Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1383&sort=-program_reference_codes
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-program_reference_codes", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1424&sort=-program_reference_codes", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1384&sort=-program_reference_codes", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1382&sort=-program_reference_codes" }, "data": [ { "type": "Grant", "id": "12128", "attributes": { "award_id": "1R21MH130797-01A1", "title": "Prospective predictors of risk and resilience trajectories of mental health in US youth during COVID-19", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Mental Health (NIMH)" ], "program_reference_codes": [], "program_officials": [ { "id": 8692, "first_name": "Ashley", "last_name": "Smith", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-08-01", "end_date": "2025-05-31", "award_amount": 267000, "principal_investigator": { "id": 27989, "first_name": "Ran", "last_name": "Barzilay", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1073, "ror": "", "name": "CHILDREN'S HOSP OF PHILADELPHIA", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "The COVID-19 pandemic has had substantial effects on youth in multiple aspects of life, raising concern about its impact on youth mental health. Indeed, mounting data suggest that youth depression and anxiety rates have increased compared to the pre-pandemic era. A key challenge is to recognize prospective predictors that can help identify youth at risk for serious mental health sequelae following COVID-19 and to disentangle the factors that contribute to resilient trajectories. Resilience, often defined as an adaptive outcome (i.e., low symptoms levels) following adversity, is driven by multiple systems including individual- and structural-level environmental factors, neurocognitive traits, and genetic factors. One approach to study resilience is to identify inter-individual variation in mental health trajectories following the pandemic, and use data collected prospectively before and early in the pandemic to better understands what determines variability in mental health trajectories under stress. The Adolescent Brain Cognitive Development (ABCD) Study (N~12,000, 52% male, recruited at age 9-10 years, 20% Black) follows diverse US youth longitudinally since 2017. The study collected multidimensional (i.e., environment, clinical, neurocognitive, genetic) data before the pandemic, and participants were ~12-13 years old when the pandemic hit. Between May 2020 to June 2021, the study team collected data on mental health and on COVID-19 related exposures at multiple time points from ~9,500 participants and will continue following participants into late adolescence. Therefore, ABCD Study creates a unique opportunity to disentangle risk and resilience factors collected prospectively in youth who were in early-mid adolescence when the pandemic hit, a critical developmental window when stress related disorders become more prevalent. In the current project, we propose to leverage the multi-dimensional ABCD Study data to identify factors that contribute to variability in mental health trajectories in US youth during the COVID-19 pandemic. We will first use latent growth mixture modeling to identify trajectories of internalizing symptoms over time. Thereafter, we will characterize the individual stressors and the structural (based on geocoded address) environmental exposures- before and early in the pandemic- that contribute to trajectories of risk and resilience (Aim 1). In addition, we will leverage the deep phenotyping that was conducted pre-COVID-19 to identify clinical and neurocognitive risk and resilience factors (Aim 2). Lastly, we will explore whether participants' genetic information (i.e., polygenic risk for psychiatric disorders) can help explain variability in mental health trajectories during the pandemic (Aim 3). The proposed research will identify what factors contribute to resilience (i.e., resilience factors); and who will show risk or resilience trajectory in response to chronic (pandemic-imposed) stress. The study addresses key gaps that are critical considering the expected chronic stress that is (and will likely keep being) imposed on youth due to the pandemic and other future adversities. Findings will improve risk stratification in youth exposed to chronic adversity and will identify targets for interventions aimed at enhancing resilience.", "keywords": [ "13 year old", "Address", "Adolescence", "Adolescent", "Age", "Anxiety", "Back", "Black race", "Brain", "COVID-19", "COVID-19 pandemic", "Chronic", "Chronic stress", "Clinical", "County", "Data", "Data Analyses", "Development", "Dimensions", "Early Intervention", "Emotional", "Environment", "Environmental Exposure", "Environmental Risk Factor", "Exposure to", "Financial Hardship", "Fostering", "Future", "Genes", "Genetic", "Genotype", "Global Warming", "Goals", "Growth", "Health", "Height", "Household", "Individual", "Intervention", "Life", "Longitudinal Studies", "Measures", "Mental Depression", "Mental Health", "Mental disorders", "Modeling", "Neighborhoods", "Neurocognitive", "Outcome", "Participant", "Pattern", "Persons", "Phenotype", "Post-Traumatic Stress Disorders", "Preventive measure", "Process", "Psychiatry", "Psychopathology", "Research", "Risk", "Risk Factors", "Risk Marker", "SARS-CoV-2 infection", "Sampling Studies", "Schools", "Social Interaction", "Source", "Stress", "Symptoms", "System", "Teenagers", "Time", "Trauma", "Youth", "child depression", "childhood anxiety", "clinical phenotype", "cognitive development", "cohort", "comparison group", "coronavirus disease", "deprivation", "emotion regulation", "experience", "genetic information", "improved", "inter-individual variation", "male", "pandemic disease", "pandemic stress", "peer", "pre-pandemic", "preventive intervention", "promote resilience", "prospective", "psychologic", "recruit", "resilience", "resilience factor", "response", "risk stratification", "sex", "stress related