Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1385&sort=-program_reference_codes
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-program_reference_codes", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1397&sort=-program_reference_codes", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1386&sort=-program_reference_codes", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1384&sort=-program_reference_codes" }, "data": [ { "type": "Grant", "id": "11661", "attributes": { "award_id": "5R21EB031336-02", "title": "Dynamic Nuclear Polarization of Aerosols - A Novel Approach for Imaging Water Vapor and Enabling Lung Imaging", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Biomedical Imaging and Bioengineering (NIBIB)" ], "program_reference_codes": [], "program_officials": [ { "id": 22251, "first_name": "SHUMIN", "last_name": "Wang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-03-01", "end_date": "2023-12-31", "award_amount": 203188, "principal_investigator": { "id": 22252, "first_name": "Leeor", "last_name": "Alon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 832, "ror": "", "name": "NEW YORK UNIVERSITY SCHOOL OF MEDICINE", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22253, "first_name": "ALEXEJ", "last_name": "JERSCHOW", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 832, "ror": "", "name": "NEW YORK UNIVERSITY SCHOOL OF MEDICINE", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Detecting and characterizing lung disorders and their impacts on the airways by imaging is extremely challenging due to the low tissue density. Few options exist to characterize the changes in the microscopic properties of air access and tissue changes in diseases such as asthma, pneumonia, bronchitis, Covid-19, and chronic obstructive pulmonary disease. MRI with hyperpolarized gasses, such as 3He and 129Xe have been used to fill this gap, which however have their own limitations related to cost, complexity of implementation, compatibility of existing equipment, and some non-negligible biological effects of the gasses. This project will deliver an alternative approach, based on aerosolized hyperpolarized water vapor (AHWV), which will be fully biocompatible, portable, compatible with existing imaging hardware, and will allow probing lung volume at different length scales. The approach is based on Overhauser Dynamic Nuclear Polarization (ODNP) of water, followed by aerosolization of hyperpolarized water such that it can be imaged. For this exploratory program, we will develop an open-source, low field (0.2T) ODNP system to hyperpolarize water in the liquid phase that will be rapidly vaporized by an aerosolization reactor. Relaxation properties of water in vapor form will be studied at different magnetic field strengths, temperatures and aerosolization approaches to determine the optimal conditions for vapor polarization, delivery into the measurement volume and optimization of sensitivity. The method will be on a mouse animal model on a 3T animal scanner. Overall, we will establish an effective method to hyperpolarize and aerosolize water and will develop the necessary tools required to acquire hyperpolarized water-in-air images in void-spaces. The study is expected to lay the foundation for this new portable, cost-effective, and flexible imaging modality for the airways.", "keywords": [ "Address", "Aerosols", "Air", "Airway Disease", "Anatomy", "Anesthetics", "Animal Model", "Animals", "Asthma", "Biological", "Bronchitis", "COVID-19", "Chronic Obstructive Pulmonary Disease", "Clinical", "Compensation", "Dedications", "Detection", "Development", "Diagnostic", "Diameter", "Disease", "Electronics", "Equipment", "Foundations", "Gases", "Goals", "Human", "Image", "Imaging Techniques", "Inhalation", "Investigation", "Length", "Liquid substance", "Lung", "Lung diseases", "Magnetic Resonance Imaging", "Magnetism", "Measurement", "Methods", "Microscopic", "Mind", "Morbidity - disease rate", "Morphologic artifacts", "Motion", "Mus", "Nebulizer", "Noise", "Nuclear", "Oxygen", "Particle Size", "Patients", "Phase", "Pneumonia", "Predisposition", "Property", "Protocols documentation", "Protons", "Quality of life", "Radiation", "Radiation exposure", "Relaxation", "Research", "Research Project Grants", "Signal Transduction", "Speed", "Spirometry", "System", "Techniques", "Technology Assessment", "Temperature", "Testing", "Tissues", "Toxic effect", "Ultrasonics", "Validation", "Water", "Work", "X-Ray Computed Tomography", "aerosolized", "biomaterial compatibility", "clinical implementation", "cohort", "cost", "cost effective", "density", "design and construction", "diagnostic value", "disease diagnostic", "flexibility", "imaging approach", "imaging modality", "implementation cost", "in vivo", "innovation", "lung imaging", "lung volume", "magnetic field", "microwave electromagnetic radiation", "novel", "novel diagnostics", "novel strategies", "open source", "particle", "portability", "programs", "pulmonary function", "pulmonary symptom", "soft tissue", "technology validation", "tool", "transmission process", "vaping", "vapor", "ventilation", "water vapor" ], "approved": true } }, { "type": "Grant", "id": "11662", "attributes": { "award_id": "5R01AA029081-02", "title": "COVID Impacts on Alcohol Use in Communities Affected by Repeated Disasters", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Alcohol Abuse and Alcoholism (NIAAA)" ], "program_reference_codes": [], "program_officials": [ { "id": 6068, "first_name": "I-Jen", "last_name": "Castle", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-03-01", "end_date": "2025-02-28", "award_amount": 545477, "principal_investigator": { "id": 2705, "first_name": "Lynsay", "last_name": "Ayer", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 515, "ror": "https://ror.org/00f2z7n96", "name": "RAND Corporation", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 515, "ror": "https://ror.org/00f2z7n96", "name": "RAND Corporation", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Summary/Abstract Excessive drinking is a major problem in the United States, particularly among coastal communities surrounding the Gulf of Mexico, where nearly one in four residents screen positive for alcohol misuse. Stressors related to the COVID-19 pandemic and associated response policies (e.g., stay-at-home orders, closure of schools and businesses) may have increased alcohol misuse particularly for those disproportionately affected by the pandemic and job loss, like racial/ethnic minorities and women. This