Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=4&sort=-funder
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-funder", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1397&sort=-funder", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=5&sort=-funder", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=3&sort=-funder" }, "data": [ { "type": "Grant", "id": "10285", "attributes": { "award_id": "1R41DC020415-01", "title": "Adaptive olfactory threshold testing in the clinical assessment of anosmia", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Deafness and Other Communication Disorders (NIDCD)" ], "program_reference_codes": [], "program_officials": [ { "id": 22552, "first_name": "Roger", "last_name": "Miller", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-08-10", "end_date": "2023-07-31", "award_amount": 252118, "principal_investigator": { "id": 25143, "first_name": "STEVEN D", "last_name": "MUNGER", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1909, "ror": "", "name": "REDOLYNT, LLC", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true }, "abstract": "Smell disorders are highly impactful in daily life. Gas leaks and spoiled food are undetectable dangers. Adequate nutrition is compromised as food become unpalatable without the core contribution smell plays in flavor perception. Affected individuals also feel disconnected from the world and other people, contributing to an increased incidence of depression. Smell disorders may also be early indicators of other serious health problems such as rhinosinusitis, skull base tumors, cerebrospinal fluid leaks, or neurological diseases such as Alzheimer's disease, Parkinson's disease or multiple sclerosis. Smell disorders are also much more common than most people believe, with one major pre-COVID-19 study finding that over 12% Americans age 40 and older had hyposmia (a reduced ability to smell) or anosmia (an inability to smell). However, despite substantial prevalence and significant health impacts, smell disorders remain routinely underdiagnosed, in part because routine olfactory screening is not a part of primary care. A major impediment to incorporating objective, validated smell tests in routine healthcare is that the current options are too time consuming and/or expensive. Thus, a new option is needed if smell testing is to be embraced by medical providers as a part of routine screening, analogous to the ubiquitous Snellen eye chart and handheld audiometer used in many primary care clinics. Roughly a third of US adults receive an annual physical or preventive care visit. Including smell tests in such visits would result in over 75 million tests per year. When an olfactory disorder is diagnosed or suspected, it typically results in referrals to specialists (e.g., neurology, otolaryngology) and in procedures such as surgeries, imaging, and endoscopy that are billable to health insurance. Thus, we expect that a low cost, rapid smell test would provide a substantial return on investment for healthcare systems. To address this unmet need for a robust, rapid, inexpensive, cross-cultural test of olfactory function that can be administered in varied settings, we designed the Adaptive Olfactory Measure of Threshold (ArOMa-T). The ArOMa-T includes multiple concentrations of a single odorant spaced over several log units of concentration and encapsulated in peel- and-burst labels on a foldable card. The card is paired with an adaptive algorithm, implemented via a website or app, that guides the patient through a sequence of odorant concentrations where each is selected based on prior responses. By skipping non-informative concentrations, this test rapidly determines the patient's odor detection threshold. The ArOMa-T can be self-administered and produced inexpensively at scale. In this proposal, we will pursue three Specific Aims to move the ArOMa-T towards commercialization: we will (1) compare the performance of the ArOMa-T against other validated smell tests; (2) develop an accompanying application for real-time processing of the adaptive algorithm; and (3) assess provider experience with the test and app in a real world clinical setting. Together, these studies will establish the technical merit, feasibility and commercial potential of the ArOMa-T.", "keywords": [ "Address", "Adult", "Affect", "Affordable Care Act", "Age", "Algorithms", "Alzheimer&apos", "s Disease", "American", "Anosmia", "COVID-19", "COVID-19 associated anosmia", "Cerebrospinal Fluid", "Clinic", "Clinical", "Clinical assessments", "Code", "Collaborations", "Consumption", "Detection", "Devices", "Diagnosis", "Diagnostic Reagent Kits", "Discrimination", "Encapsulated", "Endoscopy", "Europe", "Eye", "Feedback", "Food", "Functional disorder", "Gases", "Health", "Health Insurance", "Health Personnel", "Healthcare", "Healthcare Systems", "Image", "Incidence", "Individual", "Instruction", "Insurance", "Insurance Carriers", "Investments", "Joint Commission on Accreditation of Healthcare Organizations", "Label", "Language", "Life", "Measures", "Medical", "Medicare", "Mental Depression", "Multiple Sclerosis", "National Health and Nutrition Examination Survey", "Neurology", "Notification", "Odors", "Olfaction Disorders", "Operative Surgical Procedures", "Otolaryngology", "Output", "Pamphlets", "Paper", "Parkinson Disease", "Patient Self-Report", "Patients", "Pennsylvania", "Perception", "Performance", "Persons", "Phenylethyl Alcohol", "Play", "Prevalence", "Preventive care", "Primary Health Care", "Procedures", "Provider", "Quality of life", "Safety", "Secure", "Self Administration", "Series", "Skull Base Neoplasms", "Smell Perception", "Specialist", "Tablets", "Test Result", "Testing", "Time", "Training", "Universities", "Visit", "Visual impairment", "Work", "base", "cognitive load", "commercialization", "cost", "design", "experience", "hyposmia", "memory recall", "nervous system disorder", "nutrition", "olfactory disorder", "olfactory threshold", "pain scale", "pandemic disease", "performance tests", "programs", "response", "rhinosinusitis", "routine screening", "screening", "smartphone Application", "smell test", "web site" ], "approved": true } }, { "type": "Grant", "id": "10237", "attributes": { "award_id": "3R13HD110322-01S1", "title": "International Workshops on HIV Pediatrics", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 10382, "first_name": "Sonia S", "last_name": "Lee", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-08-25", "end_date": "2025-07-31", "award_amount": 64999, "principal_investigator": { "id": 25609, "first_name": "ELAINE Janine", "last_name": "ABRAMS", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 781, "ror": "", "name": "COLUMBIA UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "The International Workshop on HIV Pediatrics is organized on an annual basis prior to the biennially planned IAS or AIDS Conference. This workshop is the only meeting entirely devoted to research in