Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=5&sort=award_amount
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=award_amount", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1442&sort=award_amount", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=6&sort=award_amount", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=4&sort=award_amount" }, "data": [ { "type": "Grant", "id": "14853", "attributes": { "award_id": "1I01CX002739-01", "title": "Characteristics and Determinants of Post-COVID Neurocognitive Dysfunction", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2024-07-01", "end_date": "2028-06-30", "award_amount": null, "principal_investigator": { "id": 31536, "first_name": "Roger", "last_name": "Bedimo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 31537, "first_name": "Amy Yomiko", "last_name": "Vittor", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2503, "ror": "https://ror.org/01nzxq896", "name": "VA North Texas Health Care System", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Neurologic symptoms are among the most common post-acute sequelae of COVID-19 (PASC). Recent studies show that there is a very high rate of neurocognitive changes among Veterans surviving acute COVID- 19 infection. The long-term neurocognitive changes of this infection could be even worse and remains incompletely characterized. Moreover, neurological sequelae have been considered the most disabling of the long-term complications. Possible mechanisms of neuronal damage from SARS CoV-2 infection include direct viral CNS invasion through the cribriform plate or hematogenous route, or retrograde neuronal dissemination, or indirect injury mediated by systemic inflammation, and secondary degenerative mechanisms. Whether neurocognitive changes can be predicted by biomarkers – or imaging evidence of – inflammation, neuronal damage or disruption of blood brain barrier has never been evaluated in a well-characterized cohort. Furthermore, no treatment strategies exist at present, but preliminary data suggests that antivirals may prevent the occurrence of cognitive impairment in PASC. VHA has established a nationwide COVID-19 cohort early in the pandemic. This objective of this cohort – called Epidemiology, Immunology and Clinical Characteristics of COVID-19 (EPIC3) – is to characterize the natural history, clinical outcomes, and the development of immunity while also gathering biospecimens for future study as questions emerge about this new pathogen. We will leverage the data and samples from this study to compare participants who received antivirals during their acute COVID-19 illness with those who did not, by 1) conducting longitudinal cognitive assessments of participants of EPIC3 and characterize trajectories of cognitive changes, using a novel tablet-based tool; 2) carrying out detailed longitudinal analyses of biomarkers of neuronal damage, neurodegeneration and blood-brain barrier disruption or participants with and without COVID-19, and 3) performing advanced structural and functional imaging of a subset of these participants. We will then correlate biomarkers and imaging findings to the presence, degree and trajectories of neurocognitive changes in COVID-19 patients who did and did not receive antivirals. We have assembled a multidisciplinary team with expertise critical to answering the challenging questions posed by neurocognitive changes of PASC. Expected findings of our study will have immediate clinical impact: 1) they will establish whether PASC is an additional goal for antiviral therapy, 2) they will establish a benchmark for standardized, validated assessment of possible neurocognitive changes in patients with COVID-19; this will provide a basis for future interventions and management guidelines; 2) determine whether these cognitive changes could be predicted or monitored using well validated biomarkers of neuronal damage and/or blood-brain barrier disruption; 3) determine whether structural and function brain imaging could assist in further studies of mechanisms of neuronal damage and/or neurocognitive dysfunction from COVID-19 infection. Here we propose addressing current gaps in our understanding of cognitive function in PASC by following the trajectories of cognitive function over three years using validated, tablet-based neuropsychological tests, analyzing the relationship between co-morbidities prevalent amongst veterans such as PTSD and depressive disorders and cognitive impairment following COVID-19. This study will link key neurological and immunological markers, clinical outcomes, and imaging of cerebral blood flow and demyelination, thereby contributing a cohesive understanding of the mechanisms of neurological injury.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "8960", "attributes": { "award_id": "1I01HX003269-01A2", "title": "Social and Behavioral Determinants of Health in High-Risk 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": "2021-10-01", "end_date": "2025-09-30", "award_amount": null, "principal_investigator": { "id": 24796, "first_name": "MATTHEW L", "last_name": "MACIEJEWSKI", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1497, "ror": "", "name": "VETERANS ADMIN PALO ALTO HEALTH CARE SYS", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 24797, "first_name": "Donna Michelle", "last_name": "Zulman", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1497, "ror": "", "name": "VETERANS ADMIN PALO ALTO HEALTH CARE SYS", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Background. Social factors exert a substantially more potent impact on health than does health care, especially among disadvantaged populations such as VA users. Adverse social determinants of health (SDH)—factors such as housing instability, food insecurity, social isolation, and transportation barriers—are linked to problems with access, poorer clinical outcomes, and increased health care costs. Despite the clinical and business case for integrating SDHs into health care, these factors are not systematically assessed or addressed in clinical settings. Significance/Impact. This study will leverage a previous survey of Veterans at high-risk for hospitalization, and a new survey to be fielded to a nationally-representative sample of Veterans, to determine how SDHs influence clinical, health care utilization, and experience outcomes. Review of findings by key stakeholders will generate recommended SDH measures for universal screening within VA. These steps, coupled with qualitative interviews about