proposal addresses the NIAAA priorities described in NOT-AA-20- 011, helping to lay groundwork for public health emergencies such as COVID-19. We plan to examine patterns and predictors of change in alcohol consumption in vulnerable Gulf Coast communities over the course of the pandemic, including as vaccines and new variants emerge and unemployment persists. Prospective studies are rare in disaster research, but the proposed study will address this gap by collecting two new waves of survey data from an existing, population representative cohort of 2,520 Gulf Coast residents we have been following since 2016 via the Survey of Trauma, Resilience, and Opportunity in Neighborhoods in the Gulf (STRONG). The new work will build on extensive baseline data about mental health, alcohol misuse, employment history, disaster exposure, and social resources. The proposed work also builds on our team's productive line of longitudinal studies of alcohol misuse, including studies examining interactions between individual- and community-level risk factors, the role of stress and trauma, co-occurrence of mental health symptoms, and psychosocial reactions to risks and disasters in the Gulf Coast region. Two factors unique to COVID-19 are massive increases in unemployment and growing feelings of loneliness caused by stay-at-home orders, both of which might change people's drinking behavior. Through two new survey waves we will: estimate the magnitude of changes in frequency and quantity of alcohol consumption following the onset of COVID-19; examine trajectories of change in alcohol misuse within individuals; identify pre-COVID-19 predictors of patterns of change (e.g., demographic characteristics, cumulative trauma exposure, co-occurring mental health symptoms); and determine whether COVID-19-related losses (i.e., unemployment, loneliness) predict change in alcohol use over time. Existing and new data will be mergeable via a common respondent identifiers and also be geocoded, providing a unique resource for public health research and response. Results from this study could significantly advance scientific knowledge and clinical practice for vulnerable Gulf Coast residents.", "keywords": [ "Address", "Adult", "Affect", "Age", "Alcohol consumption", "American", "Baseline Surveys", "Black race", "Businesses", "COVID-19", "COVID-19 outbreak", "COVID-19 pandemic", "Cessation of life", "Characteristics", "Communities", "Consumption", "Coping Skills", "Country", "County", "Data", "Data Collection", "Disasters", "Employment", "Ethnic Origin", "Event", "Feeling", "Florida", "Frequencies", "Future", "Heavy Drinking", "Hurricane", "Individual", "Job loss", "Knowledge", "Loneliness", "Longitudinal Studies", "Longitudinal Surveys", "Louisiana", "Marketing", "Mental Health", "Mexico", "National Institute on Alcohol Abuse and Alcoholism", "Neighborhoods", "Oils", "Participant", "Pattern", "Persons", "Policies", "Population", "Productivity", "Prospective Studies", "Race", "Reaction", "Recording of previous events", "Repetitive Sequence", "Reporting", "Research", "Resources", "Respondent", "Retrospective Studies", "Risk", "Risk Factors", "Role", "Sampling", "Scientific Advances and Accomplishments", "Stress", "Stretching", "Surveys", "Symptoms", "Technology", "Texas", "Time", "Trauma", "Unemployment", "United States", "Vaccinated", "Vaccination", "Vaccines", "Variant", "Woman", "Work", "adverse outcome", "alcohol misuse", "alcohol use disorder", "binge drinking", "clinical practice", "cohort", "coronavirus disease", "drinking", "drinking behavior", "epidemiology study", "ethnic minority", "experience", "gulf coast", "infection rate", "men", "pandemic disease", "post-COVID-19", "protective factors", "psychosocial", "public health emergency", "public health research", "racial minority", "resilience", "response", "risk mitigation", "school closure", "sex", "social", "stay-at-home order", "stressor", "trauma exposure" ], "approved": true } }, { "type": "Grant", "id": "11663", "attributes": { "award_id": "5U19AI167903-02", "title": "Systems biological assessment of B cell responses to vaccination", "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": [], "start_date": "2022-03-07", "end_date": "2027-02-28", "award_amount": 409240, "principal_investigator": { "id": 23528, "first_name": "Scott Dexter", "last_name": "Boyd", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 266, "ror": "https://ror.org/00f54p054", "name": "Stanford University", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 266, "ror": "https://ror.org/00f54p054", "name": "Stanford University", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "– Project 3 The focus of Project 3 is to study antigen-specific B cell and plasma cell responses in the context of two timely and fundamental topics in vaccinology: (i) Immunology of COVID-19 vaccines, and (ii) the impact of the microbiota on immune responses to vaccination. The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 (CoV-2), and the vaccines developed to combat this pathogen, have underscored a need for greater understanding of primary antibody responses in humans. We will use a systematic panel of cutting- edge humoral immunity analyses to thoroughly characterize antibodies elicited by two CoV-2 vaccines, and the B cell and plasma cell clonal populations required for B cell memory and sustained antibody titers. Our focus will be on the serological, B cell and plasma cell responses elicited by a lipid nanoparticle mRNA vaccine (Pfizer-BioNTech), and a Matrix M-adjuvanted recombinant protein vaccine (Novavax). Combining these analyses with studies of innate immunity (Project 1) and T cell (Project 2) responses to these vaccines should highlight cellular mechanisms correlated with the strength and durability of antibody responses. Rare serious anaphylactoid adverse reactions have been reported for mRNA vaccines, particularly in individuals with a history of food allergy, and those with IgG antibodies specific for polyethylene glycol (PEG). We will examine potential B cell contributions to these anaphylactoid reactions, using specimens from affected individuals who received SARS-COV-2 mRNA vaccines. Finally, we will address the role of the microbiome on humoral immunity to vaccination, with a similar strategy of serological, memory B cell and plasma cell analyses in participants with or without temporarily ablated microbiota following antibiotic treatment. Of particular importance in the aforementioned studies, we will not only analyze peripheral blood B