Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1385&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=1397&sort=funder", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1386&sort=funder", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1384&sort=funder" }, "data": [ { "type": "Grant", "id": "12115", "attributes": { "award_id": "1F30NS131053-01A1", "title": "Sex differences in the effects of prior social isolation stress on stroke outcomes", "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": 21493, "first_name": "JAMES I", "last_name": "KOENIG", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-01", "end_date": "2028-08-31", "award_amount": 36288, "principal_investigator": { "id": 27978, "first_name": "Macy", "last_name": "Zardeneta", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "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": "Social isolation increases risk of all-cause mortality and chronic diseases such as obesity, cardiovascular disease, dementia, and stroke.12,13 A lack of social connectedness, or isolation, is exacerbated with age due to partner loss, family disconnect, and a narrowing of social networks. However, with the ongoing COVID-19 pandemic and long periods of social distancing, social isolation has become a widespread phenomenon. As such, it is urgent to elucidate the physiological effects of social isolation (SI) and subsequent vulnerability to injury or disease. Stroke is a leading cause of death worldwide and is the cause of 1 in 6 cardiovascular related deaths. Ischemic stroke accounts for over 80% of overall incidence.14,15 Social isolation after stroke is of clinical relevance due to the recovery process requiring patients to spend many hours in physical and occupational therapies away from family members, loss of mobility, and language impairment. Thus while social isolation in stroke patients has often been studied during the recovery period,16,17 a recent study showed that the risk of death due to stroke was higher when comparing the most isolated patients to the least isolated patients prior to stroke.18 In the following proposed studies the overarching hypothesis that prior-social isolation (SI) mediates worsened stroke outcomes will be tested. The immediate goal is to identify, if any, sex differences in prior-SI and stroke severity. The long-term goal is to understand the mechanism by which prior-SI affects stroke severity and propose a potential therapy for mitigating harmful effects of prior-SI. This will be studied in the following 3 aims: Aim 1: To investigate the effect of pre-stroke social isolation on stroke severity and outcome. -Sub-Aim 1a: To investigate the hypothesis that prior-SIS worsens acute post-stroke outcomes. -Sub-Aim 1b: To investigate the hypothesis that prior SIS worsens post-stroke cognitive impairment. Aim 2: To test the hypothesis that stroke outcomes are exacerbated by prior social isolation stress (SIS) due to maladaptive cellular changes and inflammation in the central nervous system. -Sub Aim 2a: To test the hypothesis that prior-SIS increases stroke-induced blood brain barrier permeability. -Sub Aim 2b: To test the hypothesis that prior-SIS will induce a neuroinflammatory state in which microglia and astrocytes become activated, leading to worsened stroke outcomes. Considering the extensive isolation undergone by the majority of the population throughout the COVID-19 pandemic, it is critical to consider the long-term effects of prior-SIS on stroke. These findings advance our understanding and awareness of the future implications of COVID-19. This training plan's focus on elucidating the effects of stressors on brain health and vulnerability to disease fit well with my goal of becoming a physician scientist in the field of neurology. The procedures described in this application are well established in the sponsor's lab, and the pilot data was acquired by me while learning these techniques.", "keywords": [ "Acute", "Acute Disease", "Adhesives", "Adult", "Affect", "Age", "Animals", "Area", "Astrocytes", "Awareness", "Biological", "Biological Assay", "Blood", "Blood - brain barrier anatomy", "Brain", "Brain Infarction", "CCL3 gene", "COVID-19", "COVID-19 pandemic", "Cardiovascular Diseases", "Cardiovascular system", "Cause of Death", "Cell Line", "Cells", "Central Nervous System", "Cessation of life", "Chronic Disease", "Data", "Dementia", "Dextrans", "Disease", "Dose", "Endothelin-1", "Excision", "Family", "Family member", "Female", "Flow Cytometry", "Fluorescein-5-isothiocyanate", "Forelimb", "Future", "General Population", "Goals", "Histologic", "Histology", "Hour", "Housing", "Human", "Immune", "Impaired cognition", "Incidence", "Infarction", "Inflammation", "Inflammatory", "Injury", "Intravenous", "Ischemic Stroke", "Label", "Learning", "Long-Term Effects", "Magnetic Resonance Imaging", "Matrix Metalloproteinases", "Measurement", "Measures", "Mediating", "Memory", "Microglia", "Minocycline", "Mission", "Modeling", "National Institute of Neurological Disorders and Stroke", "Nervous System", "Neurology", "Obesity", "Occupational Therapy", "Outcome", "Patient Isolation", "Patients", "Perfusion", "Persons", "Phagocytosis", "Pharmaceutical Preparations", "Phase", "Physical therapy", "Physicians", "Physiological", "Population", "Procedures", "Process", "Proteins", "Protocols documentation", "RANTES", "Rattus", "Recovery", "Research", "Risk", "Scientist", "Serum", "Severities", "Sex Differences", "Social Distance", "Social Network", "Social isolation", "Stress", "Stroke", "Survivors", "TLR4 gene", "Techniques", "Testing", "Tight Junctions", "Training", "Vibrissae", "Weight", "Work", "blood-brain barrier permeabilization", "brain health", "clinically relevant", "cytokine", "dementia risk", "experience", "glial activation", "inhibitor", "intraperitoneal", "language impairment", "male", "middle age", "mortality", "mortality risk", "nervous system disorder", "neuroinflammation", "novel", "object recognition", "physical process", "post stroke", "post stroke cognitive impairment", "sex", "social", "stressor", "stroke model", "stroke outcome", "stroke