prevention and treatment of HIV infection in infants, children, and adolescents, making it the premier forum for the world’s leading researchers. By bringing together experts from different disciplines with presentations in a variety of formats, the meeting offers a collaborative setting where the latest developments are presented, discussed, interrogated, and evaluated. The 14th Workshop will take place in Montreal, Canada and virtually, July 27-28, 2022, prior to the 24th International AIDS Conference. The program will include topics from among the following: HIV prevention in adolescents and pregnant/breastfeeding persons; prevention of vertical transmission; clinical issues in HIV- exposed uninfected children; pediatric HIV case finding; HIV treatment in infants, children, adolescents and pregnant/breastfeeding persons; clinical management and coinfections/complications for infants, children, adolescents and pregnant/breastfeeding persons; and COVID-19. Given previous success with this format, we expect the 15th and 16th editions to follow this same pattern, including similar program and schedule. The meeting format is also highly innovative. Moving from a more traditional format of plenaries and oral abstract sessions, the organizers have introduced unique approaches including structured debates, oral poster presentations, poster walks, clinical-case presentations, curated panel discussions, video presentations and a social program including a networking breakfast where junior investigators meet with senior researchers. Attendance has increased substantially in the last several years with 370 delegates in 2021; highly favorable annual evaluations underscore the Workshop’s importance. The aims of the workshop are to provide a platform for presentation and discussion of the latest developments in the field; to gather leading researchers involved in pediatric and perinatal HIV in a stimulating, interactive forum; to promote the next generation of research by supporting junior and international investigators; and to promote diversity with the inclusion of international, multiracial leadership, faculty, and scholarship recipients. The objective of this proposal is to provide support for three annual workshops including participation of key plenary speakers as well as members from the community of adolescents living with HIV infection, and to increase the number of scholarships for junior investigators and investigators from low-income countries.", "keywords": [ "15 year old", "AIDS prevention", "Accounting", "Acquired Immunodeficiency Syndrome", "Adherence", "Adolescence", "Adolescent", "Adult", "Africa South of the Sahara", "Age", "Aging", "Breast Feeding", "COVID-19", "Canada", "Caring", "Child", "Childhood", "Clinical", "Clinical Management", "Collaborations", "Communities", "Complex", "Development", "Diagnosis", "Discipline", "Educational workshop", "Evaluation", "Faculty", "Formulation", "Future", "HIV", "HIV Infections", "HIV antiretroviral", "Human immunodeficiency virus test", "Income", "Individual", "Infant", "Infection", "International", "International AIDS", "Intervention", "Leadership", "Oral", "Participant", "Pattern", "Perinatal Infection", "Persons", "Population", "Pregnancy in Adolescence", "Prevention", "Prevention strategy", "Regimen", "Research", "Research Personnel", "Research Support", "Schedule", "Scholarship", "Structure", "Vertical Disease Transmission", "Viral", "Walking", "Woman", "Work", "antiretroviral therapy", "case finding", "co-infection", "ethnic minority", "girls", "innovation", "low income country", "meetings", "member", "men", "minority investigator", "multi-racial", "next generation", "pediatric human immunodeficiency virus", "pediatric human immunodeficiency virus infection", "perinatal HIV", "posters", "pregnant", "prevent", "programs", "racial minority", "scale up", "social", "success", "symposium", "transmission process", "treatment strategy", "uptake", "virtual", "young adult", "young woman" ], "approved": true } }, { "type": "Grant", "id": "10309", "attributes": { "award_id": "1R56AI163386-01A1", "title": "An antioxidant enzyme to suppress hyperinflammation induced by 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": 6115, "first_name": "DIPANWITA", "last_name": "Basu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-08-19", "end_date": "2023-07-31", "award_amount": 380317, "principal_investigator": { "id": 26267, "first_name": "Jing", "last_name": "Wen", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 818, "ror": "", "name": "UNIVERSITY OF CALIFORNIA LOS ANGELES", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The COVID-19 pandemic has taken a significant toll on people worldwide, and current treatment is mainly supportive. While the pathogenesis of COVID-19 remains elusive, accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have virally driven hyperinflammation and immune dysregulation. We propose herein reactive oxygen species contribute to hyperinflammation and immune dysregulation in severe COVID-19 patients, which can be treated by an antioxidant enzyme—catalase that regulates cytokine production, protects against oxidative injury, and represses replication of SARS-CoV-2. This therapeutic based on catalase, the most abundant antioxidant enzyme ubiquitously present in the liver, erythrocytes and alveolar epithelial cells, is the most effective catalyst to breakdown hydrogen peroxide and minimize the downstream reactive oxygen species. The potential of catalase as a therapeutic agent has been explored for different diseases in vitro and in mouse models, including influenza-associated pneumonia, respiratory infections caused by respiratory syncytial virus (RSV), and inflammatory disease associated with oxidative stress. However, the efficacy of catalase has been hampered by its poor stability and short plasma half-life. Particularly, in the context of COVID-19 patients, death of the alveolar cells and inflammation could result in high local concentrations of proteases, further deteriorating the stability of catalase. We recently published an effective delivery system of catalase using the nanocapsule technology. Catalase delivered by nanocapsules assists to regulate production of cytokines and protect oxidative injury, as demonstrated in human leukocytes and alveolar epithelial cells, and repress replication of SARS-CoV-2 in rhesus macaques, without noticeable toxicity. In this proposal, we will further investigate the immunoregulatory effect of catalase nanocapsules on hyperinflammation induced by SARS-CoV-2 ex vivo, further optimize their biodistribution, pharmacokinetics, and delivery efficiency to SARS-CoV-2 infected organs, and test their therapeutic efficacy in the SARS-CoV-2 infection mice developing respiratory disease resembling severe COVID-19. Success of this project may provide an effective therapeutic solution for the pandemic, as well as treatment of hyperinflammation induced by