Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1391&sort=title
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=title", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1419&sort=title", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1392&sort=title", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1390&sort=title" }, "data": [ { "type": "Grant", "id": "15532", "attributes": { "award_id": "1R21NS140036-01", "title": "Utilizing a novel hamster model to determine neurologic and behavioral abnormalities of offspring from mothers infected with SARS-CoV-2", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Neurological Disorders and Stroke (NINDS)" ], "program_reference_codes": [], "program_officials": [ { "id": 6896, "first_name": "WILLIAM PATRICK", "last_name": "Daley", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-12-15", "end_date": "2026-11-30", "award_amount": 240000, "principal_investigator": { "id": 32072, "first_name": "Eliseo A", "last_name": "Eugenin", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32073, "first_name": "Kenneth Steven", "last_name": "Plante", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 851, "ror": "", "name": "UNIVERSITY OF TEXAS MED BR GALVESTON", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "A novel coronavirus, severe acute respiratory syndrome 2 (SARS-CoV-2), emerged in 2019 and led to the worldwide COVID-19 pandemic with over 773 million human infections and 7 million deaths by the end of 2023. Four years later, the full implications of this pandemic remain unclear. Though the acute syndrome has been extensively characterized, more cryptic complications such as long-COVID and neuro-PASC demonstrate that this illness still requires intensive study. Additionally, maternal infection has been linked to negative fetal outcomes including stillbirth. Recent studies implicate SARS-CoV-2 in neurologic aberrations of offspring born to infected mothers. It is crucial that these clinical findings are confirmed through laboratory studies to interrogate the mechanism of any such impacts. A proactive approach to this issue can help alleviate the societal impact of a large influx of children potentially exhibiting neurodevelopmental issues as a result of gestational COVID-19 exposure. As such, the objective of this study is to develop the golden Syrian hamster model to examine the role of maternal infection. The hamster model has been used to great effect in characterizing COVID-19 variants as it does not require adapted virus, demonstrates human-like illness and pathology, and is capable of transmission. Additionally, our group has shown its functional role in a common neuro-PASC sign of illness, anosmia. Utilizing classical virology, molecular biology, histopathology, and extensive neuroimaging, we also expect to gain insight into the mechanisms involved. We further plan on utilizing behavioral studies that we have adapted for hamsters to determine long-term neurodevelopment impacts on the offspring. We will accomplish this through two aims. In Specific Aim 1, we will focus on the impact of maternal infection in utero. Initial studies will focus on the direct effects of maternal infection on the female reproductive tract and developing fetus. Additionally, we will determine which tissues are capable of being productively infected and whether vertical transmission occurs. We will also determine the inflammatory state of the placenta and fetus. Our multidisciplinary team will do an in-depth analysis on neurodevelopment to identify any acute fetal neurologic aberrations resulting from maternal infection. In Specific Aim 2, we will explore the behavioral and neurologic implications of maternal infection on the resulting offspring. We have optimized tests for depression, muscle weakness, and cognition/memory in the golden Syrian hamster model. We expect that even in the absence of acute fetal abnormality or vertical transmission, the inflammatory state of the infected dams will cause detrimental long-term neurological impacts in the resulting pups analogous to those reported in human offspring. In addition to the behavioral testing, we will perform extensive histopathologic analysis, neuroimaging, and c-Fos straining to assess the impact of maternal infection. The proposed studies will generate a novel maternal-fetal hamster model of COVID-19. Our results can be utilized to better prepare public health entities to the long-term societal impacts of COVID-19 maternal infection and to provide a powerful tool to the research community for mechanistic and interventional studies.", "keywords": [ "2019-nCoV", "Acute", "Address", "Animal Model", "Anosmia", "Behavioral", "Brain", "COVID-19", "COVID-19 impact", "COVID-19 pandemic", "Cells", "Cessation of life", "Child", "Clinical", "Clinical Research", "Cognition", "Communities", "Defect", "Development", "Diagnosis", "Exhibits", "FOS gene", "Fetal Development", "Fetus", "Goals", "Hamsters", "Histopathology", "Human", "Immune", "Immunocompetence", "Impairment", "Incidence", "Infant", "Infection", "Inflammatory", "Inflammatory Response", "Influenza A virus", "Intervention Studies", "Investigation", "Kinetics", "Knowledge", "Laboratory Study", "Late pregnancy", "Life", "Link", "Long COVID", "Long-Term Effects", "Longitudinal Studies", "Medical", "Memory", "Mental Depression", "Mental Health", "Mental disorders", "Mesocricetus auratus", "Modeling", "Molecular Biology", "Mothers", "Muscle Weakness", "Nervous System Physiology", "Neurodevelopmental Disorder", "Neurologic", "Neurologic Signs", "Neurologic Symptoms", "Neurological observations", "Outcome", "Ovary", "Pathology", "Persons", "Physiological", "Placenta", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Pregnancy", "Productivity", "Public Health", "Pulmonary Pathology", "Readiness", "Recording of previous events", "Reporting", "Reproducibility", "Reproduction", "Research", "Risk", "Rodent Model", "Role", "SARS coronavirus", "SARS-CoV-2 exposure", "SARS-CoV-2 infection", "SARS-CoV-2 variant", "Syndrome", "Testing", "Therapeutic", "Thrombus", "Tissues", "Uterus", "Vagina", "Vertical Transmission", "Virus", "Virus Diseases", "Work", "acute COVID-19", "behavior test", "behavioral study", "clinically relevant", "clinically significant", "congenital infection", "cytokine", "economic impact", "female reproductive system", "female reproductive tract", "fetal", "immune activation", "in utero", "inflammatory marker", "insight", "mortality", "multidisciplinary", "neurodevelopment", "neuroimaging", "neurologic sequelae of COVID-19", "novel", "novel coronavirus", "offspring", "pandemic disease", "pup", "reproductive", "stem", "stillbirth", "tool", "transmission process", "vaccine evaluation", "viral transmission", "virology" ], "approved": true } }, { "type": "Grant", "id": "10499", "attributes": { "award_id": "3R01MH127961-01A1S1", "title": "Utilizing All of Us data to examine the impact of COVID-19 on mental health among people living with HIV", "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": 24064, "first_name": "Lori", "last_name": "Scott-Sheldon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-08-16", "end_date": "2023-11-30", "award_amount": 107340, "principal_investigator": { "id": 4919, "first_name": "Xiaoming", "last_name": "Li", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 930, "ror": "", "name": "UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA", "address": "", "city": "", "state": "SC", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 930, "ror": "", "name": "UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA", "address": "", "city": "", "state": "SC", "zip": "", "country": "United States", "approved": true }, "abstract": "In response to the NOSI (NOT-PM-22-002), we propose to expand the resilience conceptual framework in our parent grant (1R01MH127961-01A1, 12/2021-11/2026) to a different context (COVID-19) and a new population (people living with HIV [PLWH] in the United States). Further, we propose to explore if a resilience approach can be used to mitigate the negative impacts of COVID-19 on the mental health among PLWH. We will leverage multiple datasets from the All of Us program, including electronic health records (EHR), a series of COVID-19 Participant Experience (COPE) surveys, and other self-reported survey data. Integrating these data from about 12 thousand PLWH who participated in COPE, we will: 1) examine the trends and patterns of mental health outcomes (i.e., psychiatric disorder diagnoses via ICD-10 and mental health assessments via survey) among PLWH before and after the COVID-19 outbreak; and 2) identify protective factors at multiple socioecological levels including the individual level (e.g., resilience), interpersonal level (e.g., social support), and health institutional level (e.g., health service accessibility) that may mitigate the negative impacts of the COVID-19 pandemic on mental health outcomes among PLWH, especially the subgroups with socially disadvantaged status (low income and low education) and stigmatized identities (racial/ethnic minorities, sexual and gender minorities). Based on rich data from a large cohort of PLWH, the findings will advance our understanding of their mental health needs during the pandemic and mental health disparities of PLWH in the US and inform tailored health interventions to improve mental health outcomes among PLWH, especially those from disadvantaged subgroups. Our study goal is aligned with the Office of AIDS Research's and National Institute of Mental Health's research priorities in terms of social sciences studies and health disparities reduction. The proposed study will leverage existing NIH investment, capitalize on a rapid understanding of mental health needs among PLWH, stimulate additional collaborations with the All of Us program, and promote the translation of All of Us data to public health implications. The experience and preliminary data obtained from this supplement will position us for further efforts in utilizing All of Us data to improve mental and other health outcomes of PLWH in the US.", "keywords": [ "Acquired Immunodeficiency Syndrome", "Address", "Affect", "Age-Years", "Aging", "All of Us Research Program", "Anxiety", "Anxiety Disorders", "COVID-19", "COVID-19 impact", "COVID-19 outbreak", "COVID-19 pandemic", "COVID-19 pandemic effects", "COVID-19 vaccination", "Caring", "Chronic Disease", "Code", "Collaborations", "Complement", "Complex", "Data", "Data Analyses", "Data Science", "Diabetes Mellitus", "Diagnosis", "Disadvantaged", "Education", "Electronic Health Record", "Ethnic Origin", "Financial Hardship", "Fostering", "Fright", "Gender Identity", "Goals", "HIV", "Health", "Health Promotion", "Health Services Accessibility", "High Prevalence", "Hypertension", "Immune system", "Impairment", "Income", "Individual", "International Statistical Classification of Diseases and Related Health Problems Tenth Revision (ICD-10)", "Intervention", "Investments", "Knowledge", "Loneliness", "Low income", "Lung diseases", "Measures", "Mental Health", "Mental disorders", "Mental health promotion", "Mood Disorders", "National Institute of Mental Health", "Outcome", "Participant", "Patient Self-Report", "Pattern", "Personal Satisfaction", "Personality Disorders", "Persons", "Population", "Positioning Attribute", "Prevention", "Psyche structure", "Public Health", "Race", "Reduce health disparities", "Research", "Research Priority", "Risk Factors", "SARS-CoV-2 infection", "Sample Size", "Schizophrenia", "Series", "Services", "Sexual and Gender Minorities", "Social Identification", "Social Sciences", "Social support", "Stigmatization", "Stress", "Subgroup", "Substance Use Disorder", "Surveys", "Symptoms", "Testing", "Translations", "United States", "United States National Institutes of Health", "Vulnerable Populations", "base", "cloud based", "cohort", "comorbidity", "design", "disparity reduction", "effective intervention", "ethnic minority", "experience", "health assessment", "health disparity", "high risk", "improved", "large scale data", "multiple datasets", "negative affect", "pandemic disease", "parent grant", "parent project", "programs", "protective factors", "psychologic", "psychosocial wellbeing", "public health emergency", "racial and ethnic", "recruit", "resilience", "response", "sexual identity", "social disadvantage", "social stigma", "socioeconomic disadvantage", "stress related disorder", "theories", "trend" ], "approved": true } }, { "type": "Grant", "id": "15586", "attributes": { "award_id": "5R21AI180741-02", "title": "Utilizing alternative dietary interventions to alter gut microbiome and improve T cell responses to viral infection in obesity", "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": 6181, "first_name": "Deborah", "last_name": "Hodge", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-11-16", "end_date": "2025-10-31", "award_amount": 222787, "principal_investigator": { "id": 29197, "first_name": "Nancie", "last_name": "MacIver", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 817, "ror": "", "name": "UNIV OF NORTH CAROLINA CHAPEL HILL", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "Obesity is associated with chronic inflammation and an impaired immune response to infection from select viruses, including influenza and SARS-CoV-2, leading to increased morbidity and mortality. Many studies have demonstrated a critical role for T cells in this setting, with primary and memory T cell responses to viral infection impaired in mice and humans with obesity. Given the high prevalence