Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1405&sort=program_officials
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=program_officials", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1442&sort=program_officials", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1406&sort=program_officials", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1404&sort=program_officials" }, "data": [ { "type": "Grant", "id": "16152", "attributes": { "award_id": "5F31AI191656-02", "title": "Enhancing responses to mRNA-lipid nanoparticle vaccines via utilization of endogenous lipid function", "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": 32556, "first_name": "TIMOTHY A", "last_name": "GONDRE-LEWIS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-01", "end_date": "2028-08-31", "award_amount": 50114, "principal_investigator": { "id": 44234, "first_name": "Emily Frances", "last_name": "Daley", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2627, "ror": "", "name": "UNIVERSITY OF PENNSYLVANIA", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "mRNA - lipid nanoparticle (LNP) vaccines developed against SARS-CoV-2 proved to be a transformative technology that saved millions of lives during the COVID-19 pandemic. In this vaccine platform, LNPs function as both a delivery agent and a powerful adjuvant, but the mechanisms contributing to LNP adjuvanticity are not fully understood, hindering future vaccine design. In this proposal I will investigate how selectively altering the lipids within an LNP impacts biodistribution and cell-specific protein translation from mRNA following intramuscular administration, and whether these alterations can promote stronger cellular and humoral adaptive immune responses. Phosphatidylserine (PS) is a negatively charged phospholipid normally present on the inner leaflet of a cell’s plasma membrane but can become exposed on the outer leaflet during apoptosis. When this occurs, PS is sensed by scavenger receptors of phagocytic antigen presenting cells (APCs), triggering phagocytosis. Globotriaosylceramide (Gb3) is a glycosphingolipid that promotes migration of germinal center B cells from the dark zone to the light zone by enhancing a B cell receptor (BCR) signaling cascade that results in a decrease of CXCR4 expression. By incorporating these endogenous lipids into LNP formulations, this proposal will test if they can direct cell and tissue-specific protein expression from mRNA-LNPs, and if they can impact humoral and cellular immune responses. In Aim 1 I will determine the cellular uptake pathway for these modified LNPs in vitro and their biodistribution in vivo. In Aim 2 I will elucidate how incorporation of PS and Gb3 lipids into LNPs impacts adaptive immune responses in vivo. Overall, I hypothesize that adaptive immune responses to mRNA-lipid nanoparticle vaccines can be specifically modulated based on incorporation of endogenous lipids into the LNP formulation. The ability to alter immune responses to mRNA-LNP vaccines by leveraging endogenous lipid function within an LNP would be hugely beneficial in creating more tailored, effective vaccines against both existing and emerging infectious pathogens.", "keywords": [ "2019-nCoV", "Adjuvant", "Adjuvanticity", "Antibody Affinity", "Antibody Diversity", "Antibody titer measurement", "Antigen-Presenting Cells", "Antigens", "Apoptosis", "Apoptotic", "B-Cell Antigen Receptor", "B-Lymphocytes", "Biodistribution", "CD19 gene", "CD4 Positive T Lymphocytes", "CD8-Positive T-Lymphocytes", "CD8B1 gene", "COVID-19 pandemic", "CXCR4 gene", "Cell membrane", "Cells", "Charge", "Chemicals", "Cholesterol", "Communicable Diseases", "Complex", "Cytosol", "DNA cassette", "Dendritic Cells", "Development", "Disease", "Eating", "Evaluation", "Flow Cytometry", "Formulation", "Fostering", "Future", "Genetic Transcription", "Glycosphingolipids", "Green Fluorescent Proteins", "Helper-Inducer T-Lymphocyte", "Humoral Immunities", "Immune response", "In Vitro", "Inbred BALB C Mice", "Intercalated Cell", "Intramuscular", "Knowledge acquisition", "Light", "Lipids", "Luciferases", "Macrophage", "Malignant Neoplasms", "Measures", "Membrane", "Memory B-Lymphocyte", "Messenger RNA", "Modeling", "Mus", "Nucleosides", "Organ", "Pathway