virus infection in general.", "keywords": [ "2019-nCoV", "Age", "Air", "Alveolar Cell", "Antibodies", "Antibody Therapy", "Biodistribution", "Biomedical Engineering", "Blood - brain barrier anatomy", "Blood Circulation", "Brain", "COVID-19", "COVID-19 pandemic", "COVID-19 pathogenesis", "COVID-19 patient", "COVID-19 therapeutics", "COVID-19 treatment", "Cell membrane", "Cessation of life", "Chemicals", "Chronic Disease", "Collaborations", "Communicable Diseases", "Diabetes Mellitus", "Diffuse", "Disease", "Disease Outbreaks", "Drug Kinetics", "Effectiveness", "Enzyme Stability", "Enzymes", "Epithelial Cells", "Erythrocytes", "Foundations", "Future", "Goals", "Growth Factor", "Half-Life", "Homeostasis", "Human", "Hydrogen Peroxide", "Immune", "Immunosuppression", "In Vitro", "Infection", "Inflammation", "Inflammatory", "Influenza", "International", "Intravenous Immunoglobulins", "Janus kinase", "Laboratories", "Leukocytes", "Liquid substance", "Liver", "Macaca mulatta", "Molecular", "Molecular Target", "Monoclonal Antibodies", "Morbid Obesity", "Mus", "Natural Immunity", "Nature", "Neoplasm Metastasis", "Neuraxis", "Organ", "Oxidative Stress", "Oxygen", "Patients", "Peptide Hydrolases", "Persons", "Plasma", "Pneumonia", "Production", "Proteins", "Protocols documentation", "Public Health", "Publishing", "Pulmonology", "Reactive Oxygen Species", "Repression", "Research", "Research Personnel", "Respiratory Disease", "Respiratory Tract Infections", "Respiratory syncytial virus", "Risk Factors", "Role", "SARS-CoV-2 infection", "Smoking", "Steroids", "System", "Technology", "Testing", "Therapeutic", "Therapeutic Agents", "Therapeutic Monoclonal Antibodies", "Therapeutic Uses", "Time", "Tissues", "Toxic effect", "Treatment Efficacy", "Viral", "Virus Diseases", "Virus Replication", "Water", "Work", "alveolar epithelium", "anakinra", "antioxidant enzyme", "base", "career", "catalase", "catalyst", "cell behavior", "cytokine", "immunogenicity", "immunoregulation", "improved", "mortality", "mouse model", "multidisciplinary", "nanocapsule", "nanoencapsulated", "oxidative damage", "pandemic disease", "patient subsets", "prevent", "severe COVID-19", "success", "therapeutic enzyme", "therapeutic protein", "therapeutically effective", "tocilizumab", "treatment strategy", "virology" ], "approved": true } }, { "type": "Grant", "id": "10277", "attributes": { "award_id": "1R44AI165129-01A1", "title": "New Technology for High-Resolution Antibody Profiling for 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": 9207, "first_name": "Michael", "last_name": "Minnicozzi", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-08-19", "end_date": "2024-07-31", "award_amount": 978625, "principal_investigator": { "id": 26235, "first_name": "Mark", "last_name": "Lim", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1908, "ror": "", "name": "AMBERGEN, INC", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Summary/Abstract The SARS-CoV-2 virus has infected to date 35 million and killed over 600,000 persons in the U.S. alone. Despite initial success of the vaccines, the emergence of increasingly more infectious variants such as the delta variant, coupled with vaccine hesitancy and insufficiently effective therapies, has resulted in a continued and deepening national and world-wide pandemic crisis. Moreover, a significant fraction of COVID-19 patients (~35%), even those who are initially asymptomatic, suffer long-term debilitating effects (“long-COVID”). Recent reports correlate the structure of specific SARS-CoV-2 induced antibodies with potentially lethal proinflammatory responses in acute COVID-19. Studies have also linked the antibody response to long-COVID. Moreover, the nature of the antibody response to vaccination correlates with breakthrough infections. Thus, the ability to rapidly perform high- resolution, highly multiplexed antibody response profiling can provide an essential tool, ultimately leading to more effective diagnostics, prognostics, vaccines and treatments for both acute and long-term disease. However, current antibody profiling methods produce a very limited view of the humoral repertoire. To address this unmet need, AmberGen proposes to further develop in Phase II its mass spectrometric bead-array technology for in-depth immune-profiling, termed PC-BAMS-IP™. This will provide researchers with a new and powerful tool for high- resolution antibody profiling which unlike current technology facilitates 2-dimensions of multiplexing. This is accomplished using arrayed photocleavable mass-tag (PC-MT) encoded beads bearing viral antigens to bind serum antibodies, along with a range of PC-MT encoded probes to simultaneously measure the full breadth of bead-bound antibody types. Mass spectrometry imaging (MSI) of the bead-arrays facilitates the decoding of thousands of different PC-MTs, thereby revealing the full complexity of the antibody response and a means to correlate it with disease severity/outcome. Feasibility studies focused on SARS-CoV-2 demonstrate the ability of PC-BAMS-IP™ to perform simultaneous 2-dimensional antibody profiling of both the Fab traits (antigen binding function) and Fc traits (immune effector function). The proposed 2-year Phase II project will expand on this progress, including: i) design, synthesis and evaluation of 25 plug-and-play PC-MT encoded beads for SARS-CoV-2 antigen immobilization and 25 PC-MT probes to simultaneously query a range of Fc traits of the bead-bound serum antibodies; ii) initial validation of the PC-BAMS-IP™ assay using control and COVID-19 convalescent sera, including comparison to Luminex® xMAP® technology, the existing gold-standard for 1-dimensional multiplex antibody profiling; and iii) demonstrate that PC-BAMS-IP™ can distinguish severe and mild COVID-19. This work will be facilitated by our continued collaboration with leading experts including Prof. Cathy Costello (BU, world- renowned mass spectrometry expert), Dr. Jason Amsden (Duke University, mass spectrometric instrument development), Prof. Rahm Gummuluru (BU, Vice Chair of Microbiology, a leading virologist), and Prof. Plamen Ivanov (BU, Director, Keck Laboratory for Network Physiology, advanced statistical physics).", "keywords": [ "2019-nCoV", "Acute", "Address", "Analysis of Variance", "Antibodies", "Antibody Response", "Antigens", "Binding", "Biological Assay", "Boston", "COVID-19", "COVID-19 pandemic", "COVID-19 patient", "Characteristics", "Classification", "Cohort Analysis", "Collaborations", "Coupled", "Cross Reactions", "Device or Instrument Development", "Diagnostic", "Dimensions", "Disease", "Epitopes", "Evaluation", "Feasibility Studies", "Fluorescence", "Gold", "Human", "IgG1", "Immobilization", "Immune", "Immune response", "Immunoglobulin Isotypes", "Individual", "Label", "Laboratories", "Link", "Long COVID", "Mass Spectrum Analysis", "Measures", "Methods", "Microbiology", "Modeling", "Nature", "Noise", "Outcome", "Patients", "Persons", "Phase", "Physics", "Physiological", "Physiology", "Play", "Postdoctoral