Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1384&sort=end_date
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=end_date", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=end_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1385&sort=end_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1383&sort=end_date" }, "data": [ { "type": "Grant", "id": "14582", "attributes": { "award_id": "1U01AI172800-01A1", "title": "A Phase 1/2a, randomized study of a Tfh-targeting genetic vaccine adjuvant designed to induce broad, durable immune responses", "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": 6243, "first_name": "BROOKE ALLISON", "last_name": "Bozick", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-05-07", "end_date": "2029-04-30", "award_amount": 1435214, "principal_investigator": { "id": 31244, "first_name": "Kara W", "last_name": "Chew", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 31245, "first_name": "STEVEN Grant", "last_name": "DEEKS", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 31246, "first_name": "DENNIS J.", "last_name": "HARTIGAN-O'CONNOR", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 818, "ror": "", "name": "UNIVERSITY OF CALIFORNIA LOS ANGELES", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "This U01-supported clinical trial will test a unique T follicular helper (Tfh)-targeting vaccine approach, “s3”, that we predict will generate exceptionally broad and long-lived antigen-specific antibody responses, characteristics likely to result in resilient vaccines that maintain protection over long periods. The “s3” adjuvant moiety is an anti- CD3 antibody fragment (scFv) that safely induces a potent Tfh and B-cell response to an immunogen to which it is fused. The combined immunogen simultaneously targets immunogen-specific B cells and local Tfh cells, thus accelerating and expanding B-cell development. Using the RBD immunogen in a low dose Ad35 vector, we showed in macaques that s3 safely stimulates high NAb titers that are stable for >10 months. The major deficiencies of current SARS-COV-2 and other vaccines (such as influenza) are limited durability and breadth of protection, even with booster vaccination. Over the course of 6 months, serum antibodies in COVID- naïve vaccine recipients decline by one order of magnitude. Booster vaccination confers greater durability but notable declines in serum NAb titers occur by 4-6 months. Limited mucosal IgA responses is another major deficit that may underlie failure of current vaccine options to prevent acquisition at the site of virus entry. Finally, the breadth of responses is limited, even with bivalent vaccines. These vaccine deficiencies have been linked repeatedly to inadequate T-cell help. Thus, new approaches that provide abundant T-cell help, such as the proposed s3 approach, are needed to deliver more effective SARS-CoV-2 as well as pancoronavirus, influenza, and other vaccines. We will test the safety and immunogenicity of the s3 adjuvant using Ad35 as the vector and the SARS-CoV-2 BA.5 receptor-binding domain (RBD) as the immunogen. We will compare a vaccine with s3 (CoTend-s3B) against one lacking s3 (CoTend-B). The vaccines will be given as a “booster” vaccine on the background of prior SARS-CoV-2 spike mRNA vaccination. This approach will allow us to evaluate the ability of CoTend-s3B to (i) boost pre-existing antibodies and (ii) recruit new naïve B cells with new specificity for BA.5 RBD. Aim 1. Test safety of s3-adjuvanted/Tfh-targeted (CoTend-s3B) and unadjuvanted (CoTend-B) SARS- CoV-2 RBD vaccines. The primary safety readouts are local and systemic reactions, grade 3+ adverse events (AEs), serious adverse events, AEs of special interest (including thrombotic events), and anti-PF4 antibodies. Aim 2. Evaluate intensity, breadth, and durability of adaptive immune responses to CoTend-s3B compared to CoTend-B in blood and saliva. We hypothesize that Tfh responses to CoTend-s3B will support NAb responses of sufficient breadth and potency for long-lived protection against SARS-CoV-2 variants. Aim 3. Examine the mechanisms of s3 adjuvant activity in germinal centers. Tfh targeting via s3 is predicted to generate robust germinal-center reactions that democratize recruitment of naïve B cells and spur development of long-lived plasma cells.", "keywords": [ "2019-nCoV", "Acceleration", "Address", "Adenoviruses", "Adjuvant", "Adverse event", "Antibodies", "Antibody Response", "Antibody titer measurement", "Antigens", "B Cell Proliferation", "B-Cell Development", "B-Lymphocytes", "Blood", "CD3 Antigens", "COVID-19", "COVID-19 vaccine", "Characteristics", "Chimeric Proteins", "Clinical Trials", "Democracy", "Development", "Disease", "Dose", "Economics", "Elderly", "Event", "FDA approved", "Failure", "Future", "Grant", "Health system", "Helper-Inducer T-Lymphocyte", "Human", "Immune response", "Immunization", "Immunoglobulin A", "Immunoglobulin Class Switching", "Immunoglobulin Fragments", "Immunology", "Individual", "Infection", "Infection prevention", "Inflammatory", "Influenza", "Knowledge", "Link", "Macaca", "Monoclonal Antibody HuM291", "Mucous Membrane", "Participant", "Pathway interactions", "Phase", "Plasma Cells", "Population", "Public Health", "RNA vaccination", "RNA vaccine", "Randomized", "Reaction", "Role", "SARS-CoV-2 spike protein", "SARS-CoV-2 variant", "Safety", "Saliva", "Sampling", "Secondary Immunization", "Series", "Serious Adverse Event", "Serum", "Site", "Special Event", "Specificity", "Structure of germinal center of lymph node", "System", "T cell response", "T-Lymphocyte", "Technology", "Testing", "Vaccine Adjuvant", "Vaccines", "Virus", "adaptive immune response", "antigen-specific T cells", "booster vaccine", "design", "draining lymph node", "genetic vaccine", "immunogenicity", "improved", "interest", "neutralizing antibody", "nonhuman primate", "novel", "novel strategies", "novel vaccines", "pandemic disease", "pathogen", "peripheral blood", "post SARS-CoV-2 infection", "prevent", "receptor binding", "recruit", "resilience", "response", "safety testing", "secondary endpoint", "success", "thrombotic", "tool", "transmission process", "vaccine development", "vaccine failure", "vaccine response", "vaccine strategy", "vaccinology", "vector" ], "approved": true } }, { "type": "Grant", "id": "14586", "attributes": { "award_id": "1R01NS136683-01", "title": "Therapeutic Electrical Stimulation Using Wireless, Resorbable Implants to Accelerate Diaphragm Muscle Reinnervation after Phrenic Neuropathy", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Neurological Disorders and Stroke (NINDS)" ], "program_reference_codes": [], "program_officials": [ { "id": 24007, "first_name": "LINDA LOUISE", "last_name": "Bambrick", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-05-15", "end_date": "2029-04-30", "award_amount": 680366, "principal_investigator": { "id": 31251, "first_name": "Colin", "last_name": "Franz", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1086, "ror": "", "name": "REHABILITATION INSTITUTE OF CHICAGO D/B/A SHIRLEY RYAN ABILITYLAB", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "Project Abstract: Phrenic Neuropathy, a condition that impairs diaphragm muscle function, often leads to serious respiratory problems and requires mechanical ventilation. Our research proposal aims to enhance recovery from this condition through a novel Therapeutic Electrical Stimulation protocol, in conjunction with a custom-made, wireless, bioresorbable implant. Informed by a rising incidence of Phrenic Neuropathy due to complications from severe COVID-19 and greater diagnostic capabilities and other factors, this proposal is the result of collaboration among a multidisciplinary team with substantial expertise in all aspects of this proposed work. In general, there is a common misconception that recovery from peripheral axon injury is usually good, due to the fact there is some spontaneous axon regeneration, but this does not match the reality that recovery is actually slow and incomplete for approximately 90% of patients. This is also true for patients with Phrenic Neuropathy. Our data and others show that 68-96% of these patients have incomplete or no functional recovery of the diaphragm muscle. Despite varying causes of Phrenic Neuropathy, its impact on respiratory function and individual quality of life is significant. At its worst, people with Phrenic Neuropathy may require mechanical ventilation, but more typically they are severely limited in their ability to engage in routine exertion required for activities of daily life. Currently, clinical and surgical approaches do not sufficiently address the issue of slow axon regrowth. Our project aims to rectify this by developing a Therapeutic Electrical Stimulation protocol that can restore diaphragm muscle innervation and function faster and more completely than ever before. Briefly, our approach is focused on three specific aims: 1) determining if repeated Therapeutic Electrical Stimulation sessions are more effective than a single session, 2) assessing if repeated sessions enhance brain-derived neurotrophic factor-TrkB signaling more than a single session or control, and 3) establishing how essential brain-derived neurotrophic factor-TrkB signaling is to the effects of Therapeutic Electrical Stimulation treatment. We aim to deliver a new therapeutic electrical stimulation paradigm to accelerate diaphragm muscle innervation and improve functional outcomes after Phrenic Neuropathy, providing new insights into the underlying mechanism of how brain-derived neurotrophic factor-TrkB signaling can enhance muscle reinnervation. The prior success of clinical translation from rat model to human clinical trials for Therapeutic Electrical Stimulation to treat other nerve injuries implies a great opportunity to move quickly towards clinical translation upon the successful completion of these aims.", "keywords": [ "Acceleration", "Acute", "Address", "Admission activity", "Alleles", "Axon", "Back", "Brain-Derived Neurotrophic Factor", "Breathing", "CREB1 gene", "Clinic", "Clinical", "Clinical Trials", "Collaborations", "Complex", "Custom", "Data", "Diagnostic tests", "Dose", "Effectiveness", "Electric Stimulation", "Electric Stimulation Therapy", "Electrophysiology (science)", "Exertion", "Frequencies", "Genes", "Growth", "Head and Neck Neoplasms", "Hindlimb", "Hospitals", "Hour", "Human", "Impairment", "Implant", "In Situ Hybridization", "Incidence", "Individual", "Knock-in", "Length", "Life", "Link", "Measurement", "Mechanical ventilation", "Methods", "Modeling", "Motor Neurons", "Muscle", "Muscle Fibers", "Muscle function", "Natural regeneration", "Nature", "Nerve", "Neuromuscular Junction", "Neuromuscular conditions", "Neurons", "Neuropathy", "Neurotrophic Tyrosine Kinase Receptor Type 2", "Operative Surgical Procedures", "Outcome", "Patients", "Performance", "Peripheral", "Persons", "Phosphorylation", "Phosphotransferases", "Placebos", "Protocols documentation", "Public Health", "Quality of life", "Randomized Controlled Trials", "Rat Transgene", "Rattus", "Recovery", "Recovery of Function", "Reporting", "Research", "Research Proposals", "Respiratory Diaphragm", "Respiratory Failure", "Respiratory physiology", "Rodent", "SARS-CoV-2 infection", "Safety", "Shortness of Breath", "Signal Transduction", "Speed", "Structure of phrenic nerve", "Surgeon", "Symptoms", "Testing", "Therapeutic Effect", "Therapeutic Uses", "Translating", "Trauma", "Up-Regulation", "Western Blotting", "Work", "activating transcription factor 1", "axon injury", "axon regeneration", "clinical implementation", "clinical translation", "clinically relevant", "design", "diagnostic value", "disability", "experimental study", "functional improvement", "gain of function", "improved", "insight", "loss of function", "mRNA Expression", "multidisciplinary", "muscle reinnervation", "nerve injury", "nerve repair", "nerve supply", "novel", "novel therapeutics", "peripheral nerve repair", "pressure", "reconstruction", "reinnervation", "repaired", "respiratory", "sciatic nerve", "sciatic nerve injury", "severe COVID-19", "success", "ultrasound", "wireless" ], "approved": true } }, { "type": "Grant", "id": "14595", "attributes": { "award_id": "1R01CA288403-01", "title": "Decoupling acute toxicities and antitumor efficacy in adoptive cell therapy", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Cancer Institute (NCI)" ], "program_reference_codes": [], "program_officials": [ { "id": 22844, "first_name": "MONICA", "last_name": "Zamisch", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-05-01", "end_date": "2029-04-30", "award_amount": 