Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1392&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": null, "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1391&sort=-program_officials" }, "data": [ { "type": "Grant", "id": "12073", "attributes": { "award_id": "1I21HX003503-01A1", "title": "Understanding and Improving Video-Based Primary Care Delivery to Veterans", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2023-09-01", "end_date": "2025-02-28", "award_amount": null, "principal_investigator": { "id": 27925, "first_name": "Claudia", "last_name": "Der-Martirosian", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1708, "ror": "https://ror.org/05xcarb80", "name": "VA Greater Los Angeles Healthcare System", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Background: [With the onset of the COVID-19 pandemic, VA primary care (PC) experienced a substantial increase in video-based encounters, nationwide. This rapid uptake of video-based care in PC clinics, however, varied by site. Given that the VA is committed to continue expanding VA Video Connect (VVC), which is the main videoconferencing platform at the VA, more research is needed to comprehensively examine why and how VVC was successfully adopted at some sites and understand why VVC expansion was limited at other sites.] Significance/Impact: [Barriers and facilitators to video-based care are many and multifaceted. This study will examine patient, provider, and site-level characteristics of VVC use in PC at high and low VVC sites, and identify patient-centered, provider-recommended, and leadership supported VVC guidelines that are context-specific for PC clinics. This study will contribute more generally to our understanding of what is needed to achieve acceptance of video technology. Such knowledge will be helpful for VA, as well as the delivery of healthcare in general. In-depth understanding about challenges and successes of VVC use will inform future improvements of VVC policies, processes, and procedures for all Veterans, across all VA facilities.] Innovation: This study will examine Veterans’ perspectives about how VVC in PC can be improved to better meet their needs when using video-based care. This is an understudied topic. Furthermore, by learning about the providers’ and leadership’s perspectives on how VVC can be implemented more effectively, we will better understand the full context of VA video care. [This 18-month pilot study will create context-specific VVC playbook for high and low VVC using sites that will be patient-centered, provider-recommended, and leadership supported. This will help improve delivery of video-based primary care and patient outcomes at the VA.] Specific Aims: This pilot study’s overall objective is to identify strategies to improve VVC use for all Veterans. 1) Identify PC clinic sites in the top 5% and bottom 5% of VVC use nationally by examining patient, provider, and site-level variations in VVC use since the onset of COVID-19 (March 2020-March 2024, aka study period). 2) Characterize patient-, provider-, site-specific factors associated with VVC use in PC, nationwide, during the study period. 3) Evaluate barriers and facilitators to using VVC in PC from patients, providers, and leadership (VISN/VAMC/CBOC) perspectives at 3 high and 3 low VVC using sites in PC (identified in Aims 1 & 2). Methodology: [The non-adoption, abandonment, scale-up, spread, and sustainability (NASSS) framework will be used for all aspects of the proposed study (data collection, analyses, synthesis of quantitative and qualitative findings). Two sequential, mixed methods approaches will be used, where quantitative analyses (Aims 1 & 2) will first inform the sampling and data collection for the qualitative interviews (Aim 3, n=60) at 3 high and 3 low VVC sites with patients, providers, and leadership. Using the explanatory mixed methods, the qualitative data will then help explain quantitative findings. In addition to in-depth interviews, the qualitative research will include document reviews on video-based care and VVC use for all 6 study sites After completing all analyses, quantitative and qualitative study findings will be mapped into the NASSS framework, which will help inform the development of patient-centered, provider-recommended, leadership-supported, and context-specific VVC playbook for PC clinics. The playbook will include strategies on how to improve VVC for high and low VVC sites. In close collaboration with all study operation partners (OCC, OPC, VEO), study Co-Investigators, and Veteran Engagement Groups (VEG), the playbook will be assessed for feasibility and usability.] Next Steps/Implementation: [To assess the effectiveness of the VVC playbook, future studies can pilot test the playbook at PC clinics at multiple VA sites. Pilot testing the playbook will provide the opportunity to receive feedback from different sites on how best to make the playbook suitable for all sites at the VA, nationally.]", "keywords": [ "Adopted", "Ambulatory Care", "COVID-19", "COVID-19 pandemic", "Caregivers", "Caring", "Characteristics", "Clinical", "Collaborations", "Data", "Data Collection", "Development", "Effectiveness", "Equipment", "Familiarity", "Feedback", "Future", "Guidelines", "Health", "Health Personnel", "Health Services Accessibility", "Home", "Individual", "Interruption", "Intervention", "Interview", "Knowledge", "Leadership", "Learning", "Literature", "Logistics", "Maps", "Methodology", "Methods", "Modality", "Patient-Focused Outcomes", "Patients", "Persons", "Pilot Projects", "Policies", "Primary Care", "Procedures", "Process", "Provider", "Qualitative Research", "Recommendation", "Regression Analysis", "Research", "Research Personnel", "Schedule", "Site", "Structure", "Technology", "Telephone", "Time", "Time Series Analysis", "Training and Education", "Update", "Variant", "Veterans", "Videoconferencing", "Visit", "Work", "care delivery", "care outcomes", "effectiveness evaluation", "experience", "health care delivery", "improved", "innovation", "operation", "pandemic disease", "patient oriented", "pilot test", "preference", "primary care clinic", "primary care patient", "sample collection", "scale up", "success", "sustainability framework", "telehealth", "uptake", "usability", "video delivery", "virtual", "willingness" ], "approved": true } }, { "type": "Grant", "id": "12090", "attributes": { "award_id": "1I01HX003635-01A1", "title": "Leveraging COVID-19 to modernize depression care for VA primary care populations", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2023-09-01", "end_date": "2025-08-31", "award_amount": null, "principal_investigator": { "id": 27447, "first_name": "Lucinda B", "last_name": "Leung", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1708, "ror": "https://ror.org/05xcarb80", "name": "VA Greater Los Angeles Healthcare System", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Background: As part of comprehensive suicide prevention, VA integrated mental and physical health services to better detect and treat depression. Primary care nurses conduct screening annually. Clinicians, including Primary Care Mental Health