patient", "therapeutic target", "vasoconstriction" ], "approved": true } }, { "type": "Grant", "id": "12116", "attributes": { "award_id": "3R15HD109732-01A1S1", "title": "New Nasal Spray Influenza Vaccine for Children (Research Supplement for Post Baccalaureate Diversity Candidate)", "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": 6155, "first_name": "Sai Prasanna", "last_name": "Majji", "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": 145772, "principal_investigator": { "id": 27086, "first_name": "MINGTAO", "last_name": "ZENG", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1987, "ror": "", "name": "TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER AT EL PASO", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "New Nasal Spray Influenza Vaccine for Children (Research Supplement for R15HD109732) Project Summary/Abstract: Influenza is still a global public health problem for children despite a vigorous campaign for influenza vaccination in many countries. Recent emergence of the COVID-19 can also complicate influenza in children and make it more desirable to vaccinate young children against influenza. Influenza vaccines must be reformulated annually because of the antigenic shift and drift of circulating influenza viral strains. However, reformulated seasonal flu vaccines do not always match the circulating strains, and there is the ever-present threat that avian influenza viruses may adapt for transmission in humans. Additionally, currently available antiviral drugs against influenza are facing the twin challenges of evolved drug resistance and nonspecific side effects. Therefore, there is an urgent need for developing novel drugs, vaccines, and combinatory therapies against influenza virus infection. In this proposed research, we hypothesize that a universally prophylactic and therapeutic influenza vaccine for children can be developed through creation of a self-attenuated influenza virus (SAIV) that expresses artificial microRNAs (amiRNAs) targeting viral and/or host gene expression that are essential for viral replication. In order to evaluate this hypothesis, we propose the following 3 specific aims for this research: Specific Aim 1: To evaluate the efficacy of a candidate prophylactic and therapeutic SAIV vaccine generated by viral gene-targeted attenuation. Specific Aim 2: To assess the efficacy of a candidate SAIV vaccine generated by host gene-targeted attenuation. Specific Aim 3: To produce and evaluate additional dual viral and host factor-targeted prophylactic and therapeutic SAIV vaccines. Our proposed SAIV vaccines developed in this research will be extensively investigated in young mouse model of influenza infection. We anticipate that the proposed research will identify a novel and safe universal influenza vaccine and molecular therapy that could be further developed as a therapeutic vaccine to prevent future influenza reinfection in children. Furthermore, this research program will significantly strengthen the research environment in Texas Tech University Health Sciences Center at El Paso, and provide research training opportunities for graduate students, medical students, and undergraduate students, throughout the 3-year performance period. This research supplement fund will support the diversity candidate, Ms. Alejandra Munoz, for 2 year post-baccalaureate research training through this research program.", "keywords": [ "Antiviral Agents", "Attenuated", "Avian Influenza A Virus", "COVID-19", "Child", "Country", "Drug resistance", "Environment", "Funding", "Future", "Gene Expression", "Gene Targeting", "Health Sciences", "Human", "Infection", "Influenza", "Influenza Therapeutic", "Influenza vaccination", "Integration Host Factors", "Medical Students", "MicroRNAs", "Molecular", "Nose", "Performance", "Postbaccalaureate", "Preventive vaccine", "Public Health", "Research", "Research Training", "Texas", "Therapeutic", "Twin Multiple Birth", "Universities", "Vaccinated", "Vaccines", "Viral", "Viral Genes", "Virulent", "Virus", "Virus Replication", "attenuation", "efficacy evaluation", "graduate student", "influenza infection", "influenza virus strain", "influenza virus vaccine", "influenzavirus", "mouse model", "novel", "novel therapeutics", "novel vaccines", "prevent", "programs", "prophylactic", "public health relevance", "seasonal influenza", "side effect", "therapeutic vaccine", "training opportunity", "transmission process", "undergraduate student", "universal influenza vaccine", "vaccine development" ], "approved": true } }, { "type": "Grant", "id": "12117", "attributes": { "award_id": "1UG3OD035519-01", "title": "Retaining the diverse CANDLE cohort to advance ECHO Cohort solution-oriented research and identify early-life modifiable risk factors for obesity and mental health problems in children", "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": 10604, "first_name": "SUSAN ALISON", "last_name": "Laessig", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-01", "end_date": "2025-05-31", "award_amount": 1505914, "principal_investigator": { "id": 22912, "first_name": "Nicole Renee", "last_name": "Bush", "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": [ { "id": 22914, "first_name": "Kaja Zabrina", "last_name": "LeWinn", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 27979, "first_name": "Qi", "last_name": "Zhao", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 847, "ror": "", "name": "UNIVERSITY OF TENNESSEE HEALTH SCI CTR", "address": "", "city": "", "state": "TN", "zip": "", "country": "United States", "approved": true }, "abstract": "Over 25% of children suffer from mental health problems and/or develop obesity. Mental health problems often emerge early through a broad range of symptoms before canalizing into disorders like depression, which affects over 15% of adolescents in the U.S. Risk for obesity also increases with age from 13% in early childhood to 22% in adolescence. Childhood diseases greatly impact adult health, and alarmingly, rates of child mental health problems and obesity are increasing, particularly for youth of color. Myriad early life