disorder", "stressor", "structural determinants", "substance use", "suicidal behavior", "trait", "young adult" ], "approved": true } }, { "type": "Grant", "id": "12129", "attributes": { "award_id": "1K01MH131797-01A1", "title": "Building a Community-Based Mental Health Literacy Intervention for African American Young Adults", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Mental Health (NIMH)" ], "program_reference_codes": [], "program_officials": [ { "id": 26585, "first_name": "Maggie", "last_name": "Sweeney", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-08-01", "end_date": "2028-07-31", "award_amount": 197181, "principal_investigator": { "id": 27990, "first_name": "Alexandria Gabrielle", "last_name": "Bauer", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1732, "ror": "", "name": "RUTGERS, THE STATE UNIV OF N.J.", "address": "", "city": "", "state": "NJ", "zip": "", "country": "United States", "approved": true }, "abstract": "Black/African American young adults are at elevated risk for trauma and related mental health concerns (e.g., PTSD, substance use) yet are less likely to engage in mental health care than other groups, due to substantial and complex barriers to care. These disparities have been exacerbated by, and compounded with, psychological and emotional distress due to the COVID-19 pandemic. Promoting mental health literacy (MHL), defined as knowledge and beliefs related to mental health (e.g., recognition, prevention, and management of symptoms) may be an important first step to improving mental health outcomes for Black/African American young adults. This K01 Mentored Research Scientist Development Award will partner with a Community Advisory Board to develop a community based MHL intervention, focused on trauma and substance use, for Black/African American young adults. The culturally tailored intervention will be guided by the Theory of Planned Behavior (TPB) and social ecological model as guiding frameworks, with intervention components designed to promote TPB dimensions (i.e., behavioral, normative, and control beliefs related to mental health care utilization) with resources at the individual, interpersonal, and organizational levels. Following development, the intervention will be piloted among Black/African American young adults aged 18-35 years old (N = 80), recruited from diverse community sites (e.g., colleges/universities, barbershops and hair salons, churches, community organizations). Participants will complete a baseline survey assessing primary and secondary outcomes (e.g., current MHL; stigma; beliefs, attitudes, and norms; history of mental health care), with re-assessment mid-intervention and post-intervention. Post-study focus groups with intervention participants (N = 30) will be held to elicit feedback on relevance, feasibility, acceptability, and satisfaction with the intervention, to inform refinement and future dissemination efforts. Successful completion of the proposed study will also benefit the PI, an early career researcher with goals to A) develop expertise in community engagement and theoretically-driven translational research methods and B) build community capacity to prevent mental illness, support recovery, and improve health outcomes with underserved and oppressed communities. The PI is currently an Assistant Research Professor at Rutgers University at the Center of Alcohol & Substance Use Studies, within the Graduate School of Applied and Professional Psychology. Her long-term career goals include becoming a tenure-track, independent investigator; contributing to recruitment and mentorship of underrepresented students; and advancing health and social equity for underserved and minoritized communities.", "keywords": [ "Adult", "African American", "Age", "Alcohol consumption", "American", "Area", "Attitude", "Baseline Surveys", "Behavior", "Behavioral", "Belief", "Black race", "COVID-19 pandemic", "COVID-19 pandemic effects", "Church", "Clinical", "Collaborations", "Communities", "Complex", "Counseling", "Development", "Dimensions", "Disparity", "Educational Curriculum", "Educational Materials", "Educational workshop", "Elements", "Emotional", "Ensure", "Equity", "European", "Feedback", "Focus Groups", "Fostering", "Future", "Gender", "Goals", "Hair", "Health", "Healthcare Systems", "Hispanic", "Individual", "Intervention", "Knowledge", "Learning", "Mental Depression", "Mental Health", "Mental Health Services", "Mental disorders", "Mental health promotion", "Mentored Research Scientist Development Award", "Mentors", "Mentorship", "Methods", "Modeling", "Outcome", "Participant", "Perception", "Planning Theory", "Positioning Attribute", "Post-Traumatic Stress Disorders", "Prevention", "Provider", "Psychologist", "Psychology", "Public Health", "Recording of previous events", "Recovery Support", "Research", "Research Assistant", "Research Methodology", "Research Personnel", "Resources", "Risk", "Sampling", "Schools", "Services", "Signs and Symptoms", "Site", "Socioeconomic Status", "Substance Use Disorder", "Symptoms", "Translational Research", "Trauma", "Underrepresented Students", "Universities", "Woman", "Writing", "aged", "barrier to care", "behavioral construct", "behavioral outcome", "care burden", "career", "career development", "college", "community based research", "community building", "community engaged research", "community engagement", "community organizations", "community setting", "coping", "design", "emotional distress", "experience", "graduate school", "health care service utilization", "health literacy", "improved", "intervention participants", "intervention refinement", "member", "men", "mental development", "minority communities", "peer", "post intervention", "prevent", "primary outcome", "professor", "psychoeducation", "psychoeducational", "psychologic", "psychological distress", "psychosocial", "racial disparity", "recruit", "satisfaction", "secondary outcome", "social", "social stigma", "substance use", "substance use treatment", "symptom management", "tenure track", "theories", "therapy design", "trauma