Integration (PC-MHI) specialists, follow up as-needed for treatment. Depression detection and management processes are complex, involve multilevel stakeholders, and subject to significant disruption from COVID-19 and from resulting expansion of telehealth aiming to preserve care access. Fewer VA visits during the pandemic may signify lowered depression care quality and worsened patient outcomes. Significance: Depression affects 1 in 5 Veterans and is a leading cause of suicidality and disability. It contributes substantially to the current pandemic-related mental health crisis. Depression symptoms, including suicidal thoughts/behaviors, and related functional impairment have increased since COVID onset. Partnering with Primary Care, Mental Health, and Connected Care leaders, we propose to study pandemic-related service disruptions for depression, which may help to mitigate acute care use and mortality in the Veteran population. We apply established depression quality indicators from our prior research to a broad national scale at a critical time. We will also obtain feedback to improve current hybrid (virtual/in-person) care models from VA providers and Veterans who screened positive, including those who were not detected to have depression. Specific Aims: To improve virtual and in-person services for the VA primary care population during recovery, this proposal will examine how the pandemic disrupted depression care delivery mechanisms, including expanded telehealth, and patient outcomes. Our Specific Aims are: 1) To examine engagement in guideline- concordant care for depression (virtual or in-person) following screening, before and during the pandemic; 2) To compare psychiatric emergency/hospital visits and mortality from suicide between Veterans who screened positive and were detected versus not detected to have depression by clinicians; 3) To understand VA patients’ and providers’ current perspectives on addressing new depressive episodes using virtual and in-person modalities during the pandemic and eventual recovery. Methodology: Given hypothesized care disruption (lowered care quality) during COVID-19, Aim 1 proposes to extend our preliminary VISN methods nationally to assess the VA population’s trajectory from a new positive depression (and suicide-risk) screen to appropriate treatment (i.e., medication, therapy) in FY19-22/23. We will also examine the changing mix of virtual and in-person depression care delivered. Aim 2 will use interrupted time series analyses to explore the extent to which acute care use may be mitigated by clinician detection of depression nationally. We will also compare mortality rates between patients detected and not detected to have depression. Sub-analyses will reveal where (e.g., clinics with low PC-MHI access) and for whom (e.g., minorities) detection does not systematically occur, and downstream negative sequelae, to guide future intervention. Finally, Aim 3 will interview (1) 40 Veterans who were detected and not detected to have depression per Aims 1 & 2 about care-seeking behavior change, digital divide, etc. and (2) 40 VA primary care and PC-MHI providers about staffing shortage, telehealth adoption, etc. across three VAs (GLA, Syracuse, and Durham). In addition to contextualizing disrupted care findings, qualitative data will help isolate best practices on patient-to-provider and provider-to-provider (e.g., handoffs) interactions in hybrid depression care models. Next Steps/Implementation: The COVID-19 pandemic provides the VA with an opportunity to improve upon a system-wide proactive response to depression and suicide, one that is conceptualized to care for the entire Veteran population. This proposed research will provide the basis for testable hypotheses (e.g., acceptable virtual depression treatments in primary care), and clinical recommendations (e.g., satisfactory virtual provider- to-provider handoffs for new patient referrals), to improve virtual and in-person VA depression services.", "keywords": [ "Address", "Adoption", "Affect", "Behavior", "COVID-19", "COVID-19 pandemic", "Caring", "Clinic", "Clinical", "Complex", "Consultations", "Data", "Detection", "Drops", "Feedback", "Feeling suicidal", "Future", "Guidelines", "Health", "Health Services Accessibility", "Hospitalization", "Hospitals", "Hybrids", "Interruption", "Intervention", "Interview", "Los Angeles", "Mental Depression", "Mental Health", "Mental Health Services", "Methodology", "Methods", "Minority", "Modality", "Modeling", "Modernization", "Morbidity - disease rate", "Outcome", "Patient-Focused Outcomes", "Patients", "Persons", "Pharmaceutical Preparations", "Population", "Primary Care", "Primary Nursing Care", "Process", "Provider", "Quality Indicator", "Quality of Care", "Recommendation", "Recovery", "Research", "Services", "Solid", "Specialist", "Suicide", "Suicide prevention", "System", "Testing", "Time", "Time Series Analysis", "Veterans", "Visit", "Work", "acute care", "adverse outcome", "behavior change", "care delivery", "care seeking", "collaborative care", "connected care", "coronavirus disease", "cost", "current pandemic", "depression prevention", "depressive symptoms", "digital", "disability", "effective therapy", "experience", "follow-up", "functional disability", "improved", "innovation", "military veteran", "mortality", "multidisciplinary", "pandemic disease", "physical conditioning", "physical health service", "population based", "population health", "preservation", "provider to provider", "psychiatric emergency", "response", "routine screening", "screening", "suicidal", "suicidal behavior", "suicidal risk", "suicide mortality", "telehealth", "tool", "virtual", "virtual healthcare" ], "approved": true } }, { "type": "Grant", "id": "12137", "attributes": { "award_id": "1U19AG076581-01A1", "title": "GXI Interactions", "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": [], "start_date": "2023-08-15", "end_date": "2028-07-31", "award_amount": 609537, "principal_investigator": { "id": 27997, "first_name": "John", "last_name": "Blangero", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 748, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH SCIENCE CENTER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "By 2050, more than 2 billion people worldwide will be over the age of 65, with older adults outnumbering children for the first time in recorded history. This predicted major demographic shift highlights the importance of improving our understanding of factors that contribute to healthy brain aging. Currently, the biological bases of brain aging are poorly understood. Brain aging (often focused on cognitive decline) is characterized by numerous phenotypes that undoubtedly involve multiple environmental and genetic factors. Overtly pathological brain aging is seen in major neurological diseases such as Alzheimer’s disease and related dementias (ADRD); the prevalence of ADRD is expected to double every 20 years. On top of this existing public health crisis, we are now experiencing a global pandemic that appears to negatively influence neurological function. Growing evidence indicates that SARS-CoV-2 infection causes