Fellow", "ROC Curve", "Reagent", "Reporting", "Research", "Research Personnel", "Resolution", "SARS-CoV-2 B.1.617.2", "SARS-CoV-2 antibody", "SARS-CoV-2 antigen", "SARS-CoV-2 exposure", "Sampling", "Sensitivity and Specificity", "Serology", "Serum", "Severity of illness", "Signal Transduction", "Structure", "System", "Technology", "Universities", "Vaccination", "Vaccines", "Validation", "Variant", "Viral Antigens", "Virus", "Work", "antigen binding", "base", "breakthrough infection", "cohort", "design", "distinguished professor", "effective therapy", "glycosylation", "improved", "mass spectrometric imaging", "medical schools", "new technology", "pandemic disease", "pathogen", "predictive modeling", "professor", "prognostic", "response", "severe COVID-19", "success", "tool", "trait", "two-dimensional", "vaccine hesitancy", "virus infection mechanism" ], "approved": true } }, { "type": "Grant", "id": "10349", "attributes": { "award_id": "1U2CCA271903-01", "title": "High-throughput immunoproteomics for cancer biomarker discovery", "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": 23577, "first_name": "CHRISTOS F", "last_name": "PATRIOTIS", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-09-01", "end_date": "2027-08-31", "award_amount": 710300, "principal_investigator": { "id": 26310, "first_name": "Karen S.", "last_name": "Anderson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 26311, "first_name": "JOSHUA", "last_name": "LABAER", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 912, "ror": "", "name": "ARIZONA STATE UNIVERSITY-TEMPE CAMPUS", "address": "", "city": "", "state": "AZ", "zip": "", "country": "United States", "approved": true }, "abstract": "The goal of the ASU Biomarker Characterization Center is to improve ovarian and lung cancer screening through the development of biologically-relevant circulating immune biomarkers. The scientific approach of our Center is based on several fundamental principles. First, that altered cancer protein expression, structure, and post- translational modifications induce host autoantibodies to create circulating biomarkers. Second, that alterations in microbial antigen expression (such as respiratory pathogens) also induce immunity, often detected in benign rather than malignant disease. Third, that the protein modifications, as well as the immune response to these neoantigenic structures, are heterogeneous between people, and that serologic biomarkers may complement circulating protein biomarkers. We will take a systems immunology approach to discover three types of antibodies, anti-microbial antibodies, autoantibodies and anti-aberrant glycoprotein antibodies. Our proposal builds on our extensive experiences with cancer biomarker discovery and immunoproteomics technology development. Our previous results on autoantibody biomarkers have been confirmed in blinded phase 2 multicenter validation studies and led to a CLIA-certified commercial blood test. Our results have shown that multiplexed panels of autoantibodies are required for adequate predictive value. With prior EDRN support, we have developed a set of innovative immunoproteomics technologies, namely high-density nucleic acid programmable protein array (HD-NAPPA), contra-capture protein array (CCPA) and multiplexed in solution protein array (MISPA), that, together with the largest full-length human and microbial gene collection at our DNASU plasmid repository, enable us to study antibodies against the full human proteome, microbial proteomes and the human O-glycoproteome for antibody biomarker signatures in cancer. Our Meso Scale Diagnostics (MSD) team has fielded over 3,000 instruments worldwide, and over 700 commercially available biomarker assay kits. Our expertise at serologic assay development was selected by Operation Warp Speed to use the V-PLEX® serology panels as the basis of its standard binding assays for immunogenicity assessments in all funded Phase III clinical trials of COVID vaccines. We will use our MSD MultiArray platform to migrate the top serologic and protein markers for their utility in our target clinical applications. We will collaborate with experts on lung and ovarian cancer screening at Vanderbilt University Medical Center, Boston University, MD Anderson Cancer Center, and German Cancer Research Center, who will also provide access to high-quality well-characterized samples to develop circulating biomarkers to enhance ovarian cancer screening or to distinguish benign from malignant pulmonary nodules. Adhering to the principles of PRoBE design, we will perform Phase I discovery by screening protein arrays with cancer patient and control sera for cancer or control-specific antibodies. Candidate biomarkers for both lung and ovarian cancers will undergo Phase 2 validation.", "keywords": [ "ART protein", "Academic Medical Centers", "Address", "Adoption", "Antibodies", "Autoantibodies", "Autoantigens", "B-Lymphocyte Epitopes", "B-Lymphocytes", "Benign", "Binding", "Biological Assay", "Biological Markers", "Blinded", "Blood Tests", "Boston", "Breast", "CLIA certified", "Cancer Center", "Cancer Control", "Cancer Detection", "Cancer Patient", "Cancer Vaccines", "Carcinogenesis Mechanism", "Clinical", "Collection", "Complement", "Data", "Development", "Diagnostic", "Disease", "Early Detection Research Network", "Early Diagnosis", "Environment", "Enzyme-Linked Immunosorbent Assay", "Epitopes", "Funding", "Future", "Genes", "German population", "Glycoproteins", "Goals", "Heterogeneity", "Human", "Human Papillomavirus", "Image", "Immune", "Immune Sera", "Immune response", "Immunity", "Immunoassay", "Immunoglobulin G", "Immunologic Markers", "Immunology", "Individual", "Institutes", "Laboratories", "Length", "Lung nodule", "Malignant - descriptor", "Malignant Neoplasms", "Malignant neoplasm of lung", "Malignant neoplasm of ovary", "Measures", "Methods", "Migration Assay", "Monitor", "Morbidity - disease rate", "Mutation", "NCI Center for Cancer Research", "Nodule", "Nucleic Acids", "Ovarian", "Persons", "Phase", "Phase III Clinical Trials", "Plasmids", "Polysaccharides", "Post-Translational Protein Processing", "Predictive Value", "Production", "Protein Array", "Proteins", "Proteome", "Proteomics", "Reproducibility", "Sampling", "Screening for Ovarian Cancer", "Screening for cancer", "Serology", "Serology test", "Serum", "Specificity", "Speed", "Structural Protein", "Structure", "Symptoms", "System", "Technology", "Tumor Antigens", "Universities", "Vaccine Design", "Vaccines", "Validation", "antimicrobial", "assay development", "base", "biomarker discovery", "biomarker panel", "biomarker signature", "cancer biomarkers", "cancer diagnosis", "candidate marker", "circulating biomarkers", "clinical application", "clinical assay development", "clinical diagnosis", "clinical diagnostics", "clinical implementation", "coronavirus disease", "density", "design", "diagnostic platform", "disease