implementation challenges, will inform the future integration of high-value patient-reported SDH measures into VA’s health record. Innovation. The proposed work is innovative in its evaluation of a broad array of SDHs in high-need Veterans to identify candidate measures for electronic health record (EHR) integration. The study will leverage a theoretically-driven survey of SDH measures with a data-driven approach to identifying the associations between these SDHs and a range of health, utilization, and patient experience outcomes. Results from these analyses will inform a facilitated deliberative process to prioritize high-value, validated, and actionable measures that are predictive of outcomes that are important to Veterans and the VA. Specific Aims. In Aim 1, we will use data from an Office of Primary Care-funded survey of Veterans at high-risk for hospitalization to examine relationships between patient-reported SDH measures and utilization, cost, and days in the community outcomes. In Aim 2, we will field a survey to a nationally-representative sample of VA patients to determine the association between SDH measures and key outcomes, and to examine the prevalence of SDHs in subpopulations of Veterans who are disproportionately affected by disparities (e.g., women, racial/ethnic minorities, and rural Veterans). Aims 1 and 2 will inform partner and stakeholder discussions in Aim 3 to identify measures that are associated with key outcomes and that are perceived by operations partners as actionable (i.e., addressable through VA or community services) and thereby good candidates for EHR integration. Methodology. In Aim 1, we will leverage data from an operations-funded survey that our team administered in 2018. Using survey data for 4,685 Veterans at high-risk for hospitalization, we will examine the association between patient-reported SDHs and utilization (i.e., VA and Medicare emergency department visits and hospitalizations), VA and Medicare costs, and days in the community. In Aim 2, we will field a similar survey to a nationally-representative sample of Veterans, evaluate the association between SDHs, patient experiences (e.g., perceived access and coordination), and 12-month VA emergency department visits, hospitalizations, and costs, and describe the prevalence of SDHs in the general VA population and Veterans who are at risk for health disparities. In Aim 3, we will use a facilitated deliberative process with key stakeholders to prioritize actionable SDH measures for EHR integration, and then conduct qualitative interviews with health system leaders, clinicians, staff, and patients to examine implementation barriers and facilitators to assessing select SDH measures at point of care. Implementation/Next Steps. This study addresses health equity, particularly relevant in light of COVID-19, and will be conducted with partners from VA’s Offices of Primary Care, Health Equity, Rural Health, and Women’s Health. The study is especially timely with VA’s transition to the new Cerner EHR as the proposed aims will identify SDH measures for potential EHR integration that are concise, actionable, and predictive of important outcomes.", "keywords": [ "Academy", "Accident and Emergency department", "Address", "Affect", "Area", "Bed Occupancy", "Behavioral", "Businesses", "COVID-19", "COVID-19 pandemic", "Caregivers", "Caring", "Clinical", "Communities", "Community Services", "Coupled", "Data", "Disadvantaged", "Economics", "Electronic Health Record", "Emergency department visit", "Environmental Risk Factor", "Evaluation", "Financial Hardship", "Funding", "Future", "Goals", "Health", "Health Care Costs", "Health system", "Healthcare", "Hospital Costs", "Hospital Departments", "Hospitalization", "Hospitals", "Individual", "Integrated Health Care Systems", "Intervention", "Interview", "Lead", "Leadership", "Life", "Light", "Link", "Measurement", "Measures", "Medicare", "Medicine", "Methodology", "Minority", "Modeling", "Outcome", "Patients", "Population", "Positioning Attribute", "Predictive Value", "Prevalence", "Prevention", "Primary Health Care", "Procedures", "Process", "Recommendation", "Reporting", "Research", "Research Personnel", "Respondent", "Rest", "Risk", "Risk Adjustment", "Rural", "Rural Health", "Sampling", "Screening procedure", "Shapes", "Social isolation", "Surveys", "System", "Time", "Transportation", "Trust", "United States Department of Veterans Affairs", "Variant", "Veterans", "Veterans Health Administration", "Woman", "Women&apos", "s Health", "Work", "base", "clinical care", "cost", "disadvantaged population", "economic outcome", "ethnic minority population", "experience", "food insecurity", "health care service utilization", "health care settings", "health disparity", "health equity", "health record", "high risk", "housing instability", "implementation barriers", "implementation facilitators", "improved", "innovation", "interoperability", "operation", "outcome prediction", "patient population", "point of care", "racial and ethnic", "screening", "social", "social factors", "social health determinants", "social vulnerability" ], "approved": true } }, { "type": "Grant", "id": "15399", "attributes": { "award_id": "1I01BX006408-01", "title": "Mechanism of the adrenal stress response protection against therapy-induced lethal immune activation", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2024-07-01", "end_date": "2028-06-30", "award_amount": null, "principal_investigator": { "id": 31998, "first_name": "XIANG-AN", "last_name": "LI", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2032, "ror": "", "name": "VA MEDICAL CENTER - LEXINGTON, KY", "address": "", "city": "", "state": "KY", "zip": "", "country": "United States", "approved": true }, "abstract": "Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for hematologic malignancies and other diseases, in which the donor's stem cells are used to replace the recipient's damaged or destroyed cells. The Veterans Health Administration has been offering allo-HCT services since 1982, which have saved thousands of veterans' lives. However, this life-saving therapy comes at a cost - lethal immune activation caused by cytokine release syndrome (CRS). Currently, glucocorticoids (GC) and IL-6 antagonists are used for CRS treatment, but some patients do not respond well to treatment. A limitation is that CRS may cause irreversible organ injury before treatment is initiated, as the indicator of treatment is CRS itself. Therefore, there is an urgent need to identify patients at high