neurological complications of short-term consequence including acute neuropathy, encephalopathy, anosmia, and hypoxic/ischemic brain injury, and longer-term consequences including cognitive impairment and neuropsychiatric disturbances. The interindividual variation in the neurobiological responses to SARS-CoV-2 is marked. As with most complex phenotypes, causal determinants likely include both genetic and environmental factors. However, no genetic epidemiological study has yet considered differential neurophenotypic response to infection. Thus, delineating the genetic architecture of ADRD-relevant neurophenotypic responses to SARS-CoV-2 will offer important biological insights, which in turn could provide strategies for fostering healthy brain aging in the presence of future infectious challenges. Our project will assess the genetic basis of ADRD-relevant endophenotypic response (across a two year period with three examinations) to SARS-CoV-2 infection in a set of older (>60 years of age) adults from diverse populations (Amerindians from Argentina [ n=3000], US Native Americans [n=250], Mexican Americans [n=500], Puerto Ricans [n=125], African Americans [n=125], and Africans [n=300]) using whole genome sequence (WGS) data in a case/control design (75% post-infection cases, 25% never infected controls). The data generated will enable estimating the importance of genetics in disease response and the identification of key genes involved in the response. Our specific aims are to: 1) detect genetic influences on endophenotypic responses to SARS-CoV-2 infection using WGS data through testing for genotype×infection interaction in neurocognitive measures (neurocognitive measures, neuroimaging measures, and blood-based biomarkers); 2) search for sequence variation in genes and gene pathways influencing response to SARS-CoV-2 infection; and 3) test whether between-population variation in mean responses to infection has a genetic component. This project represents the genetic component of a large, integrated U19 application to examine the effect of COVID-19 on risk for ADRD in understudied ethnicities. Through the proposed project, we will identify causal genetic factors that underly differential response in ADRD risk to COVID-19.", "keywords": [ "2019-nCoV", "Acute", "Acute Respiratory Distress Syndrome", "Adult", "African", "African American population", "Age", "Age Years", "Alzheimer&apos", "s Disease", "Alzheimer&apos", "s disease related dementia", "Alzheimer&apos", "s disease risk", "Amerindian", "Anosmia", "Argentina", "Biological", "COVID-19", "COVID-19 impact", "COVID-19 morbidity", "COVID-19 mortality", "COVID-19 patient", "Caucasians", "Cause of Death", "Child", "China", "Cities", "Complex", "Data", "Dementia", "Disease", "Elderly", "Encephalopathies", "Environmental Risk Factor", "Ethnic Origin", "Etiology", "Fostering", "Future", "Gene Expression", "Gene Frequency", "Genes", "Genetic", "Genetic Variation", "Genotype", "Heritability", "Hypoxic-Ischemic Brain Injury", "Impaired cognition", "Individual", "Infection", "Joints", "Measures", "Methods", "Mexican Americans", "Modeling", "Morbidity - disease rate", "Native Americans", "Nerve Degeneration", "Nervous System Physiology", "Neurobiology", "Neurocognitive", "Neurologic", "Neurons", "Neuropathy", "Parkinson Disease", "Pathologic", "Pathology", "Pathway interactions", "Patients", "Persons", "Phenotype", "Pneumonia", "Population", "Population Heterogeneity", "Predisposition", "Prevalence", "Proteins", "Public Health", "Puerto Rican", "Recording of previous events", "Risk", "SARS-CoV-2 infection", "South American", "Stroke", "Symptoms", "Testing", "Time", "Variant", "acute hypoxemic respiratory failure", "aging brain", "blood-based biomarker", "brain based", "cohort", "dementia risk", "design", "endophenotype", "experience", "genetic architecture", "genetic epidemiology", "genome-wide", "health care service utilization", "high risk", "human old age (65+)", "identity by descent", "improved", "insight", "inter-individual variation", "mortality", "nervous system disorder", "neuroimaging", "neuropsychiatry", "pandemic disease", "response", "whole genome" ], "approved": true } }, { "type": "Grant", "id": "12144", "attributes": { "award_id": "2P20GM121307-06", "title": "Stress Exacerbates Myocardial Ischemic Injury by Blocking Estrogen's Antidoxidant Protection in the Female Heart", "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": [], "start_date": "2023-08-01", "end_date": "2028-06-30", "award_amount": 219000, "principal_investigator": { "id": 28004, "first_name": "Diana", "last_name": "Cruz Topete", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 835, "ror": "", "name": "LOUISIANA STATE UNIV HSC SHREVEPORT", "address": "", "city": "", "state": "LA", "zip": "", "country": "United States", "approved": true }, "abstract": "The psychological stress associated with the COVID-19 pandemic has led to an unprecedented increase in stress disorders. High-stress levels closely correlate with clinical depression and cardiovascular disease. In contrast to men, women are more reactive to the cardiovascular effects of mental stress. In particular, young women have a higher susceptibility to the harmful effects of stress, and increased stress levels have been shown to correlate with a higher risk of mortality and complications after a heart attack in women. Women have been disproportionally affected by the psychological effects of this pandemic. Therefore, it is critical to investigate the molecular pathways underlying the stress response, depression, and cardiovascular disease. The present proposal aims to test if increases in the primary stress hormones glucocorticoids inhibit estrogen protection in the female heart by altering the reductive/oxidative state in cardiomyocytes. To accomplish this goal, we propose identifying the mechanism whereby stress downregulates the activation of the cyclin-dependent kinase inhibitor 1A (Cdkn1A or p21) and the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling in cardiomyocytes and the whole heart. The p21-Nrf2 signaling pathway is essential to limit oxidative stress damage in hypoxia/reperfusion injury in vitro. We will investigate if the activation of the glucocorticoid receptor (GR) by restraining stress (model of mental stress which leads to a phenotype that mimics depression in humans) inhibits the estrogen receptor (ER)-mediated activation of the p21-Nrf2 signaling pathway in the context of hypoxia/reoxygenation. Using a transgenic mouse model lacking the GR in the heart, we will investigate if the activation of this stress receptor to changes in cardiac reductive/oxidative balance in response to ischemia/reperfusion (I/R) injury in female hearts by altering estrogen signaling. We will also test if restoring p21 expression (AAV delivery approach) in female hearts improves the cardiac outcomes after stress by reducing the production of reactive oxygen species. If funded, this project will provide critical knowledge on the cardiac consequences of stress and depression at the physiological and molecular level for the female heart. Also, the data gathered from the experiments