Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1406&sort=funder
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=funder", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1424&sort=funder", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1407&sort=funder", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=funder" }, "data": [ { "type": "Grant", "id": "12050", "attributes": { "award_id": "5R13ES034643-02", "title": "2022-2024 US DOHaD Society Meetings", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Environmental Health Sciences (NIEHS)", "NIH Office of the Director" ], "program_reference_codes": [], "program_officials": [ { "id": 7983, "first_name": "Thaddeus", "last_name": "Schug", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-07-01", "end_date": "2025-06-30", "award_amount": 13000, "principal_investigator": { "id": 25593, "first_name": "PHU V.", "last_name": "TRAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 764, "ror": "https://ror.org/017zqws13", "name": "University of Minnesota", "address": "", "city": "", "state": "MN", "zip": "", "country": "United States", "approved": true }, "abstract": "The fundamental concept of Developmental Origins of Health and Diseases (DOHaD), which posits that early- life events or exposures determine the health outcomes across the life span, has been well represented by the US DOHaD Society exemplified by its annual national meeting since its inception in 2016. Its annual meeting brings together investigators with diverse backgrounds who otherwise may not likely interact, including those researching in the areas of developmental biology, life course epidemiology, nutrition, environmental toxicology, cancer, stress, and endocrinology. Such individuals span institutions across the US from universities to industry to government agencies (NIH, EPA, NIEHS) to share knowledge and recent advancements on how environmental toxicants, nutrients, pharmaceutical agents, pathogens, gut microbiota, stress, and emerging factors influence developing fetuses and newborns, and thereby contribute to their health and disease across the life span. Further, presentations also delve into how such factors might lead to harmful effects in the subsequent generations, i.e., transgenerational effects. The major goal of the US DOHaD Society’s annual meeting is to foster multidisciplinary interactions and promote collaborations on these diverse topics. The second objective is to provide opportunity for trainees (graduate students, postdoctoral fellows, and junior faculty) to interact with world-renown experts, facilitating the development of future scientists and career opportunities in the field. The third objective is to continue promoting diversity, inclusivity, and equal representation of sex, gender and underrepresented minority groups as speakers and session leaders. Notably, women and minority represented >50% and >20% speakers and moderators, respectively, over the last five meetings. The past five conferences have been enormously successful, particularly the 2021 hybrid (in-person and virtual) meeting despite the ongoing COVID pandemic. Such successes provide impetus for continued and permanent annual meetings. The 6th, 7th, and 8th Annual Meetings will again be a hybrid format and held at the University of Minnesota (Minneapolis, 2022), the Mercy’s Children Hospital (Kansas City, 2023) and the Rizzo Center (Chapel Hill, 2024), respectively. The theme for the 2022 meeting will be “Environmental Exposures: Assessment Methodologies, Mechanisms, and Health Outcomes”. Analogous to the 2021 meeting, the program will include a dedicated day on career development and grant writing that will be provided in kind to all trainees. Preliminary themes for 2023 and 2024 will cover topics including maternal microbiota and child development, exosomes as carriers of biomarkers, effects of maternal supplemental folate, choline and DHA on offspring health outcomes associated with epigenomic changes, and epidemiological analyses of long-term health outcomes associated with heat stress during pregnancy and lactation. In short, the strength of the U.S. DOHaD Society lies in its diversity in terms of the research it represents and those researching these areas.", "keywords": [ "Advocate", "Alcohols", "American", "Area", "Australia", "Award", "Awareness", "Biological Markers", "Biomedical Research", "COVID-19 pandemic", "Child Development", "Choline", "Chronic Disease", "Cities", "Collaborations", "Data", "Dedications", "Development", "Developmental Biology", "Disease", "Elderly", "Endocrine Disruptors", "Endocrinology", "Ensure", "Environment", "Environmental Exposure", "Epidemiologist", "Epidemiology", "Ethnic Origin", "Event", "Exposure to", "Faculty", "Fellowship", "Fetal Development", "Folic Acid", "Fostering", "Funding", "Future", "Gender", "Generations", "Goals", "Government Agencies", "Grant", "Health", "Heat Stress Disorders", "Hormones", "Human Development", "Hybrids", "Individual", "Industry", "Institution", "International", "Intervention", "Investigation", "Kansas", "Knowledge", "Lactation", "Leadership", "Life", "Life course epidemiology", "Long-Term Effects", "Longevity", "Malignant Neoplasms", "Mammals", "Measures", "Medical", "Methodology", "Michigan", "Minnesota", "Minority", "Minority Groups", "Minority Recruitment", "Mission", "National Institute of Environmental Health Sciences", "Netherlands", "Newborn Infant", "North Carolina", "Nutrient", "Nutritionist", "Outcome", "Participant", "Pathology", "Pediatric Hospitals", "Perinatal", "Persons", "Pharmaceutical Preparations", "Pharmacologic Substance", "Physicians", "Postdoctoral Fellow", "Pregnancy", "Prevention strategy", "Productivity", "Public Health Applications Research", "Public Policy", "Research", "Research Methodology", "Research Personnel", "Risk", "Role", "Science", "Scientist", "Singapore", "Societies", "Source", "South Africa", "Stress", "Students", "Surveys", "Toxic Environmental Substances", "Toxicology", "Training", "Travel", "Underrepresented Minority", "Underserved Population", "United States", "United States National Institutes of Health", "Universities", "Woman", "Writing", "career", "career development", "coronavirus disease", "cost", "disorder risk", "diversity and inclusion", "environmental chemical", "environmental chemical exposure", "environmental toxicology", "epigenomics", "exosome", "experience", "fetal", "gender minority", "graduate student", "gut microbiota", "improved", "indexing", "interest", "maternal