cells and plasmablasts, but also monitor lymph node germinal center reactions by fine-needle aspiration, and sample bone marrow plasma cells in the same participants, to comprehensively study humoral immunity to vaccination in humans. The combined impact of these investigations will likely be clinically significant in guiding the development of future vaccination strategies by uncovering the B cell and plasma cell specificities, differentiation pathways, and longevity stimulated by new SARS-CoV-2 vaccine platforms, and in clarifying the role of the microbiome in vaccine responses to novel antigens.", "keywords": [ "2019-nCoV", "Ablation", "Acute", "Address", "Adjuvant", "Adverse reactions", "Affect", "Affinity", "Allergic", "Antibiotic Therapy", "Antibiotics", "Antibodies", "Antibody Response", "Antibody titer measurement", "Antigens", "Avidity", "B-Cell Antigen Receptor", "B-Lymphocytes", "B-cell receptor repertoire sequencing", "Basophils", "Binding", "Biological Assay", "Blood", "Bone Marrow", "COVID-19", "COVID-19 pandemic", "COVID-19 vaccine", "Cells", "Clinical", "Clone Cells", "Collaborations", "DNA", "Data Analyses", "Development", "Ensure", "Epitopes", "Fine needle aspiration biopsy", "Food Hypersensitivity", "Future", "Glycoproteins", "Human", "Humoral Immunities", "Immune response", "Immunity", "Immunoglobulin G", "Immunoglobulin M", "Immunology", "Individual", "Infection", "Investigation", "Label", "Longevity", "Measures", "Memory B-Lymphocyte", "Methods", "Monitor", "Monoclonal Antibodies", "Natural Immunity", "Participant", "Pathogenicity", "Pathway interactions", "Phenotype", "Plasma Cells", "Plasmablast", "Polyethylene Glycols", "Population", "RNA vaccination", "RNA vaccine", "Rabies", "Rabies Vaccines", "Reaction", "Recombinant Proteins", "Recording of previous events", "Reporting", "Role", "SARS-CoV-2 antigen", "Sampling", "Serology", "Shapes", "Specificity", "Specimen", "Structure of germinal center of lymph node", "T-Lymphocyte", "Vaccination", "Vaccinee", "Vaccines", "Variant", "Viral", "Virus", "Virus Diseases", "adaptive immunity", "biological systems", "clinically significant", "combat", "coronavirus disease", "data management", "in vitro Assay", "lipid nanoparticle", "lymph nodes", "microbiome", "microbiota", "monoclonal antibody production", "multiplex assay", "novel", "novel coronavirus", "pathogen", "peripheral blood", "recruit", "response", "transcriptome", "vaccination strategy", "vaccine development", "vaccine platform", "vaccine response", "vaccinology", "variants of concern" ], "approved": true } }, { "type": "Grant", "id": "11664", "attributes": { "award_id": "5K23AA029729-02", "title": "Developing a modified brief alcohol-focused intervention tailored for patients with alcohol use disorder in opioid agonist treatment", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Alcohol Abuse and Alcoholism (NIAAA)" ], "program_reference_codes": [], "program_officials": [ { "id": 22502, "first_name": "Mariela", "last_name": "Shirley", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-03-15", "end_date": "2027-02-28", "award_amount": 161808, "principal_investigator": { "id": 22503, "first_name": "Ryan W", "last_name": "Carpenter", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1503, "ror": "", "name": "UNIVERSITY OF MISSOURI-ST. LOUIS", "address": "", "city": "", "state": "MO", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1503, "ror": "", "name": "UNIVERSITY OF MISSOURI-ST. LOUIS", "address": "", "city": "", "state": "MO", "zip": "", "country": "United States", "approved": true }, "abstract": "7. Project Summary/Abstract This K23 Mentored Patient-Oriented Research Career Development Award involves complementary research and training plans to develop and then pilot a modified motivational enhancement therapy and cognitive behavioral therapy (MET-CBT) intervention tailored to target alcohol use in patients with alcohol use disorder (AUD) in opioid agonist treatment (OAT). Alcohol use is an under-recognized contributor to the opioid crisis, greatly increasing the risk of overdose when used together with opioids. Further, alcohol use and related problems are prevalent among patients in OAT and significantly increase the risk of opioid relapse and treatment dropout. Office-based buprenorphine treatment, a fast-growing form of OAT, is effective at treating opioid use disorder and decreasing risk of opioid overdose, but relapse rates are high in the first year of treatment. With nearly 130 individuals dying each day from an opioid overdose and evidence of recent increases in overdoses during the COVID-19 pandemic, there is an urgent need to increase treatment retention. Reducing alcohol use and use-related problems in patients receiving buprenorphine may have a significant indirect effect on improving buprenorphine outcomes. However, past randomized clinical trials (RCTs) have found no condition effect for brief alcohol-focused intervention for patients in OAT, despite considerable evidence that these interventions are generally effective at reducing alcohol use. Critically, past work examined standard alcohol interventions that were not tailored to individuals in OAT, suggesting that there are unique and significant challenges to alcohol intervention in patients receiving buprenorphine. This K23 project will first qualitatively interview patients with AUD in their first year of office-based buprenorphine treatment and buprenorphine providers to directly inform modifications to an existing MET-CBT protocol, tailoring the intervention to fit the needs and challenges of buprenorphine treatment. Following treatment development and refinement, 60 participants will be randomized to receive two MET-CBT sessions or treatment as usual in a proof-of-concept RCT. Key RCT outcomes will be the feasibility and acceptability of the modified MET-CBT intervention. Sustained benefit will also be evaluated at 1- and 3-month follow-ups in exploratory analyses. Through addressing AUD in people receiving OAT, this proposal is closely aligns with national priorities to improve OAT-related outcomes and to respond to the opioid overdose crisis.", "keywords": [ "Address", "Alcohol abuse", "Alcohol consumption", "Alcohols", "Attention", "Behavior Therapy", "Buprenorphine", "COVID-19 pandemic", "Clinic", "Cognitive Therapy", "Development", "Dropout", "Enrollment", "Feedback", "Focus Groups", "Goals", "Individual", "Intervention", "Intervention Studies", "Interview", "Knowledge", "Lead", "Letters", "Mentored Patient-Oriented Research Career