described in this grant will promote the importance of sex as a factor to consider when considering antioxidant therapies in heart disease and failure.", "keywords": [ "Adult", "Affect", "Aging", "Behavior", "Biological", "Biological Assay", "Biology", "CDKN1A gene", "COVID-19 pandemic", "Cardiac", "Cardiac Myocytes", "Cardiovascular Diseases", "Cell Survival", "Centers of Research Excellence", "Chronic", "Clinical", "Collaborations", "Confocal Microscopy", "Data", "Disease", "Equilibrium", "Estrogen Receptors", "Estrogens", "Exposure to", "Female", "Funding", "Genomics", "Glucocorticoid Receptor", "Glucocorticoids", "Goals", "Grant", "Harvest", "Heart", "Heart Diseases", "Heart Injuries", "Heart failure", "Hormones", "Human", "Hypoxia", "Imaging Techniques", "Immunoprecipitation", "In Vitro", "Individual", "Infarction", "Injury", "Intervention", "Ischemia", "Knowledge", "Major Depressive Disorder", "Mediating", "Mental Depression", "Mental disorders", "Mentors", "Mesenchymal Stem Cells", "Modeling", "Molecular", "Mus", "Myocardial Infarction", "Myocardial Ischemia", "Neonatal", "Outcome", "Oxidation-Reduction", "Oxidative Stress", "Pathway interactions", "Persons", "Phenotype", "Physiological", "Placenta", "Positioning Attribute", "Predictive Value", "Predisposition", "Process", "Production", "Proteins", "Psyche structure", "Psychological Stress", "Reactive Oxygen Species", "Receptor Inhibition", "Regulation", "Reperfusion Injury", "Reperfusion Therapy", "Reporting", "Research", "Risk", "Serum", "Signal Pathway", "Signal Transduction", "Stress", "Stress Tests", "TP53 gene", "Testing", "Transcription Coactivator", "Transcriptional Regulation", "Transgenic Mice", "Uncertainty", "United States", "Wild Type Mouse", "Woman", "antioxidant therapy", "biological adaptation to stress", "body system", "cardiovascular effects", "clinical predictors", "experience", "experimental study", "global health", "heart function", "high risk", "improved", "ischemic injury", "male", "men", "mortality risk", "mouse model", "nuclear factor-erythroid 2", "pandemic impact", "psychologic", "receptor", "response", "restraint stress", "sex", "stem cells", "stress disorder", "stress reduction", "young woman" ], "approved": true } }, { "type": "Grant", "id": "12149", "attributes": { "award_id": "1P01AI172531-01", "title": "Antibody Core", "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": [], "start_date": "2023-08-21", "end_date": "2028-05-31", "award_amount": 208535, "principal_investigator": { "id": 28011, "first_name": "Ali Hassan", "last_name": "Ellebedy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 625, "ror": "https://ror.org/04a9tmd77", "name": "Icahn School of Medicine at Mount Sinai", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "The SARS-CoV-2 pandemic represents an exceptional public health crisis highlighting the need for better understanding of the mechanisms controlling broadly protective immune responses and generating vaccine candidates able to elicit such responses. The program project entitled “Programming Long-lasting Immunity to Coronaviruses (PLUTO)” proposes a comprehensive research plan towards designing pan-sarbecovirus and pan-betacoronavirus vaccines with broad protection by applying in-depth B cell characterization in the context of coronavirus immune histories imprinted by successive vaccinations and/or infections. Two complementary research projects will establish correlates of robust, durable and protective coronavirus humoral immunity (Project 1) as well as design and test efficacy of viral variant-proof pan-sarbecovirus and pan-betacoronavirus vaccines (Project 2). The Cores will synergize with the two research projects to support the successful completion of the research aims. The Administrative Core will manage the consortium, coordinate cross-project activities, and create the structure and environment needed to accomplish PLUTO’s goals. The Antibody Core will develop large panels of recombinant monoclonal antibodies (mAbs) against coronavirus spike proteins to define specificity and breath of immune responses elicited by coronavirus infections and/or vaccinations in humans and animal models. The Animal Model Core will provide a central resource with approvals, facilities, and expertise to assess efficacy of broadly cross-reactive coronavirus antibodies and vaccines in robust pre-clinical models against a spectrum of coronaviruses, including Select Agents. A multidisciplinary team of scientists from five institutions who have an outstanding track record of working collaboratively will conduct the proposed studies. The Research Projects will collaborate with each other and with the Antibody and Animal Model Cores, coordinated by the Administrative Core. The integrated and synergistic activities across Projects and Cores will drive the successful completion of the program project’s ambitious research agenda, enabling achievement of the long-term PLUTO goal of developing variant-proof pan-sarbecovirus and pan-betacoronavirus vaccines. These findings will contribute to curbing the current SARS-CoV-2 pandemic and mitigate the risk of future pandemics with coronaviruses.", "keywords": [ "2019-nCoV", "Acceleration", "Achievement", "Activities of Daily Living", "Animal Model", "Antibodies", "Antigens", "B-Lymphocytes", "Bacillus anthracis", "Binding", "Blood", "Bone Marrow", "COVID-19", "COVID-19 pandemic", "COVID-19 therapeutics", "Cell Separation", "Chronic", "Circulation", "Clinical", "Clinical Trials", "Clostridium difficile", "Collaborations", "Coronavirus", "Coronavirus Infections", "Coronavirus spike protein", "Development", "Diagnostic tests", "Dose", "Enterotoxins", "Environment", "Epitope Mapping", "Epitopes", "FDA approved", "Generations", "Goals", "Human", "Humoral Immunities", "Immune", "Immune response", "Immunity", "Immunize", "Immunologics", "Infection", "Inflammatory", "Institution", "Knowledge", "Life", "Malignant Neoplasms", "Maps", "Metabolic Diseases", "Methodology", "Middle East Respiratory Syndrome Coronavirus", "Moderna COVID-19 vaccine", "Monoclonal Antibodies", "Mus", "Neurons", "Nucleosides", "Peripheral Blood Mononuclear Cell", "Pfizer-BioNTech COVID-19 vaccine", "Pharmaceutical Preparations", "Pre-Clinical Model", "Productivity", "Proteins", "Public Health", "Publishing", "RNA vaccination", "RNA vaccine", "Recombinants", "Recording of previous events", "Research", "Research Project Grants", "Resources", "Respiratory syncytial virus", "SARS coronavirus", "SARS-CoV-2 antibody", "SARS-CoV-2 spike protein", "SARS-CoV-2 variant", "Sarbecovirus", "Scientist", "Screening procedure", "Specificity", "Specimen", "Structure", "Technology", "Therapeutic", "Time", "United States", "Universities", "Vaccination", "Vaccine Design", "Vaccinee", "Vaccines", "Variant", "Viral", "Virus", "Washington", "Work", "betacoronavirus", "betacoronavirus vaccine", "cohort", "coronavirus vaccination", "coronavirus vaccine", "cross reactivity", "design", "efficacy evaluation", "efficacy testing", "flexibility", "future pandemic", "human coronavirus", "human disease", "human model", "human monoclonal antibodies", "imprint", "improved", "insight", "lymph