Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1391&sort=abstract
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=abstract", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1419&sort=abstract", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1392&sort=abstract", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1390&sort=abstract" }, "data": [ { "type": "Grant", "id": "5476", "attributes": { "award_id": "3U19AI057266-18S1", "title": "Vaccine Induced Immunity in the Young and Aged", "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": 19078, "first_name": "Chao", "last_name": "Jiang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-06-02", "end_date": "2023-04-30", "award_amount": 2782096, "principal_investigator": { "id": 19079, "first_name": "Rafi", "last_name": "Ahmed", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "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": "While many strides have been made in the study of human immune responses, numerous knowledge gaps still remain. Many infections and immune-mediated diseases are localized to specific tissues, or organs but little is known about tissue/organ-specific immunity. A major overall goal of this CCHI program to this end is to understand memory CD8 T cells differentiation in the blood, tissues and organs. We have added Dr. Donna Farber to our CHHI-EVC team this cycle. She has established a unique human tissue resource enabling acquisition of blood and various tissues from deceased organ donors, we will therefore analyze virus-specific memory CD8 T cells in various tissues of deceased organ donors and address questions regarding the anatomic distribution and the epigenetic, transcriptional and phenotypic profile of virus-specific CD8 T cells elicited by live- attenuated virus vaccines and with minimal risk of antigenic re-exposure. The second major goal of this program is to elucidate the molecular mechanisms of “trained immunity” after YFV vaccination and viral infection to and harness this knowledge for future development of new classes of vaccines and immunotherapies. We will address the following questions. To what extent is so called “innate memory” caused by the effects of an ongoing adaptive immune response (for example, via paracrine signaling), versus a cell intrinsic property of innate cells, similar to the classic phenomenon of immune memory exhibited by memory T or B cells? Is there an enhanced response of DCs and monocytes, (similar to a memory response in the adaptive immune system), during secondary vaccination or infection? If so, what are the cellular and molecular mechanisms involved? Finally, the third overall goal is to identify signaling and transcription factor (TF) networks associated with T memory cell differentiation and survival and quantify how these networks change with age. This will be achieved in the following projects: Project 1: Immune memory (Ahmed, Hellerstein, Farber); Project 2: Innate immunity (Pulendran, Hellerstein), and Project 3: Immune senescence (Goronzy, Greenleaf). Supported by the following Core A: Adminstration (Ahmed); Core B: Single cell and integrative genomics (Bosinger, Greenleaf); Core C: Clinical and biostatistical (Edupuganti, Kulkanya, Yu).", "keywords": [ "Adaptive Immune System", "Address", "Age", "Anatomy", "Attenuated Live Virus Vaccine", "B-Lymphocytes", "Biometry", "Blood", "CD8-Positive T-Lymphocytes", "Cell Aging", "Cell Differentiation process", "Cell Survival", "Cells", "Clinical", "Development", "Epigenetic Process", "Exhibits", "Future", "Genetic Transcription", "Genomics", "Goals", "Human", "Immune", "Immune response", "Immunity", "Immunologic Memory", "Immunotherapy", "Infection", "Knowledge", "Localized Disease", "Mediating", "Memory", "Molecular", "Natural Immunity", "Organ", "Organ Donor", "Paracrine Communication", "Phenotype", "Property", "Signal Transduction", "T cell differentiation", "T memory cell", "T-Lymphocyte", "Tissues", "Training", "Vaccination", "Vaccine Design", "Vaccines", "Virus", "Virus Diseases", "adaptive immune response", "aged", "human tissue", "minimal risk", "monocyte", "programs", "response", "senescence", "tissue resource", "transcription factor", "vaccine-induced immunity" ], "approved": true } }, { "type": "Grant", "id": "4924", "attributes": { "award_id": "3U19AI057266-19S1", "title": "Vaccine Induced Immunity in the Young and Aged", "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": 17758, "first_name": "Chao", "last_name": "Jiang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-06-02", "end_date": "2023-04-30", "award_amount": 409523, "principal_investigator": { "id": 17759, "first_name": "Rafi", "last_name": "Ahmed", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "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": "While many strides have been made in the study of human immune responses, numerous knowledge gaps still remain. Many infections and immune-mediated diseases are localized to specific tissues, or organs but little is known about tissue/organ-specific immunity. A major overall goal of this CCHI program to this end is to understand memory CD8 T cells differentiation in the blood, tissues and organs. We have added Dr. Donna Farber to our CHHI-EVC team this cycle. She has established a unique human tissue resource enabling acquisition of blood and various tissues from deceased organ donors, we will therefore analyze virus-specific memory CD8 T cells in various tissues of deceased organ donors and address questions regarding the anatomic distribution and the epigenetic, transcriptional and phenotypic profile of virus-specific CD8 T cells elicited by live- attenuated virus vaccines and with minimal risk of antigenic re-exposure. The second major goal of this program is to elucidate the molecular mechanisms of “trained