exposure", "trend", "underserved community", "university student", "young ad" ], "approved": true } }, { "type": "Grant", "id": "12130", "attributes": { "award_id": "1R01GM147211-01A1", "title": "YloC, a new ribonuclease of Bacillus subtilis", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 27797, "first_name": "Michael T.", "last_name": "Bender", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-08-01", "end_date": "2027-04-30", "award_amount": 354900, "principal_investigator": { "id": 27991, "first_name": "DAVID H", "last_name": "BECHHOFER", "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": "PROJECT SUMMARY: Our laboratory has, for many years, studied the essential process of mRNA decay in the model Gram-positive bacterium, Bacillus subtilis. We have identified several ribonuclease (RNase) enzymes of B. subtilis and have elucidated the role they play in mRNA turnover. The viability of a B. subtilis strain lacking all of the known 3’-to-5’ exoribonucleases prompted us to pursue identification of additional RNase activities. Using classic protein biochemistry, we recently identified a novel RNase, named YloC. YloC is an endoribonuclease with a hexameric structure, an unusual characteristic that is shared with only one other RNase: the Nsp15 protein of the SARS-CoV family. Initial experiments suggest that, although YloC has ribonuclease activity in vitro, it may function as an adapter for RNA interactions in vivo. Although proteins with significant homology to YloC are widespread in bacterial species, there is no published information on the structure of any member of this protein family. The current proposal seeks to elucidate the structure and function of YloC, as follows: • Mutagenize highly conserved residues of YloC to determine the effect on several properties – including ribonuclease activity, RNA binding, and structure – and to clarify functional domains of the protein. • Identify high-affinity RNA ligands of YloC via SELEX procedures with random-sequence oligonucleotides and with genomic RNA sequences. • Characterize how the strong interaction of YloC with E. coli polynucleotide phosphorylase (PNPase) acts in small RNA (sRNA) regulation in E. coli and possibly in B. subtilis. • Determine the three-dimensional structure of the highly homologous E. coli YicC protein bound to an RNA substrate, as well as the structure of YloC and/or its homologs from thermophilic bacterial species. This work will build on an initial determination of the structure of YicC. RELEVANCE: Ribonucleases play essential roles in RNA turnover and processing. A thorough understanding of the proteins that bind to and act enzymatically on RNA molecules will enable design of antimicrobial agents that disrupt such proteins and thereby interfere with bacterial cell growth.", "keywords": [ "5&apos", "-exoribonuclease", "Adaptor Signaling Protein", "Affect", "Affinity", "Alanine", "Awareness", "Bacillus subtilis", "Bacteria", "Binding", "Binding Proteins", "Biochemical", "Biological Assay", "Biological Process", "Biology", "Biophysics", "C-terminal", "Catalysis", "Cells", "Characteristics", "Code", "Coronavirus", "Endoribonucleases", "Enzyme Inhibition", "Enzymes", "Escherichia coli", "Exonuclease", "Family", "Family member", "Gene Deletion", "Genes", "Gram-Positive Bacteria", "Homologous Gene", "In Vitro", "Laboratories", "Ligands", "Messenger RNA", "Modeling", "Mutagens", "N-terminal", "Names", "Nucleotides", "Oligonucleotides", "Organism", "Outcome", "Pancreatic ribonuclease", "Physiological Processes", "Play", "Polyribonucleotide Nucleotidyltransferase", "Procedures", "Process", "Property", "Protein Biochemistry", "Protein Family", "Proteins", "Publishing", "RNA", "RNA Binding", "RNA Sequences", "RNA chemical synthesis", "Regulation", "Regulatory Element", "Reporting", "Ribonucleases", "Role", "SARS coronavirus", "Sequence Homology", "Small RNA", "Specific qualifier value", "Specificity", "Structure", "Tertiary Protein Structure", "Testing", "Transcript", "Virulence", "Work", "antibiotic design", "antimicrobial drug", "cell growth", "design", "endonuclease", "environmental change", "experimental study", "follow-up", "genome-wide", "genomic RNA", "in vitro activity", "in vivo", "insight", "mRNA Decay", "member", "microorganism", "model organism", "mutant", "novel", "poly A specific exoribonuclease", "prototype", "recruit", "response", "thermophilic organism", "three dimensional structure" ], "approved": true } }, { "type": "Grant", "id": "12131", "attributes": { "award_id": "1R24OD035459-01", "title": "Automation of Liquid Nitrogen Freezer for Cryopreservation of Unique Human Biospecimens at the Vanderbilt Biospecimen Storage Facility", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "NIH Office of the Director" ], "program_reference_codes": [], "program_officials": [ { "id": 27589, "first_name": "FLAUBERT", "last_name": "Tchantchou", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-08-01", "end_date": "2024-07-31", "award_amount": 252800, "principal_investigator": { "id": 27992, "first_name": "Alexander", "last_name": "Bick", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 456, "ror": "https://ror.org/05dq2gs74", "name": "Vanderbilt University Medical Center", "address": "", "city": "", "state": "TN", "zip": "", "country": "United States", "approved": true }, "abstract": "Large, high-dimensional clinical, genetic and biomarker data linked to bio-repositories are driving basic, clinical and translational research. For the past 20 years, Vanderbilt University Medical Center (VUMC) has made long-term strategic investments in translational sciences as a platform for excellence across clinical and basic science departments and is internationally recognized as a leader in such fields as personalized medicine, vaccinology, and cancer care and research. As examples, BioVU, Vanderbilt’s large-scale biorepository, contains detailed de-identified human phenotype information linked to de-identified discarded samples and genotypes. Viably cryopreserved human specimens enabled the Vanderbilt Vaccine Center to