heterogeneity", "experience", "glycosylation", "glycosyltransferase", "immunogenic", "immunogenicity", "improved", "improved outcome", "innovation", "instrument", "lung cancer screening", "microbial", "microorganism antigen", "migration", "mortality", "multiplex assay", "novel", "operation", "po" ], "approved": true } }, { "type": "Grant", "id": "5437", "attributes": { "award_id": "1R01AI168373-01", "title": "COVID-19 Vaccine Effectiveness in Pregnant Women and their Infants", "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": 18983, "first_name": "DIPANWITA", "last_name": "Basu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-03-10", "end_date": "2027-02-28", "award_amount": 579524, "principal_investigator": { "id": 18985, "first_name": "Ousseny", "last_name": "Zerbo", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 769, "ror": "", "name": "KAISER FOUNDATION RESEARCH INSTITUTE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Abstract: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) which emerged in December 2019 and has since led to an unprecedented global pandemic with high morbidity and mortality. Current authorized vaccines against SARS-CoV-2 demonstrated 70 – 95% efficacy in clinical trials, but the pivotal efficacy trials on which the emergency use authorizations are based did not include pregnant women. Thus, in the midst of a massive vaccination campaign, COVID-19 vaccine effectiveness in pregnant women and their infants is unknown. Pregnant women are at increased risk of COVID-19 infection and hospitalization, but currently there is no strong recommendation for or against COVID-19 vaccination during pregnancy. Additionally, COVID-19 vaccine uptake among pregnant women and factors associated with being vaccinated or unvaccinated are unknown. We propose to 1) estimate COVID-19 vaccine effectiveness for preventing laboratory-confirmed COVID-19 infection or COVID-19 hospitalization in pregnant women, 2) determine effectiveness of COVID-19 vaccination during pregnancy in preventing COVID-19 infection or hospitalization among infants during the first year of life; and determine whether effectiveness varies by trimester of vaccination and 3) estimate COVID-19 vaccination rates among pregnant women over time and among unvaccinated pregnant women, identify sociodemographic, geographic clusters and healthcare utilization patterns associated with being unvaccinated. We are well-positioned at Kaiser Permanente Northern California, a large integrated healthcare system with stable, diverse membership and comprehensive longitudinal electronic health records (EHR), to address the research aims. By using EHR data, the study will be cost effective and timely; providing information on COVID- 19 vaccine effectiveness among pregnant women and assessing whether maternal vaccination provides protection for their infants who are currently ineligible to receive COVID-19 vaccine. The proposed research can lead to evidence-based recommendations regarding COVID-19 vaccination in pregnant women and will provide critical information regarding characteristics of unvaccinated pregnant women that will be necessary for future development of targeted interventions to improve vaccine coverage among pregnant women.", "keywords": [ "2019-nCoV", "Address", "Affect", "Age", "Birth", "Black race", "COVID-19", "COVID-19 pandemic", "COVID-19 prevention", "COVID-19 vaccination", "COVID-19 vaccine", "California", "Cessation of life", "Characteristics", "Clinical Trials", "Data", "Development", "Diphtheria", "Effectiveness", "Electronic Health Record", "FDA Emergency Use Authorization", "Future", "General Population", "Geography", "Goals", "Hospitalization", "Infant", "Influenza", "Influenza vaccination", "Integrated Health Care Systems", "Intervention", "Laboratories", "Lead", "Life", "Morbidity - disease rate", "Mothers", "Observational Study", "Outcome", "Pattern", "Persons", "Pertussis", "Pertussis Vaccine", "Population Heterogeneity", "Positioning Attribute", "Pregnancy", "Pregnant Women", "Prenatal care", "Public Health Practice", "Randomized Clinical Trials", "Recommendation", "Research", "Risk", "Risk Factors", "SARS-CoV-2 infection", "Series", "Tetanus", "Time", "Vaccinated", "Vaccination", "Vaccines", "Woman", "base", "cost effective", "effectiveness evaluation", "efficacy trial", "evidence based guidelines", "health care service utilization", "improved", "infant outcome", "low socioeconomic status", "maternal vaccination", "mortality", "novel", "pandemic disease", "prevent", "sociodemographic factors", "sociodemographics", "uptake", "vaccine acceptance", "vaccine distribution", "vaccine effectiveness" ], "approved": true } }, { "type": "Grant", "id": "5530", "attributes": { "award_id": "3P01AG041710-07S1", "title": "Health and Aging in Africa: Longitudinal Studies of an INDEPTH Community", "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": 19216, "first_name": "MINKI", "last_name": "CHATTERJI", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2013-09-15", "end_date": "2022-05-31", "award_amount": 697533, "principal_investigator": { "id": 19217, "first_name": "LISA F", "last_name": "BERKMAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 961, "ror": "", "name": "HARVARD SCHOOL OF PUBLIC HEALTH", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "The Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI) study examines biological, social, and economic determinants of disease and their effects on functional, health and cognitive outcomes among an aging population in South Africa. The emergence of the COVID-19 pandemic has profoundly impacted South Africa over the last 9 months, leading to stringent government lockdowns and widespread community transmission of SARS-CoV-2. COVID-19 has been demonstrated to be of particular risk to older adults around the world, especially those with underlying conditions including dementia and cardiometabolic disease. Gathering data on COVID-19 and accounting for the impact of this important public health crisis on personal and population health will be essential to fulfill the aims of the HAALSI P01 parent grant. In particular, Project 1’s aims focus on predictors and consequences of Alzheimer’s disease and related dementias (ADRD), attempting to identify diseases and social conditions that increase risk for cognitive impairment and decline. By leveraging the depth of longitudinal data available on the HAALSI cohort, including data on social and economic conditions, biomarkers, cognitive function, chronic conditions including HIV/AIDS and cardiometabolic disease, and genetic risks, as well as a subsample with MRIs and in-depth dementia assessments, we have a unique opportunity for novel research on causal relationships between dementia and COVID-19. Our research will facilitate better understanding of who is at risk of COVID-19 and why, and what the longer-term impacts might be on cognitive health of the cohort. We