600313, "principal_investigator": { "id": 31261, "first_name": "Yong", "last_name": "Lu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1455, "ror": "", "name": "METHODIST HOSPITAL RESEARCH INSTITUTE", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Adoptive cell therapy (ACT) with chimeric antigen receptor (CAR) T cells has demonstrated impressive response rates in B cell malignancies, but ACT has not mediated sustained responses in solid tumors. CD19 CAR T cell therapy has reached up to 80% response rate in the clinic; however, the main side effects are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which occur in 37–83% and about 25-35% of patients, respectively. Furthermore, one of the major obstacles in ACT is the heterogeneity of targeted antigens and relapse due to antigen escape. Recently, we screened a cohort of 16 FDA-approved anti-inflammatory drugs and identified clofazimine (CLF) as the top candidate for its desired bifunctional effect for anti-CRS/ICANS and anti-antigen escape roles. Aim 1 will determine the role of CLF in reducing macrophage-derived ROS to curtail CRS/ICANS. Aim 2 will determine the role of CLF in driving dsRNA/dsDNA signals in macrophages for the eradication of tumors. We expect this study to demonstrate the ability of CLF in potentiating the anti-antigen escape capacity in ACT, curbing intractable CRS, and may also fill a desperate clinical need to improve the dismal patient survival with ICANS. This strategy of repurposing the clinically approved CLF may hold great promise to overcome a critical obstacle in realizing the full potential of ACT with CAR-T cells. This translationally relevant work could then lay the foundation for future clinical trials.", "keywords": [ "Adoptive Cell Transfers", "Adoptive Immunotherapy", "Anti-Inflammatory Agents", "Antigen Targeting", "Antigens", "Aryl Hydrocarbon Receptor", "Automobile Driving", "B lymphoid malignancy", "CAR T cell therapy", "CD19 gene", "Cessation of life", "Chronic", "Clinic", "Clinical", "Clinical Management", "Clinical Trials", "Coculture Techniques", "Disease", "Dose", "Double-Stranded RNA", "Effector Cell", "Event", "FDA approved", "Foundations", "Future", "Heterogeneity", "Human", "Immune", "Immune response", "Inflammatory", "Interferon alpha", "Interleukin-1", "Interleukin-6", "Leprosy", "Leukocytes", "Literature", "Lymphoma", "Macrophage", "Malignant Neoplasms", "Malignant neoplasm of ovary", "Mechanics", "Modeling", "Monoclonal Antibodies", "Mus", "NADPH Oxidase", "NF-kappa B", "Neurotoxicity Syndromes", "Pathway interactions", "Patients", "Pharmaceutical Preparations", "Prevention", "Production", "RNA Interference", "Reactive Oxygen Species", "Receptor Signaling", "Recurrence", "Relapse", "Reporting", "Role", "SKOV3 cells", "Signal Transduction", "Solid Neoplasm", "T-Lymphocyte", "Testing", "Therapeutic", "Toxic effect", "Tumor Antigens", "Tumor Immunity", "Up-Regulation", "Work", "acute toxicity", "anti-tumor immune response", "chimeric antigen receptor", "chimeric antigen receptor T cells", "chronic graft versus host disease", "cohort", "complement C2a", "cytokine", "cytokine release syndrome", "ds-DNA", "improved", "in vivo", "mortality", "neoplastic cell", "novel", "patient derived xenograft model", "prevent", "programs", "response", "screening", "side effect", "tocilizumab", "tumor", "tumor eradication", "tumor xenograft" ], "approved": true } }, { "type": "Grant", "id": "14599", "attributes": { "award_id": "1R01NS135147-01A1", "title": "Nosocomial pneumonia impairs the cerebrovasculature", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Neurological Disorders and Stroke (NINDS)" ], "program_reference_codes": [], "program_officials": [ { "id": 10021, "first_name": "RODERICK A", "last_name": "CORRIVEAU", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-05-16", "end_date": "2029-04-30", "award_amount": 546966, "principal_investigator": { "id": 31272, "first_name": "Amy R", "last_name": "Nelson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 615, "ror": "https://ror.org/01s7b5y08", "name": "University of South Alabama", "address": "", "city": "", "state": "AL", "zip": "", "country": "United States", "approved": true }, "abstract": "Postoperative pneumonia occurs in ~2-8% of patients following various surgeries and increases the length of hospital stay and mortality. Pneumonia is a common cause of sepsis. Some pneumonia survivors, including those with post-intensive care unit syndrome, suffer from cognitive deficits, reducing their quality of life and inflicting healthcare and financial hardships. Strikingly, pneumonia-associated microorganisms (e.g., P. aeruginosa) trigger lung endothelial production and release of several cytotoxic amyloids (e.g., tau and Aβ) that are key pathological hallmarks of dementia. Cytotoxic tau produced by lung endothelial cells in response to bacterial pneumonia infection accumulates in the brain, reduces dendritic spine density, impairs learning and memory, and causes neuronal tauopathy. We recently found that P. aeruginosa infection causes blood-brain barrier breakdown and gliosis. There is growing appreciation and strong evidence that neurovascular uncoupling, cerebral blood flow reductions and dysregulation, and breakdown of the blood-brain barrier, including the loss of pericytes, are early events leading to cognitive decline and dementia, including in the setting of pneumonia and infections. Apolipoprotein (APOE)-ε4 is the greatest genetic risk factor for sporadic dementia, increases infection severity (e.g., SARS-CoV-2) and promotes blood-brain barrier damage and pericyte degeneration. Whether pneumonia-elicited lung endothelial cytotoxic tau variants initiate blood-brain barrier breakdown to induce neurovascular unit dysfunction (e.g., pericyte injury, gliosis, and impaired hemodynamics), and whether APOE- ε4-induced neurovascular unit dysfunction exacerbates the negative impact of lung endothelial tau on the brain remains to be determined and are the focus of this study. Using state-of-the-art methodologies, this proposal innovatively uses 1) fast-speed, high-resolution two-photon intravital microscopy, 2) quantitative tau and neurovascular unit plasma assays, 3) pathological assessment of lung tau and neurovascular unit dysfunction in post-mortem