risk and protective factors, often inequitably distributed and made more striking by the COVID-19 pandemic, have been associated with these outcomes; however, without large national samples and systematic identification of priority factors, clear targets for preventive interventions remain elusive. To address these critical issues, our interdisciplinary team leverages the unique power of ECHO Cohort data to conduct environment-wide scans for early life predictors of adolescent depression and obesity to identify and prioritize the most powerful targets for prevention, with a focus on sex-specific associations and improving causal inference (Aim 1). We also take a developmentally-informed, hypothesis-driven approach to understand the intergenerational relations between maternal childhood and pregnancy stress with childhood psychopathology risk, and if associations are sex- specific or buffered by family and community-level protective factors (Aim 2). To do this, we calculate a new, specialized neurodevelopmental outcome, the p-factor, which draws on multiple indicators of behavior and mental health to generate a single latent factor of general psychopathology in childhood and adolescence. This parsimonious, transdiagnostic measure is ideally suited for population-based child development studies that lack deep mental health phenotyping. Finally, we retain the socioeconomically and racially diverse CANDLE cohort (64% African American, 30% White; 700 mother-child dyads in the ECHO Program (Aim 3). Our success collecting ECHO Cohort data and contributions to diversity are self-evident: of the 69 ECHO cohorts, CANDLE ranks #1 in African American participants and #3 in records contributed to ECHO’s REDCap Central. Our team strongly contributes to collaborative science, leading multiple working groups, publishing and disseminating ECHO Cohort findings, supporting measurement development and data harmonization, and co- leading DEI efforts. Impact: We will generate robust evidence for prevention targets, including protective factors, to mitigate the public health impact of child mental health problems and obesity. We examine sex- specific associations and ensure that results are generalizable to youth of color, enhancing the potential of our findings to improve health equity. A transdiagnostic measure of pediatric psychopathology (p-factor) will be useful to many investigators and is well-suited to the examination of multiple exposures. The CANDLE study notably contributes to the diversity of the ECHO Cohort, and our experienced team’s continued leadership and partnerships during the next phase of ECHO will advance collaborative science to improve child health.", "keywords": [ "Address", "Adolescence", "Adolescent", "Adolescent obesity", "Adult", "Affect", "African American", "Age", "Behavior", "Buffers", "COVID-19 pandemic", "Chemicals", "Child", "Child Development", "Child Health", "Child Mental Health", "Child Rearing", "Childhood", "Clinical", "Clinical Psychology", "Cohort Analysis", "Collaborations", "Color", "Communities", "Data", "Data Element", "Data Set", "Development", "Diagnostic", "Disease", "Early identification", "Elements", "Ensure", "Environment", "Epidemiology", "Evaluation", "Family", "Future", "Health", "Inequity", "Intergenerational Relations", "Intervention", "Lead", "Leadership", "Life", "Measurement", "Measures", "Mental Depression", "Mental Health", "Methods", "Mothers", "Neighborhoods", "Obesity", "Outcome", "Outcome Measure", "Participant", "Personal Satisfaction", "Phase", "Phenotype", "Pregnancy", "Prevention", "Properdin", "Protocols documentation", "Psychopathology", "Public Health", "Publishing", "Recommendation", "Records", "Research", "Research Personnel", "Risk", "Risk Factors", "Sampling", "Scanning", "Science", "Specificity", "Stress", "Symptoms", "Visit", "age group", "central database", "child depression", "children of color", "cohort", "data harmonization", "depressive symptoms", "disability-adjusted life years", "early childhood", "experience", "health equity", "improved", "indexing", "maternal stress", "middle childhood", "modifiable risk", "novel", "obesity risk", "participant enrollment", "physical conditioning", "population based", "preventive intervention", "programs", "protective factors", "racial diversity", "sex", "social", "sociodemographics", "socioeconomics", "study population", "success", "working group", "years of life lost" ], "approved": true } }, { "type": "Grant", "id": "12118", "attributes": { "award_id": "1R21AI173494-01A1", "title": "COVID-19 imprints airway basal cells to impair epithelium regeneration", "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": "2023-08-25", "end_date": "2025-07-31", "award_amount": 264341, "principal_investigator": { "id": 27980, "first_name": "Xingbin", "last_name": "Ai", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 736, "ror": "https://ror.org/002pd6e78", "name": "Massachusetts General Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "COVID-19 (CoV19) is caused by SARS-CoV-2 infection of the airway epithelium resulting in extensive damage in the lower respiratory tract. Since 2020, CoV19 has claimed over 1 million lives in the United States surpassing the death toll of the 1918 H1N1 influenza pandemic. Clinical studies show that the mortality and morbidity of CoV19 is associated with secondary infection. Given a central role of the airway epithelium as a barrier against pathogens, preliminary studies tested whether airway basal stem cells (BSCs) are impaired in their regenerative function in CoV19 patients. Of note, BSCs are a major type of stem cells responsible for epithelium regeneration following respiratory viral infection in humans. In preliminary studies, we derived 6 lines of BSCs from severe cases of CoV19 using tracheal aspirate (TA) as a source of bronchial BSCs. These CoV19-exposed BSCs were tested free of virus; however, they show early cell cycle arrest, sustained STAT3 hyperactivity, and defective differentiation in air-liquid interface. In contract, BSCs derived from TA of control patients with neurogenic and cardiogenic