microbiota", "meetings", "microbiome", "multidisciplinary", "novel", "nutrition", "offspring", "pathogen", "pre-doctoral", "prevent", "programs", "recruit", "sex", "societal costs", "sound" ], "approved": true } }, { "type": "Grant", "id": "12051", "attributes": { "award_id": "5R21AI161521-02", "title": "Adjuvant combination for SARS-CoV-2 vaccine for the elderly", "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": 6908, "first_name": "JENNIFER L.", "last_name": "Gordon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-07-08", "end_date": "2024-06-30", "award_amount": 195625, "principal_investigator": { "id": 25595, "first_name": "Elena", "last_name": "Vassilieva", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 265, "ror": "https://ror.org/03czfpz43", "name": "Emory University", "address": "", "city": "", "state": "GA", "zip": "", "country": "United States", "approved": true }, "abstract": "Severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) is currently causing the coronavirus disease (COVID-19) in pandemic proportion. According to John Hopkins university data tracker, there were 120,217,175 global cases and 2,660,456 deaths worldwide on March 15, 2021. The disease ranges from asymptomatic to lethal, with the elderly patients most severely affected. Finding a successful strategy to protect most vulnerable aged population is vital. However, it is possible that protein-based vaccines will not be as effective in individuals over 65 years of age as in healthy younger adults. There are also indications that RNA vaccines that are currently used under emergency authorization elicit vaccine responses appear weaker in elderly . Protein-based vaccines are considered safe but they lack the ability to elicit Th1 type of responses especially needed for protection in aged populations. Recently we developed a novel combination adjuvant for use with a licensed influenza subunit vaccine in high-risk aged population and tested it in an aged mouse model. The formulation combines an agonist of the stimulator of interferon gene (STING) pathway 2,3’-cGAMP and saponin Quil-A. Activation of the STING pathway leads to production of interferons and cytokines in target cells, and enhances development of the immune response to vaccine antigens, while saponins stimulate both the Th1 immune response and cytotoxic T lymphocyte production against protein antigens. By co-delivering these two compounds, cGAMP and Quil-A, with the vaccine we combined their adjuvant potential and improved the protective immunity of influenza vaccine in the aged mice more effectively than either a 4x antigen dose or MF-59-like adjuvant, which are two current vaccination options for persons over 65 years of age. We propose that this combination will also potentiate the protective responses to a candidate SARS-CoV-2 vaccine and will test this in aged mice. We will test this hypothesis using both sexes of aged mice. As saponins have been previously shown to increase the duration of immune response we will also determine the persistence of neutralizing antibodies in vaccinated animals. Although we do not anticipate reactogenicity of this formulation based on our experience, we will also test if a novel and safer saponin Titerquil 1-0-5-5 can be used instead of Quil-A. The results will be directly relevant for development of SARS-CoV-2 protein vaccines for high-risk aged populations. The combination adjuvant can be directly added to existing vaccines.", "keywords": [ "2019-nCoV", "Address", "Adjuvant", "Adult", "Affect", "Age Years", "Agonist", "Animals", "Antigens", "Authorization documentation", "COVID-19 vaccine", "Cells", "Cessation of life", "Clinical Research", "Combined Vaccines", "Cytotoxic T-Lymphocytes", "Data", "Development", "Disease", "Dose", "Elderly", "Emergency Situation", "Formulation", "Immune response", "Immunity", "Individual", "Influenza", "Interferons", "Licensing", "MF59", "Mus", "Outcome", "Pathway interactions", "Persons", "Production", "Proteins", "Quil A", "RNA vaccine", "Recombinant Proteins", "Research", "Safety", "Saponins", "Stimulator of Interferon Genes", "Subunit Vaccines", "Testing", "Translations", "Universities", "Vaccinated", "Vaccination", "Vaccine Antigen", "Vaccines", "aged", "aging population", "authority", "coronavirus disease", "cytokine", "experience", "high risk", "immunogenicity", "immunosenescence", "improved", "influenza virus vaccine", "middle age", "mouse model", "neutralizing antibody", "novel", "older patient", "pandemic disease", "response", "sex", "vaccine candidate", "vaccine development", "vaccine response", "young adult" ], "approved": true } }, { "type": "Grant", "id": "12052", "attributes": { "award_id": "5F31AA029932-02", "title": "Impact of the COVID-19 Pandemic on Alcohol Use and Outcomes: The Role of Health Disparities", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Alcohol Abuse and Alcoholism (NIAAA)" ], "program_reference_codes": [], "program_officials": [ { "id": 7190, "first_name": "Beverly", "last_name": "Ruffin", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-07-01", "end_date": "2024-06-30", "award_amount": 31694, "principal_investigator": { "id": 25504, "first_name": "Courtney Lynn", "last_name": "Vaughan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 887, "ror": "", "name": "HENRY M. JACKSON FDN FOR THE ADV MIL/MED", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "The novel coronavirus (SARS-CoV-2) outbreak has resulted in a world-wide pandemic infection designated COVID-19. While attention has focused on prevention and treatment of SARS CoV-2 infection, the mental health consequences of the pandemic also need to be examined, to include the effect of the pandemic on alcohol use and problems. There is evidence that different racial/ethnic groups may be differentially affected by the pandemic and may therefore have different alcohol use outcomes, and both theory and data suggest that vulnerable groups who have experienced the highest level of exposure to the pandemic may be most at risk for increased alcohol use following the pandemic. To address these questions, this Diversity F31 application will take advantage of a unique resource associated with NIAAA and directed by Co-Sponsor Ramchandani. As part of the ongoing NIAAA longitudinal study of the pandemic impact on alcohol use, up to 500 participants, including non-drinkers, light drinkers, non-treatment-seeking heavy drinkers, as well as treatment-seeking individuals with alcohol use disorder, will be assessed by phone and/or online over 2 years. Data from this study will be used by the applicant to address the first two aims. Specific Aim 1 will examine if the impact of the