risk of CRS and provide preventive therapy. We recently reported that the adrenal stress response, defined by a 6-fold increase in induced GC (iGC) production, is an essential host response against therapy- induced lethal immune activation. We identified scavenger receptor BI (SR-BI), an HDL receptor, as a key regulator for iGC production. Using SR-BI null mice as an adrenal stress response deficiency model, we demonstrated that the adrenal stress response protects against therapy-induced death by controlling CRS. Conversely, relative adrenal insufficiency (RAI) - the absence of adrenal stress response - is a risk factor for CRS. Our study provides proof-of-concept that diagnosing RAI may help identify patients at risk of CRS, and selective GC therapy for patients with RAI prior to the onset of CRS may reduce mortality from therapy-induced lethal immune activation. The goal of this application is to delineate the mechanisms of the adrenal stress response protection against CRS in allo-HCT-induced lethal immune activation and to translate the mechanistic findings into a precision medicine approach to prevent CRS in allo-HCT- induced lethal immune activation.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "6912", "attributes": { "award_id": "1IK2RX003546-01A2", "title": "Enhanced Home-Based Exercise Therapy for Peripheral Arterial Disease through Mobile Health and Remote Monitoring", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2021-10-01", "end_date": "2026-09-30", "award_amount": null, "principal_investigator": { "id": 22750, "first_name": "Arash", "last_name": "Harzand", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1477, "ror": "https://ror.org/05eq41471", "name": "Veterans Health Administration", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true } ] }, "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": "An estimated 8.5 million Americans (or 7% of US adults) and nearly 10% of veterans are estimated to have peripheral arterial disease (PAD). Significantly debilitating and negatively impacting quality of life, the primary symptom of PAD is claudication (reproducible leg pain with ambulation) that leads to impaired mobility, loss of functional independence, and a heightened risk for amputation. Veterans are at an increased risk of developing symptomatic PAD due to their disproportionately high rates of PAD risk factors such as diabetes, smoking, and hypertension, the most prominent PAD risk factors. Supervised exercise therapy is proven to decrease claudication and enhance mobility in PAD; however, fewer than 25% of eligible patients enroll. Participation in this facility-based program requires travel to a rehabilitation center 3 times per week for 12-weeks, which can be burdensome and costly for Veterans, many of whom live in rural areas and on fixed incomes. There is, therefore, a need to develop a convenient and effective alternative exercise rehabilitation program for Veterans with PAD, particularly in light of safety considerations now associated with this population’s travel to group facilities in the current COVID pandemic. A promising approach to increase access to exercise rehabilitation for PAD is remote, home-based exercise therapy (HBET). Our group has successfully delivered a smartphone-enabled HBET program to Veterans with coronary artery disease with a 3-fold increase in participation and high satisfaction (80%). To this end, we are committed to utilizing technology innovations to implement HBET for Veterans with PAD successfully. HBET programs combine self-led walking exercises with health coaching and exercise tracking with a wearable activity monitor. Adapting HBET to PAD is difficult, however, due to the added complexity of an exercise prescription that requires the patient to walk until they experience near-maximal leg pain. Even with active coaching, successfully implementing HBET for PAD with long-term adherence has been difficult in the past. Our goal, therefore, is to leverage newer mobile health (mHealth) tools to adapt HBET for PAD. We propose to test our technology-enhanced approach for HBET by partnering with a successful VA lifestyle program, MOVE!, which has demonstrated success in achieving sustained weight loss and reduced diabetes onset through lifestyle modification. As increased physical activity is a core element of MOVE!, participation may help increase adherence with HBET for PAD. Our newly proposed program, Smart MOVE!, will be a multi-component program featuring a tailored version of MOVE! and a novel mHealth device called the LifeQ to improve convenience, access, and adherence to HBET for PAD. Aim 1 (Years 1-2): Identify barriers and facilitators to MOVE! participation among Veterans with PAD. Aim 2 (Years 1-2): Evaluate the feasibility of the LifeQ device to monitor exercise during HBET Aim 3 (Years 2-5): Determine the feasibility of proceeding with Smart MOVE! through a pilot randomized trial. As a VA physician actively treating Veterans with PAD, I have seen first-hand the challenges they face in accessing guideline-directed treatments such as supervised exercise. This study will lay the groundwork and provide evidence to proceed with Smart MOVE!, a much-needed patient-centered exercise rehabilitation program for PAD. Additionally, the proposed training plan will support my progress towards becoming an independent VA rehabilitation clinician-scientist focused on improving care quality and treatment outcomes for Veterans with PAD.", "keywords": [ "Accelerometer", "Activities of Daily Living", "Adherence", "Adult", "Affect", "American", "Amputation", "Behavioral", "Body Weight decreased", "COVID-19 pandemic", "Cardiac rehabilitation", "Cellular Phone", "Clinical", "Complex", "Coronary Arteriosclerosis", "Data", "Devices", "Diabetes Mellitus", "Elements", "Enhancement Technology", "Enrollment", "Exercise", "Exercise Therapy", "Face", "Goals", "Gold", "Guidelines", "Health", "Health Technology", "Home", "Hospitals", "Hypertension", "Impairment", "Income", "Indirect Calorimetry", "Intervention", "Interview", "Leadership", "Leg", "Life Style", "Life Style Modification", "Light", "Measurement", "Monitor", "Myocardial Infarction", "Oxygen Consumption", "Pain in lower limb", "Patient Education", "Patients", "Peripheral arterial disease", "Physical activity", "Physicians", "Population", "Provider", "Quality of Care", "Quality of life", "Rehabilitation Centers", "Rehabilitation therapy", "Reproducibility", "Resolution", "Risk", "Risk