respiratory failure have no such defects. Similar to our findings in vitro, antibody staining of fatal CoV19 lung sections revealed increased senescence and defective differentiation of BSCs. In addition, CoV19- exposed BSCs in vitro maintained, at least partially, an inflammatory gene signature that was found in BSCs in vivo by single cell-seq of lung samples from CoV19 patients. As such, BSCs derived from TA of CoV19 patients provide a viable cell model to investigate how CoV19 impairs epithelial regeneration by inducing an inflammatory memory in BSCs. Mechanistically, CoV19-exposed BSCs exhibit unique chromatin opening at sites enriched for transcriptional factors mediating the inflammatory pathways, such as STAT3. Based on these preliminary findings, we hypothesize that inflammation in CoV19 causes an epigenetic memory in BSCs to impair epithelium regeneration. Leveraging our ability to derive TA BSCs, Aim1 will test whether CoV19 uniquely reprograms BSCs compared to other acute respiratory infections. Aim 2 will identify the molecular mediators of the inflammatory memory in CoV19-exposed BSCs using complementary assays. The rescue assay will test whether blocking STAT3 hyperactivity and reversing epigenetic modification in CoV19-exposed BSCs will normalize their role in epithelial regeneration. The disease-mimicking assay will assess the activity of inflammatory signals in memory induction in healthy control BSCs. The proposed exploratory studies will lay the foundation for future delineation of inflammatory signals and intracellular mediators in the disease memory of BSCs using genetic approaches and animal models of SARS-CoV-2 infection. Our findings will inform therapeutics to facilitate epithelial regeneration in severe cases of CoV19.", "keywords": [ "2019-nCoV", "ATAC-seq", "Acute respiratory infection", "Age", "Air", "Animal Model", "Antibodies", "Basal Cell", "Biological Assay", "Biopsy", "COVID-19", "COVID-19 impact", "Cell Cycle Arrest", "Cell Line", "Cell Separation", "Cell Survival", "Cell model", "Cells", "Cessation of life", "Chromatin", "Chronic lung disease", "Clinical Research", "Contracts", "Coronavirus", "Defect", "Derivation procedure", "Disease", "EZH2 gene", "Endowment", "Epigenetic Process", "Epithelium", "Exhibits", "Foundations", "Functional disorder", "Future", "Gene Expression", "Genetic study", "Goals", "Health", "Human", "Hyperactivity", "Immune", "Impairment", "In Vitro", "Infection", "Inflammation", "Inflammation Mediators", "Inflammatory", "Intubation", "Lead", "Liquid substance", "Lower respiratory tract structure", "Lung", "Lung diseases", "Mediating", "Mediator", "Medical Waste", "Memory", "Methods", "Microscopic", "Modeling", "Modification", "Molecular", "Morbidity - disease rate", "Mus", "Natural Immunity", "Olfactory Pathways", "Organ", "Pathogenesis", "Pathway interactions", "Patient Care", "Patients", "Phenotype", "Play", "Procedures", "Proliferating", "Research", "Respiratory Disease", "Respiratory Failure", "Respiratory Tract Infections", "Risk", "Risk Reduction", "Role", "SARS-CoV-2 infection", "SARS-CoV-2 negative", "STAT3 gene", "Sampling", "Signal Transduction", "Site", "Skin", "Source", "Spanish flu", "Stains", "Testing", "Therapeutic", "Trachea", "United States", "Viral Respiratory Tract Infection", "Virus", "acute infection", "airway epithelium", "alveolar type II cell", "aspirate", "chemokine", "cytokine", "epigenetic memory", "epithelial stem cell", "epithelium regeneration", "genetic approach", "genetic signature", "genomic locus", "imprint", "in vivo", "mortality", "multimodality", "pandemic disease", "pandemic influenza", "pathogen", "prevent", "programs", "receptor", "regeneration function", "respiratory", "response", "secondary infection", "senescence", "stem cell proliferation", "stem cells", "stem-like cell", "therapeutic target", "transcription factor", "transcriptome" ], "approved": true } }, { "type": "Grant", "id": "12119", "attributes": { "award_id": "1R01MH132415-01", "title": "Understanding the Regional Ecology of a Future HIV Vaccine", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Drug Abuse (NIDA)", "National Institute of Mental Health (NIMH)" ], "program_reference_codes": [], "program_officials": [ { "id": 21190, "first_name": "Michael J", "last_name": "Stirratt", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-08-01", "end_date": "2028-05-31", "award_amount": 780044, "principal_investigator": { "id": 27981, "first_name": "DOLORES", "last_name": "ALBARRACIN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 232, "ror": "https://ror.org/00b30xv10", "name": "University of Pennsylvania", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "The U.S. experience with COVD-19 vaccination has shown that an individual's decision to vaccinate stems from many factors, including beliefs related to vaccine safety1; the norms of family, peers, and community2,3; media sources4; and federal, state, and local policy5,6. Many of these factors stem from a historical evolution and regional idiosyncrasies, including regional differences in vaccination exemptions, levels of state funding, public health communications, religious and political sentiments, and, often, longstanding reluctance to vaccinate. Although there is evidence that these factors contribute to vaccination in several domains, no past research has examined the ecology of this evolution for any vaccine. As a result, if a new HIV vaccine were introduced in the near future, comprehensive, rigorous knowledge about the impact of vaccine factors, information circulating in the community, norms, and public health policies would be paramount. This project will investigate the interplay of these ecological factors at the state or county level, to predict over-time changes in individual intentions to vaccinate against HIV if a vaccine were approved, as well as individual vaccination against other diseases such as influenza, Hepatitis A, and COVID-19 among Men Who Have Sex with Men (MSM). The project will study the impact of the ecology of vaccination on a future HIV vaccine by linking longitudinal surveys of diverse