immunity” after YFV vaccination and viral infection to and harness this knowledge for future development of new classes of vaccines and immunotherapies. We will address the following questions. To what extent is so called “innate memory” caused by the effects of an ongoing adaptive immune response (for example, via paracrine signaling), versus a cell intrinsic property of innate cells, similar to the classic phenomenon of immune memory exhibited by memory T or B cells? Is there an enhanced response of DCs and monocytes, (similar to a memory response in the adaptive immune system), during secondary vaccination or infection? If so, what are the cellular and molecular mechanisms involved? Finally, the third overall goal is to identify signaling and transcription factor (TF) networks associated with T memory cell differentiation and survival and quantify how these networks change with age. This will be achieved in the following projects: Project 1: Immune memory (Ahmed, Hellerstein, Farber); Project 2: Innate immunity (Pulendran, Hellerstein), and Project 3: Immune senescence (Goronzy, Greenleaf). Supported by the following Core A: Adminstration (Ahmed); Core B: Single cell and integrative genomics (Bosinger, Greenleaf); Core C: Clinical and biostatistical (Edupuganti, Kulkanya, Yu).", "keywords": [ "Adaptive Immune System", "Address", "Age", "Anatomy", "Attenuated Live Virus Vaccine", "B-Lymphocytes", "Biometry", "Blood", "CD8-Positive T-Lymphocytes", "Cell Aging", "Cell Differentiation process", "Cell Survival", "Cells", "Clinical", "Development", "Epigenetic Process", "Exhibits", "Future", "Genetic Transcription", "Genomics", "Goals", "Human", "Immune", "Immune response", "Immunity", "Immunologic Memory", "Immunotherapy", "Infection", "Knowledge", "Localized Disease", "Mediating", "Memory", "Molecular", "Natural Immunity", "Organ", "Organ Donor", "Paracrine Communication", "Phenotype", "Property", "Signal Transduction", "T cell differentiation", "T memory cell", "T-Lymphocyte", "Tissues", "Training", "Vaccination", "Vaccine Design", "Vaccines", "Virus", "Virus Diseases", "adaptive immune response", "aged", "human tissue", "minimal risk", "monocyte", "programs", "response", "senescence", "tissue resource", "transcription factor", "vaccine-induced immunity" ], "approved": true } }, { "type": "Grant", "id": "15802", "attributes": { "award_id": "1R21AI183054-01A1", "title": "Formation of a Novel SARS-CoV-2 Nucleocapsid Dimer: Impacts on Viral and Cellular Processes", "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": 32891, "first_name": "MARY KATHERINE BRADFORD", "last_name": "PLIMACK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-08", "end_date": "2027-06-30", "award_amount": 438983, "principal_investigator": { "id": 23536, "first_name": "Emily A.", "last_name": "Bruce", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1131, "ror": "", "name": "UNIVERSITY OF VERMONT & ST AGRIC COLLEGE", "address": "", "city": "", "state": "VT", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1131, "ror": "", "name": "UNIVERSITY OF VERMONT & ST AGRIC COLLEGE", "address": "", "city": "", "state": "VT", "zip": "", "country": "United States", "approved": true }, "abstract": "While most SARS-CoV-2 research to date has focused on the biological consequences of mutations seen in the Spike (S) protein, the nucleocapsid protein (N) is also under selective pressure and an array of mutations within this protein have been documented in different Variants of Concern (VOCs). In this study, we identified three SARS-CoV-2 variants (Beta, Iota, and Delta) that encode different cysteine mutations, all introduced into the linker region of N. These mutations facilitate a highly stable N-N dimer mediated by the introduction of a cysteine and the formation of a di-sulfide bond. Beta, Iota, and Delta variants isolated and grown at BSL-3 all contained a novel cysteine residue in the linker region of N, which appear to be unique introductions amongst pandemic- causing Betacoronaviruses. Nucleoproteins encoding these cysteine mutations and transiently expressed in HEK-293T cells also form a dimer in the absence of other viral machinery. Removal of these cysteine mutations in the linker abolishes dimer formation. Notably, our biochemical studies also revealed this dimer is highly stable and can be visualized on standard non-reducing SDS-PAGE gels. Our proposal focuses on the G215C mutation, which quickly rose to dominance within the Delta lineages and mutations back to wildtype within transmission chains were quickly followed by a reversion to a cysteine at this position. Using reverse genetics, Drs Johnson and Menachery will construct a SARS-CoV-2 Delta virus that reverts the nucleocapsid cysteine back to the ancestral sequence to specifically evaluate N dimer impact on infection. This proposal aims to study the biological impact of stable N dimer formation during infection by characterizing viral growth kinetics (in vitro and in vivo) as well as the effect on viral fitness and transmission in the hamster model. Notably, a related virus (G215C in the WA1 background) showed substantially increased growth both in vitro and in vivo, suggesting that stable N dimer formation is important for viral replication. The stably dimerized form of N is highly enriched in virions (vs. the cellular environment) and we hypothesize it is increasing the efficiency of encapsidation and thus the stability of the viral RNA during transmission. As the cysteines we observe in the nucleocapsid linker lie near/on the N/NSP3 binding interface we will use proteomics to determine how the cellular and viral binding partners of the nucleoprotein change with/without this disulfide bond. Overall, the observation that mutations introducing a cysteine in the N linker have arisen multiple independent