pandemic on alcohol use is different in individuals who identify as Black/African Americans compared to those who identify as White, and in individuals who report lower levels of income/education compared to those who report higher levels of income/education. Specific Aim 2 will examine mediators of increased alcohol use among vulnerable groups, including the effect of increases in post-pandemic stress and financial impact following the onset of the pandemic. In addition, a sample of 40 Black/African Americans will be invited to take part in a 6-week Ecological Momentary Assessment (EMA) study administered by the applicant, which will be used to address Specific Aim 3. Specific Aim 3 will examine predictors of alcohol use in a group of Black/African Americans using Ecological Momentary Assessment, to include measures of perceived discrimination and financial stress. Overall, this study may help to clarify which vulnerable groups are most at risk of increased alcohol use and problems post-pandemic, and increase understanding of the mechanisms that give rise to increased alcohol use and problems in these individuals.", "keywords": [ "Address", "Affect", "African American population", "Alcohol abuse", "Alcohol consumption", "Alcoholic beverage heavy drinker", "Alcohols", "Attention", "Black Populations", "Black race", "COVID-19", "COVID-19 pandemic", "COVID-19 pandemic effects", "COVID-19 treatment", "Cellular Phone", "Chronic stress", "Communities", "Data", "Data Set", "Disease Outbreaks", "Ecological momentary assessment", "Education", "Educational Status", "Ethnic Population", "Exposure to", "Financial Hardship", "Health system", "Heavy Drinking", "Hurricane", "Income", "Individual", "Infection", "Job loss", "Light", "Longitudinal Studies", "Measures", "Mediating", "Mediator", "Mental Health", "National Institute on Alcohol Abuse and Alcoholism", "Outcome", "Outcomes Research", "Participant", "Prevention", "Relapse", "Reporting", "Research", "Resources", "Risk", "Role", "SARS-CoV-2 infection", "Sampling", "Stress", "Stressful Event", "Subgroup", "Telephone", "Time", "Vulnerable Populations", "acute stress", "addiction", "alcohol use disorder", "current pandemic", "experience", "health disparity", "novel coronavirus", "pandemic disease", "pandemic impact", "pandemic stress", "perceived discrimination", "post-pandemic", "pre-pandemic", "racial population", "theories", "therapy development", "traumatic event" ], "approved": true } }, { "type": "Grant", "id": "12053", "attributes": { "award_id": "5R01HL164561-02", "title": "Cardiovascular Health of Low-Income Working-Age Adults in the US: Health Care Access, Policy, and the Pandemic", "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": 25596, "first_name": "GABRIEL", "last_name": "Anaya", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-07-01", "end_date": "2027-06-30", "award_amount": 763034, "principal_investigator": { "id": 25597, "first_name": "Rishi Kumar", "last_name": "Wadhera", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 771, "ror": "https://ror.org/04drvxt59", "name": "Beth Israel Deaconess Medical Center", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "In the United States, declines in cardiovascular mortality have stalled, and there is growing concern that these population-level trends may reflect an increase in the burden of cardiovascular risk factors and disease in low- income working-age adults (18 to 64 years). However, these patterns have not been well characterized on a national scale. The COVID-19 pandemic has only magnified the critical need to track the cardiovascular health of the low-income working-age population. The pandemic has led to substantial disruptions in health care, and created enormous spillover effects, including unemployment and deepening financial hardship, which have fallen more heavily on low-income adults. These changes may widen inequities in health insurance coverage, health care access, and affordability, and ultimately, worsen cardiovascular health for years to come. In the wake of the pandemic, policymakers are now weighing whether to expand the Medicare program to increase access to health care. Understanding the potential effects of this policy change on the cardiovascular health of low-income adults could inform federal strategies to improve health equity nationwide. Building on our team’s expertise in the linkage and analysis of large datasets, the application of epidemiological and econometric methods, and the evaluation of health policies, we will examine changes in cardiovascular risk factors, disease, and outcomes in low-income working-age adults, assess the impact of the pandemic on health care coverage, access, and affordability as well as cardiovascular morbidity and mortality, and determine the potential effects of expanding Medicare on the cardiovascular health of this population. To do so, we will use a unique combination of national survey data, state all-payer and national Medicaid claims, and CDC epidemiological data. In Aim 1, we will perform a national analysis that determines whether the prevalence, treatment, and control of cardiovascular risk factors, incidence of acute cardiovascular events, and cardiovascular mortality were increasing in low-income working-age adults prior to the pandemic. In Aim 2, we will examine whether the pandemic was associated with short- and long-term changes in health care coverage, access, and affordability, cardiovascular morbidity and mortality, and self- reported health in low-income working-age adults using interrupted time series analyses. In Aim 3, we will evaluate the effects of Medicare on health care access and affordability, the screening, treatment and control of cardiovascular risk factors, and self-reported health in low-income adults using quasi-experimental approaches. This research will advance our understanding of changes in cardiovascular morbidity and mortality among low-income working-age adults, before and after the pandemic, and provide critical insights on the implications of expanding Medicare on health care access, affordability, and cardiovascular health for this population. Cardiovascular disease remains the leading cause of death in the US, and our work will ultimately inform public health and policy strategies to improve cardiovascular outcomes – and equity – nationwide.", "keywords": [ "Acute", "Adult", "Age", "Behavioral Risk Factor Surveillance System", "Black race", "COVID-19 pandemic", "Cardiovascular Diseases", "Cardiovascular system", "Caring", "Cause of Death", "Centers for Disease Control and Prevention (U.S.)", "Cessation of life", "Data", "Data Set", "Death Rate", "Disease", "Eligibility Determination", "Enrollment", "Epidemiology", "Equity", "Evaluation", "Event", "Financial Hardship", "Goals", "Health", "Health Insurance", "Health Policy", "Health Services Accessibility", "Healthcare", "Heart failure", "Hospitalization", "Incidence", "Income", "Inequity", "Insurance Carriers", "Insurance Coverage", "Interruption", "Left", "Link", "Low income", "Medicaid", "Medical", "Medicare", "Methods", "Morbidity - disease rate", "Myocardial Infarction", "National Health and Nutrition Examination Survey", "Outcome", "Patient Self-Report", "Pattern", "Persons", "Policies", "Policy Maker", "Population", "Prevalence", "Public Health", "Public Policy", "Publishing", "Quasi-experiment", "Research", "Risk Factors", "Rural Community", "Source", "Stroke", "Subgroup", "Surveys", "Time", "Time Series Analysis", "Unemployment", "United States", "Vulnerable Populations", "Work", "aging population", "cardiovascular disorder epidemiology", "cardiovascular disorder risk", "cardiovascular health", "cardiovascular risk factor", "econometrics", "epidemiologic data", "experience", "falls", "health care availability", "health equity", "health inequalities", "improved", "insight", "large datasets", "mortality", "pandemic disease", "pandemic impact", "population health", "programs", "public health insurance", "response", "screening", "social health determinants", "socioeconomics", "trend" ], "approved": true } }, { "type": "Grant", "id": "12054", "attributes": { "award_id": "5R21AI171574-02", "title": "Roles of human surfactant collectin variants in the susceptibility of COVID-19", "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": 27781, "first_name": "Mary Katherine Bradford", "last_name": "Plimack", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-07-08", "end_date": "2024-06-30", "award_amount": 203750, "principal_investigator": { "id": 25598, "first_name": "GUIRONG", "last_name": "WANG", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2060, "ror": "", "name": "UPSTATE MEDICAL UNIVERSITY", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "More than 4.8 million people have died due to coronavirus disease 2019 (COVID-19) in less than two years. COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Morbidity and mortality following SARS-CoV-2 infection are predominantly due to a robust influx of inflammatory cells and cytokines into the lungs resulting in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Individuals exhibited different degree of disease severity after SARS-CoV-2 infection. Human Surfactant proteins A and D (hSP-A and hSP-D), two members of C-type lectin (surfactant collectin), are pattern recognition proteins, and they play a critical role as a first-line host defense and innate immunity in the mucosal surfaces of the lung and other organs. Our preliminary data and recent in vitro studies demonstrated that hSP-A and hSP-D can bind to SARS-CoV-2 Spike protein and inhibit viral entry and replication in lung epithelial cells. Interestingly, the genes of hSP-A and hSP-D are highly polymorphic, and several genetic variants (alleles) for each of them have been identified in the general population. However, the mechanistic roles of hSP- A and hSP-D genetic variants in the pathogenesis of COVID-19 are unknow. The long-term goal is to determine the roles of hSP-A and hSP-D genetic variants in susceptibility and severity to SARS-CoV-2-induced ALI/ARDS and to develop novel variant-specific therapeutic drug for the treatment of COVID-19. This proposal aims to determine molecular interaction of surfactant collection and Spike protein, and define the mechanistic roles of hSP-A and hSP-D genetic variants causing individual susceptibilities to COVID-19. Our central hypothesis is that hSP-A and hSP-D genetic variants differentially influence susceptibility and severity to SARS-CoV-2-induced ALI/ARDS by inhibiting SARS-CoV-2 infectivity and modulating mucosal innate immunity and pathophysiology. Recently, we have generated a new double-humanized transgenic (double-hTG) mouse model, which express human angiotensin-converting enzyme-2 (SARS-CoV-2 cognate receptor) and hSP-A or hSP-D genetic variant. This double-hTG model provides us with a powerful tool to study the innate immune response and mechanistic roles of hSP-A and hSP-D variants following SARS-CoV-2 infection. We propose two specific aims to test our hypothesis: Aim 1: Study the interactions of hSP-A or hSP-D genetic variants with SARS-CoV-2 spike protein and the inhibitory effect on viral entry and replication in lung epithelial cells. Aim 2: Define the differential roles of hSP-A genetic variants in inhibiting viral infectivity and modulating SARS-CoV-2-induced ALI through regulating TLRs/NF-kB/IFN signaling in a double-hTG mouse model. The proposal is strongly supported by our preliminary data and available novel double-hTG model suitable for COVID-19 study. We expect that the successful completion of the proposed studies will establish a novel COVID-19 murine model, and have a better understanding of the innate immune roles of hSP-A and hSP-D in COVID-19 pathogenesis that is crucial to develop novel immunomodulatory therapies and personalized medicine.", "keywords": [ "2019-nCoV", "ACE2", "Acute Lung Injury", "Acute Respiratory Distress Syndrome", "Alleles", "Amino Acids", "Antibodies", "Binding", "C-Type Lectins", "COVID-19", "COVID-19 pathogenesis", "COVID-19 susceptibility", "COVID-19 treatment", "Cells", "Cellular biology", "Cessation of life", "Code", "Collagen", "Collectins", "Collection", "Communicable Diseases", "Country", "Data", "Development", "Disease", "Disease Outcome", "Epithelial Cells", "Exhibits", "Functional disorder", "General Population", "Genes", "Genetic Polymorphism", "Genetic Variation", "Goals", "Host Defense", "Human", "Immune", "In Vitro", "Individual", "Inflammatory", "Innate Immune Response", "Interdisciplinary Study", "Interferons", "Investigation", "Link", "Lung", "Microbe", "Modeling", "Molecular", "Molecular Biology", "Morbidity - disease rate", "Mucous Membrane", "Mus", "NF-kappa B", "Natural Immunity", "Nuclear", "Organ", "Outcome", "Pathogenesis", "Patients", "Pattern Recognition", "Persons", "Pharmacotherapy", "Play", "Population", "Positioning Attribute", "Predisposition", "Proteins", "Public Health", "Pulmonary Surfactant-Associated Protein A", "Pulmonary Surfactant-Associated Protein D", "Reporting", "Research", "Respiratory Tract Infections", "Role", "SARS-CoV-2 B.1.617.2", "SARS-CoV-2 inhibitor", "SARS-CoV-2 