have two specific analytic aims to support these goals: (1) To assess how cognitive and genetic factors related to ADRD influence risk for SARS-CoV-2 infection and COVID-19 severity; and (2) To evaluate biological and socioeconomic pathways through which the COVID-19 pandemic may influence cognitive function, cognitive change, and incident dementia. To fulfill these aims we will utilize our planned Wave 3 survey to capture cognitive outcomes, and supplement existing HAALSI data with (1) a telephone survey to capture individual experiences during the COVID-19 pandemic; and (2) serological assays to assess SARS-CoV-2 infection. The telephone survey instrument has been harmonized with HRS sister study COVID modules to allow for cross national comparisons on COVID-19 exposures, health behaviors, and social consequences. Venous blood for SARS-CoV-2 serological assays will be collected during the planned HAALSI Wave 3 fieldwork in 2021, using tried-and-tested practices already in place in the Agincourt, field setting, in South Africa. We expect that this project will provide insight into mechanisms through which dementia and APOE genotype leads to SARS-CoV-2 infection and severe illness, and insight into the biological and socioeconomic pathways through which the COVID-19 pandemic may influence cognitive function, cognitive change and incident dementia. Our data collection and analyses will contribute to a better understanding of how COVID-19 impacts vulnerable populations in South Africa, regionally and around the world.", "keywords": [ "2019-nCoV", "AIDS/HIV problem", "Acceleration", "Accounting", "Address", "Affect", "Africa", "African", "Aging", "Alzheimer&apos", "s disease related dementia", "Behavior", "Biological", "Biological Markers", "Blood", "COVID-19", "COVID-19 pandemic", "COVID-19 severity", "Cardiometabolic Disease", "Cardiovascular Diseases", "Cerebrovascular Disorders", "Chronic", "Clinical Data", "Cognition", "Cognitive", "Communities", "Data", "Data Analyses", "Data Collection", "Dementia", "Disease", "Distress", "Economic Conditions", "Economics", "Education", "Elderly", "Environment", "Event", "Funding", "Future", "Genetic", "Genetic Predisposition to Disease", "Genetic Risk", "Genotype", "Goals", "Government", "Handwashing", "Health", "Health behavior", "Impaired cognition", "Incidence", "Individual", "Infection", "Lead", "Life", "Link", "Longitudinal Studies", "Longitudinal cohort", "Masks", "Neurocognitive", "Neurologic Effect", "Onset of illness", "Outcome", "Participant", "Pathway interactions", "Pattern", "Personal Satisfaction", "Physical Function", "Policies", "Population", "Prevalence", "Public Health", "Research", "Risk", "Risk Factors", "Rural", "SARS-CoV-2 antibody", "SARS-CoV-2 infection", "SARS-CoV-2 transmission", "Sampling", "Serology test", "Severities", "Severity of illness", "Shock", "Sister", "Site", "Social Conditions", "Social Distance", "Social Network", "South Africa", "Structure", "Subgroup", "Surveys", "Symptoms", "System", "Telephone", "Testing", "Venous", "Virus", "Vulnerable Populations", "aging population", "apolipoprotein E-4", "base", "caregiving", "cognitive change", "cognitive function", "cognitive impairment no dementia", "cognitive reserve", "cohort", "comorbidity", "coronavirus disease", "dementia risk", "disorder risk", "economic determinant", "experience", "global health", "health difference", "individual variation", "insight", "mortality", "novel", "pandemic disease", "parent grant", "population health", "response", "rural South Africa", "severe COVID-19", "social", "social determinants", "social vulnerability", "sociodemographics", "socioeconomics" ], "approved": true } }, { "type": "Grant", "id": "5337", "attributes": { "award_id": "1R21AI163548-01A1", "title": "Host response-based diagnostics for identifying bacterial versus viral causes of lower respiratory infection in resource-limited settings", "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": 18731, "first_name": "Erik J.", "last_name": "Stemmy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-01", "end_date": "2024-04-30", "award_amount": 283617, "principal_investigator": { "id": 18732, "first_name": "GAYANI", "last_name": "TILLEKERATNE", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 246, "ror": "https://ror.org/00py81415", "name": "Duke University", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "Project Summary/ Abstract Lower respiratory tract infection (LRTI) is a common reason for antibacterial use and misuse globally. Limitations associated with current LRTI diagnostics are a major driver of antibacterial overuse. Pathogen- based diagnostics have limited sensitivity and do not distinguish infection from colonization. In low- or middle- income countries (LMICs), LRTI diagnosis is further hindered by limited laboratory infrastructure. Host-based diagnostics that leverage the host’s response to infection and broadly classify infection as viral or bacterial in etiology could greatly reduce inappropriate antibacterial use for LRTI. Previously, we showed that novel, peripheral blood-based gene expression classifiers accurately identified bacterial versus viral febrile respiratory illness in a South Asian population. While promising, these classifiers require the collection of a blood sample, which may be challenging in pediatric populations or in LMIC settings with limited resources. Emerging data suggest that the host response in the nasopharynx may also help identify class of infection. Nasopharyngeal sampling offers the possibility of an integrated diagnostic that combines both pathogen and host response detection in a single sample, which would be especially attractive in LMIC settings. The objective of this application is to determine the performance characteristics of NP-based gene expression classifiers at differentiating viral versus bacterial LRTI in a South Asian population. The following aims are proposed 1) to derive NP-based gene expression classifiers to discriminate viral versus bacterial LRTI, and 2) to transfer the NP-based classifier to a real-time polymerase chain reaction (RT-PCR) assay that has potential to be translated to a clinical platform. Comprehensive microbiological and molecular testing for respiratory viral and bacterial pathogens will be completed. Subjects will be adjudicated as having viral versus bacterial LRTI, and RNA sequencing will be performed using NP samples. Machine-learning approaches will identify host gene expression classifiers that discriminate viral versus bacterial LRTI. The genes identified in the NP-based classifier will be migrated onto customized, TaqMan Low-Density Array (TLDA) cards and RT-PCR will be performed. Gene expression will be quantified and logistic regression performed to identify viral versus bacterial LRTI. The expected outcome of this proposal is a significant improvement in our knowledge of how novel NP-based gene expression classifiers perform at identifying