Development Award", "Mentors", "Methods", "Modification", "Nurse Practitioners", "Opioid", "Outcome", "Overdose", "Participant", "Patient Self-Report", "Patients", "Persons", "Physicians", "Population", "Professional counselor", "Protocols documentation", "Provider", "Public Health", "Randomized", "Relapse", "Reporting", "Research", "Research Personnel", "Resources", "Risk", "Rural", "Sampling", "Specialist", "Structure", "Therapeutic Intervention", "Time", "Training", "Treatment outcome", "United States", "Variant", "Work", "acceptability and feasibility", "addiction", "alcohol intervention", "alcohol related problem", "alcohol use disorder", "buprenorphine treatment", "cost", "drinking", "effective therapy", "follow-up", "improved", "individualized medicine", "innovation", "intervention effect", "motivational enhancement therapy", "opioid agonist therapy", "opioid epidemic", "opioid overdose", "opioid use", "opioid use disorder", "overdose risk", "peer support", "randomized clinical trials", "recruit", "reduced alcohol use", "suburb", "theories", "therapy development", "treatment as usual", "treatment risk", "urban setting" ], "approved": true } }, { "type": "Grant", "id": "11665", "attributes": { "award_id": "5R21DA055427-02", "title": "A telehealth tDCS approach to decrease cannabis use: Towards reducing multiple sclerosis disability in multiple sclerosis", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Drug Abuse (NIDA)" ], "program_reference_codes": [], "program_officials": [ { "id": 22510, "first_name": "Aidan", "last_name": "Hampson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-03-15", "end_date": "2024-02-29", "award_amount": 208436, "principal_investigator": { "id": 22511, "first_name": "Leigh", "last_name": "Charvet", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 832, "ror": "", "name": "NEW YORK UNIVERSITY SCHOOL OF MEDICINE", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 27548, "first_name": "Giuseppina", "last_name": "Pilloni", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 832, "ror": "", "name": "NEW YORK UNIVERSITY SCHOOL OF MEDICINE", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Cannabis is used by up to half of the U.S. >1 million people living with the neurologic condition of multiple sclerosis (MS), which is the most common chronic and progressive CNS disease to affect adults of working age. Growing evidence shows that cannabis use actually worsens MS disability for many, and specifically contributes to the commonly (>75%) disabling feature of cognitive impairment. However, for the many patients seeking to reduce or discontinue their use, there are few if any accessible interventions available, leaving both clinicians and investigators to only counsel for its discontinuation. To meet this critical need, our expert team connects our extensive work in the use of noninvasive brain stimulation in MS to its established applications in the treatment of substance use disorders. Although the neural circuitry contributing to this cycle of addiction is well known, there are no neural circuit based therapeutics available for cannabis use disorder (CUD) treatment. We propose a novel and readily scalable approach that is highly accessible due to its telehealth delivery that allows all study procedures to be completed form home. Our innovative approach will use repeated sessions of transcranial direct current stimulation (tDCS) applied to the dorsolateral prefrontal cortex (DLPFC) as a target of negative affect that is identified as a key component in perpetuating disordered substance use. A core feature of Koob & Volkow’s 3-stage model of addiction, negative affect both results from disordered use and drives continued use. We therefore hypothesize that reducing distress in this context will lead to reduced cannabis use. We overcome a major limitation in the clinical evaluation of tDCS to date with our remote protocol, enabling access to treatment and providing extended treatments for adequate evaluation of its cumulative benefits. We will recruit a readily available sample of patients with MS and CUD, to evaluate 20 daily (M-F) sessions over one month, using RS-tDCS as a tool to decrease distress (Aim 1) and reduce cannabis use (Aim 2). As tDCS is ideally paired with a concurrent activity to increase benefit and to maintain consistent “brain state” to evaluate its effects, stimulation will be paired with guided mindfulness meditation. In the context of this evaluation, we will collect cognitive and symptomatic measures towards our ultimate objective of evaluating its effects on disease burden. We will collect follow-up outcomes at one-, two- and three-months post-intervention. Public Health Significance: We will pioneer our RS-tDCS telehealth intervention for individuals seeking to discontinue cannabis, evaluated in people living with MS and applicable across the many patients with chronic brain disorders for whom cannabis may contribute to their disability. With the COVID-19 pandemic driving unprecedented rates of substance use disorders, the need for scalable, remote therapeutics that can be coupled with telehealth behavioral techniques is even more critical.", "keywords": [ "Adult", "Adverse effects", "Affect", "Age", "Anxiety", "Assessment tool", "Automobile Driving", "Back", "Behavioral", "Brain", "Brain Diseases", "COVID-19", "COVID-19 pandemic", "Cannabis", "Central Nervous System Diseases", "Cephalic", "Chronic", "Cognitive", "Consumption", "Counseling", "Coupled", "Data", "Data Analyses", "Dependence", "Disease", "Distress", "Double-Blind Method", "Drug usage", "Electrodes", "Eligibility Determination", "Emotional", "Evaluation", "Functional Magnetic Resonance Imaging", "Future", "Goals", "Health Services Accessibility", "Health Status", "Home", "Impaired cognition", "Individual", "Interdisciplinary Study", "Intervention", "Joints", "Knowledge", "Left", "Linear Regressions", "Link", "Literature", "Marijuana", "Measures", "Mental Depression", "Modeling", "Multiple Sclerosis", "Neurobiology", "Neurologic", "Outcome", "Participant", "Patients", "Pattern", "Perception", "Persons", "Phase", "Prefrontal Cortex", "Procedures", "Process", "Protocols documentation", "Public Health", "Publications", "Questionnaires", "Randomized", "Regulation", "Research Personnel", "Rural Community", "Sampling", "Schedule", "Substance Use Disorder", "Supervision", "Symptoms", "Techniques", "Testing", "Therapeutic", "Time", "Urban Community", "Urine", "Work", "addiction", "behavioral health", "burden of illness", "cannabis