nodes", "multidisciplinary", "murine monoclonal antibody", "natural antibodies", "neutralizing antibody", "novel", "pathogenic microbe", "programs", "response", "risk mitigation", "single cell technology", "single-cell RNA sequencing", "synergism", "technology platform", "vaccine candidate", "vaccine development", "variants of concern", "ward" ], "approved": true } }, { "type": "Grant", "id": "12163", "attributes": { "award_id": "1I21HX003593-01A1", "title": "Virtual Care Coordination in VA Primary Care-Mental Health Integration", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2023-08-01", "end_date": "2025-01-31", "award_amount": null, "principal_investigator": { "id": 28029, "first_name": "Taona", "last_name": "Haderlein", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1708, "ror": "https://ror.org/05xcarb80", "name": "VA Greater Los Angeles Healthcare System", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Background: Among newly initiated Primary Care-Mental Health Integration (PC-MHI) patients, same day access to PC-MHI from primary care or other select medical clinics (e.g., emergency department/urgent care) is a Veterans Health Administration (VA) Strategic Analytics for Improvement and Learning (SAIL) performance measure (mnemonic: pcmhi7). Prompt initiation of mental health care after a medical visit increases the likelihood of subsequent mental health follow-up visits, enhancing quality of care. Yet, despite the rapid VA virtual care expansion during COVID-19, factors that influence virtual same day access to PC-MHI are unknown. Significance: Preliminary studies from this research group found that in a large VA medical center, PC-MHI same day access rates were nearly twice as high for in-person visits compared to virtual visits. Accordingly, PC-MHI patients who initiate care virtually may experience poorer medical and mental health outcomes from loss to follow-up. This finding reflects a knowledge gap that exists across disciplines in both VA and non-VA settings regarding effective strategies for virtual care coordination. The proposed study addresses multiple HSR&D Priority Areas: Access to Care, Mental Health, Primary Care Practice, Virtual Care/Telehealth. Innovation & Impact: The proposed research would be the first to characterize factors that influence same day access to PC-MHI among patients who use virtual care to initiate mental health services, including mutable clinic characteristics that may be amenable to intervention. By identifying specific predictors of same day access to PC-MHI from primary care, the proposed study will advance understanding of factors that affect virtual same day access while also identifying specific targets for future interventions, improving quality of care, and relatedly, medical and mental health outcomes, for Veterans who seek PC-MHI care virtually. Moreover, the study will advance scientific knowledge by providing data to inform strategies for effective interdisciplinary virtual care coordination. Specific Aims: 1) Identify multi-level characteristics associated with virtual and in-person PC-MHI same day access in a national VA sample. 2) Assess barriers, facilitators, and strategies for successful virtual care coordination in PC-MHI. Methodology: The study will use a mixed methods design. For Aim 1 (Quantitative), a national cohort of Veterans who initiated PC-MHI mental health services during FY2019 − FY2021 will be identified. PC-MHI same day access will be determined based on the presence or absence of a primary care or other select medical clinic visit on the same day as the initial PC-MHI appointment, per the Mental Health SAIL definition. A multi-level generalized linear model will be used to evaluate predictors of virtual and in-person same day access. For Aim 2 (Qualitative), semi-structured qualitative interviews with PC-MHI mental health providers and primary care providers from two VA healthcare systems (one urban, one rural) will be conducted to identify barriers, facilitators, and strategies for virtual care coordination in PC-MHI. Next Steps/Implementation: In partnership with the Office of Mental Health and Suicide Prevention, the Office of Connected Care, and the Office of Primary Care, the findings will be applied toward an HSR&D Merit Review Award grant proposal to develop an intervention to improve virtual care coordination in PC-MHI.", "keywords": [ "Accident and Emergency department", "Address", "Adoption", "Affect", "Ambulatory Care Facilities", "Applications Grants", "Appointment", "Area", "Award", "COVID-19", "COVID-19 pandemic", "Caring", "Characteristics", "Clinic", "Clinic Visits", "Clinical", "Communities", "Data", "Day Care", "Discipline", "Electronic Health Record", "Ethnic Origin", "Funding", "Future", "Goals", "Health Personnel", "Health Services Accessibility", "Healthcare Systems", "Intervention", "Interview", "Knowledge", "Learning", "Linear Models", "Measures", "Medical", "Medical Care Team", "Medical center", "Mental Health", "Mental Health Services", "Methodology", "Methods", "Modality", "Modeling", "Outcome", "Patient Care", "Patient-Focused Outcomes", "Patients", "Performance", "Persons", "Pilot Projects", "Primary Care", "Provider", "Quality of Care", "Race", "Reporting", "Research", "Risk", "Role", "Rural", "Sampling", "Scientific Advances and Accomplishments", "Services", "Specific qualifier value", "Structure", "Suicide prevention", "Telephone", "Time", "Urban Health", "Veterans", "Veterans Health Administration", "Visit", "care coordination", "cohort", "connected care", "design", "experience", "follow-up", "handbook", "health care settings", "improved", "innovation", "medical specialties", "primary care clinic", "primary care practice", "primary care provider", "primary care team", "research study", "rural healthcare", "telehealth", "therapy development", "urgent care", "video chat", "virtual", "virtual healthcare", "virtual patient", "virtual visit" ], "approved": true } }, { "type": "Grant", "id": "12178", "attributes": { "award_id": "1UC7AI180312-01", "title": "Facility Management, Maintenance and Operations Core", "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": [], "start_date": "2023-08-18", "end_date": "2028-07-31", "award_amount": 1081907, "principal_investigator": { "id": 28047, "first_name": "George Parsons", "last_name": "Langan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 289, "ror": "https://ror.org/024mw5h28", "name": "University of Chicago", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "(Core 1/C1Facilities@HTRL) Core 1 Facility Management, Maintenance and Operations Core (C1Facilities@HTRL) The Facility Management, Maintenance, and Operations Core will operate the Howard T Ricketts Regional Biocontainment Laboratory (HTRL) A/BSL3 to ensure continuous containment through decontamination, retesting, certification, preventive maintenance, repair, or replacement of existing equipment and building systems as well as compliance with Biosecurity, Environmental Health and Biosafety regulations. Central to this facility's past and future success is the collective approach of HTRL management which involves four