human tissue, 4) lung endothelium targeted mice and adeno-associated viruses, and 5) anti-tau antibodies. This proposal tests the scientifically supported and novel hypotheses that 1) lung endothelial tau disrupts the neurovascular unit, 2) APOE-ε4 exacerbates the impact of lung endothelial tau on the neurovascular unit, and 3) anti-tau antibodies to prevent neurovascular unit dysfunction caused by pneumonia. This is a translational preclinical project bridging in vitro experiments, experimental models and clinical samples, and is pioneering in that it synthesizes experts in lung and brain biology to understand the impact of pneumonia-elicited lung endothelial tau on neurovascular unit functions, with consideration of health disparities.", "keywords": [ "2019-nCoV", "Address", "Amyloid", "Amyloid beta-Protein", "Antibodies", "Apolipoproteins", "Autopsy", "Bacterial Pneumonia", "Biological Assay", "Biological Markers", "Biology", "Blood", "Blood - brain barrier anatomy", "Blood Circulation", "Brain", "Cerebrovascular Circulation", "Cerebrovascular system", "Clinical", "Clinical Research", "Cognitive deficits", "Data", "Dementia", "Dendritic Spines", "Dependovirus", "Endothelial Cells", "Endothelium", "Event", "Experimental Models", "Financial Hardship", "Functional disorder", "Genotype", "Gliosis", "Healthcare", "Hospital Mortality", "Impaired cognition", "Impairment", "In Vitro", "Incidence", "Infection", "Injury", "Intensive Care Units", "Knowledge", "Learning", "Length of Stay", "Link", "Lung", "Maintenance", "Memory", "Methodology", "Mus", "Neurologic Deficit", "Neurons", "Nosocomial pneumonia", "Operative Surgical Procedures", "Organ", "Pathologic", "Pathology", "Patients", "Pericytes", "Peripheral", "Phosphorylation", "Plasma", "Platelet-Derived Growth Factor Receptor", "Pneumonia", "Postoperative Period", "Production", "Protein Isoforms", "Pseudomonas aeruginosa", "Pseudomonas aeruginosa infection", "Quality of life", "Regulation", "Resolution", "Sampling", "Sepsis", "Severities", "Speed", "Survivors", "Syndrome", "Tauopathies", "Testing", "Variant", "Viral Pneumonia", "Work", "apolipoprotein E-4", "brain dysfunction", "cerebral hemodynamics", "cytokine", "cytotoxic", "density", "experience", "experimental study", "genetic risk factor", "health disparity", "hemodynamics", "human tissue", "imaging study", "innovation", "intravital microscopy", "microorganism", "mild cognitive impairment", "neurovascular", "neurovascular injury", "neurovascular unit", "normal aging", "novel", "pathogen", "pre-clinical", "prevent", "response", "sarkosyl", "tau Proteins", "tau aggregation", "two-photon" ], "approved": true } }, { "type": "Grant", "id": "14606", "attributes": { "award_id": "1K01DA060294-01", "title": "Applying the Traditional Ecological Knowledge framework to develop and evaluate a nature-based culturally grounded substance misuse intervention for Native American families.", "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": 26314, "first_name": "ALEXA RUTH", "last_name": "Romberg", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-05-01", "end_date": "2029-04-30", "award_amount": 182360, "principal_investigator": { "id": 31277, "first_name": "Helen", "last_name": "Russette", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 344, "ror": "https://ror.org/00za53h95", "name": "Johns Hopkins University", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "The overall long-term objectives for this K01 proposal are to (1) develop and evaluate a nature-based culturally grounded (NBCG) substance misuse intervention tailored to Native American teenage mothers and their young children that live in a tribal community (2) while also advancing my research and professional capacity to become an independent research investigator. Although Native Americans (NA) demonstrate high abstinence rates from alcohol, the generations of trauma and oppression, ongoing discrimination, COVID-19 pandemic-related consequences, and drug companies disproportionately targeting Black, Indigenous, people of color (BIPOC) communities have contributed to NAs experiencing the highest mortality rates from overdose, suicide and alcoholic liver disease (deaths of despair) as of 2020. NA young women experience heightened risk of interpersonal violence that places them at risk for substance use disorder (SUD) and other risk-taking behaviors, which can result in unplanned pregnancies. Their children are then placed in the cycle of addiction as these children are at heightened risk for early problem emotional and behavioral development, partly due to impaired sleeping, which has demonstrated increased risk for later substance misuse. These alarming statistics warrant investigation of a promising culturally grounded substance misuse intervention that targets both young mothers and their children with the goal of breaking the cycle of addiction by way of restoring our traditional and ceremonial knowledges and practices with the land. To do this work, we need Indigenous frameworks. The traditional ecological knowledge (TEK) framework is the theoretical underpinning for the proposed study. Due to the close relational ties NAs and other Indigenous people have to our land and water, TEK posits additional cultural and spiritual mechanisms between the natural environment and human health and wellbeing. The proposed specific aims of this study are to: 1) develop NBCG programming to enhance an evidence- based home-visiting model to fit the needs of the local context; 2) test the NBCG intervention to determine feasibility and acceptability; and, 3) evaluate the NBCG intervention for effectiveness and efficiency and refine modules to maximize fit to the local context to set the stage for a future R01 fully powered Hybrid Type II trial examining implementation and program effectiveness against maternal substance misuse and child negative child emotional and behavioral development, risk factors for later substance misuse. This K01 incorporates a community-engaged exploratory mixed methods sequential study design to inform, evaluate and refine the NBCG intervention. This study will shed light on proposed theoretical mechanisms (e.g., sleep quality, sense of connectedness) between nature-based culturally grounded experiential learning (i.e., NBCG intervention) and resilience