of obesity and viral infections with influenza and coronavirus worldwide, it is critically important to understand T cell dysfunction in obesity and identify novel strategies to improve immune response to infection in this high-risk population. T cell function and metabolism are closely linked, and many studies have demonstrated that changes to T cell metabolism influence T cell fate and function. We have found that activated T cells from obese animals have an altered metabolic profile characterized by increased glucose uptake, increased conversion of glucose to pyruvate, and increased mitochondrial oxidation. This represents a unique cellular metabolic phenotype of glucose oxidation that is not utilized by naive, memory, or activated T cells from lean animals and may mechanistically explain obesity- associated T cell dysfunction. Interestingly, we found that weight loss achieved by continuous low-fat diet was unable to improve obesity-associated inflammation, normalize T cell metabolism, or improve survival to influenza infection in obese mice. Thus, alternative approaches to decrease obesity-associated inflammation and/or restore T cell metabolism may be needed to improve T cell responses to viral infection in individuals with obesity. Alternative dietary approaches using variations of time-restricted feeding such as intermittent calorie restriction, intermittent fasting, or alternate day fasting have been shown to be beneficial to both weight loss and multiple indices of health, including metabolic disease, inflammation, and immune response to bacterial infection. Recent publications suggest that the immunomodulation seen following time-restricted feeding is at least partially mediated by changes in the gut microbiome. Indeed, it is now well established that the gut microbiome of mice and humans with obesity is different than the gut microbiome of lean animals, and it is the prevailing view that these changes in gut microbiome in obesity drive adipose and system inflammation and thereby influence immune cell responses. Therefore, the overall objective of this R21 proposal is to determine the effects of time- restricted feeding on gut microbiome diversity, T cell function and metabolism, and survival to influenza infection. We hypothesize that weight loss achieved through time-restricted feeding will alter the gut microbiome and reduce obesity-induced inflammation, thereby restoring T cell metabolism and function, resulting in decreased morbidity and increased survival to influenza infection. Successful completion of these studies will identify metabolic and microbiome-related mechanisms underlying T cell dysfunction in obesity and test the impact of alternative dietary approaches on T cell response to viral infection.", "keywords": [ "16S ribosomal RNA sequencing", "2019-nCoV", "Adipose tissue", "Animals", "Antibody titer measurement", "Bacterial Infections", "Body Weight decreased", "CD8-Positive T-Lymphocytes", "Caloric Restriction", "Cell Physiology", "Cells", "Cellular Metabolic Process", "Chronic", "Coronavirus", "DNA", "Dietary Intervention", "Dose", "Fasting", "Fat-Restricted Diet", "Functional disorder", "Glucose", "Health", "High Prevalence", "Human", "Immune", "Immune response", "Immunity", "Impairment", "Individual", "Infection", "Inflammation", "Influenza", "Intermittent fasting", "Link", "Measures", "Mediating", "Memory", "Metabolic", "Metabolic Diseases", "Mitochondria", "Monitor", "Morbidity - disease rate", "Mus", "Obese Mice", "Obesity", "Outcome", "Publications", "Pulmonary Pathology", "Pyruvate", "Role", "Stains", "System", "T cell response", "T memory cell", "T-Cell Activation", "T-Lymphocyte", "Testing", "Thinness", "Time-restricted feeding", "Vaccination", "Variant", "Viral Load result", "Virus", "Virus Diseases", "cohort", "dietary approach", "fecal transplantation", "glucose uptake", "gut microbiome", "healthy weight", "high risk population", "immunoregulation", "improved", "indexing", "influenza infection", "innovation", "metabolic phenotype", "metabolic profile", "microbiome", "microbiome alteration", "mortality", "novel strategies", "oxidation", "pandemic influenza", "response", "seasonal influenza", "transcriptome sequencing" ], "approved": true } }, { "type": "Grant", "id": "13157", "attributes": { "award_id": "1R21AI180741-01", "title": "Utilizing alternative dietary interventions to alter gut microbiome and improve T cell responses to viral infection in obesity", "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": 6181, "first_name": "Deborah", "last_name": "Hodge", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-11-16", "end_date": "2025-10-31", "award_amount": 171816, "principal_investigator": { "id": 29197, "first_name": "Nancie", "last_name": "MacIver", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 817, "ror": "", "name": "UNIV OF NORTH CAROLINA CHAPEL HILL", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "Obesity is associated with chronic inflammation and an impaired immune response to infection from select viruses, including influenza and SARS-CoV-2, leading to increased morbidity and mortality. Many studies have demonstrated a critical role for T cells in this setting, with primary and memory T cell responses to viral infection impaired in mice and humans with obesity. Given the high prevalence of obesity and viral infections with influenza and coronavirus worldwide, it is critically important to understand T cell dysfunction in obesity and identify novel strategies to improve immune response to infection in this high-risk population. T cell function and metabolism are closely linked, and many studies have demonstrated that changes to T cell metabolism influence T cell fate and function. We have found that activated T cells from obese animals have an altered metabolic profile characterized by increased glucose uptake, increased conversion of glucose to pyruvate, and increased mitochondrial oxidation. This represents a unique cellular metabolic phenotype of glucose oxidation that is not utilized by naive, memory, or activated T cells from lean animals and may mechanistically explain obesity- associated T cell dysfunction. Interestingly, we found that weight loss achieved by continuous low-fat diet was unable to improve obesity-associated inflammation, normalize T cell metabolism, or improve survival to influenza infection in obese mice. Thus, alternative approaches to decrease obesity-associated inflammation and/or restore T cell metabolism may be needed to improve T cell responses to viral infection in individuals with obesity. Alternative dietary approaches using variations of time-restricted feeding such as intermittent calorie restriction, intermittent fasting, or alternate day fasting have been shown to be beneficial to both