "Blood Pressure", "Boston", "COVID-19 pandemic", "Cardiopulmonary", "Cardiovascular Diseases", "Cardiovascular system", "Centers for Disease Control and Prevention (U.S.)", "Cessation of life", "Childhood Asthma", "Clinical Trials", "Consensus", "Country", "Cross-Over Trials", "Crossover Design", "Data", "Developed Countries", "Devices", "Diet", "Dryness", "Educational workshop", "Exposure to", "Fasting", "Feedback", "Filtration", "Focus Groups", "Future", "Goals", "Health", "Health Benefit", "Home", "Hour", "Household", "Income", "Indoor Air Pollution", "Inflammation", "Interleukin-6", "Intervention", "Intervention Studies", "Interview", "Knowledge", "Lead", "Link", "Location", "Low Income Population", "Measurement", "Measures", "Meta-Analysis", "Morbidity - disease rate", "Outcome", "Participant", "Particulate", "Particulate Matter", "Persons", "Pollution", "Power Sources", "Predisposition", "Process", "Protocols documentation", "Public Health", "Publishing", "Qualifying", "Questionnaires", "Randomized", "Research", "Risk", "Sampling", "Spottings", "Standardization", "Time", "Tobacco", "Translating", "United States Environmental Protection Agency", "United States National Institutes of Health", "Vulnerable Populations", "Whole Blood", "Work", "acceptability and feasibility", "air filter", "air monitoring", "ambient air pollution", "cost", "efficacy trial", "epidemiology study", "experience", "feasibility testing", "feasibility trial", "fine particles", "health assessment", "health organization", "health related quality of life", "high risk population", "improved", "inclusion criteria", "indoor concentrations", "inflammatory marker", "innovation", "meter", "mortality", "multi-site trial", "noise perception", "particle", "peripheral blood", "pilot trial", "pollutant", "portability", "prevent", "randomized trial", "randomized clinical trials", "recruit", "respiratory", "satisfaction", "systematic review", "systemic inflammatory response" ], "approved": true } }, { "type": "Grant", "id": "15729", "attributes": { "award_id": "2537244", "title": "Collaborative Research: Belmont Forum Collaborative Research: BIOrepositories build Adaptive and Resilient Capacity (BioARC)", "funder": { "id": 3, "ror": "https://ror.org/021nxhr62", "name": "National Science Foundation", "approved": true }, "funder_divisions": [ "Unknown", "Intl Global Change Res & Coord" ], "program_reference_codes": [], "program_officials": [ { "id": 7800, "first_name": "Maria", "last_name": "Uhle", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-15", "end_date": null, "award_amount": 762760, "principal_investigator": { "id": 32782, "first_name": "Kelly", "last_name": "Speer", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32779, "first_name": "Elizabeth", "last_name": "Roberts", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 32780, "first_name": "Cody W", "last_name": "Thompson", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 32781, "first_name": "Derek Van", "last_name": "Berkel", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 301, "ror": "https://ror.org/0272j5188", "name": "Northern Arizona University", "address": "", "city": "", "state": "AZ", "zip": "", "country": "United States", "approved": true }, "abstract": "This award provides support to U.S. researchers participating in a project competitively selected by a 55-country initiative on global change research through the Belmont Forum. The Belmont Forum is a consortium of research funding organizations focused on support for transdisciplinary approaches to global environmental change challenges and opportunities. It aims to accelerate delivery of the international research most urgently needed to remove critical barriers to sustainability by aligning and mobilizing international resources. Each partner country provides funding for their researchers within a consortium to alleviate the need for funds to cross international borders. This approach facilitates effective leveraging of national resources to support excellent research on topics of global relevance best tackled through a multinational approach, recognizing that global challenges need global solutions. Working together in this Collaborative Research Action, the partner agencies have provided support to foster global transdisciplinary research teams of natural, health and social scientists and stakeholders from across the globe to improve understanding of climate, environment and health pathways to protect and promote health. The projects will provide crucial new understanding into the health implications arising from the impacts of climate change and variability on; 1) decision-science approaches