Factors", "Safety", "Scientist", "Smoking", "Stroke", "Structure", "Supervision", "Symptoms", "Technology", "Testing", "Time", "Training", "Travel", "Treatment outcome", "Vertebral column", "Veterans", "Walking", "aged", "base", "behavior change", "claudication", "cost", "design", "evidence base", "exercise prescription", "exercise program", "exercise regimen", "exercise rehabilitation", "experience", "functional independence", "functional loss", "functional outcomes", "high risk", "improved", "improved mobility", "informant", "innovation", "mHealth", "mortality risk", "multi-component intervention", "novel", "patient oriented", "primary outcome", "programs", "randomized trial", "remote monitoring", "rural area", "satisfaction", "success", "symptomatic improvement", "tool" ], "approved": true } }, { "type": "Grant", "id": "11529", "attributes": { "award_id": "5I01RX003622-02", "title": "Exercise-based Program for Rehabilitation of Veterans with Severe Mental Illness", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2022-06-01", "end_date": "2026-05-31", "award_amount": null, "principal_investigator": { "id": 23883, "first_name": "GRETCHEN L", "last_name": "HAAS", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1477, "ror": "https://ror.org/05eq41471", "name": "Veterans Health Administration", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 23884, "first_name": "Vishwajit Laxmikant", "last_name": "Nimgaonkar", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1477, "ror": "https://ror.org/05eq41471", "name": "Veterans Health Administration", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "This is a Hybrid 1, effectiveness-implementation study of yoga-based exercise (YE) as an adjunctive tool for rehabilitation among persons with Severe Mental Illness (SMI), defined here as schizophrenia (SZ), schizoaffective disorder (SZA) and bipolar I disorder (BP1). SMIs are common, severe and devastating conditions that cause enormous disability world-wide. Many features of SMI can be treated effectively, yet the long-term outcome has not improved much over the past century. The lack of improvement may be due to ineffective treatment of functional deficits in SMI patients, particularly in terms of community functioning, defined here as social, leisure, employment, and life skills functioning in the community. Complementary and Integrative Medicine (CIM) therapies that improve community functions are thus of great interest for treating Veterans with SMI and thereby target an area of high priority for the VA. Prior studies have shown short-term benefits of YE for improving cognitive deficits and community functions among persons with SMI. While the published studies are encouraging, the longer-term benefits of YE are untested, particularly for community functioning. The profile of Veterans with SMI who will accept and adopt YE is also unknown. We have conducted pilot studies and a randomized controlled trial (RCT) for individuals with SMI in India using short-term, simplified YE combined with medications. Recently, we also concluded RELIEVE, a RCT of adjunctive YE for Veterans with post-traumatic stress disorder (PTSD) in the USA (VA RR&D Merit award, PI: L Davis, PsyD). We found encouraging improvements from all our studies, but our Indian and US YE protocols are impractical for Veterans with SMI. For example, some postures may be difficult for older Veterans with amotivation and/or physical disabilities. Therefore, in Aim 1, we will design and evaluate adaptations of the Indian and US YE protocols in a non-religious context (mindfulness, stretching, toning and breathing exercises). We will consult our Indian and US colleagues, our Veterans with SMI and their VA therapists to adapt the protocol for our SMI population. We will also adapt our control condition, the Wellness Lifestyle Program (WLP), from our recently completed RELIEVE study. In Aim 2, we will conduct a 2-armed RCT in which consenting Veterans with SMI will be randomly assigned to one of 2 arms: YE and treatment as usual (TAU, any prescribed treatment) or WLP+ TAU. Unlike prior short-term YE RCTs, the two arms will continue 12 months, including an initial 12-week training period consisting of two supervised sessions per week, followed by a 12-week training period consisting of one supervised session per week, and monthly refresher training sessions offered for the remaining 6 months. We will conform to all COVID-19 related requirements for YE and WLP. Our Hybrid 1 trial will compare the efficacy of YE versus WLP. Primary outcomes are self-report and performance-based measures of community functioning; secondary outcomes are cognition and physical fitness measures. Our goals in Aim 3 are to understand demographic/clinical features of Veterans with SMI who are more likely to accept and adopt YE to enable long-term rehabilitation, by analysis of the RCT data (Aim 3A). We will also conduct qualitative interviews with Veterans who have SMI and participated in the YE intervention arm, referring clinicians, and the Yoga instructor to identify barriers and facilitators for implementation (Aim 3B). The project thus aims to advance our long-term goals for improving the quality of life for Veterans with SMI and to provide evidence to guide home- based and over the longer term, community-based YE practice, consistent with the Mission Act and the VA Strategic Plan. Our experience in conducting a variety of SMI research for over 25 years offers strong support for successful completion of the proposal.", "keywords": [ "Adopted", "Adoption", "Affect", "Area", "Award", "Bipolar I", "Breathing Exercises", "COVID-19", "Characteristics", "Clinic", "Clinical", "Cognition", "Cognitive deficits", "Communities", "Community Integration", "Complementary Medicine", "Consent", "Consolidated Framework for Implementation Research", "Consult", "Data", "Disease", "Elements", "Employment", "Ensure", "Exercise", "Family", "Frequencies", "Goals", "Health", "Health Personnel", "Healthcare", "Home", "Hybrids", "Impaired cognition", "Impairment", "India", "Individual", "Integrative Medicine", "Intervention", "Interview", "Leisures", "Life", "Life Style", "Measures", "Mental Health", "Mission", "Muscle Contraction", "Outcome", "Participant", "Patient Self-Report", "Patients", "Pattern", "Persons", "Pharmaceutical Preparations", "Physical Fitness", "Pilot Projects", "Population", "Post-Traumatic Stress Disorders", "Posture", "Prevalence", "Protocols documentation", "Publishing", "Quality of life", "Randomized", "Randomized Controlled Trials", "Recording