withdrawal", "coping", "craving", "data integration", "disability", "efficacy evaluation", "executive function", "experience", "follow-up", "high reward", "high risk", "innovation", "marijuana use", "marijuana use disorder", "member", "mindfulness meditation", "multiple sclerosis patient", "negative affect", "negative emotional state", "neural circuit", "neuroregulation", "noninvasive brain stimulation", "novel", "post intervention", "psychological distress", "recruit", "reduce symptoms", "research clinical testing", "substance use treatment", "telehealth", "timeline", "tool", "video visit" ], "approved": true } }, { "type": "Grant", "id": "11666", "attributes": { "award_id": "5U01AI168634-02", "title": "Evolution of T cell immunity in blood and tissues over childhood", "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": 6621, "first_name": "Mercy R.", "last_name": "Prabhudas", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-03-16", "end_date": "2027-02-28", "award_amount": 807646, "principal_investigator": { "id": 7597, "first_name": "Donna L.", "last_name": "Farber", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 745, "ror": "", "name": "SCRIPPS RESEARCH INSTITUTE, THE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 781, "ror": "", "name": "COLUMBIA UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Immune system development during infancy and childhood sets the stage for a lifetime of protective immunity. Infants and children are known to be more susceptible to ubiquitous respiratory and mucosal pathogens for which adults have prior exposures. However, our recent experience in the COVID-19 pandemic, in which children were markedly less susceptible than adults to disease from infection with the novel respiratory virus SARS-CoV-2, indicate that children's immune systems can be highly effective to newly encountered pathogens. The diverse repertoire of naïve T cells, their ability to differentiate to tissue homing effector cells, which mediate pathogen clearance at infection sites, and the subsequent generation of long-lived memory T cells are critical events in immune responses that are not defined in children. Identifying the mechanisms by which T cells respond to antigenic challenges and establish immunological memory throughout infancy and childhood are essential for improving vaccines and immunotherapies to protect the next generation. My laboratory has been studying early life immunity in mouse models and novel human samples, including tissues from infant and pediatric organ donors, with a focus on how protective tissue resident memory T cells (TRM) become established in early life and mature over childhood. We pioneered the study of human tissue immunity in organ donor tissues, identifying that the majority of T cells across tissues in the body are TRM, which begin to form in early life in intestines and mature over age. We have identified fundamental and intrinsic differences in infant compared to adult T cells at the earliest stages in T cell activation and have investigated anti-viral immunity to SARS-CoV-2 in different pediatric cohorts. Our central hypothesis is that pediatric T cell responses are distinct due to intrinsic signaling mechanisms, the specific tissue environment, and the antigenic exposure history. In this study, we will build on our results, human samples, and cohorts to elucidate mechanisms for the distinct responses of pediatric T cells and their differentiation fate, maturation in tissues, and evolving response to vaccines. In aim 1, we will identify mechanisms for the distinct activation of pediatric naïve T cells, including how early events during T cell conjugate formation and cell division impact cell fate in early life and childhood for mouse and human T cells. In aim 2, we will elucidate TRM differentiation pathways and the role of the tissue in TRM maturation by high dimensional single cell profiling of human TRM in intestines and lungs across all ages of childhood, and use mouse models to address the role of persistence and tissue environment in TRM maturation. In aim 3, we will analyze vaccine-specific immune responses and evolution over childhood in established cohorts of children who previously had different clinical manifestations of SARS-CoV-2 infection, or were not infected. We will assess virus-specific T cell and antibody responses to the current COVID mRNA vaccines over time and age. Together, the proposed studies will comprehensively define immune system maturation over this critical and formative window of childhood.", "keywords": [ "2019-nCoV", "Address", "Adult", "Age", "Antibodies", "Antibody Response", "Antigen-Presenting Cells", "Antigens", "Blood", "Blood specimen", "COVID-19 pandemic", "COVID-19 vaccine", "Cell Maturation", "Cell division", "Cells", "Child", "Childhood", "Clinical", "Collaborations", "Development", "Disease", "Effector Cell", "Environment", "Event", "Evolution", "Exhibits", "Exposure to", "Gene Expression", "Gene Expression Profile", "Generations", "Genes", "Health", "Homing", "Human", "Immune", "Immune response", "Immune system", "Immunity", "Immunologic Memory", "Immunotherapy", "Individual", "Infant", "Infection", "Inflammatory", "Influenza", "Intestines", "Knowledge", "Laboratories", "Life", "Lung", "Mediating", "Modeling", "Molecular Profiling", "Mucous Membrane", "Multisystem Inflammatory Syndrome in Children", "Mus", "Nature", "Organ Donor", "Organ Procurements", "Pathway interactions", "Pediatric cohort", "Phenotype", "Population", "Predisposition", "Process", "Proliferating", "Property", "RNA vaccine", "Recording of previous events", "Role", "SARS-CoV-2 immunity", "SARS-CoV-2 infection", "Sampling", "Shapes", "Signal Transduction", "Site", "Syndrome", "Systems Development", "T cell differentiation", "T cell response", "T memory cell", "T-Cell Activation", "T-Cell Receptor", "T-Lymphocyte", "Time", "Tissue Donors", "Tissue Sample", "Tissues", "Vaccination", "Vaccines", "Virus", "adaptive immune response", "adaptive immunity", "antiviral immunity", "cohort", "coronavirus disease", "design", "experience", "high dimensionality", "human tissue", "immunological synapse", "improved", "infancy", "insight", "mouse model", "mucosal site", "next generation", "novel", "pathogen", "pathogenic virus", "pediatric patients", "prevent", "respiratory", "respiratory infection virus", "respiratory virus", "response", "tissue resident memory T cell", "transcriptome" ], "approved": true } }, { "type": "Grant", "id": "11667", "attributes": { "award_id": "5U19AI168631-02", "title": "Viral