pathogenesis", "SARS-CoV-2 spike protein", "SARS-CoV-2 variant", "Severities", "Severity of illness", "Signal Pathway", "Signal Transduction", "Surface", "System", "Techniques", "Testing", "Therapeutic", "Transgenic Mice", "Transgenic Model", "United States", "Variant", "Viral", "Viral Load result", "alveolar epithelium", "carbohydrate structure", "cytokine", "design", "disease phenotype", "genetic variant", "genome wide association study", "immunomodulatory therapies", "immunoregulation", "in vivo", "innate immune function", "innovation", "member", "mortality", "mouse model", "novel", "novel therapeutic intervention", "personalized medicine", "post SARS-CoV-2 infection", "receptor", "surfactant", "tool", "viral entry inhibitor", "virology" ], "approved": true } }, { "type": "Grant", "id": "12055", "attributes": { "award_id": "5R42TR004277-03", "title": "Teleconsent: Enabling informed consent for remote care and research", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Center for Advancing Translational Sciences (NCATS)" ], "program_reference_codes": [], "program_officials": [ { "id": 25599, "first_name": "MEENA UMA", "last_name": "Rajagopal", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-07-01", "end_date": "2024-04-30", "award_amount": 868011, "principal_investigator": { "id": 25600, "first_name": "Brandon M", "last_name": "Welch", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1864, "ror": "", "name": "DOXY.ME, LLC", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": ". Informed consent is legal and ethical requirement in health care and research that assures that individuals have the autonomy to make informed care and research decisions at their own volition, under no coercion or undue influence, and with reasonable understanding of the risks, benefits, and responsibilities of their decisions as they would in-person. Obtaining informed consent is a required yet challenging requirement that can impede participation in health care and clinical research. As a result of the COVID-19 pandemic, telemedicine has proven to be an effective way to deliver health and research services to patients remotely. Yet, providers and researchers (“consenters”) are still required to obtain and document informed consent from patients and research participants (“consentees”). Conventional informed consent approaches are not compatible with telemedicine presenting logistical, technical and security barriers such as travel and cost burdens, low comprehension, confusion and dissatisfaction, alterations in clinical workflows, compliance challenges, and concern over clinical equipoise. Teleconsent is an innovative and proven solution for obtaining remote informed consent developed by Doxy.me, Inc and Medical University of South Carolina. Teleconsent allows consenters to (1) meet and discuss the informed consent by video with consentees over a telemedicine platform, (2) share and collaboratively complete the consent document in real-time, and (3) generate electronically signed copies of the consent for immediate download by both parties. Our Phase I STTR research identified enhancements such as an improved mobile interface, interface for consenters to build and manage consent forms, and the ability for consentees to read consent forms in advance. Optimizing teleconsent to meet the demands of its users is critical, especially during these unprecedented times of the COVID-19 pandemic when most individuals engage in remote care and research. The objective of this Phase II proposal is to refine and expand teleconsent features and deploy them on a large-scale via doxy.me. To achieve this objective, we will refine prototype teleconsent enhancements via iterative user experience assets design and evaluate them employing formal usability methods (Aim 1); build an enhanced, scalable teleconsent interface using Large-Scale Scrum principles and test the new teleconsent features via a formal user acceptance testing program (Aim 2); and implement teleconsent at a large scale with doxy.me providers and researchers to determine performance and measure impact using quantitative metrics for success (Aim 3). Achieving these aims to expand teleconsent features and conduct a large-scale implementation will increase the capacity of consenters to improve the efficiency of the remote informed consent, which will improve recruitment, simplify consent workflows, and enhance telemedicine engagement.", "keywords": [ "Academia", "Agreement", "COVID-19 pandemic", "Caring", "Clinical", "Clinical Research", "Coercion", "Collaborations", "Communication", "Comprehension", "Computer software", "Confusion", "Consent", "Consent Forms", "Development", "Electronics", "Engineering", "Equipoise", "Ethics", "Feedback", "Goals", "Grant", "Health", "Health Personnel", "Healthcare", "Hybrids", "Individual", "Industry", "Informed Consent", "Legal", "Licensing", "Measures", "Medical", "Methods", "Outcome", "Participant", "Patients", "Performance", "Persons", "Phase", "Process", "Provider", "Research", "Research Personnel", "Respondent", "Risk", "Security", "Services", "Small Business Technology Transfer Research", "South Carolina", "Telemedicine", "Testing", "Time", "Travel", "Universities", "Volition", "Work", "base", "cost", "decision research", "design", "experience", "handheld mobile device", "improved", "innovation", "novel", "preference", "pressure", "programs", "prospective", "prototype", "recruit", "remote consent", "remote health care", "response", "sociodemographics", "success", "teleconsent", "undue influence", "usability", "virtual consent" ], "approved": true } }, { "type": "Grant", "id": "12056", "attributes": { "award_id": "5R01AI170715-02", "title": "Antibody Durability Dynamics", "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": 10255, "first_name": "Joseph J.", "last_name": "Breen", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-07-01", "end_date": "2027-06-30", "award_amount": 686383, "principal_investigator": { "id": 25602, "first_name": "Duane R.", "last_name": "Wesemann", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 891, "ror": "https://ror.org/04b6nzv94", "name": "Brigham and Women's Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Antibodies specific for pathogenic threats can provide immediate protection from infectious disease but longevity of an antibody responses after vaccination or infection can be highly variable. Responses induced by some live vaccines can persist for a lifetime, whereas protein-based vaccines are in general shorter lasting. However, antibody durability is not necessarily linked to the use of live