and resistance against addiction (NIDA Objective 2.1).", "keywords": [ "Abstinence", "Active Learning", "Address", "Advocate", "Age", "Alcoholic Liver Diseases", "Alcohols", "Behavior", "Behavior Therapy", "Behavioral", "Black Indigenous People of Color", "COVID-19", "COVID-19 pandemic", "Cessation of life", "Child", "Clinical Trials", "Communities", "Death Rate", "Decision Making", "Development", "Discrimination", "Effectiveness", "Effectiveness of Interventions", "Emotional", "Enrollment", "Environment", "Evaluation", "Evidence based intervention", "Family", "Fostering", "Future", "Generations", "Goals", "Ground Substance", "Health", "Home visitation", "Human", "Indigenous", "Inequity", "Interpersonal Violence", "Intervention", "Intervention Studies", "Interview", "Investigation", "Knowledge", "Life", "Measures", "Mentors", "Methods", "Modeling", "Mothers", "National Institute of Drug Abuse", "Native American population", "Native Americans", "Nature", "Overdose", "Personal Satisfaction", "Persons", "Pharmaceutical Preparations", "Policies", "Program Effectiveness", "Protocols documentation", "Randomized", "Recording of previous events", "Research", "Research Design", "Research Personnel", "Resistance", "Risk", "Risk Factors", "Risk Taking", "Salish and Kootenai", "Sample Size", "Seasons", "Sleep disturbances", "Spirituality", "Structure", "Substance Use Disorder", "Substance abuse problem", "Suicide", "Testing", "Training", "Trauma", "Tribes", "Waiting Lists", "Water", "Work", "acceptability and feasibility", "addiction", "career", "design", "evidence base", "experience", "health inequalities", "hybrid type 2 trial", "implementation evaluation", "implementation measures", "implementation science", "implementation strategy", "implementation/effectiveness", "improved", "intergenerational", "novel", "programs", "randomized trial", "recruit", "resilience", "response", "satisfaction", "sleep quality", "sobriety", "social interventions", "statistics", "substance misuse", "substance misuse prevention", "success", "teenage mother", "therapy design", "tool", "trial design", "tribal community", "tribal leader", "unintended pregnancy", "young mother", "young woman" ], "approved": true } }, { "type": "Grant", "id": "14618", "attributes": { "award_id": "1U01CA287008-01", "title": "The COVID-19 and Cancer Consortium (CCC19) Registry", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Cancer Institute (NCI)" ], "program_reference_codes": [], "program_officials": [ { "id": 31300, "first_name": "Kelly", "last_name": "Filipski", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-05-01", "end_date": "2029-04-30", "award_amount": 732687, "principal_investigator": { "id": 31301, "first_name": "Sonya", "last_name": "Reid", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 31302, "first_name": "Jeremy Lyle", "last_name": "Warner", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1416, "ror": "https://ror.org/01aw9fv09", "name": "Rhode Island Hospital", "address": "", "city": "", "state": "RI", "zip": "", "country": "United States", "approved": true }, "abstract": "People with cancer have a higher risk of infections in general because of vulnerabilities arising from their cancer and its treatments. This is especially true for the novel coronavirus, SARS-CoV- 2. People with cancer are twice as likely to die from COVID-19 compared to the general population, with some subgroups appearing to fare much worse. The pandemic has also led to significant disruption in cancer screening, diagnosis, and treatment, which is anticipated to lead to an indirect increase in morbidity and mortality in this population. Thus, studying COVID-19 in people with cancer is highly warranted. In this U01 project, “The COVID-19 and Cancer Consortium (CCC19) Registry”, we leverage the established CCC19 registry (NCT04354701), which is the largest registry of adults with COVID-19 and cancer in North America, to answer a number of important scientific questions. In Aim 1, we evaluate how anticancer treatments, anti- COVID-19 treatments, vaccination, and, importantly, their interactions modify short- and long- term complications. We will explore whether race, ethnicity, and sociodemographic factors (e.g., insurance, access to treatment) are associated with outcomes. We will explore whether data- driven feature selection with machine-learning algorithms reveals unrecognized associations. In Aim 2, we hypothesize that there will be measurable changes in cancer recurrence and progression in patients who survive COVID-19. We will also investigate whether anticancer treatment modifications, which we have observed in 40% of patients who were on anticancer therapy at the time of infection, will affect longer-term prognosis. In Aim 3, we will develop methods to measure ascertainment and collider biases, which are some of the most important sources of bias in registry-based study designs. Along with these aims, we will continue to support and maintain the CCC19 registry and promote its use by the general community, following the FAIR principles.", "keywords": [ "2019-nCoV", "Acute", "Adrenal Cortex Hormones", "Adult", "Advanced Malignant Neoplasm", "Affect", "Biometry", "COVID-19", "COVID-19 impact", "COVID-19 pandemic", "COVID-19 survivors", "COVID-19 treatment", "Cancer Prognosis", "Caring", "Case Study", "Cause of Death", "Clinical", "Communicable Diseases", "Communities", "Community Clinical Oncology Program", "Community Practice", "Comprehensive Cancer Center", "Data", "Data Coordinating Center", "Decision Making", "Dedications", "Diagnosis", "Disease", "Disease remission", "Enrollment", "Ethnic Origin", "FAIR principles", "General Population", "Goals", "Health Services Accessibility", "Hematologic Neoplasms", "Heterogeneity", "Histology", "Hodgkin Disease", "Hospitalization", "Immune system", "Immunity", "Immunocompromised Host", "Immunotherapy", "Impairment", "Infection", "Insurance", "JAK2 gene", "Journals", "Knowledge", "Lead", "Malignant Neoplasms", "Malignant neoplasm of cervix uteri", "Malignant neoplasm of lung", "Malignant neoplasm of urinary bladder", "Measurable", "Measures", "Melanoma", "Methods", "Minority", "Modification", "Morbidity - disease rate", "North America", "Oncology", "Outcome", "Patients", "Persons", "Pharmaceutical Preparations", "Population", "Primary