isolate monoclonal antibodies against COVID-19 that were developed into Evusheld, a therapy to prevent COVID-19 in at-risk individuals. Cooperative Human Tissue Network at VUMC is one of only six funded by the National Cancer Institute to procure and distribute human tissues to researchers throughout the US, Canada, and internationally. These resources and others provide an accelerating engine of discovery. Collectively these endeavors are providing powerful predictors of disease risk, disease progression or response to therapy and underpinning studies delineating the fundamental mechanism of disease as well as translation to the clinic. These large-scale initiatives generate a massive number of valuable human and animal tissue samples. These tissues can only be viably cryopreserved when stored in liquid nitrogen. The size of these biorepositories is exceeding the capacity of individual investigators or groups to effectively curate, maintain sample integrity and rapidly retrieve samples for further study. Many of these materials could not be replaced and are of international importance. To meet this large and growing need, a specialized automated -190°C Cryogenic Freezer for Sample Storage system is necessary to manage, store and retrieve the tens of thousands of biorepository samples. This proposal seeks to obtain funding for the purchase of an Azenta BioStore Cryo M60 robotic liquid nitrogen freezer system that can accommodate all large biorepositories at Vanderbilt. With such a system Vanderbilt can provide the necessary institutional support, environment and expertise to ensure cost- effective, quality assured management, storage and retrieval of these critical samples and reagents. The technology is durable and scalable and therefore it can be predicted that this automated system will enable a broad range of investigators and propel basic, clinical and translational research long into the future.", "keywords": [ "Academic Medical Centers", "Acceleration", "Automation", "Automobile Driving", "Award", "Basic Science", "Biological", "Biological Markers", "Biological Sciences", "COVID-19 pandemic", "COVID-19 patient", "COVID-19 prevention", "Canada", "Clinic", "Clinical", "Clinical Research", "Clinical Sciences", "Collection", "Cooperative Human Tissue Network", "Cryopreservation", "Data", "Disease", "Disease Progression", "Ensure", "Environment", "Friends", "Funding", "Future", "Genetic", "Genotype", "Glass", "Human", "Individual", "Infrastructure", "Institution", "International", "Investigation", "Investments", "Link", "Liquid substance", "Monitor", "Monoclonal Antibodies", "National Cancer Institute", "Nitrogen", "Phenotype", "Reagent", "Recovery", "Research Personnel", "Resource Sharing", "Resources", "Retrieval", "Risk", "Robotics", "SARS-CoV-2 antibody", "Safety", "Sampling", "Services", "Specimen", "System", "Technology", "Temperature", "Tissue Sample", "Tissues", "Transition Temperature", "Translational Research", "Translations", "United States", "United States National Institutes of Health", "Vaccines", "Water", "Withdrawal", "animal tissue", "anticancer research", "biobank", "cancer care", "cell preparation", "cost", "cost effective", "cryogenics", "disorder risk", "high dimensionality", "human disease", "human tissue", "improved", "migration", "personalized medicine", "preservation", "repository", "treatment response", "vaccinology" ], "approved": true } }, { "type": "Grant", "id": "12132", "attributes": { "award_id": "1K01AG078545-01A1", "title": "A Diet Intervention Study To Mitigate Fatigue Symptoms And To Improve Muscle And Physical Function In Older Adults With Post-Acute COVID-19 Syndrome", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Aging (NIA)" ], "program_reference_codes": [], "program_officials": [ { "id": 11335, "first_name": "BASIL A", "last_name": "ELDADAH", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-08-15", "end_date": "2028-07-31", "award_amount": 124227, "principal_investigator": { "id": 27993, "first_name": "Galya", "last_name": "Bigman", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 793, "ror": "", "name": "UNIVERSITY OF MARYLAND BALTIMORE", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Nearly one in five American adults who survived the coronavirus disease (COVID-19) are still suffering from post-acute COVID-19 syndrome (PACS),42 a complex systemic disease manifests in fatigue and muscle weakness that substantially limits one or more major life activities.35-41,92 For older adults, having PACS coupled with an inadequate diet may compound their health deterioration and hasten their physical function decline. 43- 44 Nutritional studies demonstrate that a whole diet comprises foods high in anti-inflammatory activities, e.g., whole grains, fruits, vegetables, and omega-3 fatty acid-rich foods substantially reduce disease-related fatigue, likely by reducing inflammation.49-50 U.S. adults who followed the Dietary Guidelines for Americans (DGA) were more likely to preserve muscle grip strength than those who did not.17 Since fatigue and physical function are interrelated, a ‘Whole-Diet Approach’56,61,62 aligned with the DGA60 with a focus on nutrients high anti- inflammatory activities may be an effective strategy to ameliorate recovery from PACS in older adults. This project proposes to examine, in a 16-week randomized-controlled dietary intervention, the effect of the ‘Whole- Diet Approach’ on mitigating symptoms of PACS related to nutrition, e.g., fatigue and muscle weakness and will explore the underlying mechanisms via biomarkers. The sample will comprise men and women aged 50 years or older with PACS, including underrepresented minorities (50% Non-Hispanic-Blacks). At baseline, N=56 eligible participants will be randomized to either: 1) a dietary intervention following the new DGA with a focus on nutrients high in anti-inflammatory activities via foods and or supplements (e.g., vitamin D, omega-3, and whey); or 2) attention control. Aim 1. In a 16-week, randomized-controlled trial, we will examine the effect of the Whole-Diet Approach (WDA) on the Healthy Eating Index (HEI) and fatigue compared to attention control in adults with PACS. Aim 2. To assess the impact of the dietary intervention following the WDA on muscle mass, strength, and physical function compared to attention control in adults with PACS. Aim 3. To explore the mechanism of decreased fatigue and improved muscle and physical function by examining changes in nutritional and inflammatory biomarkers from baseline to 16 weeks. The proposed dietary intervention to attenuate PACS in older adults is a feasible study relevant to public health. The University of Maryland Baltimore provides a unique opportunity to be trained by a multidisciplinary team of mentors who are experts in clinical trials, muscle, physical function, nutrition, geriatrics, statistics, and COVID-19 to conduct this study successfully. The findings can be translated into a new strategy to counteract fatigue and physical function decline following PACS. The K01 Award will provide me with the training I need to become an independent investigator in dietary trials to advance the field of nutrition and aging while gaining the skills and experience in leadership and mentorship to launch my career in academia.", "keywords": [ "2019-nCoV", "Abate", "Academia", "Adherence", "Adult", "Aging", "American", "Anti-Inflammatory Agents", "Attenuated", "Baltimore", "Biological Markers", "Black Populations", "COVID-19", "Clinical Trials", "Complex", "Control Groups", "Coupled", "Deterioration", "Diet", "Dietary Fiber", "Dietary Intervention", "Dietitian", "Disease", "Dual-Energy X-Ray Absorptiometry", "Education", "Elderly", "Equilibrium", "Equipment and supply inventories", "Exhibits", "Fatigue", "Feasibility Studies", "Food", "Fruit", "Future", "Geriatrics", "Hand Strength", "Health", "Healthy Eating", "Hispanic Populations", "Hour", "Individual", "Infection", "Inflammation", "Inflammatory", "Intake", "Interleukin-6", "Intervention", "Intervention Studies", "Leadership", "Life", "Long COVID", "Maryland", "Measures", "Mentored Research Scientist Development Award", "Mentors", "Mentorship", "Muscle", "Muscle Weakness", "Muscle function", "Not Hispanic or Latino", "Nutrient", "Nutritional", "Nutritional Study", "Omega-3 Fatty Acids", "Participant", "Pathology", "Physical Function", "Physical Performance", "Plants", "Proteins", "Public Health", "Randomized", "Randomized Controlled Trials", "Recommendation", "Recovery", "Research Personnel", "Sampling", "Seafood", "Structure", "Symptoms", "Systemic disease", "Testing", "Thinness", "Training", "Translating", "Underrepresented Minority", "Universities", "Vegetables", "Vitamin D", "Walking", "Whey Protein", "Woman", "aged", "attentional control", "bean", "career", "common symptom", "comparison control", "coronavirus disease", "dietary", "dietary guidelines", "eligible participant", "ethnic minority", "experience", "group intervention", "improved", "indexing", "men", "multidisciplinary", "muscle form", "nutrition", "pandemic disease", "preservation", "prevent", "racial minority", "skills", "statistics" ], "approved": true } }, { "type": "Grant", "id": "12133", "attributes": { "award_id": "1R21AI169536-01A1", "title": "Mechanisms of antiviral immunity and tolerance in the intestinal epithelium of Jamaican Fruit Bats", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 8224, "first_name": "Kentner L.", "last_name": "Singleton", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-08-08", "end_date": "2025-07-31", "award_amount": 214575, "principal_investigator": { "id": 25077, "first_name": "Diane", "last_name": "Bimczok", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 987, "ror": "", "name": "MONTANA STATE UNIVERSITY - BOZEMAN", "address": "", "city": "", "state": "MT", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 987, "ror": "", "name": "MONTANA STATE UNIVERSITY - BOZEMAN", "address": "", "city": "", "state": "MT", "zip": "", "country": "United States", "approved": true }, "abstract": "The gastrointestinal (GI) tract is a major target organ for viral infection in bats, but infections rarely cause typical symptoms of viral enteritis such as diarrhea. The long-term goal of our project is to understand the specific innate immune response mechanisms of the intestinal epithelium that enable bats to sustain viral infection without experiencing cytopathic effects and intestinal barrier dysfunction. We hypothesize that protective type I and type III interferon (IFN) responses in Jamaican Fruit Bats (Artibeus jamaicensis, JFBs) enable persistent, asymptomatic viral infection of the gastrointestinal epithelium. To test our hypothesis, we will utilize a novel in vitro model of the JFB intestine, 3-D enteroids, which are complex long-term cultures of primary intestinal epithelial cells generated from adult tissue-derived stem cells. Responses in the gut epithelium of JFBs will be compared to those induced in human enteroids. In Aim 1, we will define type I/III IFN responses of JFB enteroids to viral infection. In Aim 2, we will determine to what extent type I/III IFNs impact viral replication and barrier function in the gastrointestinal epithelium of JFBs. We will analyze intestinal epithelial cell responses to three single-stranded RNA viruses that can infect JFB cells: H18N11 influenza virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and Cedar virus, a non-pathogenic henipavirus. Specifically, we will analyze the kinetics of viral replication and type I/III IFN activation in the enteroids and will also perform a comprehensive proteomics analysis of virus-infected intestinal epithelial cells. To assess the role of virus-induced type I/III IFNs for gastrointestinal epithelial pathology, IFN signaling will be induced or inhibited, and the impact on enteroid susceptibility to viral infection will be analyzed. We also will measure epithelial cell viability, barrier and repair functions that are commonly disrupted during viral enteritis. Our project is technologically innovative, because we will, for the first time, analyze viral infection in enteroid cultures