times and been maintained during human transmission, as well as our preliminary viral growth kinetics suggest that stable N dimer formation may drive positive selection and convey a growth advantage during SARS-CoV-2 infection and/or a selective benefit during animal-to-animal transmission.", "keywords": [ "2019-nCoV", "Affect", "Animals", "Back", "Binding", "Biochemical", "Biological", "Biological Assay", "Biology", "COVID-19 pandemic", "Cell Physiology", "Cells", "Code", "Collaborations", "Coronavirus", "Cysteine", "Data", "Dimerization", "Elements", "Environment", "Epithelial Cells", "Excision", "Gel", "Genome", "Genomics", "Growth", "Hamsters", "Human", "Immune Evasion", "Immune response", "In Vitro", "Individual", "Infection", "Inflammation", "Interferons", "Kinetics", "Mass Spectrum Analysis", "Mediating", "Middle East Respiratory Syndrome", "Modeling", "Molecular Weight", "Mutation", "Nucleocapsid", "Nucleocapsid Proteins", "Nucleoproteins", "Organoids", "Pathogenesis", "Play", "Population", "Positioning Attribute", "Process", "Production", "Proteins", "Proteomics", "Public Health", "RNA", "RNA Binding", "RNA Stability", "RNA-Directed RNA Polymerase", "Research", "Role", "SARS-CoV-2 B.1.617.2", "SARS-CoV-2 infection", "SARS-CoV-2 variant", "SH2D3C gene", "Severe Acute Respiratory Syndrome", "Shapes", "Site", "System", "Testing", "Vaccines", "Variant", "Viral", "Viral Genome", "Viral Pathogenesis", "Viral Proteins", "Virion", "Virus", "Virus Replication", "Visualization", "airway epithelium", "betacoronavirus", "clinical predictors", "dimer", "disulfide bond", "fitness", "flexibility", "genomic RNA", "improved", "in vivo", "insight", "loss of function", "migration", "monomer", "mutant", "novel", "novel coronavirus", "pandemic disease", "pressure", "reverse genetics", "structural biology", "transmission process", "variants of concern", "viral RNA", "viral fitness", "viral transmission", "virology", "virus host interaction" ], "approved": true } }, { "type": "Grant", "id": "11437", "attributes": { "award_id": "1U01DK135002-01", "title": "Assessing Diabetes Risk Origins in Teens (ADROIT)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)" ], "program_reference_codes": [], "program_officials": [ { "id": 6382, "first_name": "MIRANDA MARGUERITE", "last_name": "Broadney", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-04-05", "end_date": "2029-01-31", "award_amount": 85216, "principal_investigator": { "id": 27501, "first_name": "LORRAINE E LEVITT", "last_name": "KATZ", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1073, "ror": "", "name": "CHILDREN'S HOSP OF PHILADELPHIA", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "While obesity, ancestry, family history of diabetes, insulin resistance, and puberty are all risk factors for pediatric-onset type 2 diabetes (T2D), identifying the subset of youth at greatest risk of advancing from “prediabetes” to T2D and the mechanisms underlying the deterioration remain elusive. This lack of specificity defies the medical community's ability to 1) direct care to the youth at greatest risk of pediatric onset T2D and 2) develop targeted interventions. The particularly aggressive nature of pediatric T2D and the unique hormonal milieu of the adolescent suggest while the mechanisms underlying adult-onset T2D in adults resonate in pediatric T2D, additional perturbances are operative. Our team proposes to collaborate in a multi-center study, informed by partnerships with family and community members, to define clinically accessible metrics of increased diabetes risk as well as potential mechanisms that compromise the normal adaptations to insulin resistance during adolescence. We propose a longitudinal study leveraging a 3-hour, multi-sample oral glucose tolerance test performed at baseline, 18-months, and 36-months in obese pubertal youth with pre-diabetes to 1) test the utility of the one-hour glucose in predicting T2D and deterioration in insulin secretion, 2) perform extensive phenotyping for testing the relationships of changes in insulin secretion (early phase and second phase), insulin sensitivity, incretin secretion, glucagon suppression, hepatic glucose clearance, and free fatty flux with emergence of T2D. The contributions of genetic variants, in utero environment, visceral adipose accumulation, eating behaviors, mental health issues, social determinants of health, diet, physical activity, sleep and COVID infection to perturbances in insulin secretion and sensitivity will be tested. Home health care workers will provide additional critical insight into the home environment. Glucose-potentiated arginine stimulation tests will be conducted in subsets of participants in whom glucose homeostasis is preserved, worsens, or advances to T2D. This study is anticipated to specify useful indicators of T2D risk and advance our understanding of the underpinnings of progressive defects in insulin secretion and sensitivity to inform individualized programs aimed at interrupting emergence of T2D.", "keywords": [ "Acceleration", "Adipose tissue", "Adolescence", "Adolescent", "Adult", "Algorithms", "Arginine", "Beta Cell", "Biological Markers", "Body Composition", "Caring", "Child", "Childhood", "Childhood diabetes", "Clinical", "Collaborations", "Communication", "Communities", "Community Health Aides", "Community Healthcare", "DNA", "Data", "Data Collection", "Defect", "Deterioration", "Development", "Diabetes Mellitus", "Diet", "Disease", "Eating Behavior", "Eating Disorders", "Education", "Environment", "Evaluation", "Exposure to", "Family", "Family history of", "Fatty acid glycerol esters", "Fetal Growth Retardation", "Fetal Macrosomia", "Future", "Genetic Risk", "Genomics", "Genotype", "Glucagon", "Glucose", "Goals", "Growth", "Health Personnel", "Hepatic", "Home Care Services", "Home