to adaptation and implementation, 2) food, environment, and biological security and 3) risks to ecosystems and populations. This award provides support for the U.S. researchers to cooperate in consortia that consist of partners from at least three of the participating countries to increase our knowledge of the complex linkages and pathways between the climate, environment and health to help solve complex challenges that face societies. The BioARC project seeks to develop an interdisciplinary network of scientists, health professionals, and stakeholders to build the missing physical, human, and material infrastructure to stop pandemics at their source. These various forms of infrastructure will be centered on the development of multiple in-country biorepositories spread throughout The Americas, where pathogens with pandemic potential (e.g., Zika, Andes Virus) and neglected tropical diseases (e.g., Dengue, Chagas, and hookworm infection) have previously emerged and spread. This new infrastructure will provide the critical spatial, temporal, and taxonomic sampling and associated informatics necessary to understand the role of environmental drivers in host-pathogen dynamics, enabling a more proactive and predictive approach to pathogen emergence. This project directly addresses a critical challenge to pandemic preparedness. COVID-19 directly illustrated the high costs of pandemics to human wellbeing and the persistent gaps in our approach to preventing pathogen emergence. As humans and wildlife increasingly share space, opportunities for spillovers grow. Additionally, environmental stresses can cause wildlife to shed pathogens more readily as stress induced by things like habitat loss, heat exposure, or food scarcity decreases immune functionality that would typically keep pathogen shedding low. The project will focus on improving biorepository infrastructure including equipment and databases. The project team will develop training modules on museum science, fieldwork, molecular genetics, informatics, geospatial data analysis, science communication, and interdisciplinary network development. The project will develop best practices for biorepositories and relational databases for pathogens, interdisciplinary workflows for wildlife pathogen surveillance, communication across One Health disciplines, and strategies for biorepository decision-maker coordination. The goal of developing best practices is to enable the standardization of procedures for similar efforts locally and globally, and to form the foundation for an early-warning system for zoonotic diseases that will improve U.S. national security and build the U.S. workforce. The project will reduce costs of outbreak response by creating the capacity and data to establish baselines for wildlife pathogen dynamics, detecting deviations from these baselines, informing models, and enabling timely biosecurity decisions. The project will develop a robust, enduring system to safeguard human and animal populations from infectious diseases. 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": "15796", "attributes": { "award_id": "1R44NS145848-01", "title": "Development of Tissue Engineered Tregs as a Treatment for Acute Ischemic Stroke", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Neurological Disorders and Stroke (NINDS)" ], "program_reference_codes": [], "program_officials": [ { "id": 32884, "first_name": "FLOY ANNETTE", "last_name": "GILCHRIST", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-15", "end_date": "2027-07-31", "award_amount": 1150417, "principal_investigator": { "id": 32885, "first_name": "Payam", "last_name": "Zarin", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2656, "ror": "", "name": "GENTIBIO, INC.", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "In the U.S., nearly 800,000 individuals experience a stroke each year, predominantly ischemic strokes. The economic burden of stroke is staggering, with projected stroke-related medical costs in the U.S. expected to surpass $94 billion by 2035. This underscores the urgent need for effective therapies to address this significant public health challenge. While the potential of regulatory T cells (Tregs) in promoting stroke recovery has been recognized, translating this promise into clinical success has been hampered by several obstacles. Traditional Treg therapies face challenges in manufacturing, phenotypic instability, and a lack of tissue specificity. This proposal focuses on the development of allogeneic engineered tissue Tregs (EngTregs) as a novel off-the-shelf therapeutic approach for stroke. Overexpression of ST2, the receptor for the alarmin IL-33, enhances