weight loss and multiple indices of health, including metabolic disease, inflammation, and immune response to bacterial infection. Recent publications suggest that the immunomodulation seen following time-restricted feeding is at least partially mediated by changes in the gut microbiome. Indeed, it is now well established that the gut microbiome of mice and humans with obesity is different than the gut microbiome of lean animals, and it is the prevailing view that these changes in gut microbiome in obesity drive adipose and system inflammation and thereby influence immune cell responses. Therefore, the overall objective of this R21 proposal is to determine the effects of time- restricted feeding on gut microbiome diversity, T cell function and metabolism, and survival to influenza infection. We hypothesize that weight loss achieved through time-restricted feeding will alter the gut microbiome and reduce obesity-induced inflammation, thereby restoring T cell metabolism and function, resulting in decreased morbidity and increased survival to influenza infection. Successful completion of these studies will identify metabolic and microbiome-related mechanisms underlying T cell dysfunction in obesity and test the impact of alternative dietary approaches on T cell response to viral infection.", "keywords": [ "16S ribosomal RNA sequencing", "2019-nCoV", "Adipose tissue", "Animals", "Antibody titer measurement", "Bacterial Infections", "Body Weight decreased", "CD8-Positive T-Lymphocytes", "Caloric Restriction", "Cell physiology", "Cells", "Cellular Metabolic Process", "Chronic", "Coronavirus", "DNA", "Dietary Intervention", "Dose", "Fasting", "Fat-Restricted Diet", "Functional disorder", "Glucose", "Health", "High Prevalence", "Human", "Immune", "Immune response", "Immunity", "Impairment", "Individual", "Infection", "Inflammation", "Influenza", "Intermittent fasting", "Link", "Measures", "Mediating", "Memory", "Metabolic", "Metabolic Diseases", "Mitochondria", "Monitor", "Morbidity - disease rate", "Mus", "Obese Mice", "Obesity", "Outcome", "Publications", "Pulmonary Pathology", "Pyruvate", "Role", "Stains", "System", "T cell response", "T memory cell", "T-Cell Activation", "T-Lymphocyte", "Testing", "Thinness", "Time-restricted feeding", "Vaccination", "Variant", "Viral Load result", "Virus", "Virus Diseases", "cohort", "dietary approach", "fecal transplantation", "glucose uptake", "gut microbiome", "healthy weight", "high risk population", "immunoregulation", "improved", "indexing", "influenza infection", "innovation", "metabolic phenotype", "metabolic profile", "microbiome", "microbiome alteration", "mortality", "novel strategies", "oxidation", "pandemic influenza", "response", "seasonal influenza", "transcriptome sequencing" ], "approved": true } }, { "type": "Grant", "id": "7932", "attributes": { "award_id": "1U01FD007574-01", "title": "Utilizing the Pharmacy Advances Clinical Trials (PACT) Network to Achieve Diversity in COVID Clinical Trials: A Strategic Framework", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [ { "id": 23766, "first_name": "Christine", "last_name": "Lee", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-04-01", "end_date": "2023-03-31", "award_amount": 1000000, "principal_investigator": { "id": 23799, "first_name": "GEORGE O", "last_name": "UDEANI", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1643, "ror": "", "name": "TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1643, "ror": "", "name": "TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "ABSTRACT/SUMMARY Drug development and clinical trials have been central to the exponential decline in morbidity and mortality associated with COVID-19. While disproportionate COVID-19 mortalities have been observed in underrepresented minority (URM) communities, enrollment into COVID-19 clinical trials has been challenging. Such challenges have been associated with patient, system, provider, and community barriers, including mistrust, social determinants of health, failure to meet eligibility criteria, and lack of awareness of studies. To address these issues, Texas A&M University (TAMU) has partnered with the American Association of Colleges of Pharmacy (AACP). The primary goals of this project are to employ Artificial Intelligence (AI) and Machine Learning (ML), develop a national network that would engage innovative strategies, and to train and educate researchers to advance COVID-19 health equity research in URM communities. TAMU – College of Pharmacy (COP) has established several outreach program activities designed to educate and enroll URMs in ongoing clinical trials. The NIH recently funded TAMU-COP to conduct a Moderna COVID-19 Vaccine clinical trial. TAMU recruited 25% of participants, approximately 35% are classified as URM participants, majority Hispanics. The long-term goal is to (i) Employ innovative approaches, training, and education methods to increase URM clinical trial enrollment. (ii) Improve communication strategies and informed messages for URM populations. The central hypothesis is that the hesitancy of URM participation in clinical trials stems from long- standing mistrust, lack of culturally competent messaging, lack of access to care, and underrepresentation of authentic health champions. In addition, community-based pharmacists and pharmacy faculty have a unique role as community clinical researchers in recruiting URM populations as participants in COVID-19 clinical trials. The central hypothesis will be tested via the following two aims: Aim 1: Leverage Artificial Intelligence and Machine Learning to enable environmental scans in target communities to optimize URM participation in COVID-19 clinical trials. Aim 2: Create and train a network of community-based investigators, pharmacists, and other partners to directly increase clinical trials participation among URM populations. These aims will be pursued via innovative AI/ML analytics, training, education, and community network. The immediate expected outcomes will be a better understanding of the critical elements of COVID- 19 clinical trials hesitancy in URMs and effective interventions for addressing hesitancy. It is anticipated the proposed interventions will positively impact enrollment in clinical trials.