environment", "Hormonal", "Hour", "Human", "Infection", "Institution", "Insulin", "Insulin Resistance", "Interruption", "Intervention", "Life Style", "Longitudinal Studies", "Longitudinal cohort", "Medical", "Medical Care Team", "Mental Health", "Metabolic", "Methodology", "Methods", "Mission", "Molecular", "Multicenter Studies", "Nature", "Non-Insulin-Dependent Diabetes Mellitus", "OGTT", "Obesity", "Participant", "Patients", "Pediatric Hospitals", "Phase", "Phenotype", "Philadelphia", "Physical activity", "Physical assessment", "Plasma", "Population", "Prediabetes syndrome", "Prevalence", "Process", "Prospective Studies", "Protocols documentation", "Psychosocial Factor", "Puberty", "RNA", "Reporting", "Research", "Research Design", "Resources", "Risk", "Risk Factors", "Sampling", "Science", "Secretory Cell", "Secretory Rate", "Sleep", "Specific qualifier value", "Specificity", "Standardization", "Teenagers", "Testing", "Viral", "Visceral", "Youth", "actigraphy", "adipokines", "anxiety symptoms", "base", "biobank", "blood glucose regulation", "clinical center", "community based participatory research", "coronavirus disease", "depressive symptoms", "design", "diabetes risk", "digital health", "genetic variant", "healthy weight", "high risk", "in utero", "indexing", "innovation", "insight", "insulin secretion", "insulin sensitivity", "intrauterine environment", "maternal diabetes", "member", "open source", "phenomics", "physical inactivity", "prenatal exposure", "preservation", "prevent", "programs", "recruit", "screening", "sleep health", "social health determinants", "study population", "tool" ], "approved": true } }, { "type": "Grant", "id": "5881", "attributes": { "award_id": "3RF1AG063381-01S1", "title": "Developing dynamic prognostic and risk-stratification models for informing prescribing decisions in older adults with Coronavirus Disease 2019", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Aging (NIA)" ], "program_reference_codes": [], "program_officials": [ { "id": 20134, "first_name": "Marcel", "last_name": "Salive", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2019-05-01", "end_date": "2023-04-30", "award_amount": 524715, "principal_investigator": { "id": 20135, "first_name": "JOSHUA K", "last_name": "LIN", "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": "While over 80% patients with Coronavirus Disease 2019 (COVID-19) experienced only mild illness, the mortality rates have been reported to be 6.4-13.4% in vulnerable populations, including older adults and patients with multiple co-morbidities. Pharmacological treatments are primarily used for patients with moderate to severe disease. Optimal prescribing of drug therapy relies heavily on accurate risk stratification based on patient prognosis. Since it is known that COVID-19 can often cause rapid clinical deterioration, it is critical to have a prognostic tool well-predictive of disease progression and adverse clinical outcomes, so the pharmacological treatments or other interventions can be initiated timely. Also, during the COVID-19 pandemic, many healthcare facilities need to operate beyond regular capacity with limited resources, such as mechanical ventilators, therapeutic agents, and intensive care unit (ICU) bed availability. A reliable prognostic tool is essential for optimal decisions regarding medical disposition (e.g., home monitoring vs. admission) and resource allocation (eg, ICU beds and mechanical ventilators). While there are seemingly abundant data in prognostic prediction for patients with COVID-19, there remain two major knowledge gaps. First, all of the existing prediction models only consider factors measured at hospital admission without incorporating dynamic changes of biomarkers over time. The models thus have limited clinical applicability since many of these biomarkers are repeated multiple times during a treatment course and clinicians need to know how these dynamic changes can inform medical decisions. Second, while medication use and the initiation timing are highly informative of disease severity, they were not used for prognostic prediction in the prior models. We aim to build a prospective prognostic modeling system based on near-real-time electronic health record (EHR) data from Mass General Brigham, a large care delivery network in Massachusetts that includes 2 tertiary and 11 secondary hospitals and >30 ambulatory centers. We have established the basic infrastructure and currently receive weekly data updates. The database currently has >14,000 confirmed cases of COVID-19 and are expanding at the rate of 500-1000 confirmed cases per week, allowing us to build prediction models with rich data input and ability to perform prospective validation. We will develop a dynamic prognostic tool incorporating baseline characteristics, time-varying factors with their dynamic changes, medication use and its timing to predict key clinical outcomes. Data accrued from March to August, 2020 will be used for model derivation and data from September to December, 2020 will be used for prospective validation. In addition to the predictors reported in the literature, we will search for novel predictors by screening through the rich EHR data using TreeScan, a novel, validated, statistical tool adopted by the US Food and Drug Administration (FDA) for vaccine and drug safety surveillance. We will assess age effect modification on risk factors. This will help researchers understand the vulnerability of older adults to COVID-19.", "keywords": [ "Admission activity", "Adopted", "Age", "Beds", "Biological Markers", "Biological Models", "COVID-19", "COVID-19 pandemic", "COVID-19 patient", "Cessation of life", "Characteristics", "Clinical", "Code", "Continuity of Patient Care", "Data", "Databases", "Derivation procedure", "Deterioration", "Diagnosis", "Diagnostic", "Dimensions", "Disease", "Disease