Infection", "Process", "Prognosis", "Publishing", "Quality Control", "Race", "Recurrent Malignant Neoplasm", "Registries", "Renal Cell Carcinoma", "Reporting", "Research", "Research Design", "Research Personnel", "Risk Factors", "SARS-CoV-2 infection", "Science", "Screening for cancer", "Secondary to", "Site", "Source", "Subgroup", "Time", "Underrepresented Populations", "United States", "Vaccination", "Viral Respiratory Tract Infection", "anti-cancer treatment", "cancer care", "cancer cell", "cancer diagnosis", "cancer recurrence", "cancer therapy", "cohort", "end of life", "experience", "feature selection", "future pandemic", "gastroesophageal cancer", "high risk", "infection risk", "inhibitor", "machine learning algorithm", "meetings", "mortality", "negative affect", "novel coronavirus", "operation", "pandemic disease", "programs", "recruit", "response", "sociodemographic factors", "tumor progression", "underserved community" ], "approved": true } }, { "type": "Grant", "id": "14812", "attributes": { "award_id": "1R01AI181270-01A1", "title": "Mucosal subunit vaccines against SARS CoV-2", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 6908, "first_name": "JENNIFER L.", "last_name": "Gordon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-06-05", "end_date": "2029-04-30", "award_amount": 692849, "principal_investigator": { "id": 31487, "first_name": "RAJENDAR K", "last_name": "DEORA", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 31488, "first_name": "PURNIMA", "last_name": "DUBEY", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 31489, "first_name": "Kenneth Joseph", "last_name": "Oestreich", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 778, "ror": "", "name": "OHIO STATE UNIVERSITY", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "With the emergence of SARS-CoV-2 variants with mutations in the Spike protein, there remains an urgent need for vaccines that are both effective against variants and that generate long-lived mucosal immunity. Generation of durable cell-mediated and humoral immunity is critical for optimal naturally occurring and vaccine-induced protection against respiratory pathogens, including SARS-CoV-2, and includes IFN-γ and IL-17 producing tissue- resident memory T (TRM) cells, T follicular helper (TFH) cells, germinal center (GC) and memory B cells, that contribute to the production of pathogen-specific neutralizing antibodies. Most currently approved vaccines are adjuvanted with alum, which is a strong adjuvant that elicits TH2 skewed cellular and humoral responses, associated with short-lived immunity to intracellular respiratory pathogens. Experimental adjuvants that generate TH1 and TH17 driven systemic and mucosal responses, provide effective and long-lived protection against infection. Bordetella Colonization Factor A (BcfA) is an adjuvant that elicits strong TH1 and TH17 responses and has the unique ability to attenuate the detrimental TH2 responses primed by alum. Polyfunctional IL-21 and IFN-γ (TFH1 cells) or IL-21 and IL-17 (TFH17 cells) cells are important for generation of effective antibodies against viral respiratory pathogens. The TH1/TH17 skewing properties of BcfA may promote the differentiation and function of these specialized TFH cell populations. Mucosal vaccination is a more effective means of generating tissue-resident memory that is not generated by parenterally administered alum-adjuvanted vaccines. A prime-pull regimen (systemic priming and intranasal booster) generates mucosal responses to vaccines containing TH1/TH17 skewing adjuvants and provides superior protection. We will test the overarching hypothesis that a BcfA/alum-adjuvanted subunit SARS CoV-2 vaccine containing S, M and N proteins, delivered via a heterologous prime-pull immunization regimen will reduce SARS-CoV-2 infection of the mouse respiratory tract and elicit long-lived systemic and mucosal TH1/TH17 driven immune responses.", "keywords": [ "2019-nCoV", "Adjuvant", "Adoptive Transfer", "Adult", "Animal Model", "Antibodies", "Antibody Response", "Antigens", "Attenuated", "Avidity", "Blocking Antibodies", "Bordetella", "Bordetella pertussis", "CD8B1 gene", "COVID-19 vaccine", "Cell secretion", "Cells", "Data", "Development", "Formulation", "Generations", "Helper-Inducer T-Lymphocyte", "Human", "Humoral Immunities", "IL17 gene", "Immune", "Immune response", "Immunity", "Immunization", "Immunoglobulin Class Switching", "Infection", "Inflammatory", "Interferon Type II", "Intramuscular", "K-18 conjugate", "Knockout Mice", "Laboratories", "Location", "Lung", "Mediating", "Memory", "Memory B-Lymphocyte", "Mesocricetus auratus", "Messenger RNA", "Modeling", "Mouse Strains", "Mucosal Immune Responses", "Mucosal Immunity", "Mucous Membrane", "Mus", "Mutation", "Mycobacterium tuberculosis", "Nature", "Nose", "Nucleocapsid", "Pathology", "Phenotype", "Play", "Population", "Production", "Productivity", "Property", "Proteins", "Publishing", "Regimen", "Respiratory System", "Role", "Route", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "SARS-CoV-2 variant", "Shapes", "Structural Protein", "Structure of germinal center of lymph node", "Subunit Vaccines", "T cell response", "T memory cell", "T-Lymphocyte", "Testing", "Tissues", "Transgenic Organisms", "Vaccine Design", "Vaccines", "Variant", "Viral", "Viral Proteins", "Work", "Yersinia pestis", "aluminum sulfate", "cytokine", "experimental study", "factor A", "improved", "interleukin-21", "mucosal vaccination", "mucosal vaccine", "neutralizing antibody", "novel", "parenteral administration", "pathogen", "pathogenic bacteria", "pathogenic virus", "protective efficacy", "respiratory", "respiratory pathogen", "response", "tissue resident memory T cell", "translational impact", "vaccination strategy", "vaccine delivery", "vaccine efficacy", "vaccine-induced immunity", "variants of concern" ], "approved": true } }, { "type": "Grant", "id": "14831", "attributes": { "award_id": "1K08AI180431-01A1", "title": "Induction of Broad Sarbecovirus Immunity Via A Vaccine Engineered From SARS-CoV-2 Heptad Repeat 1", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 6908, "first_name": "JENNIFER L.", "last_name": "Gordon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-05-28", "end_date": "2029-04-30", "award_amount": 181764, "principal_investigator": { "id": 