of previous events", "Refractory", "Regulation", "Rehabilitation therapy", "Relaxation", "Research", "Research Design", "Role", "Rural Community", "Safety", "Schedule", "Schizoaffective Disorders", "Schizophrenia", "Services", "Social Functioning", "Socialization", "Strategic Planning", "Stretching", "Substance Use Disorder", "Suicide prevention", "Symptoms", "Techniques", "Testing", "Time", "Training", "Veterans", "Yoga", "alcohol use disorder", "arm", "cognitive benefits", "comorbidity", "comparative efficacy", "cost", "design", "disability", "effectiveness/implementation study", "efficacy study", "exercise intervention", "exercise program", "exercise training", "experience", "future implementation", "implementation efforts", "implementation facilitators", "improved", "ineffective therapies", "instructor", "interest", "long-term rehabilitation", "mindfulness", "performance based measurement", "physically handicapped", "primary outcome", "programs", "secondary outcome", "severe mental illness", "skills", "social", "study characteristics", "tool", "treatment arm", "treatment as usual", "uptake", "virtual", "whole health" ], "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": "8217", "attributes": { "award_id": "1IK6BX005692-01", "title": "BLRD Research Career Scientist Award Application", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2021-04-01", "end_date": "2026-03-31", "award_amount": null, "principal_investigator": { "id": 24051, "first_name": "Robert", "last_name": "Raffai", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1522, "ror": "", "name": "VETERANS AFFAIRS MED CTR SAN FRANCISCO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1522, "ror": "", "name": "VETERANS AFFAIRS MED CTR SAN FRANCISCO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The overall goal of this Research Career Scientist award is to foster the nominee’s ongoing research program that is focused on the study of extracellular vesicles (EVs) and their extracellular RNA (exRNA) cargo as biomarkers and effectors of human health and disease including among Veterans. Through participation in a national NIH-funded consortium research program, the nominee is working to develop novel methods to study EVs and other carriers of exRNA for biomarker development projects. The nominee also recently reported the first evidence of intercellular signaling between macrophage EVs and hematopoietic progenitor cells to control the process of systemic and vascular inflammation and atherosclerosis cardiovascular disease. Ongoing funding from a VA Merit grant is supporting the nominee’s goal of exploring the role of circulating EVs isolated from Veterans treated for advanced vascular disease as biomarkers and contributors to disease progression including via microRNA cargo. Experiments in the lab will also test if EVs produced from anti- inflammatory macrophages can serve to control inflammation and atherosclerosis in diabetic rodent models. Furthermore, funding from a VA Invention-based Supplement Award will support pre-clinical studies testing such anti-inflammatory EVs as therapeutics to control cardiac inflammation and heart failure in a rodent model system developed and patented for the VA by the nominee. Findings from these studies could provide much needed new therapeutics in the form of EV-biologics to treat inflammatory diseases including in the cardiovascular system that is a major healthcare need among the Veteran patient population. The nominee’s internationally recognized program on EV biology has led to new collaborative research projects with VA clinician investigators at the local and offsite stations. This includes a collaborative project to test EVs produced by cultured stem cells as therapeutic mediators of skeletal muscle regeneration. Such studies have been proposed in a VA Merit grant proposal with the nominee serving as co-Investigator, which is being revised for a resubmission. The nominee is also engaged in collaborative studies with VA clinician investigators to develop biomarkers of adverse outcomes of surgical procedures used to treat advanced vascular disease among Veterans. Finally, projects proposed by the nominee through grants pending at the Department of VA and the NIH make use of EV technology and expertise developed by the nominee to address the COVID19 disease crisis. This includes by making use of new methods of EV detection in biofluids to develop biomarkers for clinical outcomes of COVID19 disease. It also includes developing new forms of engineered EVs designed to serve in improving host immune response against SARS-CoV-2 viral infection as well as to control lung inflammation. Together, the award will serve to sustain the nominee’s momentum to developing a first-in-class research program centered on the study of EVs as biomarkers and biologics to control tissue inflammation and remodeling including in the cardiovascular system. It will also allow to expand the nominees network of collaborators with clinician and basic scientists within the VA intramural research program, as well as at local, national and international sites to widely disseminate and implement expertise in the study of EVs as biologics to improve the diagnosis and treatment of diseases in priority areas to the VA. Furthermore, it will allow the nominee to increase professional service to local and national committees including within the VA and maintain teaching and mentoring to next generation research investigators and clinician scientists within the VA research program.", "keywords": [ "2019-nCoV", "Achievement", "Address", "Alzheimer&apos", "s disease model", "Anti-Inflammatory Agents", "Apolipoprotein E", "Applications Grants", "Area", "Atherosclerosis", "Award", "Biological", "Biological Markers", "Biological Models", "Biology", "Blood Circulation", "Blood Vessels", "COVID-19", "Cardiovascular Diseases", "Cardiovascular system", "Cells", "Clinical", "Collaborations", "Communication", "Coronary Arteriosclerosis", "Country", "Detection", "Diagnosis", "Diet", "Disclosure", "Disease", "Disease Progression", "Educational process of instructing", "Engineering", "Faculty", "Fostering", "Foundations", "Funding", "Goals", "Grant", "Growth", "Health", "Healthcare", "Healthcare Systems", "Heart failure", "Hematopoietic stem cells", "Host Defense", "Human", "Immune", "Immune response", "Immunologic Tests", "Inflammation", "Inflammatory", "Institution", "Intellectual Property", "International", "Intramural Research Program", "Journals", "Laboratories", "Lead", "Legal