Progression", "Drug Prescriptions", "Early Intervention", "Elderly", "Electronic Health Record", "Health care facility", "Home", "Hospitalization", "Hospitals", "Infrastructure", "Inpatients", "Intensive Care Units", "Intervention", "Knowledge", "Literature", "Massachusetts", "Measures", "Mechanical Ventilators", "Mechanical ventilation", "Medical", "Modeling", "Modification", "Monitor", "Outcome", "Patients", "Pharmaceutical Preparations", "Pharmacological Treatment", "Pharmacotherapy", "Procedures", "Prognosis", "Prognostic Factor", "Reporting", "Research Personnel", "Resource Allocation", "Resources", "Respiratory Failure", "Risk Factors", "Scanning", "Severity of illness", "Supportive care", "System", "Therapeutic", "Therapeutic Agents", "Time", "United States Food and Drug Administration", "Update", "Validation", "Vulnerable Populations", "adverse outcome", "age effect", "age group", "base", "care delivery", "clinical application", "clinically relevant", "comorbidity", "data mining", "experience", "flexibility", "high risk", "medication safety", "mortality", "novel", "older patient", "predictive modeling", "profiles in patients", "prognostic", "prognostic model", "prognostic tool", "prospective", "risk stratification", "screening", "tool", "vaccine safety" ], "approved": true } }, { "type": "Grant", "id": "9780", "attributes": { "award_id": "1R21DA054383-01A1", "title": "New brainstem targets for counteracting opioid induced apnea", "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": 23333, "first_name": "KIRAN R V", "last_name": "Vemuri", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-08-01", "end_date": "2024-07-31", "award_amount": 273000, "principal_investigator": { "id": 25529, "first_name": "JACK L", "last_name": "FELDMAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 818, "ror": "", "name": "UNIVERSITY OF CALIFORNIA LOS ANGELES", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "While prescription opioids are exceptional analgesics, they have significant side effects, especially opioid- induced persistent apnea (OIPA). A significant public health problem follows from these side effects, as overdoses caused almost 50,000 deaths in 2019, along with non-fatal overdoses that result in costly and often extended hospitalization. The “opioid epidemic” accelerated further during the COVID-19 pandemic, with a 38% increase in deaths due to synthetic opioid overdose (primarily fentanyl) compared to 2019. We propose a logical path to identifying molecules that can block or reverse OIPA that may supplement current treatments, e.g., higher efficacy and safety, longer half-life, possibly preserving opioid-induced analgesia. Opioids depress breathing by actions on two brainstem neural circuits underlying breathing movements, the preBötzinger Complex (preBötC) and the Parabrachial Nuclei (PB), both of which contains neurons expressing µ-opioid receptors (µORs). µORs are inhibitory G-protein coupled receptors (GPCRs) that depress neuronal excitability. Activation of excitatory GPCRs in preBötC and PB can counteract opioid effects on breathing. We propose to sequence the RNA in preBötC and PB neurons that express µORs to determine expression of excitatory GPCRs. Previous studies in awake mice aimed to determine whether preBötC or PB mediates depression of breathing during opioid overdose; however, opioids evoke only a modest decrease in breathing in awake mice, nowhere near an apnea observed in humans during acute opioid intoxication. We therefore propose to determine whether preBötC and/or PB are primarily responsible for OIPA in mice using a methodology in which we consistently evoke a complete apnea following opioid administration. We will select potential target excitatory GPCR receptors, that are coexpressed with µORs in the structure(s) that we find to be primarily responsible for OIPA (preBötC and/or PB). We will then determine the efficacy of the agonists of these GPCRs in counteracting OIPA in anesthetized mice. Success of this exploratory project will generate data for subsequent preclinical and translational investigation of agonists of these receptors as potential therapeutics for reversing OIPA. Prescription opioids are extremely effective painkillers, but overdose can result in death because they also stop breathing. More that 50,000 Americans die each year from opioid overdose. We propose to identify receptors, whose activation can reverse opioids’ effects on breathing.", "keywords": [ "Absence of pain sensation", "Acute", "Affect", "Agonist", "Airway Resistance", "American", "Analgesics", "Apnea", "Asphyxia", "Bombesin Receptor", "Brain Stem", "Breathing", "COVID-19 pandemic", "Cessation of life", "Clinical", "Clinical Research", "Data", "Dose", "Effectiveness", "Fentanyl", "Foundations", "Frequencies", "G alpha q Protein", "G-Protein-Coupled Receptors", "GTP-Binding Protein alpha Subunits Gs", "Gastrin releasing peptide", "Generations", "Goat", "Half-Life", "Hospitalization", "Human", "In Vitro", "Intervention", "Investigation", "Mammals", "Mediating", "Mental Depression", "Methodology", "Morphine", "Motor Neurons", "Movement", "Mus", "Muscle", "Naloxone", "Neurons", "Opioid", "Opioid Antagonist", "Opioid agonist", "Overdose", "Pattern", "Pharmaceutical Preparations", "Preparation", "Public Health", "Pump", "RNA Sequences", "Rat-1", "Rattus", "Research", "Rodent", "Safety", "Serotonin Receptors 5-HT4", "Site", "Slice", "Structure", "Substance P", "Testing", "Therapeutic", "Ventilatory Depression", "antagonist", "awake", "blood-brain barrier permeabilization", "carfentanil", "central pattern generator", "cost", "depressive symptoms", "experimental study", "in vivo", "morphine administration", "mouse model", "mu opioid receptors", "neural circuit", "neuronal excitability", "opioid