virus as long-lived antibody responses have been shown to be induced by the human papilloma virus (HPV) vaccine, a non-live viral-like particle- based platform. This suggests that distinct immunological cues can be engineered to result in the generation of longer-lived antibody responses. While memory lymphocytes also provide a system of protective efficacy, strategies to maximize robust levels of protective secreted antibodies that are stable over time is an important goal in modern immunology. Understanding the capabilities of the immune system in this context, and how available vaccines can elicit durable secreted antibody responses will be important to decipher. This is relevant to the ongoing SARS-CoV-2 pandemic and for vaccine strategies more broadly. Preliminary data suggest that antibodies induced by natural infection harbor robust long-term stability at modest levels and greater polyclonal neutralizing breadth across viral variants compared to infection-naïve vaccinees. In addition, differential antibody durability trajectories tend to favor COVID-19 convalescent subjects with dual memory B cell features of greater antibody somatic mutation and cross-coronavirus reactivity. These findings support a hypothesis that high somatical mutation and cross-reactivity in antigen-binding memory B cell repertoires early after recovery predicts antibody durability and that recalled immunity may confer greater longevity of differentiated plasma cells. This hypothesis will be examined in two aims, (i) to illuminate factors influencing anti-SARS-CoV-2 antibody durability, and (ii) to chart the functional evolution of anti-CoV memory B cell over time. For aim 1, human and mouse studies will be used to illuminate potential mechanistic insights and features connected to durable antibody responses. For aim 2, the durability and evolution of memory B cell repertoire antigen recognition capacity will be charted over time to assess the evolving relationship between secreted polyclonal and memory B cell repertoires. This work is expected to shed light on factors that influence longevity and evolution of antibody responses, which will be important for ongoing improvement of vaccine strategies.", "keywords": [ "Affinity", "Animal Model", "Antibodies", "Antibody Response", "Antigens", "Attenuated Vaccines", "Automobile Driving", "B cell repertoire", "B-Cell Activation", "B-Lymphocytes", "Binding", "COVID-19", "COVID-19 pandemic", "Cell Communication", "Communicable Diseases", "Coronavirus", "Cues", "Data", "Disease", "Dose", "Engineering", "Epitopes", "Evolution", "Frequencies", "Future", "Generations", "Goals", "Human", "Human Papilloma Virus Vaccine", "Immune", "Immune response", "Immune system", "Immunity", "Immunoglobulin G", "Immunoglobulin Somatic Hypermutation", "Immunoglobulin-Secreting Cells", "Immunoglobulins", "Immunologics", "Immunology", "Infection", "Invaded", "Light", "Link", "Longevity", "Lymphocyte", "Memory", "Memory B-Lymphocyte", "Modernization", "Mus", "Mutation", "Pathogenicity", "Plasma Cells", "Proteins", "Public Health", "RNA vaccination", "Recovery", "Research", "SARS-CoV-2 antibody", "SARS-CoV-2 infection", "Sampling", "Somatic Mutation", "Speed", "Structure of germinal center of lymph node", "System", "T-Lymphocyte", "Testing", "Time", "Vaccination", "Vaccine Design", "Vaccinee", "Vaccines", "Variant", "Viral", "Virus", "Work", "antigen binding", "cohort", "cross reactivity", "improved", "insight", "neutralizing antibody", "particle", "pathogen", "plasma cell differentiation", "polyclonal antibody", "post SARS-CoV-2 infection", "prophylactic", "protective efficacy", "response", "time interval", "vaccine access", "vaccine strategy" ], "approved": true } }, { "type": "Grant", "id": "12057", "attributes": { "award_id": "5R44AI170419-02", "title": "Rapid dissection of the biosynthesis of antiMRSA antibiotics produced in co-culture by extremophilic fungi through the development of Fungal Artificial Chromosomes", "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": 23988, "first_name": "Baoying", "last_name": "Liu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-07-01", "end_date": "2025-06-30", "award_amount": 982704, "principal_investigator": { "id": 25604, "first_name": "Chengcang Charles", "last_name": "Wu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1865, "ror": "", "name": "INTACT GENOMICS, INC.", "address": "", "city": "", "state": "MO", "zip": "", "country": "United States", "approved": true }, "abstract": "PROJECT SUMMARY. The economic and social burden of the treatment of infectious and chronic diseases is enormous, >$300B annually. The ongoing COVID-19 pandemic alone will cost the U.S. economy roughly $8 trillion over the next decade without an effective drug to date. The emergence of drug resistant microbes, the diminishing supply of novel classes of antibiotics, and the dramatic reduction in R&D of anti-infective, anti-proliferation and anti-inflammatory agents have further amplified public health concerns. Fungi are prolific producers of anti- microbial secondary metabolites (SM) and since the turn of the century have provided 45% of bioactive molecules from all microbial sources. However, environmental filamentous fungi and fungal SM biosynthetic gene clusters (BGCs) remain largely untapped due to difficulties in efficiently handling and expressing these SM BGCs. This research proposal will advance the science of functional SM metagenomics, and will further advance our newly-developed fungal artificial chromosome (FAC) technology by integrating Next-Gen Sequencing (NGS), artificial intelligence (AI), FAC heterologous expression, and direct Nuclear Magnetic Resonance (NMR) analysis. Our methodologies enable precise capture of full-length SM BGCs from any fungus, and heterologous expression of large intact silent SM BGCs-containing FAC clones for high yields of natural products (NPs). Our goals are to improve the prediction of novel BGCs and their compound production, and to discover novel NPs for clinical development of novel antibiotics and other drug leads. In proof-concept research, we successfully predicted and captured the FAC-BGC of novel antibiotic berkeleylactone A and 136 BGCs from two different fungi by FAC-NGS. Phenomenally, we achieved at least 60% yields of discreet NP compounds as FAC crude extracts by heterologous expression of 5 of 17 BGC-FACs. We also elucidate the structures of 15 NP molecules with diverse activities, including TWO novel compounds by direct NMR analysis of FAC crude extracts, due to the high yield of some compounds. In this Phase II study, we