patent", "Los Angeles", "Lung Inflammation", "Mediator of activation protein", "Medical Research", "Medical Students", "Medical center", "Mentors", "Methods", "MicroRNAs", "Mission", "Molecular", "Myocarditis", "Operative Surgical Procedures", "Outcome", "Pathogenesis", "Peripheral", "Postdoctoral Fellow", "Principal Investigator", "Process", "Professional Organizations", "Property Rights", "Proteins", "Publications", "Publishing", "RNA", "Reporting", "Research", "Research Personnel", "Research Project Grants", "Resources", "Rodent Model", "Role", "Scientist", "Services", "Signal Transduction", "Site", "Skeletal Muscle", "Technology", "Testing", "Therapeutic", "Tissues", "Translations", "United States National Institutes of Health", "Vascular Diseases", "Ventricular Remodeling", "Veterans", "Virus", "Virus Diseases", "adverse outcome", "base", "biomarker development", "career", "design", "diabetic", "experimental study", "extracellular", "extracellular vesicles", "fighting", "graduate student", "health care delivery", "improved", "insight", "invention", "macrophage", "muscle regeneration", "neuroinflammation", "next generation", "novel", "novel therapeutics", "patient population", "preclinical study", "programs", "recruit", "research and development", "stem cells", "systemic inflammatory response", "therapeutic evaluation", "therapy development", "tissue repair", "vascular inflammation" ], "approved": true } }, { "type": "Grant", "id": "8973", "attributes": { "award_id": "1I21RX003888-01", "title": "Auditory Rehabilitation Needs in COVID-19 Survivors", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2021-12-01", "end_date": "2023-11-30", "award_amount": null, "principal_investigator": { "id": 24810, "first_name": "Kelly M.", "last_name": "Reavis", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1518, "ror": "https://ror.org/02v3txv81", "name": "Portland VA Medical Center", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1518, "ror": "https://ror.org/02v3txv81", "name": "Portland VA Medical Center", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true }, "abstract": "Project Background/Rationale: The purpose of this proposal is to quantitatively examine and qualitatively understand the impact of COVID-19 on Veterans' auditory function. Since the pandemic began, over 230,000 Veterans in the VA health care system have tested or been presumed positive for COVID-19. It has been hypothesized that COVID-19 may have adverse effects on the auditory system, although the extent is unknown. Viral induced hearing loss is not a new phenomenon and several case studies and case series have reported new onset and progression of hearing loss and tinnitus, sudden hearing loss (sudden occurrence of acute hearing loss), ear pain, noise sensitivity and otitis media with respect to COVID-19. Moreover, we are lacking an understanding of the auditory rehabilitation needs of COVID-19 survivors. This evidence is required to successfully restore and return Veterans' auditory function to improve their quality of life. Project Aims: There is a need to understand the short- and long-term consequences of COVID-19 on the auditory system, especially among Veterans who are already at risk for underlying auditory complications, and to conceptualize these within a rehabilitation framework. The specific aims of this research proposal are to (1) Quantify the burden and impact of COVID- 19 on Veterans' auditory function; and (2) Describe Veterans' experiences with auditory complications following COVID-19 with respect to timing, onset, clinical course, rehabilitation needs, and quality of life. Project Methods: This 2-year pilot project will be accomplished through a mixed-methods approach with a sequential quantitative-qualitative design. Quantitative data regarding COVID- 19 auditory sequelae will be gathered via patient surveys and review of the electronic medical record (n=1,566). Qualitative data will be gathered via semi-structured interviews with COVID- 19 patients (n=40). By focusing on the personal and lived experiences among Veterans with COVID-19, the qualitative aim will explore emerging issues and contextual nuances otherwise unmeasurable using survey methods. Data will be stratified by hospitalization history so that unique needs of Veterans with more severe disease can be examined. Anticipated Impact: Completion of the proposed study will provide evidence for the impacts of COVID-19 on the auditory system. It is our goal to immediately provide clinicians with a better understanding of this complex patient population, functional limitations, and perceived rehabilitation needs. Observed hearing loss and tinnitus may very well become chronic, so the audiological impact of the pandemic may substantially outlast the current phase. Results of this study will lead to a VA Rehabilitation Research & Development, Merit Award application exploring the longitudinal effects of COVID-19 on the ear, hearing, and tinnitus using more robust and audiometric test measures not feasible in this pilot study.", "keywords": [ "2019-nCoV", "ACE2", "Acute", "Adverse effects", "Affect", "Auditory", "Auditory system", "Award", "Bacterial Pneumonia", "Biological", "Brain", "COVID-19", "COVID-19 patient", "COVID-19 survivors", "COVID-19 treatment", "Cadaver", "Caring", "Case Series", "Case Study", "Cells", "Chronic", "Clinical", "Coagulation Process", "Cochlea", "Communicable Diseases", "Complex", "Computerized Medical Record", "Consequentialism", "Cytomegalovirus", "Data", "Disease", "Ear", "Earache", "Endothelium", "Epithelial Cells", "Functional disorder", "Future", "Goals", "Health", "Healthcare Systems", "Hearing", "Hearing Tests", "Hearing problem", "Hospitalization", "Hyperacusis", "Immune system", "Infection", "Inflammation", "Inflammatory", "Interview", "Ischemia", "Life", "Life Experience", "Literature", "Mastoid process", "Measles", "Measures", "Meningitis", "Methods", "Morbidity - disease rate", "Multiple Organ Failure", "Mumps", "Nervous system structure", "Otitis Media", "Pathway interactions", "Patients", "Phase", "Pilot Projects", "Prevalence", "Quality of life", "Receptor Cell", "Recording of previous events", "Rehabilitation therapy", "Reporting", "Research Proposals", "Respiratory Signs and Symptoms", "Respiratory System", "Respiratory distress", "Risk", "Rubella", "SARS-CoV-2 infection", "SARS-CoV-2 positive", "Structure", "Sudden Hearing Loss", "Survey Methodology", "Surveys", "Survivors", "Systemic infection", "Temporal Lobe", "Testing", "Therapeutic", "Time", "Tinnitus", "Vascular