epidemic", "opioid overdose", "opioid withdrawal", "overdose death", "parabrachial nucleus", "pre-clinical", "preBotzinger complex", "prescription opioid", "preservation", "receptor", "remifentanil", "side effect", "single-cell RNA sequencing", "success", "synthetic opioid", "therapeutic development" ], "approved": true } }, { "type": "Grant", "id": "9703", "attributes": { "award_id": "1R21DA056740-01", "title": "Recruiting active expiration to overcome opioid-induced persistent apnea", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Drug Abuse (NIDA)", "NIH Office of the Director" ], "program_reference_codes": [], "program_officials": [ { "id": 23333, "first_name": "KIRAN R V", "last_name": "Vemuri", "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": 273000, "principal_investigator": { "id": 25529, "first_name": "JACK L", "last_name": "FELDMAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 818, "ror": "", "name": "UNIVERSITY OF CALIFORNIA LOS ANGELES", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "While prescription opioids are exceptional analgesics, they have significant side effects, especially opioid-induced persistent apnea (OIPA). A significant public health problem follows from these side effects, as overdoses caused almost 50,000 deaths in 2019, along with non-fatal overdoses that result in costly and often extended hospitalization. The “opioid epidemic” accelerated further during the COVID-19 pandemic, with a 38% increase in deaths due to synthetic opioid overdose (primarily fentanyl) compared to 2019. We propose a logical path to identifying molecules that can engage active expiration, thereby increasing tolerance of opioids. Those molecules may supplement current treatments for OIPA, e.g., higher efficacy and safety, longer half-life, possibly preserving opioid-induced analgesia. Opioids depress breathing by actions on inspiratory rhythm generating regions, the preBötzinger Complex (preBötC), either directly by activating µ-opioid receptors (µORs) in preBötC, or indirectly by inhibiting tonic drive from the Parabrachial Nuclei to preBötC. µORs are inhibitory G-protein coupled receptors (GPCRs) that depress neuronal excitability. Parafacial respiratory group (pF) contains an active expiratory oscillator, which is independent of preBötC, is opioid-insensitive and is silent at rest, but can become active during certain conditions, e.g. exercise, high CO2. When it is active, it is tightly coupled to inspiration. We propose to express excitatory GPCR HM3Dq receptors (designer receptors exclusively activated by designer drugs) in pF and test whether activation of these receptors increases the dose of fentanyl required to produce persistent apnea. We will then sequence the pF neurons to determine expression of endogenous excitatory GPCRs and test the efficacy of the agonists of these GPCRs in increasing the dose of fentanyl required to produce persistent apnea in anesthetized mice. Success of this exploratory project will generate data for subsequent preclinical and translational investigation of agonists of these receptors as potential therapeutics for preventing OIPA.", "keywords": [ "Absence of pain sensation", "Acute", "Adolescent", "Agonist", "American", "Analgesics", "Apnea", "Asphyxia", "Brain Stem", "Breathing", "COVID-19 pandemic", "Carbon Dioxide", "Cessation of life", "Coupled", "Data", "Depressed mood", "Disinhibition", "Dose", "Drug Receptors", "Effectiveness", "Exercise", "Fentanyl", "Foundations", "G alpha q Protein", "G-Protein-Coupled Receptors", "Generations", "Half-Life", "Hospitalization", "Hypercapnia", "Investigation", "Lateral", "Mus", "Naloxone", "Neurons", "Opioid", "Opioid Antagonist", "Opioid agonist", "Overdose", "Pattern", "Persons", "Pharmaceutical Preparations", "Pharmacology", "Public Health", "Rattus", "Receptor Activation", "Recruitment Activity", "Relapse", "Rest", "Safety", "Structure", "Suggestion", "Testing", "Therapeutic", "Urethane", "Ventilatory Depression", "associated symptom", "carfentanil", "central pattern generator", "cost", "designer receptors exclusively activated by designer drugs", "effectiveness evaluation", "efficacy testing", "experimental study", "expiration", "mu opioid receptors", "neuronal excitability", "novel", "opiate tolerance", "opioid epidemic", "opioid overdose", "opioid withdrawal", "optogenetics", "overdose death", "parabrachial nucleus", "pre-clinical", "preBotzinger complex", "prescription opioid", "preservation", "prevent", "receptor", "respiratory", "side effect", "single-cell RNA sequencing", "success", "synthetic opioid", "therapeutic development", "ventilation" ], "approved": true } }, { "type": "Grant", "id": "11942", "attributes": { "award_id": "5R21DA056740-02", "title": "Recruiting active expiration to overcome opioid-induced persistent apnea", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Drug Abuse (NIDA)", "NIH Office of the Director" ], "program_reference_codes": [], "program_officials": [ { "id": 23333, "first_name": "KIRAN R V", "last_name": "Vemuri", "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": 156000, "principal_investigator": { "id": 25529, "first_name": "JACK L", "last_name": "FELDMAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 818, "ror": "", "name": "UNIVERSITY OF CALIFORNIA LOS ANGELES", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "While prescription opioids are exceptional analgesics, they have significant side effects, especially opioid-induced persistent apnea (OIPA). A significant public health problem follows from these side effects, as overdoses caused almost 50,000 deaths in 2019, along with non-fatal overdoses that result in costly and often extended hospitalization. The “opioid epidemic” accelerated further during the COVID-19 pandemic, with a 38% increase in deaths due to synthetic