derived from JFBs and because we also will perform a complete proteome analysis of the JFB intestinal epithelium. The proposed work is conceptually innovative, because it will define how virus-induced type I/III IFNs impact intestinal epithelial function and integrity. Our proposed work is significant, because it will provide novel insights in the epithelial cell-intrinsic innate immune mechanisms involved in asymptomatic infection of the bat intestine with viral pathogens, which has important implications for potential pathogen spillover events.", "keywords": [ "2019-nCoV", "3-Dimensional", "Adult", "Antiviral Response", "Biological Response Modifiers", "Cell Survival", "Cell physiology", "Cells", "Characteristics", "Chiroptera", "Complex", "Coronavirus", "Diarrhea", "Diet", "Disease", "Epithelial Cells", "Epithelium", "Family Pteropodidae", "Feces", "Filovirus", "Fruit", "Functional disorder", "Gastrointestinal tract structure", "Gene Expression", "Gene Expression Profile", "Gene Expression Profiling", "Goals", "Henipavirus", "Human", "Immune system", "Immunologics", "Immunology", "Individual", "Infection", "Infectious Diseases Research", "Influenza", "Innate Immune Response", "Interferon Activation", "Interferon alpha", "Interferon-beta", "Interferons", "Intestines", "Jamaican", "Kinetics", "Maintenance", "Mammals", "Measures", "Middle East Respiratory Syndrome Coronavirus", "Modeling", "Organ", "Organoids", "Outcome", "Pathogen detection", "Pathogenicity", "Pathology", "Pathway Analysis", "Pathway interactions", "Pattern", "Pattern recognition receptor", "Predisposition", "Proteome", "Proteomics", "RNA Viruses", "Recombinant Interferon Alfa", "Rectum", "Resistance", "Role", "Signal Transduction", "Simuliidae", "Small Interfering RNA", "Small Intestines", "Swab", "Symptoms", "System", "Tacaribe virus", "Testing", "Time", "Tissue-Specific Gene Expression", "Viral", "Virus", "Virus Diseases", "Virus Replication", "Work", "Zika Virus", "Zoonoses", "antiviral immunity", "chronic infection", "cytotoxicity", "enteric pathogen", "enteritis", "experience", "experimental study", "gastrointestinal epithelium", "genome annotation", "human tissue", "in vitro Model", "influenzavirus", "innate immune mechanisms", "innovation", "innovative technologies", "insight", "intestinal barrier", "intestinal epithelium", "model organism", "novel", "pathogen", "pathogen spillover", "pathogenic virus", "rectal", "repair function", "response", "small molecule inhibitor", "spillover event", "stem cell derived tissues", "transcriptomics" ], "approved": true } }, { "type": "Grant", "id": "12134", "attributes": { "award_id": "1R01HL167192-01A1", "title": "GPR68 as a novel modulator of septic lung injury", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 22454, "first_name": "GUOFEI", "last_name": "Zhou", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-08-01", "end_date": "2027-07-31", "award_amount": 621605, "principal_investigator": { "id": 27994, "first_name": "Anna", "last_name": "Birukova", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 27995, "first_name": "CHARLES C", "last_name": "HONG", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 793, "ror": "", "name": "UNIVERSITY OF MARYLAND BALTIMORE", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Severe sepsis is a common, expensive, and frequently fatal condition which is the leading cause of death in the ICU in the United States. Typically, 50% of all sepsis cases start as a pulmonary infection and vast majority of cases develop as mono-microbial sepsis. Alarming reports indicate that the frequency of gram-positive sepsis has been increasing, likely due to the ability of S. aureus to colonize intravascular catheters or surgically implanted materials, as well as the spread of antibiotic-resistant S. aureus, such as methicillin-resistant S. aureus (MRSA). Sepsis is typically accompanied by multiple organ dysfunction, cytokine storm, disseminated coagulation syndrome that often provoke indirect lung injury culminating in Acute Respiratory Distress Syndrome (ARDS). ARDS is also the primary means of respiratory failure and deaths from the ongoing COVID-19 pandemic. There are no effective pharmacological interventions for ARDS; rather, current treatment is primarily limited to respiratory support through mechanical ventilation; however, suboptimal ventilation volumes can worsen or even cause de novo lung injury. The hallmarks of ARDS are increased cytokine and chemokine levels, inflammatory cell infiltrates, fibrosis, and loss of vascular integrity. This project will test a novel hypothesis that mechano-sensitive proton sensing receptor GPR68 is a key mediator of ARDS pathophysiology that might control the magnitude of lung inflammation initiated by primary infection insult and mitigate ARDS severity associated with suboptimal mechanical ventilation. We will test this hypothesis using our novel first-in-class small molecule GPR68 inhibitor developed by our group through four specific aims: 1) To examine molecular mechanisms of GPR68 activation by pro-inflammatory factors in the in vitro and ex vivo models of inflammatory lung injury; 2) To study the functional role of GPR68 in modulation of pulmonary endothelial response to ARDS-related insults; 3) To examine mechano-sensitive regulation of GPR68 activity; 4) To evaluate a therapeutic potential of pharmacological GPR68 inhibition for mitigation of lung dysfunction in one-hit and two-hit mouse models of bacterial ALI. By better understanding how GPR68 contributes to lung barrier dysfunction and determining whether its inhibition can ameliorate the ARDS phenotype, we will be able to develop and test novel therapeutic agents for treatment of ARDS associated with sepsis, bacterial, viral infection, chemical injury, transfusion related lung injury and other.", "keywords": [ "Acids", "Acute Lung Injury", "Acute Respiratory Distress Syndrome", "Adhesions", "Animal Model", "Antibiotic Resistance", "Bacterial Model", "Blood Vessels", "COVID-19 pandemic", "Cardiology", "Catheters", "Cause of Death", "Caveolins", "Cell