will further improve our in-house FAC-NGS-AI pipeline to better predict novel fungal BGCs and their NPs, increasing the compound hit rate to 50~70% with high yield. We will completely dissect the berkeleylactone BGC and discover novel derivatives of this new antibiotic of homologous BGCs of other fungi. We will also study twelve fungi (ten fungi with no reference genomic sequences available) with an estimated 800 BGCs. This technology should improve fungal SM discovery 100~1000 fold and result in the discovery of at least five novel antibiotics, and other drug leads from un-studied/un-sequenced fungi of the toxic Berkeley Pit.", "keywords": [ "Address", "Anabolism", "Anti-Infective Agents", "Anti-Inflammatory Agents", "Antibiotics", "Antifungal Agents", "Applications Grants", "Artificial Chromosomes", "Artificial Intelligence", "Bacterial Artificial Chromosomes", "Bioinformatics", "Biological Assay", "Businesses", "COVID-19 pandemic", "Chemicals", "Chronic Disease", "Coculture Techniques", "Communicable Diseases", "Coupled", "Crude Extracts", "DNA", "Data", "Dedications", "Development", "Dissection", "Economics", "Engineering", "Environment", "Fermentation", "Gene Cluster", "Genetic Variation", "Genomics", "Goals", "High Pressure Liquid Chromatography", "Length", "Libraries", "Metagenomics", "Methodology", "Molds", "Montana", "Multi-Drug Resistance", "Natural Compound", "Natural Products", "Nuclear Magnetic Resonance", "Pathway interactions", "Pharmaceutical Preparations", "Phase", "Preparation", "Production", "Proliferating", "Public Health", "Publishing", "Research", "Research Proposals", "Science", "Services", "Small Business Innovation Research Grant", "Source", "Structure", "Technology", "Therapeutic", "Universities", "Work", "Workplace", "antimicrobial", "bioinformatics pipeline", "clinical development", "cost", "drug discovery", "drug resistant microorganism", "fighting", "fungus", "improved", "in silico", "infectious disease treatment", "innovation", "microbial", "next generation sequencing", "novel", "novel antibiotic class", "novel therapeutics", "pandemic disease", "phase 2 study", "research and development", "secondary metabolite", "social", "tool", "vector", "virtual" ], "approved": true } }, { "type": "Grant", "id": "12058", "attributes": { "award_id": "5R01HL159170-02", "title": "Using Wearable Technology to Assess Recovery and Detect Post-Operative Complications Following Cardiothoracic Surgery", "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": 25605, "first_name": "James", "last_name": "Luo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-07-01", "end_date": "2027-06-30", "award_amount": 731402, "principal_investigator": { "id": 25265, "first_name": "Xiao", "last_name": "Li", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 25606, "first_name": "Chi-Fu", "last_name": "Yang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 736, "ror": "https://ror.org/002pd6e78", "name": "Massachusetts General Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Project Summary. Every year, more than 500,000 patients undergo operations for heart and lung disease. After surgery, patients often experience pain, fatigue, and disturbed sleep that can persist for weeks to months. In addition, up to 32% of patients develop postoperative complications, which often occur after discharge from the hospital and may lead to readmission. Complications are costly and can be deadly; they are associated with a 200-300% increase in healthcare costs and a 6-fold increase in 90-day postoperative mortality. Currently, after surgery, when a patient is discharged from the hospital, the patient and their family members are responsible for monitoring the patient’s health status. Patients are usually not seen by a doctor for 2-4 weeks after discharge. Attempts to improve postoperative monitoring include home health visits and telemedicine approaches. However, these methods have been shown to be ineffective, costly, and allow for only vague and intermittent assessments of recovery. They do not detect complications until they are at a more severe stage. As such, accurate, easy-to-implement and inexpensive methods to assess postoperative recovery and to detect complications at their earliest stage—before symptom onset—are urgently needed. We previously showed that machine learning analysis of biometrics collected by wearables could detect Lyme Disease and Covid-19. We then, in a pilot study, applied our algorithm, previously developed to identify Covid- 19, to patients undergoing thoracic surgery and showed that this algorithm could detect 89% of complications a median of 3 days before symptom onset. When we evaluated the postoperative recovery of cardiothoracic patients, we showed that machine learning analysis of biometrics could classify patients into distinct recovery groups. Thus, wearables and machine learning algorithms could lead to a highly accurate and accessible method to predict complications early and improve assessments of recovery. Our overall objective is to optimize and validate our machine learning algorithm—previously developed for the early detection of Covid-19—for the detection of postoperative complications prior to symptom onset and to use machine learning analysis to predict the quality of a patient’s recovery using pre- and intraoperative data. Our project aims to first use wearables to collect high-resolution physiologic data of cardiothoracic surgical patients. We will then extend our previously developed algorithm for early detection of postoperative complications and develop an algorithm to predict the quality of a patient’s postoperative recovery. The proposed project will develop an innovative method to detect postoperative complications prior to symptom onset and predict the quality of a patient’s postoperative recovery using pre- and intraoperative data. Importantly, our proposed method could be scaled to not only improve outcomes for cardiothoracic surgical patients, but for patients undergoing other types of surgery. The results of this study will enable a future randomized trial that evaluates whether real-time postoperative monitoring with machine learning algorithms and wearables can lead to 1) earlier detection of complications, 2) earlier outpatient interventions that improve recovery and/or reduce severity of complications, and 3) decreases in unplanned hospital readmissions.", "keywords": [ "Algorithms", "Biometry", "COVID-19", "COVID-19 detection", "COVID-19 early detection", "Cardiac Surgery procedures", "Cardiovascular system", "Caring", "Classification", "Complication", "Data", "Detection", "Development", "Early