the ability of EngTregs to: (i) sense and respond to tissue damage (ST2-expressing EngTregs efficiently migrate to sites of inflammation and injury); (ii) suppress excessive inflammation (EngTregs exert potent anti-inflammatory effects through multiple mechanisms, including direct suppression of immune cells and modulation of the inflammatory environment); and (iii) actively participate in tissue repair (EngTregs produce growth factors and interact with other cells to promote tissue regeneration). Overexpression of FOXP3 ensures a stable and suppressive Treg phenotype, crucial for long-term therapeutic efficacy. A chemically induced signaling complex (CISC) enables tunable IL-2 signaling, promoting Treg survival and function while facilitating scalable manufacturing. These innovations culminate in a first-in-class allogeneic tissue EngTreg product with advantages in manufacturing scalability, cost-effectiveness, and therapeutic potential compared to conventional Treg therapies. Preliminary studies demonstrate the ability of allogeneic EngTregs to accumulate in the injured brain and improve motor skills, sensory function, learning, and memory following ischemic injury induced in the transient middle cerebral artery occlusion (tMCAO) mouse model of stroke. This proposal outlines three aims to further advance the preclinical development of EngTregs for stroke: Aim 1: Evaluate the therapeutic efficacy of EngTregs in two preclinical stroke models (permanent middle cerebral artery occlusion and photothrombosis) in both adult and aged mice, assessing a comprehensive range of functional and histological outcomes. Aim 2: Characterize the mechanism of action and define a comprehensive in vitro profile of the human EngTreg drug product, including assessment of cytokine sequestration, T cell suppression, macrophage polarization, and transcriptomic analysis. Aim 3: Assess the immunotoxicity and immunogenicity of human EngTregs to ensure clinical safety, including evaluation of cytokine release syndrome and allo-immunogenicity. Successful completion of these aims will provide critical preclinical data supporting the clinical translation of EngTregs as a novel and promising therapeutic strategy for stroke, addressing a significant unmet medical need.", "keywords": [ "AREG gene", "Acute", "Address", "Adhesives", "Adult", "Age", "Allogenic", "Antiinflammatory Effect", "Area", "Autologous", "Biological Assay", "Blood flow", "Brain Injuries", "C57BL/6 Mouse", "CCR5 gene", "CCR8 gene", "Cell Physiology", "Cell Survival", "Cell Therapy", "Cells", "Cessation of life", "Characteristics", "Chemicals", "Clinical", "Clinical Data", "Cognitive", "Complex", "Development", "Economic Burden", "Engraftment", "Ensure", "Evaluation", "FOXP3 gene", "Face", "Female", "Flow Cytometry", "Growth Factor", "Guidelines", "Health Care Systems", "High Prevalence", "Histologic", "Homing", "Human Engineering", "IL2RA gene", "Immune Cell Suppression", "In Vitro", "Individual", "Infarction", "Inflammation", "Inflammatory", "Injury", "Interleukin-13", "Interleukin-2", "Ischemic Stroke", "Learning", "Macrophage", "Mediating", "Medical", "Medical Care Costs", "Memory", "Middle Cerebral Artery Occlusion", "Mixed Lymphocyte Culture Test", "Modeling", "Motor Skills", "Mus", "Outcome", "Outcome Measure", "Patient-Focused Outcomes", "Patients", "Performance", "Persons", "Pharmaceutical Preparations", "Phase", "Phenotype", "Preclinical data", "Process", "Public Health", "Receptors Tumor Necrosis Factor Type II", "Recovery of Function", "Regulatory T-Lymphocyte", "Reperfusion Therapy", "Research", "Risk", "Safety", "Sensory", "Signal Induction", "Signal Transduction", "Sirolimus", "Site", "Specificity", "Stroke", "T cell therapy", "T-Lymphocyte", "TNFRSF1B gene", "Testing", "Therapeutic", "Tissue Engineering", "Tissues", "Toxic effect", "Translating", "Treatment Efficacy", "Upregulation", "Work", "aged", "angiogenesis", "axon injury", "blood-brain barrier permeabilization", "brain repair", "clinical translation", "cost", "cost effectiveness", "cytokine", "cytokine release syndrome", "disability", "disease heterogeneity", "effective therapy", "experience", "foot", "human tissue", "immunogenicity", "immunotoxicity", "improved", "inflammatory milieu", "inflammatory modulation", "innovation", "ischemic injury", "male", "manufacture", "manufacturing process", "migration", "morris water maze", "mortality", "mouse model", "neurogenesis", "novel", "object recognition", "old mice", "osteopontin", "overexpression", "patient subsets", "post stroke", "pre-clinical", "preclinical development", "preclinical evaluation", "programs", "public health