Immunity and VAccination (VIVA) Human Immunology Project Consortium (HIPC)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 8224, "first_name": "Kentner L.", "last_name": "Singleton", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-03-22", "end_date": "2027-02-28", "award_amount": 2265730, "principal_investigator": { "id": 21760, "first_name": "Ana", "last_name": "Fernandez-Sesma", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 625, "ror": "https://ror.org/04a9tmd77", "name": "Icahn School of Medicine at Mount Sinai", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 7185, "first_name": "Viviana A", "last_name": "Simon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 625, "ror": "https://ror.org/04a9tmd77", "name": "Icahn School of Medicine at Mount Sinai", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "The Viral Immunity and Vaccination (VIVA) Human Immunology Project Consortium (HIPC) will carry out a comprehensive systems immunology program to assess the dynamic human immune response to SARS-CoV- 2, seasonal influenza viruses and tetravalent and trivalent dengue vaccines and subsequent infections by those pathogens. It will generate comprehensive innate, cellular and adaptive immune signatures that correlate with vaccine outcomes. The VIVA HIPC will leverage recent advances in human immune profiling methods to characterize the diverse states of the human immune system before and after vaccination against these viral pathogens of great public health concern using novel immune phenotyping and genomics strategies that generate data and tools to be used for downstream data analysis and functional investigations. The proposed studies will use longitudinal biospecimens from established human cohorts of respiratory infections and vaccinations in the US and Argentina as well as from vaccine trials in the US (provided by the Clinical Core, Core B). In addition, validation experiments using human tonsils sourced from healthy individuals and exposed ex vivo to the different vaccine types will be conducted. Three complementary, well-integrated projects will produce in-depth human immune profiles and signatures of SARS-CoV-2 vaccinations and infections (Project 1), seasonal influenza vaccinations and infections (Project 2) as well as dengue vaccine and human challenge studies (Project 3). Unique in our approach is the use of longitudinal cohorts for in vivo profiling, supported by ex vivo human tonsillar histoculture (HC) models for infection and vaccination. Our holistic approach will provide cutting- responses to vaccinations and infections by the Immune Phenotyping Core (Core C), genomics/transcriptomics, including scRNAseq, CITEseq and spatial tissue transcriptomics by the Genomics Core (Core D), and experimental vaccinations in primary human tonsillar histocultures (HC) in Projects 1, 2 and 3. Data mining, bioinformatics to identify the network components and infer their interactions and correlations important for vaccine outcomes will be done by the Data management and Analysis Core (Core E). The VIVA HIPC will make the data, analyses and immune profiles generated available to the scientific community by coupling our local data infrastructure to ImmPort (directly or through the HIPC Coordinating Center). This integration will ensure full and timely release of clinical, sample, and experimental metadata in synchrony with genomic data releases to standard data repositories including SRA, GEO, and Genbank (Core E). The VIVA team (Drs. Krammer, Garcia-Sastre, Durbin, Gamarnik, van Bakel and Sebra) led by Dr. Fernandez-Sesma and Dr. Simon includes physicians, physician scientists and scientists with complementary expertise in viral immunology, viral pathogenesis, vaccinology, genomics, data analysis and a proven track record of collaboration and excellence.", "keywords": [ "2019-nCoV", "Area", "Argentina", "Bioinformatics", "Biological Assay", "Biological Models", "COVID-19 vaccination", "COVID-19 vaccine", "Cells", "Cellular Indexing of Transcriptomes and Epitopes by Sequencing", "Characteristics", "Classification", "Clinical", "Clinical Trials", "Collaborations", "Communicable Diseases", "Communities", "Coupling", "Cryopreserved Cell", "Data", "Data Analyses", "Data Set", "Dengue", "Dengue Vaccine", "Dengue Virus", "Development", "Differentiation Antigens", "Ensure", "Enzyme-Linked Immunosorbent Assay", "Epidemic", "Flow Cytometry", "Foundations", "Frequencies", "Genbank", "Generations", "Genes", "Genomic approach", "Genomics", "Goals", "Human", "Immune", "Immune response", "Immune system", "Immunity", "Immunization", "Immunoglobulins", "Immunologic Memory", "Immunologics", "Immunology", "Individual", "Infection", "Influenza A virus", "Influenza B Virus", "Influenza vaccination", "Innate Immune Response", "Investigation", "Learning", "Longitudinal cohort", "Lymphoid Tissue", "Maintenance", "Maps", "Measures", "Mediating", "Metadata", "Methods", "Modeling", "Morbidity - disease rate", "Pathway interactions", "Peripheral Blood Mononuclear Cell", "Phenotype", "Physicians", "Physiological", "Plasma", "Population", "Population Characteristics", "Prevention strategy", "Public Health", "Qualifying", "Research Personnel", "Respiratory Tract Infections", "SARS coronavirus", "Sampling", "Scientist", "Seasons", "Serology", "Serotyping", "Source", "Standardization", "System", "Techniques", "Technology", "Testing", "Tissues", "Tonsil", "Vaccinated", "Vaccination", "Vaccinee", "Vaccines", "Validation", "Viral", "Viral Antigens", "Viral Pathogenesis", "Virus", "Virus Diseases", "World Health", "adaptive immune response", "adaptive immunity", "cell type", "cohort", "data infrastructure", "data management", "data mining", "data repository", "data standards", "experimental study", "genomic data", "holistic approach", "human disease", "immunological status", "in vivo", "influenza infection", "influenzavirus", "live attenuated influenza vaccine", "mortality", "mosquito-borne", "network models", "next generation", "novel", "pandemic disease", "pathogen", "pathogenic virus", "phenotypic data", "predictive modeling", "programs", "response", "seasonal influenza", "sequencing platform", "tool", "transcriptomics", "vaccination outcome", "vaccine candidate", "vaccine immuno" ], "approved": true } }, { "type": "Grant", "id": "11668", "attributes": { "award_id": "5U19AI168631-02", "title": "Immune Phenotyping Core", "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": [], "start_date": "2022-03-22", "end_date": "2027-02-28", "award_amount": 