31510, "first_name": "Samuel David", "last_name": "Stampfer", "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": "Current COVID-19 vaccines fail to induce strong cross-reactive neutralizing antibodies against circulating SARS- CoV-2 variants, which have undergone extensive mutation in the neutralizing epitopes of spike protein. Booster vaccinations with variant-matched vaccines primarily strengthen immunity towards epitopes shared with the original strain, leading to poor neutralizing activity against variants and failing to induce strong protection. This biased immune response towards the ancestral strain is termed “original antigenic sin”. It results in repeated infections with new variants regardless of vaccination status. The overall goal of this proposal is to develop an improved SARS-CoV-2 vaccine that can induce broadly cross- reactive neutralizing antibody responses against current and future variants by targeting a highly conserved epitope in the heptad repeat 1 (HR1) region of the spike protein. When presented on spike protein, it is poorly immunogenic and anti-HR1 antibodies rarely form naturally. Dr. Stampfer has developed an engineered antigen, composed only of the HR1 epitope, that induces high titer anti-HR1 antibodies in mice. This immunogen also functions as a scaffold when linked to an additional epitope, the receptor binding motif (RBM), which mutates frequently between different SARS-CoV-2 variants and can induce very potent neutralizing antibodies. The HR1 portion of such a vaccine has the potential to induce broadly neutralizing antibodies against all variants, while the RBM portion can function as a seasonal component targeting current circulating strains, all without boosting non-neutralizing cross-reactive epitopes on spike protein. Three Aims are proposed. Aim 1 investigates the immunogenicity and protection of the HR1 and RBM-HR1 vaccines against the current circulating SARS-CoV-2 variants in naïve mice, while Aim 2 evaluates their efficacy as boosters in mice with prior mRNA COVID-19 vaccination. Aim 3 will isolate vaccine-induced HR1-specific B-cells to generate broadly-active anti-HR1 monoclonal antibodies for prophylactic and therapeutic evaluation in mouse challenge experiments. Long term, this lays the groundwork for future larger projects testing the optimized vaccine and anti-HR1 therapeutics in nonhuman primates and humans, and in designing HR1-based vaccines for other viruses. The research will be conducted at the Emory Vaccine Center, with multiple vaccinology labs whose close proximity encourages new collaborations and the sharing of methodology and equipment, along with on-site nonhuman primates for future preclinical vaccine testing. Dr. Stampfer’s career goal is to develop better vaccines for viral pathogens by using protein structure data to design antigens that induce strong immunity to critical epitopes. His career development plan includes hands-on training in vaccine development, neutralization assays, and monoclonal antibody isolation, along with didactic and online courses in immunology, antibody engineering, biostatistics, and grant-writing. The mentorship team of physician-scientists and viral vaccinologists will ensure productive research and training, helping him launch his career as an independent researcher.", "keywords": [ "2019-nCoV", "Absenteeism at work", "Adoptive Transfer", "Amino Acid Receptors", "Amino Acids", "Animals", "Anti-viral Agents", "Antibodies", "Antibody Response", "Antigens", "Area", "B-Lymphocytes", "Binding", "Biological Assay", "Biometry", "COVID-19", "COVID-19 vaccination", "COVID-19 vaccine", "Cell Separation", "Cessation of life", "Chimeric Proteins", "Collaborations", "Coronavirus", "Data", "Development", "Development Plans", "Economics", "Engineering", "Ensure", "Enzyme-Linked Immunosorbent Assay", "Epitopes", "Equipment", "FDA approved", "Family", "Funding", "Future", "Goals", "Grant", "Human", "Immune", "Immune response", "Immunity", "Immunize", "Immunocompromised Host", "Immunology", "Individual", "Infection", "Infection prevention", "Influenza", "K-18 conjugate", "Learning", "Length", "Light", "Link", "Measures", "Mentors", "Mentorship", "Messenger RNA", "Methodology", "Minority Groups", "Monoclonal Antibodies", "Morbidity - disease rate", "Mus", "Mutate", "Mutation", "Paramyxovirus", "Persons", "Physicians", "Population", "Positioning Attribute", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Productivity", "Protein Engineering", "Proteins", "RNA vaccine", "Research", "Research Personnel", "SARS-CoV-2 B.1.351", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "SARS-CoV-2 variant", "Sarbecovirus", "Scientist", "Seasons", "Secondary Immunization", "Severe Acute Respiratory Syndrome", "Site", "Spottings", "Stains", "Structure", "T cell response", "T-Lymphocyte", "Techniques", "Testing", "Therapeutic", "Training", "Update", "Vaccinated", "Vaccination", "Vaccines", "Variant", "Viral", "Viral Vaccines", "Virus", "Work", "Writing", "antibody engineering", "asymptomatic COVID-19", "booster vaccine", "career", "career development", "cross reactivity", "cytokine", "design", "efficacy testing", "experimental study", "immunogenic", "immunogenicity", "improved", "innovation", "monoclonal antibody production", "neutralizing antibody", "nonhuman primate", "novel coronavirus", "online course", "pathogenic virus", "pre-clinical", "prevent", "prophylactic", "protein structure", "prototype", "receptor binding", "response", "scaffold", "skills", "therapeutic evaluation", "transmission process", "vaccine development", "vaccine efficacy", "vaccine evaluation", "vaccine-induced antibodies", "vaccinology", "variants of concern", "vector", "viral transmission" ], "approved": true } }, { "type": "Grant", "id": "14866", "attributes": { "award_id": "1R01MH136492-01", "title": "SARS-CoV-2 and Social Determinants of Health Impact on Inflammation Associated Depression Risk (SSIDR)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Mental Health (NIMH)" ], "program_reference_codes": [], "program_officials": [ { "id": 24495, "first_name": "Douglas L.", "last_name": "Meinecke", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-05", "end_date": "2029-04-30", "award_amount": 833123, "principal_investigator": { "id": 31552, "first_name": "Linda