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "11572", "attributes": { "award_id": "3U19AI171413-01S1", "title": "UTMB-Novartis Alliance for Pandemic Preparedness", "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": 27535, "first_name": "Ping", "last_name": "Chen", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-16", "end_date": "2025-04-30", "award_amount": 18849015, "principal_investigator": { "id": 27536, "first_name": "Thierry", "last_name": "Diagana", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 7025, "first_name": "VINEET D", "last_name": "MENACHERY", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 851, "ror": "", "name": "UNIVERSITY OF TEXAS MED BR GALVESTON", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 851, "ror": "", "name": "UNIVERSITY OF TEXAS MED BR GALVESTON", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "OVERALL – ABSTRACT Pandemic prevention and preparedness is a major scientific and societal priority that requires sustained and forward looking investments across governmental, non-governmental, academic and private sectors to develop an arsenal of countermeasures against the existential threat of viral pandemics. Combining world-leading BSL3/4 capabilities at University of Texas of Medical Branch (UTMB) and state-of-the art drug discovery technologies at Novartis, the UTMB Novartis Alliance for Pandemic Preparedness (UNAPP), is a unique and innovative partnership that brings together the multi-disciplinary expertise required to deliver high quality antiviral drug candidates. Enabled by world-leading virologists and seasoned drug hunters, UNAPP will aggressively prosecute a portfolio of 5 projects aiming to discover orally available, safe, and effective drugs against coronaviruses, flavivirus and henipavirus, three major classes of viruses with pandemic potential. The projects portfolio combines approaches targeting well validated drug targets, such as the RNA- dependent RNA polymerases and viral proteases, as well as phenotypic screening, which will allow for the discovery of clinical drug candidates and novel targets that will advance our fundamental understanding of the biology of those viruses. Four scientific Cores—Virology, High-Throughput Biology, Drug Discovery and Translational Research Cores—will provide technological and scientific expertise to support Project Teams and implement the scientific strategy toward novel antiviral drugs. The UNAPP will be governed by an Administrative Core which will be co-led by the PIs, Dr. Pei-Yong Shi and Dr. Thierry Diagana, who have a long track-record of successfully working together. Both PIs have led multiple productive collaborations focused on translational impact and combining public, private and non-governmental organizations. The Administrative Core will provide integrated decision making in scientific, operational, financial, intellectual property protection, and communication. In collaboration with all project and Core leaders, as well as with external input from a Scientific Advisory Board and NIH program officers, they will ensure that the projects portfolio leverages the full spectrum of technologies and capabilities residing in all four scientific Cores, capturing synergies across projects through cross-learning and efficient deployment of platforms relevant to multiple viruses. Because of the unique complementarity of the scientific Cores and the remarkable synergies of the project portfolio, we fully expect that the UNAPP will yield exceptional productivity and deliver all the proposed objectives: (1) Deliver 3 IND-ready candidates and 3 Development Candidates, (2) advance antiviral research, and (3) train next-generation drug hunters.", "keywords": [ "2019-nCoV", "Academia", "Air", "Antiviral Agents", "Biology", "COVID-19", "COVID-19 assay", "COVID-19 pandemic", "Cells", "Cessation of life", "Clinical", "Collaborations", "Communicable Diseases", "Communication", "Complex", "Coronavirus", "Data", "Decision Making", "Dengue", "Development", "Diagnostic", "Drug Targeting", "Education", "Emerging Technologies", "Ensure", "Faculty", "Family", "Flavivirus", "Foundations", "Future", "Generations", "Goals", "Hendra Virus", "Henipavirus", "Home", "Human", "Humanities", "Industry", "Infection", "Institution", "Intellectual Property", "Investments", "Laboratories", "Learning", "Libraries", "Life", "Machine Learning", "Marketing", "Medical", "Medicine", "Membrane Proteins", "Mentors", "Middle East Respiratory Syndrome Coronavirus", "Nipah Virus", "Nongovernmental Organizations", "Nucleosides", "Nucleotides", "Oral", "Peptide Hydrolases", "Pharmaceutical Preparations", "Pharmacologic Substance", "Phase I Clinical Trials", "Phenotype", "Polymerase", "Population Density", "Postdoctoral Fellow", "Predisposition", "Private Sector", "Privatization", "Probability", "Process", "Productivity", "Protease Inhibitor", "Quantitative Structure-Activity Relationship", "RNA-Directed RNA Polymerase", "Rationalization", "Research", "Research Activity", "Research Project Grants", "Resistance", "SARS-CoV-2 inhibitor", "Seasons", "Serotyping", "Spanish flu", "Technology", "Texas", "Training", "Translational Research", "Travel", "United States National Institutes of Health", "Universities", "Vaccines", "Viral", "Virus", "biosafety level 4 facility", "clinical candidate", "clinical investigation", "combat", "drug candidate", "drug discovery", "economic cost", "inhibitor", "innovation", "mortality", "multidisciplinary", "new technology", "next generation", "novel", "pandemic disease", "pandemic potential", "pandemic preparedness", "prevent pandemics", "programs", "public health relevance", "public-private partnership", "recruit", "response", "role model", "screening", "student training", "success", "synergism", "translational impact", "viral pandemic", "virology" ], "approved": true } }, { "type": "Grant", "id": "15792", "attributes": { "award_id": "1R21AI193885-01", "title": "UTS-1401 as a Medical Countermeasure to H-ARS Consequent to a Radiation Mass Casualty", "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": 32879, "first_name": "LANYN P", "last_name": "TALIAFERRO", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-18", "end_date": "2027-07-31", "award_amount": 157000, "principal_investigator": { "id": 32877, "first_name": "Stephen L", "last_name": "Brown", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32878, "first_name": "FREDERICK Augustus", "last_name": "VALERIOTE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2633, "ror": "", "name": "HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Abstract: Our long term objective is to develop a new class of radiation mitigating agents with attractive chemical, physical and biological characteristics required to be an effective drug that can be distributed widely. We have identified a small molecule, UTS-1401 [5-(methylthiomethyl) isoxazole-3-carboxylic acid] which demonstrates mitigation of hematopoietic stem cell death when administered at either 24h or 48h following whole body irradiation (WBI). Using the endogenous spleen colony assay, we demonstrated a mitigating effect in that the colony number with and without UTS-1401 was 3.5 ± 0.4 for a 24h interval and 2.3 ± 0.5 for a 48h interval. We have recently demonstrated a significant radioprotection for both mouse