relevance", "receptor", "repaired", "stroke model", "stroke recovery", "stro" ], "approved": true } }, { "type": "Grant", "id": "15738", "attributes": { "award_id": "1R21AI183025-01A1", "title": "Endoplasmic Reticulum (ER)-phagy in Influenza Infection", "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": "2025-08-12", "end_date": "2027-07-31", "award_amount": 433423, "principal_investigator": { "id": 2476, "first_name": "Vikas", "last_name": "Anathy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2609, "ror": "", "name": "UNIVERSITY OF VERMONT & ST AGRIC COLLEGE", "address": "", "city": "", "state": "VT", "zip": "", "country": "United States", "approved": true }, "abstract": "Influenza infection in susceptible patients results in a higher viral load, cytokine storm, tissue damage, lung function decline, and mortality. It is well known that interferons control influenza burden and inflammatory responses. However, mechanistic understandings of IFN-mediated regulation of influenza burden in the lung epithelial cells is unclear. We have identified a novel association between Endoplasmic Reticulum (ER)-specific-autophagy response, termed ER- phagy, as regulators of the influenza burden in lung epithelial cells. Characterizing the epithelial ER-Phagy-IFN axis in influenza infection will be the focus of the current application. Unraveling this axis in lung epithelial cells provides much-needed mechanistic insights into controlling viral burden and mitigating virus-induced lung injury. Our preliminary data suggest that levels of ER- phagy receptors in lung epithelial cells regulate viral burden in an IFNβ dependent manner. Based on these novel data, we hypothesize that lung epithelial cells upregulate IFNβ- and IRE1- dependent ER-phagy to diminish viral burden. We will test this hypothesis in the following specific aims: In specific aim 1, we will determine that specific ER-phagy receptors are required to decrease influenza burden in epithelial cells and subsequent lung injury. Aim 2 will use epithelial-specific knockouts of IFNAR1 receptor and recombinant interferons to determine that the type-I IFNs regulate ER-phagy activity post-IAV infection to control IAV burden and lung injury. These studies will determine that the ER-Phagy-IFN axis acts as a first line of defense in the primary site of influenza infection (epithelial cells) to decrease the IAV burden and subsequent lung injury.", "keywords": [ "Ablation", "Affect", "Architecture", "Autophagocytosis", "Autophagosome", "Cell Physiology", "Cells", "Data", "Endoplasmic Reticulum", "Epithelial Cells", "Epithelium", "Functional disorder", "Future", "Human", "Infection", "Inflammatory Response", "Influenza", "Influenza A virus", "Injury", "Interferon-α", "Interferons", "Knock-out", "Link", "Literature", "Lung", "Lysosomes", "Measures", "Mediating", "Monitor", "Mus", "Organelles", "Pathway interactions", "Patients", "Phagosomes", "Predisposition", "Process", "Proteome", "Recombinant Interferon", "Regulation", "Respiratory Failure", "Role", "Site", "Stimulus", "Stress", "Testing", "Tissues", "Upregulation", "Viral", "Viral Load result", "Viral Proteins", "Virus", "Virus Diseases", "airway epithelium", "cell type", "cytokine release syndrome", "epithelial injury", "flu", "influenza infection", "insight", "interferon alpha receptor", "lung injury", "mortality", "novel", "patient population", "pulmonary function decline", "receptor", "response", "smooth endoplasmic reticulum membrane" ], "approved": true } }, { "type": "Grant", "id": "15788", "attributes": { "award_id": "1R16GM159146-01", "title": "Building Reliable Vision-Language Assistant for Dermatology AI through Modeling Uncertainties in Multimodal LLMs", "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": 32871, "first_name": "WUHONG", "last_name": "PEI", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-12", "end_date": "2029-06-30", "award_amount": 175470, "principal_investigator": { "id": 32872, "first_name": "Zhiqiang", "last_name": "Tao", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2651, "ror": "", "name": "ROCHESTER INSTITUTE OF TECHNOLOGY", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Diagnosis delay is one of the key factors that lead to skin cancer death, especially for melanoma diagnosis during the COVID-19 pandemic. The long examination time and limited dermatological access have been the major roadblocks to the preventive treatment of skin cancers to lower the high mortality rate. Developing a clinical AI agent that can analyze digital skin images and provide timely, interactive text responses to patient symptoms and inquiries will significantly mitigate the nationwide dermatologist