522189, "principal_investigator": { "id": 21760, "first_name": "Ana", "last_name": "Fernandez-Sesma", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 625, "ror": "https://ror.org/04a9tmd77", "name": "Icahn School of Medicine at Mount Sinai", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 625, "ror": "https://ror.org/04a9tmd77", "name": "Icahn School of Medicine at Mount Sinai", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "The goal of the Immune Phenotyping Core (Core C) is to provide tools and reagents to the different projects that will be used to characterize the immune responses induced by vaccinations and infections with coronaviruses, influenza viruses and dengue viruses. The Core will leverage existing state-of-the-art serological techniques established in the Krammer laboratory, as well as multiplex analysis of cytokine and chemokine plasma profile and Cytek Aurora Spectral Flow Cytometry profiling of PBMCs and human tonsillar histocultures (HC) currently used and optimized in the Fernandez-Sesma laboratory. The following aims re proposed: Aim 1: Characterization of antibody responses to coronavirus, influenza virus and dengue virus vaccination and infection. The Core will provide assays, reagents and protocols to measure binding and functional antibody responses against SARS-CoV-2 for Project 1 and influenza viruses for Project 2. Additionally, the secretion of IgM, IgG and IgA in the supernatant of human tonsil histocultures (HC) treated with the different SARS-CoV-2 vaccines types (Project 1), influenza virus vaccines and viruses (Project 2) will be assessed. Aim 2: Characterization of cytokine/chemokine responses to coronavirus, influenza virus and dengue virus vaccination and infection. The Core will analyze the levels of cytokines and chemokines in the plasma of vaccinated/infected individuals and the supernatant of human tonsil histocultures treated with different vaccines for Projects 1, 2 and 3. Aim 3: Characterization of cellular responses to coronavirus, influenza virus and dengue virus vaccination and infection. Analysis of the cellular immune profiles of PBMCs from vaccinated/infected individuals over time, using Spectral Flow cytometry. Human tonsillar HC will be also analyzed by Cytek Aurora Spectral Flow Cytometry in order to capture early immune signatures and changes in cell populations corresponding to adaptive immune responses in those HC after treatment with different vaccines. We will obtain high-resolution data at the single-cell level to resolve the most challenging cell populations including cells expressing viral antigens. PBMCs will also be subjected to a complementary transcriptomics analysis by RNAseq conducted by the Genomics Core. These tools will serve to generate immune signatures representative of the longitudinal immune responses to vaccination and/or infection in study participants enrolled in observational non-interventional cohort studies in coordination with the Data Management and Analysis Core (Core E). Data obtained using these immunological techniques will be analyzed by the Data management and Analysis Core comparing them across the different systems used in the projects as well as in combination with the genomic data obtained in the Genomics Core (Core D) from the same samples. All data generated by the VIVA Projects and Cores, including the Immune Phenotyping Core, will be deposited by the Data Analysis Core into ImmPort.", "keywords": [ "2019-nCoV", "Aftercare", "Antibody Response", "Assessment tool", "Binding", "Biological Assay", "COVID-19 vaccine", "Cells", "Clinical", "Cohort Studies", "Collaborations", "Coronavirus", "Data", "Data Analyses", "Data Set", "Dengue Virus", "Deposition", "Enzyme-Linked Immunosorbent Assay", "Flow Cytometry", "Genomics", "Goals", "Human", "Immune", "Immune response", "Immunity", "Immunoglobulin A", "Immunoglobulin G", "Immunoglobulin M", "Immunologic Techniques", "Immunology", "Individual", "Infection", "Laboratories", "Letters", "Measures", "Mission", "Peripheral Blood Mononuclear Cell", "Phenotype", "Plasma", "Population", "Process", "Protocols documentation", "Reagent", "Resolution", "Sampling", "Serology", "Serum", "Services", "Standardization", "System", "Techniques", "Testing", "Time", "Tonsil", "Vaccinated", "Vaccination", "Vaccinee", "Vaccines", "Viral", "Viral Antigens", "Virus", "adaptive immune response", "base", "chemokine", "cytokine", "data management", "genomic data", "influenza virus vaccine", "influenzavirus", "instrument", "participant enrollment", "response", "tool", "transcriptome sequencing", "transcriptomics" ], "approved": true } }, { "type": "Grant", "id": "11669", "attributes": { "award_id": "5R01AI162684-02", "title": "Role of IRE1 Alpha in Coronavirus Infections", "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": 26420, "first_name": "MARY KATHERINE", "last_name": "Bradford", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-03-11", "end_date": "2027-02-28", "award_amount": 544713, "principal_investigator": { "id": 6427, "first_name": "Susan Leilani", "last_name": "Fink", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a recently emergent, currently pandemic virus and etiological agent of Coronavirus Induced Disease-19 (COVID-19). Despite a flood of scientific investigation, critical gaps remain in our understanding of the basic cellular processes that facilitate replication of coronaviruses, including SARS-CoV-2, and contribute to the pathogenesis of severe disease. Our preliminary data demonstrate that IRE1α, a component of the cellular response to endoplasmic reticulum (ER) stress, is required for SARS-CoV-2 replication and inflammatory cytokine responses. However, the stage(s) of the viral life cycle and downstream cellular pathways that mediate these effects remain completely unknown. ER stress and IRE1α activation are well-associated with conditions such as obesity, diabetes, hypertension, and aging, all of which are risk factors for severe manifestations of COVID-19. We hypothesize that comorbidity-associated ER stress primes both exuberant viral replication and pathogenic inflammatory cytokine production via IRE1α. This project leverages our unique ability to test this hypothesis using cell culture infection models, as well as specimens from patients with COVID-19. IRE1α inhibitors are under evaluation for treatment of non-infectious human diseases, and we propose that this project will provide preclinical evidence for the novel application of these drugs to treat infections with