Smooth Muscle", "Veterans", "Viral", "Virus", "Work", "adverse outcome", "auditory pathway", "auditory rehabilitation", "base", "comorbidity", "cytokine", "cytokine release syndrome", "design", "experience", "hearing impairment", "improved", "interest", "long term consequences of COVID-19", "male", "middle ear", "military veteran", "mortality", "novel coronavirus", "ototoxicity", "pandemic disease", "patient population", "rehabilitation research", "rehabilitation service", "rehabilitative care", "research and development", "sepsis induced ARDS" ], "approved": true } }, { "type": "Grant", "id": "6723", "attributes": { "award_id": "5I01BX005466-02", "title": "Covid-19: Fast-tracking treatment by exploiting the steroid hormone receptor/TMPRSS2 axis", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2021-04-01", "end_date": "2023-03-31", "award_amount": null, "principal_investigator": { "id": 22480, "first_name": "Kerry L.", "last_name": "Burnstein", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1500, "ror": "", "name": "MIAMI VA HEALTH CARE SYSTEM", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1500, "ror": "", "name": "MIAMI VA HEALTH CARE SYSTEM", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true }, "abstract": "COVID-19 poses a tremendous health threat, particularly to individuals overrepresented in the US Veteran community. COVID-19 mortality is greater in men than in women; while this disparity is at least partially due to factors such as higher rates of smoking, a hormonal link is likely and can be rapidly tested therapeutically by repurposing existing drugs. The viral etiologic agent of COVID-19, SARS-CoV-2 (CoV-2), attaches to human airway epithelium via the viral spike (S) protein, which binds to angiotensin-converting enzyme 2 (ACE2) on the host cell surface. Viral entry requires S protein cleavage by the serine protease TMPRSS2, which is a known transcriptional target of the androgen receptor (AR). Lung epithelial cells (a target of CoV-2 infection) express transcriptionally active AR. We hypothesize that AR up-regulates TMPRSS2 in lung epithelial cells and thereby promotes viral entry and infectivity. We propose that FDA-approved AR antagonists will decrease CoV-2 entry and spread and can be rapidly repurposed for COVID-19. IL-6 is the major cytokine released in moderate and severe COVID-19 cases and both published and our preliminary data show that IL-6 enhances AR transcriptional activity. We will therefore also examine the contribution of interleukin 6 (IL-6) to AR regulation of TMPRRS2. To facilitate these studies in a robust manner, we propose to isolate the SARS-CoV-2 entry mechanism through the use of luciferase-expressing pseudovirions that harbor the SARS-CoV-2 S protein. Such a reporter system has high reproducibility, versatility and dynamic range, allowing for the rapid, accurate and specific assessment of a large range of viral entry regulators into primary human lung epithelial cells and lung adenocarcinoma cell lines under BSL2+ conditions. We will test whether AR inhibition reduces TMPRSS2 and the requisite S protein processing thereby decreasing CoV-2 entry into host lung epithelial cells. Subsequently, we will confirm results on a subset of promising compounds using live SARS-Cov-2 in an approved BSL3 facility. Safe and effective AR antagonists are FDA approved for prostate cancer and this study will provide rationale to repurpose these drugs for use in clinical trials for COVID-19. The glucocorticoid receptor (GR) shares a common DNA response element consensus sequence with AR. Furthermore, GR upregulation of TMPRSS2 has been shown in advanced prostate cancer. Therefore, in parallel, we will examine whether TMPRSS2 is regulated by glucocorticoids (cortisol) and blocked by a GR antagonist in models of human lung epithelia. Patients taking corticosteroids (including the elderly and individuals with diabetes, hypertension and chronic inflammatory disease) are at the highest risk of death from COVID-19. The World Health Organization has provided interim guidance to avoid glucocorticoids in COVID- 19 patients with severe acute respiratory distress syndrome. Therefore, understanding GR regulation of TMPRSS2 is also essential to repurposing the TMPRSS2-inhibitory FDA-approved agents for COVID-19. Our aims are to: (1) Evaluate steroid hormone receptor (AR and GR) regulation of TMPRSS2 in human primary airway and lung epithelial cells and lung adenocarcinoma cell line models and (2) Examine the capacity of FDA-approved AR and GR antagonists to block CoV-2 entry and infectivity in human primary airway and lung epithelial cells. US Veterans represent several demographics acutely afflicted by COVID-19. Older US Veterans are particularly vulnerable because of higher comorbidities including smoking, diabetes, heart disease and hypertension. Burden on the Veteran community is also proportionally higher given the propensity for poor outcome in men as compared to women following COVID-19 infection. Since the anti-androgen therapies to be tested are FDA approved for prostate cancer treatment and have also been used safely in women with breast cancer, our study has potential for immediate impact to all veterans.", "keywords": [ "2019-nCoV", "ACE2", "Acute", "Acute Respiratory Distress Syndrome", "Address", "Adrenal Cortex Hormones", "Affect", "Agonist", "Androgen Antagonists", "Androgen Receptor", "Antiandrogen Therapy", "Binding", "COVID-19", "COVID-19 mortality", "COVID-19 patient", "COVID-19 treatment", "Cell Line", "Cell surface", "Clinical Trials", "Collaborations", "Colorado", "Communities", "Consensus Sequence", "DNA", "Data", "Diabetes Mellitus", "Disease", "Drug usage", "Elderly", "Enrollment", "Epithelial", "Epithelial Cells", "Etiology", "FDA approved", "Genetic Transcription", "Glucocorticoid Receptor", "Glucocorticoids", "Health", "Health Personnel", "Heart Diseases", "Hormonal", "Human", "Hydrocortisone", "Hypertension", "Individual", "Infection", "Interdisciplinary Study", "Interleukin-6", "Ligands", "Link", "Luciferases", "Lung", "Lung Adenocarcinoma", "Malignant neoplasm of prostate", "Measures", "Modeling", "Nuclear Receptors", "Outcome", "Patients", "Pattern", "Pharmaceutical Preparations", "Pharmacological Treatment", "Prostate Cancer therapy", "Proteins", "Proteolysis", "Publishing", "Receptor Inhibition", "Regulation", "Reporter", "Reproducibility", "Research", "Resistance", "Response Elements", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "Serine