shortage, thereby improving the early diagnosis chance and teledermatology accessibility for melanoma as well as other skin diseases. Conventional dermatology AI methods mainly focus on medical image recognition to identify skin lesions and malignancies, falling short in visual-language assistance for remote healthcare services. A conversational diagnostic AI model, which is able to answer medical questions by sensing subtle visual patterns of skin disorders/cancers, is still in urgent need. The long-term goal of this research program is to develop a reliable large visual-language (VL) model that enables conversational Dermatology AI to facilitate early melanoma diagnosis and general skin care. The proposed research will generate accurate and interpretable clinical responses by finetuning Large Language Models – LLMs (e.g., the generative AI models deployed in ChatGPT) through answering questions and visual reasoning in multimodal contexts. Specifically, the project will realize three aims: 1) Build a new multimodal LLM specifically for dermatology to discern melanoma and other skin diseases and to automatically answer questions relevant to skin lesions. 2) Study uncertainties stemming from data bias and distribution shifts to enhance the reliability of LLM-powered AI diagnosis in multimodal contexts and teledermatology environments. 3) Determine the visual relevance in LLM decisions based on the rich public dermatological images with clinical text annotations. The proposed research will establish a new multimodal LLM that interweaves visual reasoning and uncertainties to advance Dermatology AI in broad VL assistance tasks, enabling automatic conversational diagnostic in teled- ermatology and providing new insights about how LLM understands skin lesions and dermatological knowledge. A pixelwise visual instruction tuning approach and a novel multi-level uncertainty quantification framework will be developed, providing technical foundations to benefit a wide range of LLM-based healthcare research. This project will be the first large visual-language research study that investigates LLM's intelligence and reliability in coping with multimodal dermatology contexts – visual skin lesions and text clinical annotations/dialogues. The success of this project will provide transformative AI techniques in assisting early melanoma diagnosis and remote skin care, leading to better teledermatology accessibility for patient treatments, reducing mortality from skin cancers through timely detection, and revolutionizing dermatological access in public healthcare systems.", "keywords": [ "Accounting", "Artificial Intelligence enhanced", "Behavior", "Benchmarking", "Benign", "COVID-19 pandemic", "Cellular Phone", "Cessation of life", "ChatGPT", "Clinical", "Cutaneous Melanoma", "Data", "Death Rate", "Dependence", "Dermatologic", "Dermatologist", "Dermatology", "Dermoscopy", "Detection", "Development", "Diagnosis", "Diagnostic", "Disease", "Early Diagnosis", "Environment", "Evaluation", "Foundations", "Generations", "Goals", "Grain", "Hallucinations", "Health Care", "Health Care Research", "Health Care Systems", "Image", "Instruction", "Intelligence", "Knowledge", "Language", "Learning", "Lesion", "Life", "Machine Learning", "Malignant Neoplasms", "Medical", "Medical Imaging", "Melanoma", "Methods", "Modeling", "Morphologic artifacts", "Noise", "Patients", "Pattern", "Preventive treatment", "Prognosis", "Protocols documentation", "Public Health", "Research", "Resolution", "Risk", "Series", "Skin", "Skin Cancer", "Skin Care", "Skin Imaging", "Skin Malignancy", "Symptoms", "Techniques", "Text", "Time", "Training", "Translations", "Uncertainty", "Underserved Population", "United States", "Vision", "Visual", "artificial intelligence model", "chatbot", "clinical imaging", "coping", "data acquisition", "design", "digital", "diverse data", "generative artificial intelligence", "health care service", "improved", "insight", "large language model", "lens", "mortality", "multimodality", "neglect", "novel", "programs", "remote health care", "research study", "response", "skin disorder", "skin lesion", "stem", "success", "teledermatology", "trustworthiness" ], "approved": true } }, { "type": "Grant", "id": "15754", "attributes": { "award_id": "1U01AI186939-01", "title": "Mitigation of multi-organ delayed effects of acute radiation exposure (DEARE) with ACE2 agonist diminazene aceturate.", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "NIH Office of the Director" ], "program_reference_codes": [], "program_officials": [ { "id": 32816, "first_name": "CARMEN I", "last_name": "RIOS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-11", "end_date": "2030-07-31", "award_amount": 