Y.", "last_name": "Kim", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 766, "ror": "https://ror.org/02pammg90", "name": "Cedars-Sinai Medical Center", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "A Global Burden Disease survey commissioned by the World Health Organization (WHO) estimated a 27.6% increase in cases of major depressive disorder (MDD) during the COVID-19 pandemic, particularly among specific vulnerable groups including healthcare workers (HCW), those with pre-existing medical/mental health conditions, as well as ethnic minority communities, many of whom may have their wellbeing challenged from additional stressors compounded by negative social determinants of health (SDOH). Recent findings from the EMBARC study have shown that small lipid molecules called eicosanoids, which act as both activators and suppressors of inflammatory activity as well as modulators of innate and adaptive immunity, are known to have a significant impact on the subacute and chronic sequelae of SARS-CoV-2, in addition to risk for unresolved immune-mediated inflammatory conditions such as CVD. Eicosanoids have also been found to be a contributor of chronic neuroinflammatory conditions such as depression in other studies. Advanced mass spectrometry methods now allow for the rapid and accurate quantification of hundreds of upstream eicosanoid mediators representing multiple enzymatic origins. Hence, this proposal aims to provide a more detailed understanding of how upstream eicosanoid pathways can be variably active, imbalanced, and perturbed in relation to an individual’s propensity for developing depression. We will leverage the expertise of an interprofessional team, including current members of the EMBARC research study team, to test the hypothesis that: 1) SARS-CoV-2 infection and reinfections moderate development of chronic immune-mediated neuroinflammatory condition such as depression as evidenced by changes in eicosanoid profiles; and 2) health impacts of SDOH compounds depression risk following SARS-CoV-2 infection and reinfection by moderating the neuroimmune-inflammatory response. We propose a systematic approach to comprehensively investigating the components of upstream inflammatory activity in relation to outcomes across the spectrum of depression risk through the collection of longitudinal (survey, clinical, biomarker) data from a large and diverse population of people already enrolled in the EMBARC research study and will use a variety of methods (e.g., eicosanoid profiling, use of public available health equity data set) to assess SARS-CoV-2 infection and the SDOH impact on neuroinflammation that is associated with depression. This work will pave the way for follow-up studies investigating the efficacy of anti- inflammatory therapies, including both existing and novel agents, for modulating variation in distinct eicosanoids and, in turn, mental health outcomes such as depression.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "14879", "attributes": { "award_id": "1U01AG088351-01", "title": "Age related loss of immune resilience during response to severe respiratory viral infections", "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": 23647, "first_name": "MULUALEM ENYEW", "last_name": "Tilahun", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-01", "end_date": "2029-04-30", "award_amount": 528011, "principal_investigator": { "id": 24905, "first_name": "CHRISTIAN", "last_name": "FORST", "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": 24825, "first_name": "Leopoldo Nicolas", "last_name": "Segal", "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 } ] }, { "id": 31572, "first_name": "Bin", "last_name": "Zhang", "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": "Abstract. The clinical responses to respiratory viruses are very heterogenous as recently demonstrated by the COVID-19 pandemic with most aggressive clinical courses among elders, suffering the highest mortality. The pathophysiological mechanisms leading to poor outcome among elders people are not well understood. Beyond the increased mortality seen in advanced age group, older critically ill COVID-19 patients (>65yo) had higher viral loads in their lower airways and blunted anti-SARS-CoV-2 immune responses. Using host transcriptomic approaches described in our preliminary data we are identifying a pattern suggestive of maladaptive immune responses, more prominently present among elders, that leads to poor outcomes in patients with respiratory viruses. In addition, through a collaboration between Drs. Segal, Zhang and Forst, we have identified age-related signatures that are distinct from the lower airway and systemic transcriptome. Interestingly, some of these signals are also seen in a cohort of patients with influenza virus infections, suggesting a novel profiling that may uncover important mechanisms of immunoaging. Thus, using samples and data collected from patients with SARS-CoV- 2 or influenza infection, we will test the hypothesis that among older patients with respiratory virus infections, poor prognosis is characterize by maladaptive host immune responses characterized by downregulation of type 1 interferon (IFN) responses and increased inflammatory injury, thereby suppressing immune mechanisms designed to limit viral load. Here, in Aim 1 we will focus on lower airway and blood samples from critically ill COVID-19 patients. In these, we will use RNA sequencing and single cell RNA sequencing to evaluate for longitudinal host immune signatures associated with poor outcome among different age groups. Then in Aim 2 we will establish multiscale gene network models associated with poor outcome among different age groups of critically ill COVID-19 patients. Then, in Aim 3 we will perform a comparative study of age-dependent host immune response signatures and network models in COVID-19 and influenza virus infection. Therefore, this is an unprecedented opportunity to conduct investigations on paired lower airway and systemic samples from patients suffering infections with respiratory viruses across different age segments in order to identify novel mechanisms that lead to poor viral control and clinical outcomes.", "keywords": [], "approved": true } } ], "meta": { "pagination": { "page": 1384, "pages": 1405, "count": 14046 } } }