survival and hematopoietic stem cells for this compound when administered up to 72h before irradiation (Valeriote et al, Radiation Research, 202:16- 25, 2024). In this application, we propose to further examine solely the mitigating effect on the hematopoietic acute radiation syndrome (H-ARS) using survival as the endpoint in specific aim 1. Groups of Swiss mice will receive a series of graded doses of WBI (in 0.5 Gy increments) around the LD50 for this syndrome (approximately 7.5 Gy in females and 8.5 Gy in males) with and without the administration of 150 mg/kg UTS-1401. The single dose of UTS-1401 being used in all studies is the highest dose administrable due to its aqueous solubility (in tartrate buffered saline). The radiation mitigation factors will be calculated as the ratio of the LD50 for radiation plus UTS-1401 versus that for radiation alone. The degree of mitigation will be examined at 24, 48 and 72 h following WBI to determine the radiation mitigation fraction as a function of time after radiation exposure. Three routes of drug delivery, intravenous (iv), oral, and subcutaneous (sc), will be examined and compared. Radiation will be delivered by 16 MeV electrons from a Linac. In specific aim 2, we will examine the pharmacokinetics (PK) for 150 mg/kg UTS-1401 comparing the iv, oral, and sc routes to obtain a determination of both the drug kinetics and bioavailability. The AUC values will be correlated with the extent of mitigation. For both specific aims, both male and female mice will be separately studied. The results from these studies are expected to demonstrate an effective first-in-class compound, UTS-1401, which has a small molecular weight, is chemically stable, nontoxic, aqueous soluble and inexpensive with H-ARS radiation mitigating properties which extend for a number of days following WBI. The mechanism studies (not proposed here) are expected to demonstrate UTS- 1401 as a new class of agents for mitigating the cytokine storm consequent to the irradiation.", "keywords": [ "Accidents", "Acute", "Address", "Animal Model", "Animals", "Biologic Characteristic", "Biological", "Biological Assay", "Biological Availability", "Biotechnology", "Blood", "Bone Marrow", "Buffers", "Carboxylic Acids", "Cell Death", "Cells", "Chemicals", "Chernobyl Nuclear Accident", "China", "Clinical", "Conflict (Psychology)", "Cyclic GMP", "Data", "Development", "Dose", "Drug Delivery Systems", "Drug Kinetics", "Drug Stability", "Electromagnetics", "Electrons", "Employee", "Equipment and supply inventories", "Exposure to", "FDA approved", "Federal Government", "Female", "Fibrosis", "Follow-Up Studies", "Formulation", "Fukushima", "Geographic Distribution", "Goals", "Growth Factor", "Hematopoietic", "Hematopoietic System", "Hematopoietic stem cells", "Hospitals", "Individual", "Industry", "Inflammation", "Inflammatory", "Injury", "International", "Intervention", "Intravenous", "Ionizing radiation", "Iran", "Isoxazoles", "Israel", "Korea", "Lethal Dose 50", "Location", "Molecular Weight", "Mus", "North Korea", "Nuclear", "Nuclear Accidents", "Nuclear Weapon", "Oral", "Oral Administration", "Organ", "Pharmaceutical Preparations", "Pharmacologic Substance", "Pharmacology and Toxicology", "Phase", "Phase I Clinical Trials", "Physiologic pulse", "Procedures", "Process", "Property", "Radiation", "Radiation Accidents", "Radiation Protection", "Radiation Toxicity", "Radiation exposure", "Refrigeration", "Research", "Rotation", "Route", "Russia", "Saline", "Schedule", "Series", "Solubility", "South Korea", "Spleen", "Swiss Mice", "Syndrome", "System", "Taiwan", "Tartrates", "Temperature", "Terrorism", "Time", "Tissues", "Ukraine", "United States National Aeronautics and Space Administration", "Vomiting", "War", "Whole-Body Irradiation", "Work", "aqueous", "chemical stability", "cost effective", "cytokine", "cytokine release syndrome", "design", "drug development", "efficacy study", "expiration", "irradiation", "male", "manufacture", "mass casualty", "medical countermeasure", "novel", "product development", "radiation countermeasure", "radiation mitigation", "radiation response", "radioprotected", "research study", "safety study", "scale up", "small molecule", "subcutaneous", "success" ], "approved": true } }, { "type": "Grant", "id": "15791", "attributes": { "award_id": "1R21AI186055-01A1", "title": "UTS-1401: A Novel Mitigator of Radiation Injury", "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": 32876, "first_name": "ANDREA L", "last_name": "DICARLO-COHEN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2027-07-31", "award_amount": 431750, "principal_investigator": { "id": 32877, "first_name": "Stephen L", "last_name": "Brown", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32878, "first_name": "FREDERICK Augustus", "last_name": "VALERIOTE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2633, "ror": "", "name": "HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Abstract: Our long term objective is to develop a new class of radiation mitigating agents with attractive chemical, physical and biological characteristics required to be an effective drug that can be distributed widely. We have identified a small molecule, UTS-1401 [5-(methylthiomethyl) isoxazole-3-carboxylic acid] which demonstrates mitigation of hematopoietic stem cell death when administered at either 24h or 48h following whole body irradiation (WBI). Using the endogenous spleen colony assay we demonstrated a significant mitigating effect (ratio of colony number with and without UTS-1401) when drug was given 24h or 48h after radiation. We have also recently demonstrated a significant radioprotection for both mouse survival and hematopoietic stem cells for this compound for up to 72h before irradiation (Valeriote et al, Radiation Research, 202:16-25, 2024). In this application, we propose to examine solely the mitigating effect to both the hematopoietic acute radiation syndrome (H-ARS) in specific aim 1 and the gastrointestinal acute radiation syndrome (GI-ARS) in specific aim 2 following WBI (with 5% bone marrow protection for specific aim 2). Swiss mice will receive a series of graded doses of WBI around the LD50 for both syndromes with and without the administration of 150 mg/kg UTS- 1401. The single dose of UTS-1401 being used in all studies is the highest dose administrable due to its aqueous solubility (in tartrate buffered saline). The radiation mitigation factors will be calculated as the ratio of the LD50 for radiation plus UTS-1401 versus radiation alone. The degree of mitigation will be examined at 24, 48 and 72 h following WBI to determine the timeframe of mitigation after radiation exposure. Three routes of drug delivery, intravenous (iv), oral, and subcutaneous (sc), will be examined and compared. For all specific