distinct entities: Animal Resources Center, the Office of Research Safety, Facility Operations, and the Department of Microbiology. The HTRL management team is composed of outstanding leaders in their respective fields, and they utilize their expertise collaboratively to support the HTRL program with the common goal of assuring research programs are safe and successful. This approach has allowed the building to operate efficiently since its initial construction. This management structure is centered on supporting the research labs using the A/BSL3 to allow them to focus on their experimental objective, while biosafety and operational management are maintained by C1Facilities@HTRL. The core management team maintains the A/BSL3 rooms, equipment, and operations at the highest level to meet or exceed the regulatory and best-practice standards for biosafety, animal care, and research support. Furthermore, the team maintains the facility at a high level of readiness to support ongoing and future research needs of the facility, and to adapt to the needs presented by public health emergencies such as occurred with the establishment of the COVID-19 Core.", "keywords": [ "2019-nCoV", "Animal Experimentation", "Anthrax disease", "Area", "Bacillus", "Biomedical Research", "Brucella", "COVID-19", "Certification", "Chicago", "Collaborations", "Containment", "County", "Coxiella", "Decontamination", "Docking", "ESKAPE pathogens", "Ensure", "Environmental Health", "Equipment", "Future", "Goals", "Guidelines", "Humidity", "Illinois", "Infectious Diseases Research", "Influenza", "Institution", "Laboratories", "Longevity", "Maintenance", "Microbiology", "Mycobacterium tuberculosis", "Operations Research", "Organism", "Pathogenicity", "Plague", "Preventive", "Readiness", "Regulation", "Research", "Research Support", "Rickettsia", "Safety", "Secure", "Structure", "System", "Temperature", "Testing", "United States National Institutes of Health", "Universities", "Yersinia", "animal care", "animal resource", "biosafety level 3 facility", "biosecurity", "emerging pathogen", "improved", "methicillin resistant Staphylococcus aureus", "novel therapeutics", "novel vaccines", "operation", "pathogenic virus", "pressure", "programs", "public health emergency", "repaired", "research facility", "success" ], "approved": true } }, { "type": "Grant", "id": "12195", "attributes": { "award_id": "1I01HX003584-01A2", "title": "Resilience to Covid-19 Disrupted Chronic Condition Care for Older Veterans At Risk of Hospitalization: Role of VA Ambulatory Care and VA Extended Care Home and Community-Based Care Supports", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2023-08-01", "end_date": "2025-07-31", "award_amount": null, "principal_investigator": { "id": 28065, "first_name": "Lillian Chiang", "last_name": "Min", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1477, "ror": "https://ror.org/05eq41471", "name": "Veterans Health Administration", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Background: The Covid-19 pandemic disrupted the ambulatory health care of Veterans with chronic conditions, including those with the highest need for VA care. Significance/Impact: This research will study the critical role of the VA healthcare system for delivering chronic disease management during the pandemic, including office, video, and telephone care, and assess clinical outcomes of older Veterans at the highest risk for hospitalizations for chronic disease exacerbations and acute fall injuries. In addition, we will explore how VA Geriatric Extended Care Home and Community- Based Services (HCBS) mitigated Covid-19 related healthcare disruptions. Innovation: This research will implement the newest analytic tools for studying health outcomes of older Veterans, approaches to measure access to VA HCBS programs, and identify those at highest risk of disrupted and delayed chronic disease care. Specific Aims: Using state-of-the-art methods, we will address the following Aims: Aim 1A: Examine the effect of disrupted ambulatory care visits on chronic condition management (CCM) for older Veterans. We will identify changes over time (“disruption”) in ambulatory care, including the volume of face-to-face and virtual visits, video and telephone calls, that are provided by outpatient primary and specialty care outpatient clinics. We will study ~ 1 million older (age ≥65) Veterans with at least 1 of 3 chronic medical and geriatric conditions: hypertension, congestive heart failure (CHF), or falls/mobility impairment during the Covid-19 crisis (2020-21). Management of chronic conditions will be measured by medication adherence, intensity, lab monitoring, and physical therapy services. Vulnerability to service disruption will be defined using the established method in VA patients and two other methods developed specifically for geriatric patient populations, the Predicted Long-term Institutionalization (PLI) measure. Next, in Aim 1B, we will test whether facilities who were able to maintain better access to HBCS mitigated the effect of disrupted ambulatory care on performance of chronic condition care management. This critical Aim will focus on 5 HBCS programs: Home-Based Primary Care, Personal Care Services (homemaker and home health aides, respite care), Veteran Directed Care, Adult Day Care, and Skilled Home Care (e.g., physical and occupational therapy, nursing, social work) Aim 2: Examine the effect of chronic condition management disruption on hospitalizations for ACSCs and acute fall injuries. We will determine whether older Veterans with less disrupted care during the initial and second Covid-19 surges also had a lower risk of hospitalization for chronic ACSC-related hospitalizations related to CHF and hypertension or for a fall-related injury. This Aim will result in a better understanding of how to predict hospitalization for ACSCs among older Veterans according to vulnerability. Methodology: This is a longitudinal study of older Veterans in the national VA healthcare system, using VA healthcare data merged with Medicare and Medicaid long-term care data, and pharmacy files from the VA and Medicare. We will use risk scores and data sources in partnership with the GEC Data Analysis Center. Next Steps: We will identify the chronic condition management services that should be prioritized for older Veterans and a potential roadmap for how the future VA ambulatory care and GEC healthcare systems can partner to provide better chronic condition management and attain better health outcomes for older Veterans.", "keywords": [ "Acute", "Admission activity", "Adult", "Affect", "Age", "Ambulatory Care", "Ambulatory Care Facilities", "COVID-19", "COVID-19 impact", "COVID-19 pandemic", "Cardiovascular system", "Caring", "Chronic", "Chronic Disease", "Clinic Visits", "Clinical", "Communities", "Congestive Heart Failure", "Coupled", "Data", "Data Analyses", "Data Sources", "Day Care", "Diet", "Discipline of Nursing", "Disease Management", "Elderly", "Fall prevention", "Future", "Geographic Locations", "Health", "Health Care Research", "Healthcare", "Healthcare Systems", "Heart failure", "Home", "Home Health Aides", "Hospital