546000, "principal_investigator": { "id": 32817, "first_name": "Heather A", "last_name": "Himburg", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2624, "ror": "", "name": "MEDICAL COLLEGE OF WISCONSIN", "address": "", "city": "", "state": "WI", "zip": "", "country": "United States", "approved": true }, "abstract": "With the advent of hematopoietic growth factors for mitigation of acute radiation syndrome (ARS), victims of nuclear or radiological events will be more likely to survive ARS but also at greater risk for the development of a range of late multi-organ toxicities collectively referred to as the delayed effects of acute radiation exposure (DEARE). To date, there are no FDA-approved medical countermeasures (MCMs) for the treatment of DEARE. This application to RFA-AI-23-059 (Development of Candidate Radiation/Nuclear MCMs) proposes to address this unmet need and will focus on the unmet need for MCMs against two life-threatening subsyndromes of DEARE: radiation pneumonitis and nephropathy. Here, we propose to screen three candidate MCMs which target the non-canonical, alternative renin angiotensin system (RAS). As a counterbalance to the canonical RAS, the alternative RAS has broad tissue-protective function by promoting vasodilation, reducing inflammation, and reducing fibrosis. For these reasons, several recent and ongoing clinical trials are evaluating alternative RAS activators for the treatment of severe COVID-19. Data from our lab and others also supports the potential for alternative RAS activation in the treatment of radiation toxicities. Our laboratory has shown diminazene aceturate (DIZE) a small molecule agonist of the alternative RAS pathway promotes survival in rat models of ARS and DEARE. Important to this application, DIZE treatment also mitigated injury to the lung and kidney as evidenced by improved survival during the sub-syndromes of lung and kidney DEARE. Based on these data, we hypothesize the alternative RAS pathway can be targeted pharmacologically to mitigate radiation-induced multi-organ DEARE. Here, we propose a stepwise approach to targeting three key players in the alternative RAS pathway: angiotensin converting enzyme 2 (ACE2), Ang(1-7), and the Mas receptor (MasR). Each Aim of this application will target one of these players using the following lead candidate therapies: DIZE (ACE2 activator), TXA127 (synthetic Ang(1-7)), and BIO101 (MasR activator). We will evaluate the efficacy of the candidate MCMs in an established rat DEARE model which recapitulates the anticipated human sequelae of acute and delayed toxicities. For each candidate MCM, the primary outcome measure will be mitigation of all-cause mortality, which is the clinically relevant endpoint for FDA approval under the Animal Rule.", "keywords": [ "ACE2", "Acceleration", "Acute", "Acute Respiratory Distress Syndrome", "Address", "Adult", "Agonist", "Anti-Inflammatory Agents", "Antiinflammatory Effect", "Antioxidants", "Binding", "Body System", "Bone Marrow", "COVID-19", "Clinical Research", "Clinical Trials", "Data", "Development", "Dose", "Exposure to", "FDA approved", "Fibrosis", "G-Protein-Coupled Receptors", "Generations", "Goals", "Hematopoietic", "Hematopoietic Cell Growth Factors", "Homeostasis", "Human", "Hypoxia", "In Vitro", "Inflammation", "Injury", "Investigation", "Ischemic Stroke", "Kidney", "Kidney Diseases", "Laboratories", "Life", "Lung", "Modeling", "Nuclear", "Nuclear Accidents", "Oral Administration", "Organ", "Outcome Measure", "Pathway interactions", "Peptide Signal Sequences", "Phase I/II Clinical Trial", "Play", "Population", "Radiation", "Radiation Accidents", "Radiation Injuries", "Radiation Pneumonitis", "Radiation Toxicity", "Radiation exposure", "Rattus", "Recovery", "Renin-Angiotensin System", "Reproducibility", "Respiratory Failure", "Risk", "Rodent Model", "Signal Transduction", "Testing", "Therapeutic Uses", "Time", "Tissues", "Toxic effect", "Vasodilation", "Vasodilator Agents", "Work", "animal rule", "clinical investigation", "clinically relevant", "efficacy evaluation", "experience", "improved", "in vivo Model", "irradiation", "lead candidate", "mass casualty", "medical countermeasure", "mortality", "multiorgan injury", "nuclear countermeasure", "pharmacologic", "pre-clinical", "preclinical study", "primary outcome", "programs", "protective effect", "radiation mitigation", "radiation mitigator", "receptor", "response", "severe COVID-19", "small molecule", "stroke patient", "subcutaneous", "therapeutic target" ], "approved": true } } ], "meta": { "pagination": { "page": 3, "pages": 1405, "count": 14046 } } }