Protease", "Smoking", "Stanolone", "System", "TMPRSS2 gene", "Testing", "Therapeutic", "Universities", "Veterans", "Viral", "Virus", "Woman", "World Health Organization", "advanced prostate cancer", "airway epithelium", "biosafety level 3 facility", "castration resistant prostate cancer", "chronic inflammatory disease", "comorbidity", "cytokine", "demographics", "drug repurposing", "glucocorticoid receptor alpha", "high risk", "human model", "loved ones", "mRNA Expression", "male", "malignant breast neoplasm", "men", "protein expression", "receptor upregulation", "response", "severe COVID-19", "steroid hormone receptor", "therapeutic evaluation", "transcriptome", "viral entry inhibitor" ], "approved": true } }, { "type": "Grant", "id": "15678", "attributes": { "award_id": "1I01BX006894-01", "title": "NCOA7 deficiency worsens brain damage after stroke", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2025-04-01", "end_date": "2029-03-31", "award_amount": null, "principal_investigator": { "id": 32523, "first_name": "Dandan", "last_name": "Sun", "orcid": "", "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 and Innovation: Lysosomes (with an acidic milieu of pH around 4.5) contain numerous acidic hydrolases for maintaining cellular homeostasis via the degradation of unwanted cellular components. NCOA7 (nuclear receptor coactivator 7), a member of the Tre2/Bub2/Cdc16 (TBC), lysin motif (LysM), domain catalytic (TLDc) protein family, was initially implicated in the oxidative stress as oxidation resistance proteins. However, new research demonstrates that NCOA7 directly binds and modulates vacuolar H+- ATPase (V-ATPase) assembly and activity to control endolysosomal acidification. Our pilot data from SNP- edited, human stem cell-derived endothelial cells have demonstrated that allele-specific binding of the inflammatory transcription factor NF-κB to a common intronic variant SNP rs11154337 in NCOA7 controls gene expression. Namely, we found that a C/C genotype, present in ~25% of the population, promoted lower NCOA7 expression and less lysosomal acidification (Prelim Data). Global Ncoa7 transgenic knockout mice (Ncoa7-/-, KO) are viable up to 18 months of age, with comparable gross brain structure to wild-type littermate (WT). However, upon ischemic stroke, compared to WT mice, we found that Ncoa7 KO mice exhibited worsened ischemic stroke outcomes (higher mortality, worsened blood-brain barrier impairment, increased astrogliosis and microglial activation, and abnormal accumulation of myelin basic protein, MBP) (Prelim Data). Whether the above worsened ischemic stroke outcomes resulted from V-ATPase dysfunction and lysosomal de-acidification remains unknown. In this proposal, we will test our hypotheses: 1). NCOA7 plays an important role in V-ATPase activity and lysosomal function in stroke brain in a cell-specific manner; 2). NCOA7 deficient in neurons and in oligodendrocytes drives lysosomal dysfunction and oxysterol/bile acid- specific inflammation, as well as abnormal cholesterol and MBP accumulation; 3). Post-stroke administration of NCOA7 activator Compound 958 will stimulate NCOA7 activity and reduce stroke brain damage. Significance and Impact to Veterans Healthcare: Cardiovascular diseases such as hypertension and pre- hypertension are common in active US military personnel. Moreover, post-traumatic stress disorder is associated with different cardiovascular and cerebrovascular diseases in older veterans. Collectively, these are well-established risk factors for stroke. The goal of this proposal is to study cellular mechanisms underlying the worsened ischemic stroke outcomes in NCOA7 deficient conditions and to determine whether pharmacological stimulation of NCOA7 is a novel therapeutic strategy for improving acute ischemic stroke outcomes. Therefore, our proposal is closely relevant to Veterans and the VA mission. Path to translation/implementation: completion of this study will directly address our knowledge gap about role of NCOA7 in regulating lysosome function and cholesterol metabolism in the stroke brains. To explore pharmacological tools, utilizing computational modeling, we developed a novel small molecule activator of NCOA7, Compound 958, which reduced pulmonary endothelial immunoactivation and robustly improved survival of a mouse model of acute COVID-19 (Prelim Data). Our findings from this study will reveal potentials of NCOA7 as a therapeutic target for attenuating V-ATPase dysfunction in stroke brain, and efficacy of NCOA7 activator Compound 958 in stroke therapy.", "keywords": [ "Acute", "Address", "Age Months", "Alleles", "Axon", "Bile Acids", "Binding", "Blood - brain barrier anatomy", "Blood Vessels", "Brain", "Brain Diseases", "Brain Injuries", "Cardiovascular Diseases", "Catalytic Domain", "Cause of Death", "Cells", "Cerebral Ischemia", "Cerebrovascular Disorders", "Cholesterol", "Cholesterol Homeostasis", "Computer Models", "Data", "Demyelinations", "Drug Kinetics", "Endothelial Cells", "Endothelium", "Endowment", "Exhibits", "Functional disorder", "Gene Expression", "Generations", "Genotype", "Goals", "Health Care", "Heterozygote", "Homeostasis", "Hydrolase", "Hydrolysis", "Hydroxylation", "Hypertension", "Impairment", "Inflammation", "Inflammatory", "Institute of Medicine (U.S.)", "Ischemic Stroke", "Knockout Mice", "Knowledge", "Lung", "Lysosomes", "Medicine", "Military Personnel", "Mission", "Mus", "Myelin Basic Proteins", "Nerve Degeneration", "Neuroglia", "Neurological outcome", "Neurons", "Nuclear Receptors", "Oligodendroglia", "Oxidative Stress", "Pathogenesis", "Play", "Population", "Post-Traumatic Stress Disorders", "Production", "Protein Family", "Proteins", "Pulmonary Hypertension", "Recovery", "Research", "Resistance", "Risk Factors", "Role", "Scientist", "Sterols", "Stroke", "Structure", "Testing", "Transgenic Organisms", "Translations", "USP6 gene", "Variant", "Vascular Diseases", "Veterans", "acute COVID-19", "astrogliosis", "career", "cholesterol trafficking", "design", "efficacy evaluation", "glial activation", "human stem cell-derived", "improved", "innovation", "lysin", "member", "mortality", "mouse model", "neuron loss", "novel", "novel therapeutic intervention", "oxidation", "pharmacologic", "post stroke", "prehypertension", "professor", "small molecule", "stroke outcome", "stroke recovery", "stroke therapy", "therapeutic target", "tool", "transcription factor", "vacuolar H+-ATPase", "white matter" ], "approved": true } } ], "meta": { "pagination": { "page": 5, "pages": 1442, "count": 14420 } } }