aims, both male and female mice will be separately studied. Radiation will be delivered by electrons from a Linac. In specific aim 3, we will examine the pharmacokinetics (PK) for 150 mg/kg UTS-1401 comparing the iv, oral, and sc routes to obtain a determination of both the drug kinetics and bioavailability. The AUC values will be correlated with the extent of mitigation. Finally, in specific aim 4, we will address the mechanism of action with studies focused on the role of specific cytokines induced by radiation in the so-called “cytokine storm”. We will assess the time course changes of TNF-α, IL-1β, IL-6, CSF and TGF-β in blood as well as bone marrow and intestinal mucosa over 20 days following: UTS-1401 alone, 10 Gy irradiation, and the combination of UTS-1401 and radiation at a 24h interval. The results from these studies are expected to demonstrate an effective first-in-class compound, UTS-1401, which has a small molecular weight, is chemically stable, nontoxic, aqueous soluble and inexpensive with radiation mitigating properties which extend for a number of days following irradiation. The mechanism studies are expected to demonstrate UTS-1401 as a new class of agents for mitigating the cytokine storm consequent to the irradiation.", "keywords": [ "Animals", "Biologic Characteristic", "Biological", "Biological Assay", "Biological Availability", "Blood", "Bone Marrow", "Buffers", "Carboxylic Acids", "Cell Death", "Characteristics", "Chemicals", "Complex", "Data", "Development", "Dose", "Drug Delivery Systems", "Drug Kinetics", "Effectiveness", "Electrons", "Exposure to", "FDA approved", "Female", "Femur", "Formulation", "Gender", "Goals", "Hematopoietic", "Hematopoietic System", "Hematopoietic stem cells", "Hour", "Individual", "Inflammatory", "Interleukin-1 beta", "Interleukin-6", "Intestinal Mucosa", "Intestines", "Intravenous", "Ionizing radiation", "Isoxazoles", "Lethal Dose 50", "Measures", "Methods", "Molecular Weight", "Mus", "Nuclear", "Nuclear Accidents", "Nuclear Weapon", "Oral", "Pharmaceutical Preparations", "Plasma", "Property", "Radiation", "Radiation Accidents", "Radiation Dose Unit", "Radiation Injuries", "Radiation Protection", "Radiation Toxicity", "Radiation exposure", "Refrigeration", "Research", "Role", "Route", "Saline", "Sampling", "Series", "Solubility", "Spleen", "Swiss Mice", "Syndrome", "TNF gene", "Tartrates", "Technology", "Terrorism", "Testing", "Time", "Tissues", "Transforming Growth Factor beta", "United States National Institutes of Health", "War", "Weight", "Whole-Body Irradiation", "aqueous", "chemical stability", "cost effective", "cytokine", "cytokine release syndrome", "flexibility", "gastrointestinal", "gender difference", "intravenous administration", "irradiation", "male", "medical countermeasure", "mouse model", "novel", "radiation countermeasure", "radiation mitigation", "radiation mitigator", "radioprotected", "small molecule", "stem cells", "subcutaneous", "success" ], "approved": true } }, { "type": "Grant", "id": "6260", "attributes": { "award_id": "3P50MH115837-03S1", "title": "UW ALACRITY Center for Psychosocial Interventions Research", "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": 21177, "first_name": "Adam", "last_name": "Haim", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2018-05-08", "end_date": "2022-04-30", "award_amount": 165581, "principal_investigator": { "id": 21178, "first_name": "Patricia A.", "last_name": "Arean", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "ABSTRACT. The UW ALACRITY Center purpose is to address critical problems in the implementation of evidence-based psychosocial interventions (EBPIs) for underserved communities as they are delivered in primary care medicine settings. Per a recent IOM report on psychosocial intervention standards, access to EBPIs is hampered by (1) poor clinician training, (2) intervention design complexity, and (3) insufficient support to sustain quality of care. We will attempt to solve these problems by creating a team of researchers from human centered design (Drs. Fogarty, Gonzalez, Munson, Popovic), education (Raue, Popovic), implementation science (Drs. Bennett and Lyon), psychosocial interventions (Drs. Aisenberg, Arean, Kaysen, Raue), health services research (Dr. Fortney, Ratzliff and Unutzer) and research methods (Dr. Atkins and Hoeft). The Center represents a unique partnership between the School of Medicine’s Departments of Psychiatry/Behavioral Sciences and Family Medicine, the Department of Computer Science and Engineering, the Department of Communications, and the School of Social Work. The Center also bridges UW’s many resources: CoMotion (UW’s center for health technology innovation), the Institute for Translational Health Sciences (the UW CTSA), the AIMS Center (UW implementation and training center for collaborative care), and the WWAMI-region Practice Research Network (WPRN, a collaborative group of primary care practices through the states of Washington, Wyoming, Alaska, Montana and Idaho to facilitate innovative community- based research). The Administrative Core will serve as the communication hub between center cores, our two advisory boards, and will oversee the solicitation and selection of R03 level proof of concept studies. The Methods Core (MC) will provide research infrastructure to the projects. Each project will use our Discover, Design, Build and Test framework to address clinician capacity, intervention usability and intervention sustainability. The MC will also compile data from these projects to create a Typology of EBPI Targets and a Matrix of EBPI Modifications that will be shared with other researchers within and outside of UW through our online research community. Research projects will collect a common core of outcomes to determine the impact of modifying EBPI targets on clinicians’ quality delivery of care and patient-reported outcomes. The first R34 project proposes to improve clinician EPBI capacity by designing and building an Intelligent Tutor System based on adaptive training. The second R34 project will partner with the WPRN to simplify problem-solving therapy (PST), using user-centered design principles. The third R34 project will partner with the Washington Behavioral Health Integration Program (BHIP) to develop an electronic health record-supported behavioral health module and registry to support sustained clinician skill in delivering PST in primary care. All three projects, and future R03s, will test the effects modification targets of implementation outcomes (time to training, clinician skill drift), system usability, EBPI system burden, system acceptability, and patient-reported outcomes.", "keywords": [ "Action Research", "Address", "Alaska", "Algorithms", "Behavior Therapy", "Behavioral Sciences", "Case