MSM (N = 1500) to state/county/zip code data on community-based vaccine information in the media, vaccination norms, as well as vaccine and HIV policy, including LGBT friendly policies and public health communications in the media. After understanding key factors affecting HIV vaccination intentions, we will conduct an experiment with another sample of diverse MSM (N = 1,000; Aim 2). Participants will be randomized to conditions of different vaccine characteristics, information in the community, vaccination norms, and public health policies, and then complete measures of vaccine choices and intentions; the choice to enroll in a vaccination trial registry and the choice to sign up for an educational session about HIV-vaccine science as the behavioral endpoints for our experiment. Participants will also complete measures of behavioral control, attitudes, and subjective norms as the possible mediators of effects of our choice and intention outcomes. The project will be informed by extensive pilot data on vaccine policy, public health communications about vaccines and HIV, and vaccine misinformation across states and over time, as well as experience recruiting and managing cohorts of MSM and investigating the acceptability of an HIV vaccine in this population. The team includes expertise in public health, psychology, HIV medicine and HIV vaccine trials, communication, public policy, and economics, and will leverage the resources of the University of Pennsylvania, the HIV Vaccine Trials Network (HVTN), the Penn CFAR, and the Annenberg Public Policy Center (APPC) to conduct cutting edge research about the determinants of vaccination against HIV. The data obtained from this innovative project will supply the evidence base to inform policies and public health communications to promote a future HIV vaccine and other recommended vaccines among MSM.", "keywords": [ "Acquired Immunodeficiency Syndrome", "Adolescent", "Adult", "Affect", "Area", "Attitude", "Basic Science", "Behavior Control", "Behavioral", "Belief", "COVID-19", "COVID-19 vaccination", "Caring", "Characteristics", "Communication", "Communities", "County", "Data", "Data Sources", "Disease", "Ecology", "Economics", "Education", "Enrollment", "Evolution", "Family", "Friends", "Funding", "Future", "Goals", "HIV", "HIV Vaccine Trials Network", "HIV prevention trial", "HIV vaccine", "Health Policy", "Health system", "Hepatitis A", "Homophobia", "Impairment", "Individual", "Infection", "Influenza", "Institutional Racism", "Intention", "Knowledge", "Lesbian Gay Bisexual Transgender", "Link", "Longitudinal Surveys", "Measures", "Mediating", "Mediator", "Medicine", "Misinformation", "Modeling", "Outcome", "Participant", "Pattern", "Pennsylvania", "Pharmaceutical Preparations", "Phase", "Policies", "Politics", "Population", "Positioning Attribute", "Prevalence", "Privacy", "Process", "Psychology", "Public Health", "Public Policy", "Randomized", "Recommendation", "Registries", "Religion", "Research", "Risk", "Sampling", "Science", "Services", "Severities", "Shapes", "Source", "Surveys", "Testing", "Time", "Trust", "University resources", "Vaccinated", "Vaccination", "Vaccines", "behavior measurement", "cohort", "design", "ethnic minority", "evidence base", "experience", "experimental study", "health communication", "innovation", "men", "men who have sex with men", "novel vaccines", "peer", "pre-exposure prophylaxis", "recruit", "regional difference", "seropositive", "social media", "social stigma", "stem", "uptake", "vaccine development", "vaccine hesitancy", "vaccine platform", "vaccine safety", "vaccine trial", "young man" ], "approved": true } }, { "type": "Grant", "id": "12120", "attributes": { "award_id": "1UC7AI180261-01", "title": "Positioning Mason's Regional Biocontainment Laboratory for Effective 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": 27982, "first_name": "FAYNA C", "last_name": "Diaz San Segundo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-08-18", "end_date": "2028-07-31", "award_amount": 2495244, "principal_investigator": { "id": 24446, "first_name": "Farhang", "last_name": "Alem", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [ { "id": 239, "ror": "https://ror.org/02jqj7156", "name": "George Mason University", "address": "", "city": "", "state": "VA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 239, "ror": "https://ror.org/02jqj7156", "name": "George Mason University", "address": "", "city": "", "state": "VA", "zip": "", "country": "United States", "approved": true }, "abstract": "OVERALL CORE ABSTRACT George Mason University (GMU) Biomedical Laboratory (BRL) is one of 12 Regional Biocontainment Laboratories (RBLs) established through NIAID support in the early 2000s to serve as Biosafety Level 3 (BSL-3) facilities to conduct cutting edge pathogen research and serve as resources to rapidly address emerging infectious disease outbreaks. The BRL serves as a center for scientific collaboration to 1) generate advanced knowledge of pathogen biology and host interaction mechanisms, and 2) evaluate diagnostics, therapeutics and vaccines. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic exposed critical vulnerabilities to the nation’s BSL-3 research infrastructure, including the GMU BRL facility. GMU learned that there are gaps and opportunities to enhance safe BRL operations management to more effectively face sudden disease outbreaks and support a more robust pipeline of innovations for response to future pandemics. This proposal outlines activities for three cores to enhance the BRL facility, increase high containment training, and provide additional BSL-3 research services for pre-clinical innovation. The GMU RBL will 1) Implement a comprehensive BSL-3 facilities preventative maintenance and upgrade plan to ensure continuity of operations, compliance with federal regulations, and a safe and secure facility; 2) Enhance safety and quality of BSL-3 laboratory practices; and 3) Create two new research cores in high containment. The expanded Microphysiological Systems (MPS) core will enable organ-on-a- chip (OOC) and organoid models for lead