Mortality", "Hospitalization", "Hospitals", "Hypertension", "Impairment", "Improve Access", "Institutionalization", "Long-Term Care", "Longitudinal Studies", "Managed Care", "Measures", "Medical", "Medical center", "Medicare", "Medicare claim", "Medicare/Medicaid", "Methodology", "Methods", "Monitor", "Natural experiment", "Occupational Therapy", "Office Visits", "Outcome", "Outpatients", "Patients", "Performance", "Persons", "Pharmaceutical Preparations", "Pharmacy facility", "Physical Rehabilitation", "Physical therapy", "Press Releases", "Primary Care", "Productivity", "Provider", "Recovery", "Research", "Risk", "Role", "Self Care", "Services", "Social Work", "Social support", "Sodium Chloride", "Subgroup", "Telephone", "Testing", "Time", "Transportation", "Vaccines", "Variant", "Veterans", "Visit", "Workload", "aged", "analytical tool", "care systems", "clinical outcome assessment", "community based care", "community based service", "experience", "fall injury", "falls", "health care delivery", "health care service", "high risk", "human old age (65+)", "innovation", "insight", "medical specialties", "medication compliance", "novel", "pandemic disease", "patient home care", "patient population", "poor health outcome", "pre-pandemic", "preservation", "prevent", "programs", "rehabilitation service", "resilience", "respite care", "service delivery", "service programs", "skills", "team-based care", "tool", "video visit", "virtual", "virtual visit" ], "approved": true } }, { "type": "Grant", "id": "12203", "attributes": { "award_id": "1UC7AI180306-01", "title": "Biocontainment Research Support Service(s) Core", "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": [], "start_date": "2023-08-18", "end_date": "2028-07-31", "award_amount": 944931, "principal_investigator": { "id": 28073, "first_name": "Rachel M", "last_name": "Olson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1049, "ror": "", "name": "UNIVERSITY OF MISSOURI-COLUMBIA", "address": "", "city": "", "state": "MO", "zip": "", "country": "United States", "approved": true }, "abstract": "Core 3: Biocontainment Research Support Services Core The objective of the Biocontainment Research Support Services Core (BRSSC, Core 3) is to provide sustainable research resources that facilitate the pre-clinical development of medical countermeasures against emerging and re-emerging pathogens. To achieve this, the BRSSC provides world-class resources in the priority areas of aerobiology, animal modeling, immunology, imaging, and microbiology for BSL-3 bacterial and viral pathogens. The BRSSC serves the needs of MU as well as NIAID and the RBL-NBL network by focusing its capabilities to provide technical expertise under BSL-3 containment for NIAID priority pathogens and the evaluation of novel vaccines, treatments, and diagnostics. The BRSSC closely collaborates with other relevant Research Services at MU, including but not limited to the NIH-funded Resource and Research Centers for Mutant Mouse, Rat, and Swine to develop and refine novel transgenic animal models for priority pathogens such as SARS-CoV-2. The technical staff of the BRSSC is a dedicated team for conducting and supporting experiments using advanced technology, high-precision instrumentation on live samples. Added layers of primary and secondary containment allow for safe handling and usage of the unique support services that are offered in the BRSSC. For example, direct access from the vivarium to the class III glovebox and its inhalation exposure chamber eliminates the need to move infected animals through corridors or other space that may expose people. In addition, there is a high- speed cell sorter, housed within a manufacturer-supplied class II BSC, that allows recovery of live cells infected with a BSL-3 pathogen for downstream analysis. The Lionheart fluorescent microscopy system allows real-time imaging of environmentally-controlled live BSL-3 samples in multi-well format, and is useful for optimization of viral growth conditions and other live and in vitro assays without need for pathogen inactivation. Further imaging and other instrumentation available in the ABSL-3 allows for longitudinal monitoring of the infection, blood chemistry and immune responses without need to chemically inactivate sample, thereby reducing time and unwanted impact for the procedure. All of these examples illustrate the capabilities for safe conduct of BSL-3 research using advanced technology instrumentation that is available through the BRSSC. The collaborative effort between the dedicated teams of Cores 1, 2 and 3 of this UC7 application combined with regular interactions with the NIAID RBL-NBL network will maximize best practices and usage of these unique resources. To create sustainability, the BRSSC is committed to training diverse technical professionals and scientists in BSL-3/ACL- 3/ABSL-3 research. Through management of the critical resources at the LIDR, the BRSSC helps advance the development of novel medical countermeasures against BSL-3 pathogens.", "keywords": [ "2019-nCoV", "Advanced Development", "Aerosols", "Animal Model", "Animals", "Area", "Biological Assay", "Blood Chemical Analysis", "COVID-19 pandemic", "Cavia", "Cells", "Chemicals", "Collaborations", "Communicable Diseases", "Communication", "Communities", "Containment", "Controlled Environment", "Core Facility", "Custom", "Data", "Dedications", "Development", "Diagnostic", "Emerging Communicable Diseases", "Ensure", "Equipment", "Evaluation", "Event", "Family suidae", "Ferrets", "Flow Cytometry", "Funding", "Goals", "Goat", "Growth", "Hamsters", "Human Resources", "Image", "Immune response", "Immunity", "Immunology", "Infection", "Infectious Diseases Research", "Inhalation Exposure", "Investments", "Laboratories", "Maintenance", "Manufacturer", "Methodology", "Methods", "Microbiology", "Microscopy", "Missouri", "Modeling", "Monitor", "Mus", "Mutant Strains Mice", "National Institute of Allergy and Infectious Disease", "Oryctolagus cuniculus", "Persons", "Procedures", "Productivity", "Public Health", "Rattus", "Recovery", "Reproducibility", "Research", "Research Personnel", "Research Support", "Resource Development", "Resources", "Route", "Safety", "Sampling", "Scientist", "Secure", "Services", "Sheep", "Specialist", "Speed", "Structure", "System", "Technical Expertise", "Technology", "Time", "Training", "Transgenic Animals", "Translating", "United States National Institutes of Health", "Universities", "Viral", "Work", "Workforce Development", "biodefense", "biosafety level 3 facility", "cytokine", "emerging pathogen", "experience", "experimental study", "human disease", "human model", "in vitro Assay", "instrumentation", "medical countermeasure", "new outbreak", "next generation", "novel", "novel vaccines", "pathogen", "pathogen exposure", "pathogenic bacteria", "pathogenic virus", "pre-clinical", "preclinical development", "priority pathogen", "programs", "real-time images", "recruit", "research and development", "response", "vector transmission" ], "approved": true } }, { "type": "Grant", "id": "12212", "attributes": { "award_id": "1I01BX006273-01", "title": "Role of macrophages