opioid overdose (primarily fentanyl) compared to 2019. We propose a logical path to identifying molecules that can engage active expiration, thereby increasing tolerance of opioids. Those molecules may supplement current treatments for OIPA, e.g., higher efficacy and safety, longer half-life, possibly preserving opioid-induced analgesia. Opioids depress breathing by actions on inspiratory rhythm generating regions, the preBötzinger Complex (preBötC), either directly by activating µ-opioid receptors (µORs) in preBötC, or indirectly by inhibiting tonic drive from the Parabrachial Nuclei to preBötC. µORs are inhibitory G-protein coupled receptors (GPCRs) that depress neuronal excitability. Parafacial respiratory group (pF) contains an active expiratory oscillator, which is independent of preBötC, is opioid-insensitive and is silent at rest, but can become active during certain conditions, e.g. exercise, high CO2. When it is active, it is tightly coupled to inspiration. We propose to express excitatory GPCR HM3Dq receptors (designer receptors exclusively activated by designer drugs) in pF and test whether activation of these receptors increases the dose of fentanyl required to produce persistent apnea. We will then sequence the pF neurons to determine expression of endogenous excitatory GPCRs and test the efficacy of the agonists of these GPCRs in increasing the dose of fentanyl required to produce persistent apnea in anesthetized mice. Success of this exploratory project will generate data for subsequent preclinical and translational investigation of agonists of these receptors as potential therapeutics for preventing OIPA.", "keywords": [ "Absence of pain sensation", "Acceleration", "Acute", "Adolescent", "Agonist", "American", "Analgesics", "Anesthesia procedures", "Apnea", "Asphyxia", "Brain Stem", "Breathing", "COVID-19 pandemic", "Carbon Dioxide", "Cessation of life", "Coupled", "Data", "Depressed mood", "Disinhibition", "Dose", "Effectiveness", "Exercise", "Fentanyl", "Foundations", "G alpha q Protein", "G-Protein-Coupled Receptors", "Generations", "Genetic", "Half-Life", "Hospitalization", "Hypercapnia", "Lateral", "Mus", "Naloxone", "Neurons", "Opioid", "Opioid Antagonist", "Opioid Receptor", "Opioid agonist", "Overdose", "Pattern", "Persons", "Pharmaceutical Preparations", "Public Health", "Rattus", "Receptor Activation", "Recruitment Activity", "Relapse", "Rest", "Safety", "Sensory", "Structure", "Suggestion", "Testing", "Therapeutic", "Translational Research", "Urethane", "Ventilatory Depression", "associated symptom", "carfentanil", "central pattern generator", "cost", "designer receptors exclusively activated by designer drugs", "effectiveness evaluation", "efficacy testing", "experimental study", "expiration", "mu opioid receptors", "neuronal excitability", "novel", "opiate tolerance", "opioid epidemic", "opioid overdose", "opioid withdrawal", "optogenetics", "overdose death", "parabrachial nucleus", "pharmacologic", "pre-clinical", "preBotzinger complex", "prescription opioid", "preservation", "prevent", "receptor", "respiratory", "side effect", "single-cell RNA sequencing", "success", "synthetic opioid", "therapeutic development", "ventilation" ], "approved": true } }, { "type": "Grant", "id": "11075", "attributes": { "award_id": "1F30HD107932-01A1", "title": "Enhancing K-12 School Safety During a Respiratory Viral Pandemic", "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": 6835, "first_name": "Denise", "last_name": "Russo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-02-16", "end_date": "2025-02-15", "award_amount": 32612, "principal_investigator": { "id": 27048, "first_name": "Dan", "last_name": "Li", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 452, "ror": "https://ror.org/03v76x132", "name": "Yale University", "address": "", "city": "", "state": "CT", "zip": "", "country": "United States", "approved": true }, "abstract": "While progress has been made since the onset of the COVID-19 pandemic, the spread of the virus still poses a threat to school safety. There is a significant concern regarding viral transmission in K-12 schools as a result of close social interactions between children, crowded institutional environments, high risk extracurricular activities, and insufficient vaccination coverage. Children have close interactions with parents and other household members who are active in all sectors of society. Keeping K-12 schools safe is crucial to minimizing community transmission and restoring optimal societal functions. COVID-19 is unlikely to become extinct due to the emergence of new variants, rapidly waning antibodies, COVID behavioral fatigue, and low vaccination coverage. The challenges of prevention and control in K-12 schools persist, from both the current pandemic and future respiratory threats. Our study anticipates next steps of outbreak prevention and management, and the topics of study (i.e. vaccinations) are highly relevant to school safety in this or future respiratory threats (COVID, influenza). We will examine the experience of K-12 schools during the pandemic through the following aims: Aim 1: Conduct a scoping review to identify and inventory the current research and evidence quality on the impact of COVID-19 on K-12 schools Aim 2: Investigate individual stakeholder- and school administrative-level experience and concerns regarding vaccination and safety practices during the pandemic through research in local K-12 schools via stakeholder longitudinal surveys (Aim 2A) and qualitative exploratory semi-structured interviews of school administrators (Aim 2B). Aim 3: Assess the implementation of a Hardware-Assisted Bluetooth-based Infection Tracking Device (HABIT) in a high school setting through a mixed-method study. We will assess HABIT's implementation outcomes (ease of