viral versus bacterial LRTI in a South Asian population. Following successful completion of these aims, we plan to translate the NP-based classifier to a point-of-care, clinical diagnostic platform. The long-term goal of this work is to develop strategies for improving antibacterial use in LMICs and to help combat the global crisis of antimicrobial resistance.", "keywords": [ "Adult", "Anti-Bacterial Agents", "Antimicrobial Resistance", "Area", "Bacterial Infections", "Biological", "Biological Assay", "Biological Markers", "Blood", "Blood specimen", "COVID-19", "COVID-19 pandemic", "COVID-19 patient", "Characteristics", "Childhood", "Clinical", "Collection", "Consensus", "Country", "Custom", "Data", "Detection", "Diagnosis", "Diagnostic", "Enrollment", "Epithelial Cells", "Etiology", "Fever", "Funding", "Gene Expression", "Genes", "Genomic medicine", "Goals", "Immune response", "Income", "Infection", "Infrastructure", "Knowledge", "Laboratories", "Leukocytes", "Logistic Regressions", "Lower Respiratory Tract Infection", "Machine Learning", "Microbiology", "Molecular", "Nasal Epithelium", "Nasopharynx", "Outcome", "Patients", "Performance", "Polymerase Chain Reaction", "Population", "Research", "Research Infrastructure", "Resource-limited setting", "Resources", "Sampling", "South Asian", "Sputum", "Sri Lanka", "Testing", "Time", "Translating", "Viral", "Virus Diseases", "Work", "adjudicate", "adjudication", "base", "biobank", "clinical diagnostics", "cohort", "combat", "density", "diagnostic platform", "improved", "migration", "minority patient", "novel", "pathogen", "pathogenic bacteria", "pathogenic virus", "peripheral blood", "point of care", "precision medicine", "procalcitonin", "prospective", "respiratory", "transcriptome sequencing" ], "approved": true } }, { "type": "Grant", "id": "10365", "attributes": { "award_id": "1K01DE030524-01A1", "title": "Provider and Patient-generated Remote Oro-Dental Health Electronic Data Capture for Algorithmic Longitudinal Evaluation and Risk-Assessment (PROHEALER)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Dental and Craniofacial Research (NIDCR)" ], "program_reference_codes": [], "program_officials": [ { "id": 10778, "first_name": "Anissa F", "last_name": "Brown", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-09-01", "end_date": "2025-08-31", "award_amount": 159539, "principal_investigator": { "id": 26338, "first_name": "Amy Catherine", "last_name": "Moreno", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1420, "ror": "", "name": "UNIVERSITY OF TX MD ANDERSON CAN CTR", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Research. Oral cavity and oropharyngeal (OC/OPC) cancers afflict more than 53,000 individuals in the United States annually. Despite advancements in oncologic therapies, the majority of patients will experience significant toxicity burden during and after therapy, including moderate-severe xerostomia, dysphagia, reduced mouth opening (i.e. trismus), periodontal disease, and osteoradionecrosis. Remote electronic symptom monitoring through standardized assessment tools for patient reported outcomes (ePROs) is an evidence-based best practice, particularly in the COVID-19 era, yet few clinical practices have demonstrated sustainability of implementation efforts. To date, acute and chronic orodental complications afflicting OC/OPC survivors are largely managed on empirical knowledge with wide inter-provider management variability based on provider experience and available clinical information which is often incomplete, incorrect, or nonexistent. Therefore, standardization of electronic data capture of PROs and objective measures of provider-assessed orodental toxicity severity remains an unmet public health need. Our central hypothesis is that synchronous optimization of machine-readable patient- and provider-generated data collection can be achieved through prioritization of effective implementation strategies for longitudinal oro-systemic ePRO data collection (Aim 1) and creation of novel dental standards for accurate orodental toxicity reporting in both electronic health and dental records (Aim 2). As a subcomponent to Aim 2, we will also design and pilot a novel radiation odontogram to enhance treatment communication between providers. Accurate risk predictions of high-morbidity high-prevalence post-therapy orodental sequelae using high-quality electronic data from Aims 1 and 2 will be incorporated into a statistically robust machine-learning based model (Aim 3). In summary, the PROHEALER proposal fosters innovative and novel informatics approaches for data-driven risk assessment and algorithmic prevention and management of treatment-related oral health diseases afflicting OC/OPC survivors. Career Development & Training. Dr. Moreno's overarching goal is to become an internationally recognized independent research investigator with domain expertise in advanced radiation therapy techniques, clinical informatics and rigorous toxicity modeling methodologies as they pertain to improving patient quality of life and promoting precision prevention and risk-based interventions for orodental complications. This proposal presents Dr. Moreno's 5-year mentored career development plan which includes mentorship from prominent Established NIH Investigators who have committed to overseeing the progress of the proposed projects and Dr. Moreno's overall professional development. The outlined training activities build upon Dr. Moreno's clinical expertise as a Head and Neck Cancer Radiation Oncologist and her prior work in EHR utility enhancement with the inclusion of a comprehensive didactic and project-based curriculum focused on domain knowledge expansion in dental informatics, implementation science, and advanced statistical methods in risk prediction modeling.", "keywords": [ "Acute", "Address", "Adopted", "Aftercare", "Algorithms", "Area", "Assessment tool", "Award", "COVID-19", "Cancer Patient", "Cancer Survivor", "Caring", "Chronic", "Clinic", "Clinical", "Clinical Informatics", "Clinical Management", "Clinical Trials", "Collection", "Combined Modality Therapy", "Communication", "Computer Models", "Computerized Medical Record", "Data", "Data Aggregation", "Data Collection", "Decision Making", "Deglutition Disorders", "Dental", "Dental Care", "Dental Informatics", "Dental Records", "Dentists", "Development", "Development Plans", "Dimensions", "Disease", "Electronic Health Record", "Evaluation", "FAIR principles", "Fostering", "Future", "Gingiva", "Goals", "Head and Neck Cancer", "Health", "High Prevalence", "Individual", "Informatics", "International", "Interruption", "Intervention", "Knowledge", "Machine Learning", "Mandible", "Measures", "Medical", "Mentors", "Mentorship", "Methodology", "Methods", "Modeling", "Monitor", "Morbidity - disease rate", "National Institute of Dental and Craniofacial Research", "Nomenclature", "Oncologist", "Ontology", "Operative Surgical Procedures", "Oral", "Oral cavity", "Oral