and miRNA in regulating lung macrophage polarization and lung pathogenesis during respiratory virus-induced acute lung injury in normal and diabetic Syrian hamsters.", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2023-08-01", "end_date": "2027-07-31", "award_amount": null, "principal_investigator": { "id": 27400, "first_name": "Jay R", "last_name": "Radke", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2075, "ror": "https://ror.org/00mz0c648", "name": "Boise VA Medical Center", "address": "", "city": "", "state": "ID", "zip": "", "country": "United States", "approved": true }, "abstract": "Over 25% of US Veterans have diabetes, and those Veterans are at an increased risk of hospitalization and increased morbidity/mortality following severe respiratory viral infections, such as, influenza (H1N1), SARS- CoV-2 (COVID) and adenovirus (Ad). Infection with these respiratory viruses causes acute lung injury (ALI) that can result in acute respiratory distress syndrome (ARDS), with a mortality rate of ~40%. There are few therapeutic options for ALI/ARDS. Virus induced ALI/ARDS is driven primarily by uncontrolled inflammatory responses. Alveolar macrophages both induce and resolve ALI/ARDS, based on their polarization/inflammatory state. The plasticity of macrophages to vary between pro-inflammatory (M1, pro-ALI/ARDS) and anti- inflammatory (M2, anti-ALI/ARDS) phenotypes is driven by their metabolic states. Diabetes is a metabolic disorder in which levels of blood glucose are high and glycolysis is the preferred cellular metabolic pathway. Macrophages from diabetic patients have a high rate of glycolysis and an increased M1 phenotype. In addition, macrophages from diabetic patients have a lower rate of plasticity to change from M1 to M2 because of this shift to glycolysis. One possibility is that this glycolytic shift contributes to severe outcomes from respiratory viral infections in diabetic patients. The Syrian hamster is naturally permissive for influenza, SARS-CoV-2 and Ad (in contrast to other rodents that require viral adaptation). In addition, the Syrian hamster can naturally become diabetic with a high fat/high sugar diet. Ad14p1 is an emergent strain of Ad14 that has caused outbreaks of severe respiratory illness and ALI/ARDS throughout the world. Hamster infection with Ad14p1 results in a patchy bronchopneumonia, as seen in other severe human viral respiratory infections. In contrast, the prototype strain of Ad14 induces little lung inflammation. Other studies have shown that cells dying from Ad14 infection induce an M2-like human macrophage response, while cells dying from Ad14p1 infection fail to change M1 alveolar macrophages to an M2 phenotype. This dying infected cell activity is regulated by the expression of the Ad gene, E1B 20K. Cells infected by Ad14 produced sufficient E1B 20K to repolarize M1 macrophages to M2, while Ad14p1 infection does not produce sufficient E1B 20K, and the infected cells fail to alter M1 macrophage polarization. Therefore, the hamster model of Ad14p1 ALI/ARDS provides an appropriate system to study how diabetes affects macrophage polarization and pathogenesis during severe viral respiratory infections. The long-term goal of this project is to understand how emergent viruses regulate macrophage polarization to develop novel therapeutic strategies to drive macrophage polarization to an ALI/ARDS resolving phenotype in both diabetic and non-diabetic Veterans. To achieve this goal, a multi-omics approach will be used to identify and phenotype macrophages in normal and diabetic hamsters infected with Ad14p1. Transcriptomics using single-cell RNA sequencing will use gene expression profiles at the resolution of individual cells to identify and phenotype macrophages and their polarization states. Infiltrating immune cells and other lung resident cells will also be identified. Proteomics will be used to identify cytokines and chemokines that drive Ad14p1 pathogenesis. Metabolomics will be used to understand the unique metabolic changes in the lungs during Ad14p1 infection in diabetes and how those changes affect macrophage polarization. Comparative virology studies with infection of normal and diabetic hamsters with a pandemic strain of H1N1 influenza will be used to determine whether similar mechanisms of pathogenesis are involved in ALI/ARDS pathogenesis induced by other severe respiratory viruses. Finally, we will test the role of miRNA expression during prototype Ad14 and Ad14p1 infection in regulating macrophage polarization and pathogenesis, with the goals of defining mechanisms of immunomodulation and identifying candidate miRNAs that might be used as therapeutic agents against viral ALI/ARDS.", "keywords": [ "2019-nCoV", "Acute Lung Injury", "Acute Respiratory Distress Syndrome", "Adenovirus Protein", "Adenoviruses", "Affect", "Alveolar Macrophages", "Animal Model", "Anti-Inflammatory Agents", "Blood Glucose", "Bronchopneumonia", "COVID-19", "COVID-19 severity", "Cells", "Cessation of life", "Clinical", "Communicable Diseases", "Comparative Study", "Data", "Development", "Diabetes Mellitus", "Diet", "Disease", "Disease Outbreaks", "Etiology", "Fatty acid glycerol esters", "Functional disorder", "Future", "Gene Expression", "General Population", "Genes", "Glycolysis", "Goals", "Hamsters", "Hospital Mortality", "Hospitalization", "Human", "Immune response", "Impairment", "In Vitro", "Incidence", "Individual", "Infection", "Infection prevention", "Inflammation", "Inflammatory", "Inflammatory Response", "Influenza", "Influenza A Virus H1N1 Subtype", "Innate Immune Response", "Lung", "Lung infections", "Mediating", "Mesocricetus auratus", "Metabolic", "Metabolic Diseases", "Metabolic Pathway", "MicroRNAs", "Modeling", "Molecular", "Morbidity - disease rate", "Non-Insulin-Dependent Diabetes Mellitus", "Outcome", "Pathogenesis", "Pathogenicity", "Patients", "Pattern", "Phenotype", "Play", "Pneumonia", "Production", "Proteomics", "Pulmonary Inflammation", "Reporting", "Repression", "Resistance", "Resolution", "Risk", "Rodent", "Role", "SARS coronavirus", "SARS-CoV-2 infection", "Seasons", "Signal Repression", "Signal Transduction Pathway", "Structure", "System", "Testing", "Therapeutic", "Therapeutic Agents", "Therapeutic Intervention", "Veterans", "Viral", "Viral Pathogenesis", "Viral Respiratory Tract Infection", "Virus", "Virus Diseases", "candidate identification", "cell growth regulation", "chemokine", "comparative", "coronavirus disease", "cytokine", "design", "diabetic", "diabetic patient", "effective therapy", "experimental study", "high risk", "immune cell infiltrate", "immunoregulation", "in vivo", "influenza virus strain", "innovation", "lung injury", "macrophage", "metabolomics", "mortality", "multiple omics", "new therapeutic target", "non-diabetic", "novel", "novel therapeutic intervention", "pandemic disease", "permissiveness", "prevent", "prototype", "pulmonary function", "respiratory", "respiratory virus", "response", "single-cell RNA sequencing", "sugar", "transcriptomics", "virology", "western diet" ], "approved": true } } ], "meta": { "pagination": { "page": 1392, "pages": 1392, "count": 13920 } } }