SARS-CoV-2 and potentially other human coronaviruses. The experiments outlined in this proposal will determine the molecular mechanism(s) by which IRE1α supports SARS-CoV-2 infection. IRE1α is a nuclease which initiates nonconventional splicing of XBP1 mRNA, which encodes a pleiotropic transcription factor. IRE1α also targets other specific RNAs leading to their degradation. We will determine whether the requirement for IRE1α is XBP1-dependent or -independent and dissect the downstream cellular processes that facilitate SARS-CoV-2 replication and inflammatory cytokine responses (Aim 1). We will systematically identify stage(s) of the SARS-CoV-2 life cycle that require IRE1α (Aim 2). We predict that IRE1α most likely supports biogenesis of ER-derived viral replication platforms, and will focus experiments on this hypothesis. We predict that IRE1α represents a target for dual anti-viral and anti- inflammatory therapy and will test this in mouse models of SARS-CoV-2 infection (Aim 3). Finally, we will determine whether IRE1α activation occurs during human infection and ER stress is a prognostic marker for severe COVID-19. Together, the results of this project will reveal basic cellular processes occurring during coronavirus infection and host factors critical for the pathogenesis of COVID-19. .", "keywords": [ "2019-nCoV", "Affect", "Aging", "Anti-Inflammatory Agents", "Biogenesis", "COVID-19", "COVID-19 pathogenesis", "COVID-19 patient", "COVID-19 risk", "Cell Culture Techniques", "Cell physiology", "Clinical", "Coronavirus", "Coronavirus Infections", "Data", "Diabetes Mellitus", "Disease", "Endoplasmic Reticulum", "Etiology", "Evaluation", "Floods", "Future", "Genetic", "Human", "Hypertension", "Infection", "Inflammation", "Inflammatory", "Inflammatory Response", "Inflammatory Response Pathway", "Integration Host Factors", "Investigation", "Life Cycle Stages", "Mediating", "Medical", "Membrane Fusion", "Messenger RNA", "Modeling", "Molecular", "Molecular Virology", "Obesity", "Pathogenesis", "Pathogenicity", "Pathway interactions", "Pharmaceutical Preparations", "Play", "Prediction of Response to Therapy", "Process", "Production", "Prognostic Marker", "Protein Biosynthesis", "Proteins", "RNA", "RNA Splicing", "RNA replication", "Risk Factors", "Role", "SARS-CoV-2 infection", "Severity of illness", "Specificity", "Specimen", "Testing", "Therapeutic Effect", "Viral", "Virion", "Virus Diseases", "Virus Replication", "Work", "XBP1 gene", "biological adaptation to stress", "cell type", "chemical genetics", "comorbidity", "current pandemic", "cytokine", "endoplasmic reticulum stress", "experience", "experimental study", "gene induction", "genetic approach", "human coronavirus", "human disease", "in vivo", "inhibitor", "insight", "mouse model", "novel", "nuclease", "pandemic virus", "pre-clinical", "response", "severe COVID-19", "therapeutic target", "tool", "transcription factor", "virology" ], "approved": true } }, { "type": "Grant", "id": "11670", "attributes": { "award_id": "5R21AI167648-02", "title": "Evaluation of the Impact of HIV Status on the Immune Response to mRNA COVID-19 Vaccines", "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": 22685, "first_name": "Diane M.", "last_name": "Lawrence", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-03-01", "end_date": "2024-02-29", "award_amount": 242250, "principal_investigator": { "id": 10026, "first_name": "Monica", "last_name": "Gandhi", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 768, "ror": "https://ror.org/043mz5j54", "name": "University of California, San Francisco", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 10027, "first_name": "Matthew A.", "last_name": "Spinelli", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 768, "ror": "https://ror.org/043mz5j54", "name": "University of California, San Francisco", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "PROJECT SUMMARY/ ABSTRACT At this point in the COVID-19 pandemic, with vaccine roll-out ongoing, one of the most urgent questions facing people living with HIV (PLWH) and their providers is whether HIV modulates the immune response to and subsequent effectiveness of the SARS-CoV-2 vaccines. Unfortunately, phase 3 trials for all three of the U.S.-authorized vaccines did not report HIV specific data and/or did not include enough PLWH to examine the impact of HIV infection on vaccine efficacy. PLWH might plausibly experience a less durable SARS-CoV-2 specific neutralizing antibody (NAb) response to a SARS-CoV-2 vaccine, as has been seen in response to vaccines for other infections. This lack of durable NAb responses may be mediated by inflammatory state of HIV infection that persists despite adequate suppressive antiretroviral therapy (ART), T cell exhaustion, and/or lower CD4/CD8 ratios. Our preliminary work in the UCSF Long-term Impact of Infection with Novel Coronavirus (LIINC) COVID-19 recovery study has demonstrated waning antibody responses but stable CD4+ and CD8+ T cell responses among HIV-negative individuals recovering from natural SARS-CoV-2 infection. However, surrogate virus neutralization titers and IgG concentrations were lower among PLWH compared to adults without HIV following mRNA vaccination, raising concerns that PLWH might have a diminished humoral response to vaccination. Whether PLWH mount less durable humoral and cell-mediated immune responses to COVID-19 vaccines than those without HIV is largely unknown, including the mechanisms of these differences, although this information could inform clinical strategies, including additional boosters or safety measures after vaccination. This proposal will answer two vital questions about the response to vaccination among PLWH. Aim 1 will provide novel, urgently needed insights into how the SARS-CoV-2 neutralizing antibody response to a cultured B.1.617.2 (delta) variant, IgG concentration, and antibody magnitude and durability could differ by HIV status over time following mRNA-based SARS-CoV-2 vaccination, including following boosters. Aim 2 will examine T cell memory responses and germinal center development generated by mRNA-based SARS-CoV-2 vaccination among PLWH compared to those without HIV out to a year following vaccination. Harnessing, the research infrastructure of the UCSF CFAR, the LIINC study, and a large, aging population of PLWH served by the Ward 86 clinic, this analysis will leverage an ongoing cohort to address whether PLWH mount attenuated immune responses to COVID-19 vaccines. 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