health", "Osteoradionecrosis", "Outcome", "Outcome Assessment", "Patient Outcomes Assessments", "Patients", "Periodontal Diseases", "Population", "Prevention", "Process", "Provider", "Public Health", "Public Health Informatics", "Quality of life", "Radiation", "Radiation Dose Unit", "Radiation Oncologist", "Radiation therapy", "Readability", "Reporting", "Research", "Research Design", "Research Personnel", "Risk", "Risk Assessment", "Selection for Treatments", "Series", "Severities", "Standardization", "Statistical Methods", "Structure", "Survivors", "Symptoms", "System", "Systems Development", "Techniques", "Time", "Toxic effect", "Training", "Training Activity", "Trismus", "United States", "United States National Institutes of Health", "Vendor", "Work", "Xerostomia", "base", "care coordination", "career development", "clinical center", "clinical data repository", "clinical practice", "craniofacial", "data exchange", "data quality", "design", "electronic data", "evidence base", "experience", "formative assessment", "implementation barriers", "implementation efforts", "implementation evaluation", "implementation outcomes", "implementation science", "implementation strategy", "implementation study", "improved", "individualized prevention", "in" ], "approved": true } }, { "type": "Grant", "id": "10301", "attributes": { "award_id": "1R41AI162083-01A1", "title": "Novel Peptide Fusion Inhibitors for the Treatment of COVID-19", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 6115, "first_name": "DIPANWITA", "last_name": "Basu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-08-23", "end_date": "2023-07-31", "award_amount": 300000, "principal_investigator": { "id": 26257, "first_name": "ROBERT", "last_name": "TARRAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1911, "ror": "", "name": "ELDEC PHARMACEUTICALS, INC.", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "COVID-19 is caused by inhalation of the latest coronavirus (CoV) SARS-CoV-2 into the lungs, and airway epithelia are particularly susceptible to uptake this virus. Extensive evidence indicates that angiotensin converting enzyme 2 (ACE2) binds to the S1 subunit of the SARS-CoV-2 Spike protein (S1), triggering selective proteolytic cleavage that liberates the S2 subunit. S2 undergoes extensive conformational changes to form a 6- helix bundle (6-HB) between Heptad Repeat (HR)-1 and HR-2 domains of S2, which ultimately results in the fusion of the viral particle with the cell membrane and subsequent viral entry. Based on the mechanism of viral entry, and supported by crystallography studies of the ACE2•S1 interface and the 6-HB complex of S2, enormous efforts are currently under way to develop peptide-based therapeutics to target both events: the interaction of SARS-CoV-2 Spike with ACE2 receptor, and the fusion of the viral particle to the cell membrane. We have discovered that exposure of well-differentiated, primary airway epithelial cultures to tobacco smoke for extended periods of time enhances ACE2 activity and increases binding of recombinant S1, which might explain the increased susceptibility of smokers to COVID-19. The Receptor Binding Domain (RBD) in S1 is part of a highly mutable region, as revealed by the appearance of multiple highly infectious SARS-CoV-2 variants in late 2020; thus, targeting this region might not be ideal for antiviral development. In contrast, the HR regions of the S2 subunit and the interaction mode of HR-1 and HR-2 domains within the 6-HB complex are highly conserved among various CoVs, which makes it an optimal target to develop broad-spectrum antivirals. EK1 is a peptide that. The goal of this application is to develop novel peptides that target the HR1 domain of the S2 subunit to inhibit membrane fusion and pseudovirus infection of SARS-CoV-2 as well as several other CoVs. These peptides should serve as broad-spectrum CoV antivirals for the treatment of COVID-19 and subsequent COVIDs. We propose to evaluate the proteolytic stability of several peptides in the hostile environment of the lung, as the main entry way of SARS-CoV-2, including stapled and N-capped peptides with enhanced helical constraint. We will measure the proteolytic stability of the peptides ex vivo using human lung secretions obtained from smokers and non-smokers. We will use primary airway epithelial cells to interrogate the ability of the peptides to inhibit fusion and SARS-CoV-2 pseudovirus infection to healthy and smoke-exposed airway cultures. The efficacy of these peptides will be ultimately evaluated in animal models. This study will address the feasibility of helical mimics to inhibit viral fusion and suppress viral entry into airway epithelia as a novel effective treatment against COVID-19.", "keywords": [ "2019-nCoV", "ACE2", "Address", "Aerosols", "Affinity", "Angiotensin Receptor", "Animal Model", "Antiviral Agents", "Appearance", "Back", "Binding", "Binding Proteins", "Biological Availability", "Bronchoalveolar Lavage", "COVID-19", "COVID-19 therapeutics", "COVID-19 treatment", "Cell membrane", "Cell physiology", "Cell surface", "Cells", "Chemicals", "Chemistry", "Collaborations", "Complex", "Consensus Sequence", "Coronavirus", "Crystallography", "Disease", "Doctor of Philosophy", "Effectiveness", "Environment", "Enzymes", "Epithelial", "Epithelial Cells", "Event", "Formulation", "Glosso-Sterandryl", "Glycoproteins", "Goals", "Guidelines", "HIV", "Head", "Human", "Immunology", "In Vitro", "Infection", "Infection prevention", "Inflammation", "Inhalation", "Inhalators", "Institutes", "Lead", "Leukocyte Elastase", "Lung", "Measures", "Medicine", "Membrane Fusion", "Microbiology", "Modeling", "Molecular Conformation", "Mus", "Nebulizer", "Pathogenicity", "Pathway interactions", "Patients", "Pattern", "Peptide Hydrolases", "Peptides", "Persons", "Pharmacologic Substance", "Pharmacology", "Phase", "Pneumonia", "Powder dose form", "Predisposition", "Primary Infection", "Process", "Proteins", "Proteolytic Processing", "RHO Effector Domain", "Recombinants", "Reproducibility", "Research", "Resistance", "Respiratory Tract Infections", "Risk", "Role", "SARS coronavirus", "Safety", "Severe Acute Respiratory Syndrome", "Severity of illness", "Smoke", "Smoker", "Surface", "Techniques", "Testing", "Therapeutic", "Time", "Tobacco smoke", "Transgenic Mice", "Variant", "Vesicular stomatitis Indiana virus", "Viral", "Virus", "Virus Diseases", "Work", "airway epithelium", "analog", "antiviral drug development", "base", "bronchial epithelium", "coronavirus antiviral", "coronavirus disease", "cytotoxicity", "effective therapy", "exposure to cigarette smoke", "immunogenicity", "improved", "in vivo", "inhibitor", "lead optimization", "neutrophil", "non-smoker", "novel", "novel coronavirus", "pandemic disease", "particle", "peptidomimetics", "prevent", "professor", "receptor", "receptor binding", "uptake" ], "approved": true } } ], "meta": { "pagination": { "page": 4, "pages": 1397, "count": 13961 } } }