optimization, safety assessment, off target effects, toxicity, and efficacy analysis. The Advanced Animal Research (AAR) core will support pre- clinical studies starting with in vivo exposures and countermeasure testing and transitioning to advanced animal imaging, spatial tissue, and cellular analysis. Together, the cores will accelerate vaccine and therapeutic drug discovery and improve understanding of the transmission and pathogenesis of infectious agents as well as host response.", "keywords": [ "Acceleration", "Acute", "Address", "Alphavirus", "Animal Experimentation", "Applied Research", "Basic Science", "Biology", "Biomedical Research", "COVID-19 pandemic", "Capital", "Certification", "Collaborations", "Containment", "Coronavirus", "Data", "Diagnostic", "Disease Outbreaks", "Economic Burden", "Emerging Communicable Diseases", "Engineering", "Ensure", "Environment", "Face", "Filovirus", "Funding", "Health", "Immune response", "Individual", "Infectious Agent", "Infectious Diseases Research", "Knowledge", "Laboratories", "Laboratory Research", "Leadership", "Learning", "Maintenance", "Mentorship", "Modeling", "National Institute of Allergy and Infectious Disease", "Organoids", "Pathogenesis", "Positioning Attribute", "Regulation", "Research", "Research Infrastructure", "Research Personnel", "Resources", "Safety", "Secure", "Services", "System", "Testing", "Therapeutic", "Tissues", "Toxic effect", "Training", "Training Programs", "Universities", "Update", "Vaccines", "Virus Diseases", "animal imaging", "biosafety level 3 facility", "drug discovery", "efficacy evaluation", "future pandemic", "good laboratory practice", "improved", "in vivo", "innovation", "laboratory facility", "lead optimization", "microphysiology system", "operation", "organ on a chip", "pandemic preparedness", "pathogen", "pre-clinical", "preclinical study", "product development", "programs", "promote resilience", "research and development", "response", "safety assessment", "safety practice", "success", "training opportunity", "transmission process" ], "approved": true } }, { "type": "Grant", "id": "12121", "attributes": { "award_id": "1UC7AI180307-01", "title": "Resources, Workforce Development, and Animal Models for the Rutgers RBL", "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": 27982, "first_name": "FAYNA C", "last_name": "Diaz San Segundo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-08-18", "end_date": "2028-07-31", "award_amount": 3970689, "principal_investigator": { "id": 8100, "first_name": "David", "last_name": "Alland", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 925, "ror": "", "name": "RBHS-NEW JERSEY MEDICAL SCHOOL", "address": "", "city": "", "state": "NJ", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1856, "ror": "", "name": "RUTGERS BIOMEDICAL AND HEALTH SCIENCES", "address": "", "city": "", "state": "NJ", "zip": "", "country": "United States", "approved": true }, "abstract": "Overall ABSTRACT The Rutgers University Regional Biocontainment Laboratory (RBL) serves as a central facility to perform biosafety level three (BSL3) therapeutic, pathogenesis, and diagnostic research on high threat biological agents with a focus on Mycobacterium tuberculosis and SARS-CoV-2, as well as other category A, B, and C pathogens. The RBL serves academic and commercial entities within Rutgers University, the Northeast United States and nationally, while also engaging globally with companies and academic institutions through collaborations and research contracts. This proposal will provide support that enhances the RBL’s ability to fulfill its research and biothreat response/pandemic preparedness missions while also supporting an expanding faculty/staff. We propose to accomplish these goals by improving the RBL facilities, support services, BSL3 practice development and implementation and special services offerings though the execution of three aims: Aim 1. Establish a Facility management, maintenance and operations (FMMO) core. Aim 2. Establish a BSL-3 Practices core (Practice core). Aim 3. Establish a biocontainment research support service core devoted to developing animal models of BSL3 pathogens and associated support services (Animal models and related services, or AMRS core). The FMMO core will provide BSL3 and ABSL3 services, management and oversight, for routine animal husbandry, microbiology and virology services in support of investigators grant funded research projects while ensuring efficient operations and maintenance of the BSL3 facilities and providing trained staff to support the BSL3 building systems and equipment. The Practice core will develop and maintain standard operating procedures and training for research in the RBL BSL3 laboratories including best practices, emergency response, waste management, shipping, husbandry, select agent-specific practices and inventory. It will also develop and conduct biosecurity and disaster drills and liaise with other BSL3 laboratories within the RBL network as well as local, state and federal health agencies to coordinate operations and plan for joint responses to new infectious disease threats. The AMRS core will develop critical animal models including those of SARS-CoV2 and highly pathogenic influenza virus transmission, COVID-19 PASC, pulmonary impairment after TB (PIAT), and drug treatment models, and then support grant funded investigators in the performance of these models along with the advanced instrumentation needed to analyze these infected models and their tissues/cells in a BSL3 environment. Together, these three cores will significantly enhance the near- and long-term abilities of the RBL to address critical biothreats and emerging infectious diseases requiring study in a BSL3 laboratory setting, while also increasing our capacity to respond to the next public health emergency or pandemic.", "keywords": [ "2019-nCoV", "Address", "Aftercare", "Animal Husbandry", "Animal Model", "Animals", "Bacillus anthracis", "Biological Products", "Budgets", "COVID-19", "Candida auris", "Categories", "Cells", "Certification", "Chikungunya virus", "Collaborations", "Communicable