model", "Cell physiology", "Cells", "Cessation of life", "Chemical Injury", "Coagulation Process", "Collaborations", "Communities", "Data", "Development", "Discipline", "Disease", "Endothelial Cells", "Endothelium", "Extravasation", "Fibrosis", "Frequencies", "Functional disorder", "G-Protein-Coupled Receptors", "GPR68 gene", "Human", "In Vitro", "Infection", "Infiltration", "Inflammation", "Inflammatory", "Inflammatory Response", "Intervention", "Investigation", "Knowledge", "Lung", "Lung infections", "Mechanical ventilation", "Mechanics", "Mediating", "Mediator", "Modality", "Modeling", "Molecular", "Morbidity - disease rate", "Operative Surgical Procedures", "Organ", "Pathologic", "Patients", "Periodicity", "Phenotype", "Primary Infection", "Production", "Protons", "Pulmonary Inflammation", "Regulation", "Reporting", "Resolution", "Respiratory Failure", "Role", "Scientist", "Sepsis", "Severities", "Signal Transduction", "Staphylococcus aureus", "Stimulus", "Stretching", "Syndrome", "TLR2 gene", "Testing", "Therapeutic", "Therapeutic Agents", "Tidal Volume", "Tissues", "Transfusion", "United States", "Vascular Endothelium", "Viral", "Virus Diseases", "analog", "attenuation", "chemokine", "cytokine", "cytokine release syndrome", "drug discovery", "effective therapy", "fighting", "implant material", "in vivo", "in vivo Model", "inflammatory milieu", "inhibitor", "lung injury", "mechanical stimulus", "methicillin resistant Staphylococcus aureus", "mortality", "mouse model", "neutrophil", "novel", "novel therapeutics", "pathogenic bacteria", "pharmacologic", "receptor", "respiratory", "response", "sensor", "septic", "small molecule", "small molecule inhibitor", "ventilation", "virtual" ], "approved": true } }, { "type": "Grant", "id": "12135", "attributes": { "award_id": "1R41HL167254-01", "title": "Inducible HMGB1 antagonist for viral-induced acute lung injury.", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 22454, "first_name": "GUOFEI", "last_name": "Zhou", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-08-16", "end_date": "2025-07-31", "award_amount": 488080, "principal_investigator": { "id": 21313, "first_name": "JORGE C", "last_name": "BLANCO", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1447, "ror": "", "name": "SIGMOVIR BIOSYSTEMS, INC.", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 24181, "first_name": "Stefanie N.", "last_name": "Vogel", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1447, "ror": "", "name": "SIGMOVIR BIOSYSTEMS, INC.", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "For more than a decade, our work has focused on development of therapeutic interventions for viral- and bacterial-induced acute lung injury (ALI) and the more severe acute respiratory distress syndrome (ARDS). Significantly, we identified the Toll-like receptor 4 (TLR4) signaling pathway as key to the host response to influenza and secondary bacterial infection following influenza. We also identified High Mobility Group Box 1 (HMGB1), a host-derived “danger-associated molecular pattern” (DAMP), as a biomarker of disease severity for multiple respiratory viruses and detected greatly elevated levels in sera from patients hospitalized for severe influenza and SARS-CoV-2 infections. Importantly, our data indicate that HMGB1 is a central mediator of influenza-induced respiratory disease that acts by stimulating TLR4/MD-2 to elicit the potent inflammatory response associated with ALI/ARDS. Therapeutic administration of TLR4 antagonists (e.g., Eritoran and many others), as well as small molecule HMGB1 antagonists, mitigate the life-threatening pulmonary manifestations of acute lung injury (ALI) and lethality in preclinical rodent models. The identification of these promising therapeutic targets has led us to the central hypothesis that our findings may well be applicable to other ALI- inducing agents. Indeed, since our earliest reports of the efficacy of the TLR4 antagonist, Eritoran, in influenza- induced disease in both mice and cotton rats (Sigmodon hispidus, a species uniquely susceptible to non-adapted human viruses), this agent has been reported to blunt disease in animal models of Ebola virus and Dengue virus, leading to a reduction in cytokine and chemokine production and reduced disease symptoms. Given the clinical relevance of ALI and ARDS that has been exposed by the SARS-CoV-2 pandemic, and the striking similarities between influenza- and SARS-Cov-2-induced ALI/ARDS caused by a cytokine storm leading to loss of homeostasis and, ultimately, multiorgan failure and death, we propose, as the central goal of this phase I STTR, to evaluate the therapeutic efficacy of our newly developed, inflammation-inducible, adenoviral vector encoding the HMGB1 antagonist, “HMGB1 Box A,” to ameliorate severe influenza-induced inflammation. We will test the efficacy of our intervention in murine models of LPS-induced lung inflammation and mouse-adapted influenza infection, and in cotton rats challenged with non-adapted human influenza strains for which we have correlated HMGB1 levels with disease severity. We predict that our innovative strategy will provide a novel approach to treatment of inflammatory lung disease that is mediated by multiple non-infectious and infectious agents that cause ALI/ARDS.", "keywords": [ "2019-nCoV", "Acute Lung Injury", "Acute Respiratory Distress Syndrome", "Address", "Adenovirus Vector", "Adenoviruses", "Agonist", "Animal Model", "Bacterial Infections", "Biological Markers", "COVID-19 cytokine storm", "COVID-19 pandemic", "Cells", "Cessation of life", "Cotton Rats", "Data", "Dengue Virus", "Development", "Dimerization", "Disease", "Disease Progression", "Ebola virus", "Engineering", "Experimental Animal Model", "Family", "Gene Expression", "Goals", "HMGB1 gene", "Homeostasis", "Hospitalization", "Human", "Immune response", "Infectious Agent", "Inflammation", "Inflammation Mediators", "Inflammatory", "Inflammatory Response", "Influenza", "Injury", "Innate Immune Response", "Intervention", "Life", "Ligands", "Lipopolysaccharides", "Lung", "Mediating", "Mediator", "Molecular", "Multiple