use, interface, and satisfaction, acceptability, usefulness, coherence, setting, adherence, appropriateness) in a K-12 school using qualitative focus group interviews with key stakeholders, survey responses, and HABIT device usage data. We will present both the quantitative performance metrics and the qualitative contextualized insights of HABIT implementation. The proposal is the research component of a comprehensive training plan that is designed to provide a foundation for my career as a physician-scientist through the Yale MD-PhD program. Through these aims, we seek to provide insights that are essential for developing an integrated approach to keep both children and teachers safe in the event of the current and future respiratory viral outbreaks and pandemics.", "keywords": [ "Adherence", "Administrator", "Antibodies", "Attitude", "Behavior", "Behavioral", "Bluetooth", "COVID-19", "COVID-19 impact", "COVID-19 pandemic", "COVID-19 vaccination", "Case Study", "Child", "Clip", "Code", "Communities", "Connecticut", "Contact Tracing", "Crowding", "Data", "Data Collection", "Devices", "Doctor of Philosophy", "Emergency Situation", "Engineering", "Environment", "Equipment and supply inventories", "Event", "Faculty", "Fatigue", "Focus Groups", "Foundations", "Future", "Goals", "Group Interviews", "High School Student", "Hospitals", "Household", "Human Resources", "Individual", "Infection", "Influenza", "Institution", "Institutional Review Boards", "Intervention", "Interview", "Knowledge", "Literature", "Longitudinal Surveys", "Maps", "Methods", "Middle School Student", "Nature", "Nurses", "Output", "Pain", "Parents", "Participant", "Perception", "Performance", "Persons", "Phase", "Physicians", "Policies", "Prevention", "Preventive measure", "Prisons", "Privatization", "Process", "Protocols documentation", "Publishing", "Questionnaires", "Reach Effectiveness Adoption Implementation and Maintenance", "Recommendation", "Relaxation", "Research", "Role", "SARS-CoV-2 transmission", "Safety", "Schools", "Scientist", "Series", "Social Functioning", "Social Interaction", "Societies", "Statistical Data Interpretation", "Structure", "Students", "Surveys", "Training", "Transcript", "Vaccination", "Vaccines", "Variant", "Viral", "Virus", "career", "community transmission", "coronavirus disease", "current pandemic", "data cleaning", "design", "digital", "experience", "falls", "future pandemic", "high risk", "high school", "implementation evaluation", "implementation outcomes", "improved", "influenza virus vaccine", "insight", "member", "operation", "pandemic disease", "policy recommendation", "prevent outbreaks", "programs", "recruit", "respiratory", "respiratory virus", "response", "safety practice", "satisfaction", "school environment", "teacher", "vaccine hesitancy", "viral outbreak", "viral pandemic", "viral transmission", "welfare" ], "approved": true } }, { "type": "Grant", "id": "5888", "attributes": { "award_id": "3R01GM124280-04S1", "title": "Modeling ongoing SARS-CoV2 vaccination strategies in light of emerging data on immunity and viral evolution", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 20149, "first_name": "Han", "last_name": "Nguyen", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2018-06-01", "end_date": "2023-05-31", "award_amount": 173135, "principal_investigator": { "id": 20150, "first_name": "Benjamin A", "last_name": "Lopman", "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": "While SARS-CoV-2, the pathogen causing COVID-19, continues to spread, the rapid development and deployment of effective vaccines provide a means by which we can reduce its future impact. Initial vaccines have shown to be highly effective, however, the current emergence of new SARS-CoV-2 variants, together with indications that of waning immunity, means that continued repeat vaccinations are likely to be required. Here, we will build upon resources we have already developed from our ongoing project aimed at modeling potential norovirus vaccines and our previous work aimed at modeling the impact of vaccination for SARS-CoV-2 Our team has made contributions and investigated the relative population impacts of SARS-CoV-2 vaccines with different mechanisms of action; characterized patterns of virus evolution that have the potential to impact vaccine efficacy and escape; and, examined initial strategies for vaccine deployment with the aim of relaxing social distancing guidelines. We will leverage these data and modeling tools and build on this work to assess more fully the patterns of immune waning and virus evolution. We will then use these data and results and combine them with our existing SARS-CoV-2 vaccine simulation model to inform the building and the calibration of an extended model. This extended model will account for waning immunity to SARS-CoV-2 and its viral evolution. Our model will inform rapidly emerging scientific questions around continued SARS-CoV-2 vaccination and re-vaccination strategies, including both boosting and vaccine reformulation.", "keywords": [ "2019-nCoV", "Antibodies", "COVID-19", "COVID-19 vaccination", "COVID-19 vaccine", "Calibration", "Collection", "Computer Simulation", "Data", "Development", "Evolution", "Future", "Guidelines", "Immune", "Immunity", "Incidence", "Infection", "Light", "Modeling", "Norovirus", "Pattern", "Population", "Public Health", "Publications", "Recommendation", "Resources", "Role", "SARS-CoV-2 immunity", "SARS-CoV-2 infection", "SARS-CoV-2 variant", "Serology", "Social Distance", "Statistical Models", "Vaccination", "Vaccines", "Viral", "Virus", "Work", "models and simulation", "pathogen", "tool", "vaccination strategy", "vaccine distribution", "vaccine efficacy", "vaccine-induced immunity" ], "approved": true } } ], "meta": { "pagination": { "page": 1391, "pages": 1419, "count": 14184 } } }