Management", "Case Manager", "Catalogs", "Cognitive Therapy", "Common Core", "Communication", "Communities", "Community Practice", "Complex", "Counseling", "Data", "Discipline", "Education", "Effectiveness", "Electronic Health Record", "Engineering", "Environment", "Face", "Faculty", "Family Practice", "Federally Qualified Health Center", "Feedback", "Future", "Goals", "Guidelines", "Health", "Health Services Research", "Health Technology", "Healthcare", "Human", "Idaho", "Incubators", "Institute of Medicine (U.S.)", "Institutes", "Intervention", "Intervention Studies", "Learning", "Low income", "Medicine", "Mental Depression", "Mental Health", "Mentorship", "Methodology", "Methods", "Minority", "Modification", "Montana", "Outcome", "Participant", "Patient Outcomes Assessments", "Patients", "Perinatal", "Phase", "Primary Health Care", "Problem Solving", "Protocols documentation", "Psychiatry", "Psychology", "Psychotherapy", "Quality of Care", "Questionnaires", "Registries", "Reporting", "Research", "Research Design", "Research Infrastructure", "Research Methodology", "Research Personnel", "Research Project Grants", "Resources", "Rural", "Schools", "Site-Directed Mutagenesis", "Social Work", "Social Workers", "Supervision", "System", "Technology", "Testing", "Time", "TimeLine", "Training", "Training Programs", "Typology", "Universities", "Washington", "Wyoming", "base", "behavioral health", "care delivery", "care outcomes", "care seeking", "collaborative care", "community based participatory research", "computer science", "cost", "design", "disability", "effective intervention", "effectiveness testing", "ethnic minority population", "evidence base", "experience", "implementation science", "improved", "innovation", "intelligent tutoring system", "intervention participants", "medical schools", "meetings", "multidisciplinary", "novel", "problem solving therapy", "programs", "prototype", "psychosocial", "racial minority", "skills", "therapy design", "tool", "translational health science", "usability", "user centered design", "virtual" ], "approved": true } }, { "type": "Grant", "id": "11779", "attributes": { "award_id": "1I01BX006010-01A1", "title": "Vaccinating at Mucosal Surfaces with Nanoparticle-conjugated Antigen and Adjuvant", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2023-04-01", "end_date": "2027-03-31", "award_amount": null, "principal_investigator": { "id": 27656, "first_name": "SEBASTIAN", "last_name": "JOYCE", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1477, "ror": "https://ror.org/05eq41471", "name": "Veterans Health Administration", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "The incidence of tuberculosis (TB) has increased among Veterans in recent years because global TB burden has escalated with the emergence of multidrug-resistant and extremely drug resistant Mycobacterium tuberculosis (Mtb) strains. Further, current vaccines do not elicit long-lasting protective immunity against TB, especially in adults. Hence, this application addresses a critical unmet need for an effective vaccine against TB and thereby, significantly improve the quality of life of our Veterans. Herein, we propose pre-clinical studies that will identify protective CD8+ T cell epitopes and develop intranasal vaccine delivery platforms for the design of next generation TB vaccines. The global burden of TB caused by Mycobacterium tuberculosis (Mtb) infection is enormous. A third of the world’s population is currently infected with Mtb, an airborne pathogen that causes ~1.5 million deaths annually. The escalating emergence of multidrug-resistant and extremely drug resistant Mtb strains for which treatment options are costly and limited, further exacerbates global burden. This problem persists because current vaccines do not elicit long-lasting protective immunity against TB, especially in adults. The challenge is multifaceted because Mtb enters the host through the respiratory tract and, therefore, optimal protection will require installation of lung-resident CD4+ and CD8+ memory T cells positioned at the frontline to respond immediately to an infection. Traditional vaccines and approved adjuvants typically elicit weak, short- lived T cell responses, and parenteral vaccination is ineffective at installing protective immunity within the mucosae. Moreover, most virus-vectored and subunit TB vaccines employ a small subset of Mtb antigens, resulting in insufficient epitope diversity for optimal protection, partly because the epitopes that are presented during Mtb infection and confer protective immunity are not fully defined. Hence, our overall objective is to discover immunogenic, protective Mtb epitopes and to incorporate them in an innovative nanoparticle (NP)- based intranasal vaccine designed to promote a balanced CD4+ and CD8+ T cell responses in the lungs that are protective against TB. As a means to accomplish this goal, we discovered >10,000 peptides that bind to HLA- A*02:01, B*07:02, B*35:01, & B*35:03 in a high-throughput binding assay using ultrahigh-density peptide arrays. Now the challenge is to identify epitopes recognised by Mtb-reactive CD8+ T cells that can protect against infection in a preclinical, humanised HLA-Itg mouse models. Moreover, using different infection models, we have developed multiple nanoparticle platforms for simultaneous delivery of antigens and adjuvants that efficiently generate protective, tissue resident CD8+ T cells (Trm). Guided by these exciting published and preliminary results, we will test this central hypothesis: Intranasal immunization with subunit vaccines consisting of novel Mtb antigens and adjuvant will generate CD8+ Trm responses in the lungs. Installation of Mtb-reactive CD8+ Trm at the port of pathogen entry will protect against a lethal, aerosol challenge of three novel humanised mouse models with [there] clinical isolate of virulent Mtb, [including] HN878. Our strategy to test this hypothesis is to, (a) define immunodominant CD8+ T cell epitopes presented by HLA-B*07:02 that protect B7.2tg mice from Mtb infections; and (b) define common immunodominant CD8+ T cell epitopes presented by multiple B*07:02-related alleles [called B7 supertype] that protect HLA-I transgenic mouse models from Mtb infections. Our multidisciplinary team —consisting of biochemists, immunologists, microbiologists, and bioengineer, is ideally situated to pursue the stated Specific Aims. We anticipate that successful completion of the proposed research will inform next generation vaccine design against Mtb infections and TB disease. Our innovative “discover and deliver” approach to vaccine design will impact clinical practice paradigms against TB and other pulmonary infectious diseases such as SARS-COVID19 and Flu. 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