Organ Failure", "Mus", "Pathway interactions", "Patients", "Pattern", "Pattern recognition receptor", "Phase", "Predisposition", "Process", "Production", "Publishing", "Pulmonary Inflammation", "Reporting", "Research", "Resolution", "Respiratory Disease", "Respiratory Tract Infections", "Rodent Model", "SARS-CoV-2 exposure", "SARS-CoV-2 infection", "Sepsis", "Severity of illness", "Sigmodon", "Signal Pathway", "Signal Transduction", "Small Business Technology Transfer Research", "Sterility", "Structure", "Symptoms", "System", "TLR4 gene", "Testing", "Therapeutic", "Therapeutic Intervention", "Tissues", "Toll-like receptors", "Treatment Efficacy", "Viral", "Virus", "Work", "antagonist", "cell injury", "chemokine", "clinically relevant", "cytokine", "cytokine release syndrome", "efficacy testing", "human disease", "human pathogen", "inflammatory lung disease", "influenza infection", "influenza virus strain", "inhibitor", "innovation", "insight", "microorganism interaction", "mouse model", "novel", "novel strategies", "pathogen", "pre-clinical", "prototype", "receptor", "respiratory virus", "response", "small molecule", "therapeutic development", "therapeutic target", "therapeutically effective", "tool", "translational therapeutics" ], "approved": true } }, { "type": "Grant", "id": "12136", "attributes": { "award_id": "1DP2AI177896-01", "title": "Deciphering long-term virus evolution through the reconstruction of past viral genomes", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 6243, "first_name": "BROOKE ALLISON", "last_name": "Bozick", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-08-17", "end_date": "2028-07-31", "award_amount": 534762, "principal_investigator": { "id": 27996, "first_name": "Daniel", "last_name": "Blanco-Melo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2062, "ror": "", "name": "FRED HUTCHINSON CANCER CENTER", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "Viruses have imposed a significant global burden of morbidity and mortality for millennia. Just in the last century, highly pathogenic RNA viruses such as influenza A, HIV and SARS-CoV-2 resulted in devastating pandemics that directly impacted millions of individuals and altered socioeconomic dynamics worldwide. Fueled by major advances in sequencing during the last decades, the emerging field of archeovirology has begun identifying viruses that severely impacted humans prior to the 20th century. To this day, however, the pathogens responsible for important past epidemics are still unknown and there are significant gaps remaining in the evolutionary history of certain viral families, especially for RNA viruses. Using a highly collaborative and innovative approach to overcome intrinsic limitations in the identification of viral genomes from human remains, this proposal will uncover the viral diversity that existed during periods of notable epidemic outbreaks and expand our knowledge of the origins and evolution of highly pathogenic viruses. In particular, this proposal seeks to identify and characterize genomes from centuries-old RNA viruses, a goal that so far has remained elusive. Using well-established ancient DNA techniques, forensic proteomics, and improved RNA isolation methodologies, our team will reconstruct viral genomes from human remains of deadly epidemics in early colonial Mexico and preserved lung specimens from pathology collections corresponding to the industrial revolution in Great Britain. Guided by archeological and historical documentation in these two distinct historical contexts, this work will identify viruses that existed in the past ~500 years, study their origin and evolutionary relationships to modern viruses, and characterize the evolution of viral protein function in relation to their human hosts. Together, this proposal will generate a comprehensive characterization of the properties of past viral infections that will not only lead to the identification of viruses responsible for epidemics that profoundly altered human history but will also uncover evolutionary adaptations between past and present viruses and define the origins of highly pathogenic RNA viruses, providing key molecular information to prepare against the (re)emergence of highly virulent viruses in the future.", "keywords": [ "2019-nCoV", "Address", "Calibration", "Cells", "Collection", "Complement", "DNA", "DNA Viruses", "Development", "Disease", "Disease Outbreaks", "Documentation", "Ebola virus", "Epidemic", "Etiology", "Evolution", "Family", "Forensic Medicine", "Future", "Genome", "Genomics", "Goals", "Great Britain", "HIV", "Human", "Immunology", "Individual", "Industrialization", "Influenza A virus", "Knowledge", "Lead", "Life Cycle Stages", "Link", "Measles", "Medical", "Methodology", "Mexico", "Modeling", "Modernization", "Molecular", "Morbidity - disease rate", "Museums", "Paleontology", "Pathogenesis", "Pathogenicity", "Pathology", "Poliomyelitis", "Population", "Positioning Attribute", "Prevention strategy", "Property", "Proteomics", "Protocols documentation", "RNA", "RNA Viruses", "Recording of previous events", "Records", "Research", "Respiratory Tract Infections", "Sampling", "Smallpox", "Spain", "Specimen", "Symptoms", "Techniques", "Variant", "Viral", "Viral Genes", "Viral Genome", "Viral Proteins", "Virulent", "Virus", "Virus Diseases", "Work", "career", "clinically significant", "ds-DNA", "human pathogen", "improved", "innovation", "lung preservation", "microbial genome", "molecular clock", "mortality", "multidisciplinary", "novel strategies", "pandemic disease", "pathogen", "pathogenic virus", "post-doctoral training", "previous epidemic", "protein function", "reconstruction", "skills", "socioeconomics", "symptomatology", "synergism", "technology development", "tissue tropism", "transmission process", "viral RNA", "viral epidemic", "viral outbreak", "viral pandemic", "virology", "virus identification" ], "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 } } ], "meta": { "pagination": { "page": 1383, "pages": 1424, "count": 14236 } } }