Diagnosis", "Family member", "Fatigue", "Frequencies", "Future", "Goals", "Health", "Health Care Costs", "Health Personnel", "Health Status", "Heart Diseases", "Home", "Hospitals", "Intervention", "Learning", "Link", "Lung", "Lung diseases", "Lyme Disease", "Machine Learning", "Methods", "Monitor", "Operative Surgical Procedures", "Outcome", "Outcome Measure", "Outpatients", "Pain", "Patient Discharge", "Patient Monitoring", "Patient Outcomes Assessments", "Patients", "Pattern", "Physiological", "Pilot Projects", "Postoperative Care", "Postoperative Complications", "Postoperative Period", "Public Health", "Quality of life", "Recovery", "Research", "Resolution", "Severities", "Signal Transduction", "Sleep disturbances", "Symptoms", "System", "Telemedicine", "Testing", "Thoracic Surgical Procedures", "Time", "Validation", "Viral", "Visit", "algorithm development", "cost", "critical period", "experience", "high risk", "hospital readmission", "improved", "improved outcome", "innovation", "machine learning algorithm", "mortality", "mortality risk", "novel", "operation", "personalized care", "personalized predictions", "postoperative recovery", "preemptive intervention", "randomized trial", "real time monitoring", "wearable device" ], "approved": true } }, { "type": "Grant", "id": "12059", "attributes": { "award_id": "1R21HD112742-01", "title": "Designing effective RNA therapies for oocyte maturation", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 27537, "first_name": "NEELAKANTA", "last_name": "RAVINDRANATH", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-01", "end_date": "2025-08-31", "award_amount": 412500, "principal_investigator": { "id": 27910, "first_name": "Nehemiah Seth", "last_name": "Alvarez", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 27911, "first_name": "Pavla", "last_name": "Brachova", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1806, "ror": "https://ror.org/056hr4255", "name": "Eastern Virginia Medical School", "address": "", "city": "", "state": "VA", "zip": "", "country": "United States", "approved": true }, "abstract": "Infertility is a major reproductive health issue that affects ~12% of reproductively aged women in the United States. Approximately 1-3% of infertile or subfertile women have oocytes that arrest in meiosis or shortly after fertilization due to genetic variants. Unfortunately, there are no therapies for women experiencing infertility due to oocyte arrest. Strategies to restore oocyte maturation in women with oocyte arrest are of dire need in order to give these women fertility options. An emerging class of therapies, called mRNA therapeutics, utilize in vitro synthesized mRNA as a treatment for diseases and for vaccines such as the SARS-CoV-2 mRNA vaccines, but the safety and efficacy has not been explored in infertility. Microinjection of RNA into oocytes is an established tool that has enabled discovery of critical aspects of oocyte biology, but it could also be used as a therapeutic, particularly in women with oocyte arrest. Two recent studies successfully generated blastocysts in oocytes from women with genetic variants causing oocyte arrest, following the injection of in vitro synthesized wild-type RNA during assisted reproductive procedures. RNA therapies represent a novel treatment strategy for women experiencing oocyte arrest, however, rigorous testing is needed before they become an assisted reproductive technology. Considering the unique RNA processing and transcriptional quiescence of fully grown oocytes it is critical to understand how oocytes process exogenous RNA therapeutic molecules. Furthermore, synthetic therapeutic mRNA contain RNA modifications that promote RNA stability, translation, and reduce immune stimulation. Recently, our work and others have implicated RNA modifications as playing an important regulatory role in RNA stability and translation in oocytes. However, the impact of multiple RNA modifications on RNA stability, translation, and oocyte maturation has not been examined. Our goal here is to test how RNA modifications impact the function of mRNA therapeutics designed to rescue oocyte maturation defects. To understand how RNA therapeutics are processed by the oocyte and how they impact oocyte maturation and fertility, we will use a genetic knockout mouse model of the Protein Associated with Topoisomerase II Homolog 2 (Patl2 gene), which results in oocyte maturation arrest. Mice lacking PATL2 protein phenocopy women with genetic defects in Patl2, and have oocytes that fail to mature, so we predict that microinjection of an RNA therapeutic for Patl2 will restore oocyte maturation, fertilization, and birth. We will determine the effects of RNA modifications on stability and translation of therapeutic Patl2 RNA. Our studies have the potential to reveal novel aspects of RNA modifications in oocyte RNA processing and translation, as well as establish groundwork for future studies testing the safety and efficacy of RNA therapeutics to treat female infertility due to oocyte arrest.", "keywords": [ "2019-nCoV", "Affect", "Age", "Area", "Assisted Reproductive Technology", "Biological Assay", "Biology", "Birth", "Chemicals", "Child", "Compensation", "Defect", "Disease", "Embryo", "Embryo Transfer", "Embryonic Development", "Female infertility", "Fertility", "Fertilization", "Fertilization in Vitro", "Future", "Generations", "Genes", "Genetic", "Genetic Transcription", "Genome", "Goals", "Homologous Gene", "Immunologic Stimulation", "In Vitro", "Infertility", "Injections", "Knockout Mice", "Knowledge", "Live Birth", "Maternal Messenger RNA", "Measures", "Meiosis", "Messenger RNA", "Microinjections", "Modification", "Molecular", "Mus", "Mutation", "Oocytes", "Phenocopy", "Play", "Procedures", "Process", "Proteins", "RNA", "RNA Decay", "RNA Processing", "RNA Stability", "RNA vaccine", "RNA-Binding Proteins", "Regulation", "Reproductive Health", "Role", "Safety", "Somatic Cell", "Testing", "Therapeutic", "Topoisomerase II", "Translational Regulation", "Translations", "United States", "Vaccines", "Woman", "Work", "aged", "blastocyst", "design", "efficacy evaluation", "efficacy testing", "experience", "experimental study", "genetic variant", "genome sequencing", "infertility treatment", "mouse model", "novel", "oocyte maturation", "posttranscriptional", "reproductive", "safety testing", "success", "therapeutic RNA", "therapeutic candidate", "tool", "translational therapeutics", "treatment strategy" ], "approved": true } } ], "meta": { "pagination": { "page": 1406, "pages": 1424, "count": 14236 } } }