Diseases", "Computers and Advanced Instrumentation", "Containment", "Cryptococcus", "Development", "Diagnostic", "Diagnostics Research", "Disasters", "Disease model", "Emergency response", "Emerging Communicable Diseases", "Ensure", "Environment", "Equipment", "Equipment and supply inventories", "Faculty", "Francisella tularensis", "Funding", "Goals", "Grant", "HIV", "Health", "Impairment", "Institution", "Joints", "Laboratories", "Laboratory Research", "Life Cycle Stages", "Lung", "Maintenance", "Microbiology", "Mission", "Modeling", "Monkeypox", "Mycobacterium tuberculosis", "Pathogenesis", "Pathogenicity", "Performance", "Pharmacotherapy", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Procedures", "Research", "Research Activity", "Research Contracts", "Research Personnel", "Research Project Grants", "Research Support", "Research Training", "Resources", "Safety", "Scientist", "Services", "Shipping", "System", "Therapeutic", "Tissues", "Training", "Tuberculosis", "United States", "United States National Institutes of Health", "Universities", "Viral", "Virulent", "Waste Management", "Work", "Workforce Development", "Yersinia pestis", "biosecurity", "biothreat", "cost", "end of life", "improved", "influenzavirus", "laboratory facility", "operation", "pandemic disease", "pandemic preparedness", "pathogen", "public health emergency", "recruit", "response", "tuberculosis drugs", "tuberculosis treatment", "viral transmission", "virology" ], "approved": true } }, { "type": "Grant", "id": "12122", "attributes": { "award_id": "4R44AI170392-02", "title": "SARS-CoV-2 vaccines based on RBDs with engineered glycosylation sites", "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": "2023-08-17", "end_date": "2026-07-31", "award_amount": 1000000, "principal_investigator": { "id": 26186, "first_name": "MICHAEL DAVID", "last_name": "ALPERT", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1900, "ror": "", "name": "EMMUNE, INC", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true }, "abstract": null, "keywords": [], "approved": true } }, { "type": "Grant", "id": "12123", "attributes": { "award_id": "1R44AI179371-01", "title": "Monoclonal Antibody Cocktail for Treatment of Marburg Virus Disease", "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": 27983, "first_name": "JULIE", "last_name": "Dyall", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-08-11", "end_date": "2024-01-31", "award_amount": 293392, "principal_investigator": { "id": 27984, "first_name": "M Javad", "last_name": "Aman", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 22691, "first_name": "Thomas William", "last_name": "Geisbert", "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": 2065, "ror": "", "name": "ABVACC, INC.", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Ebola (EBOV) and Marburg (MARV) viruses cause hemorrhagic fever disease in humans and nonhuman primates (NHPs) with case-fatality rates as high as 90%. The 2013-2016 Ebola Virus Disease (EVD) outbreak led to over 28,000 cases and 11,000 deaths and took an enormous toll on the economy of West African nations, in the absence of any vaccine or therapeutic options. This outbreak spurred an unprecedented global effort for development of vaccines and therapeutics for EVD and led to an approved vaccine and two monoclonal antibody (mAb) therapeutics. Importantly studies with EBOV mAbs and later SARS-CoV2 mAbs established the value of mAb cocktails for effective treatment of viral diseases. In contrast to EVD, development of therapeutics for Marburg Virus Disease (MVD) has been lagging despite several MVD outbreaks including one in 2022. The investigators on this MPI Phase I/II Fast Track SBIR application have developed two classes of mAbs targeting non-overlapping epitopes within the receptor binding site (RBS) and the internal fusion loop (IFL) of MARV glycoprotein (GP). The RBS-binding mAb (MR186), provides protection primarily through effector functions, while the IFL-binder (R217) is the most potent neutralizing MARV mAb discovered to-date. MR186 has been engineered to enhance bioavailability using YTE mutation in the Fc portion, and produced in a fucosyl- transferase deficient CHO cell line to enhance effector functions (MR186-YTEAF). We are currently introducing YTE mutations into R217 Fc to generate the therapeutic candidate R217-YTE. In this proposed project we harness these complementary mechanisms of action to develop a highly effective cocktail of these two mAbs for MVD treatment. Use of mAb cocktail is also expected to reduce the risk of escape variant. The proposal has four Specific Aims. In Aim 1 (Phase I portion), R217-YTE will be produced in ExpiCHO cells and fully characterized. Superior efficacy of the cocktail will be demonstrated in a guinea pig model of MARV-Angola and this milestone will serve for transition to Phase II SBIR. Phase II Portion starts with Aim 2, in which the efficacy of the cocktail will be tested in NHP models in series of adaptively designed NHP experiments and finally the superior efficacy will be formally demonstrated in comparison with the individual mAbs. In Aim 3 we will evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of the antibodies in sera from a number of NHP efficacy studies including studies performed in Aim 1. Correlations between PK/PD data and clinical outcome will be explored. Aim 4 we will be focused on generation of stable manufacturing cell lines in CHO cells and at lease four clones of each mAb will be produced to be used for future GMP cell banks. If successful, we anticipate further development of the product under DoD or BARDA funding and approval under FDA Animal Rule.", "keywords": [ "2019-nCoV", "Africa", "African", "Aman", "Angola", "Animal Model", "Antibodies", "Antibody Therapy", "Binding", "Binding Sites", "Biological Availability", "Biological Products", "Biological Response Modifier Therapy", "Blood Chemical Analysis", "Case Fatality Rates", "Cavia", "Cell Line", "Cells", "Cessation of life", "Chinese Hamster Ovary Cell", "Clinical", "Collaborations", "Comparative Study", "Complete Blood Count", "Data", "Development", "Disease", "Disease Outbreaks", "Disease Outcome", "Dose", "Drug Kinetics", "Ebola", "Ebola Hemorrhagic Fever", "Ebola virus", "Engineering", "Epitopes", "Exhibits", "FDA approved", "Fatality rate", "Filovirus", "Fucosyltransferase", "Funding", "Future", "GP2 gene", "GTPBP1 gene", "Generations", "Glycoproteins", "Human", "Immunotherapy", "Individual", "Infection", "Injections", "Lead", "Macaca fascicularis", "Marburg Virus Disease", "Marburgvirus", "Measures", "Modeling", "Monitor", "Monoclonal Antibodies", "Mutation", "Outcome", "Pharmacodynamics", "Phase", "Property", "Regression Analysis", "Reporting", "Research", "Research Personnel", "Risk Reduction", "Sampling Studies", "Series", "Serum", "Small Business Innovation Research Grant", "Surface", "Survival Analysis", "Testing", "Therapeutic", "Therapeutic Monoclonal Antibodies", "Time", "Transfection", "Vaccines", "Variant", "Viral", "Viral Hemorrhagic Fevers", "Viremia", "Virus", "Virus Diseases", "Zaire Ebola virus", "animal efficacy", "animal rule", "antibody immunotherapy", "base", "cell bank", "clinical development", "design", "drug candidate", "effective therapy", "efficacy evaluation", "efficacy study", "experimental study", "guinea pig model", "manufacture", "neutralizing antibody", "neutralizing monoclonal antibodies", "nonhuman primate", "novel", "pathogen", "pharmacokinetics and pharmacodynamics", "primary endpoint", "product development", "protective efficacy", "prototype", "receptor binding", "secondary endpoint", "sobriety", "stable cell line", "success", "therapeutic candidate", "therapeutic development", "therapeutically effective", "vaccine development", "viral outbreak" ], "approved": true } }, { "type": "Grant", "id": "12124", "attributes": { "award_id": "1R21AI176626-01A1", "title": "HSP90 paralog selective small molecules as anti-old-world alpha-viral therapeutic leads.", "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": 10523, "first_name": "Mindy I.", "last_name": "Davis", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-08-10", "end_date": "2025-07-31", "award_amount": 247725, "principal_investigator": { "id": 24324, "first_name": "Gaya K.", "last_name": "Amarasinghe", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 827, "ror": "", "name": "WASHINGTON UNIVERSITY", "address": "", "city": "", "state": "MO", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 27985, "first_name": "Brian S J", "last_name": "Blagg", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 827, "ror": "", "name": "WASHINGTON UNIVERSITY", "address": "", "city": "", "state": "MO", "zip": "", "country": "United States", "approved": true }, "abstract": "COVID-19 pandemic highlights the impact of emerging infectious diseases and the global socioeconomic impact. Alphaviruses such as the chikungunya virus (CHIKV) has re-emerged along with many arthropod-borne viruses (arboviruses) and these viruses continue to pose a significant threat to global human health especially with recent vector expansion into non-endemic regions. CHIKV belongs to the Togaviridae family and is transmitted mainly by Aedes albopictus and Aedes aegypti mosquitose. The bent-up posture caused by CHIKV fever disease and the virus can be classified into three different lineages with distinct genotypes corresponding to their respective geographical origins. CHIKV infections cause high serum viral loads, and therefore, high viremia also contributes to rapid spread. Like other alphaviruses, there are no treatments for CHIKV and related viral infections. In recent exploratory studies, we have identified two inhibitors that inhibit CHIKV and related alphavirus Mayaro virus (MAYV). While prior studies have shown a potential role for HSP90 inhibitors, a major limitation associated with further development of HSP90 inhibitors is that pan-HSP90 activity results in toxicity. HSP90 family consists of 4 different paralogs, two cytosolic forms HSP90α (encoded by HSP90AA1), HSP90β (encoded by HSP90AB1 gene), Grp94, an endoplasmic reticulum resident HSP90 (encoded by HSP90B1) and mitochondrial Trap1. While pan-HSP90 activity provides the initial insights, they have many clinical liabilities. In our proposed studies, we will develop HSP90β specific inhibitors with reduced toxicity and enhanced efficacy as a host-directed anti- alphavirus therapeutic lead. We expect to move one or more scaffolds from hit-to-lead with selectivity index >200 and determine the mechanism of action (MOA). Collectively, we will fill a critical gap in the field.", "keywords": [ "Address", "Aedes", "Alphavirus", "Arboviruses", "Binding", "COVID-19 pandemic", "Chikungunya virus", "Classification", "Clinical", "Combined Modality Therapy", "Comparative Study", "Culicidae", "Data", "Development", "Disease", "Dose", "Emerging Communicable Diseases", "Endoplasmic Reticulum", "Exhibits", "Family", "Fever", "Frequencies", "Genes", "Genotype", "Geographic Locations", "Geography", "HSP 90 inhibition", "Health", "Heat-Shock Proteins 90", "Human", "In Vitro", "Knowledge", "Lead", "Link", "Mayaro virus", "Metabolism", "Mitochondria", "Molecular Chaperones", "Mus", "Nonstructural Protein", "O&apos", "nyong-nyong virus", "Pharmaceutical Chemistry", "Phase", "Positioning Attribute", "Posture", "Predisposition", "Property", "Proteins", "Proteomics", "Recording of previous events", "Role", "Ross river virus", "Semliki forest virus", "Serum", "Solubility", "Structure-Activity Relationship", "Testing", "Therapeutic", "Togaviridae", "Toxic effect", "Universities", "Venezuelan Equine Encephalitis Virus", "Viral", "Viral Load result", "Viral Physiology", "Viremia", "Virion", "Virus", "Virus Diseases", "Washington", "Work", "analog", "chikungunya infection", "economic impact", "efficacious treatment", "in vivo", "indexing", "inhibitor", "innovation", "insight", "lead optimization", "novel", "novel therapeutics", "paralogous gene", "pharmacologic", "prophylactic", "response", "scaffold", "small molecule", "socioeconomics", "transmission process", "vector", "virology" ], "approved": true } } ], "meta": { "pagination": { "page": 1385, "pages": 1397, "count": 13961 } } }