interactions", "Performance", "Phagocytes", "Phagocytosis", "Phosphatidylserines", "Phospholipids", "Plasma Cells", "Population", "Property", "Proteins", "RNA vaccine", "Receptor Signaling", "Scientist", "Shapes", "Signal Transduction", "Structure of germinal center of lymph node", "System", "T cell response", "Technology", "Testing", "Tissues", "Titrations", "Translations", "Vaccinated", "Vaccine Design", "Vaccines", "Variant", "Work", "adaptive immune response", "bioluminescence imaging", "design", "globotriaosylceramide", "immunogenicity", "immunoregulation", "improved", "in vivo", "in vivo imaging", "inhibitor", "intravenous administration", "lipid nanoparticle", "mRNA Expression", "mRNA Translation", "mRNA delivery", "mRNA lipid nano particle vaccine", "migration", "mimicry", "monocyte", "nanoparticle", "pathogen", "prevent", "protein expression", "response", "scavenger receptor", "secondary lymphoid organ", "trafficking", "uptake", "vaccine development", "vaccine platform" ], "approved": true } }, { "type": "Grant", "id": "16161", "attributes": { "award_id": "5K24AI190345-02", "title": "Infection prevention strategies after CAR-T cell therapy", "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": 32556, "first_name": "TIMOTHY A", "last_name": "GONDRE-LEWIS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-03", "end_date": "2030-08-31", "award_amount": 205901, "principal_investigator": { "id": 27940, "first_name": "Joshua Aiden", "last_name": "Hill", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3535, "ror": "", "name": "FRED HUTCHINSON CANCER CENTER", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "Patient-oriented research of infection prevention strategies in chimeric antigen receptor T cell therapy (CARTx) recipients will facilitate improvement in clinical outcomes and a wealth of opportunities for trainees. This award will provide protected time for Dr. Hill to mentor trainees in clinical research related to mitigating the immune-related adverse effects from CARTx, thereby reducing infectious complications. This proposal will study the use of passive and active immunotherapeutic strategies to prevent infections after CARTx, including immunoglobulin replacement therapy (IGRT) and vaccination. In Aim 1, Dr. Hill will conduct the first randomized, controlled, multicenter trial of IGRT in 150 adult CARTx recipients with serum total IgG ≤400 mg/dL at five cancer centers. These data will provide critical insights into the potential risks and benefits of IGRT in this patient population. The key objectives of this study are to evaluate whether IGRT in CARTx recipients reduces infection rates compared to placebo, and to understand the impact of IGRT on cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and healthcare resource utilization. As part of new research supported by this award, patients will be administered a validated survey to evaluate whether IGRT is associated with improvements in health-related quality of life (Aim 3), which will enable future cost-effectiveness research. In Aim 2, Dr. Hill will conduct an open-label clinical trial using an inactivated rabies vaccine in 28 CARTx recipients with relapse-free survival for ≥6 months, in addition to 10 healthy controls. Vaccination after CARTx cell therapy may provide a more durable and cost-effective approach to infection prevention than IGRT, but there are limited data to guide vaccination strategies after CARTx. The objectives of this study are to determine antibody responses, and clinical correlates of vaccine responsiveness, using a rabies virus vaccine as a neoantigen challenge. The rabies vaccine provides a unique tool to assess immune responses while patients are receiving prophylactic immunoglobulin given no or low anti-rabies immunoglobulin in these products. Dr. Hill will build on this infrastructure to study innovative vaccination strategies to improve immunogenicity in immunocompromised patients in Aim 4. He will conduct a pilot study in 20 CARTx recipients using a ‘fractional escalating dose’ delivery for the initial vaccine dose, followed by a booster ‘bolus’ dose. The objectives of this study are to determine whether the fractional escalating dose strategy improves the proportion of patients who develop protective antibody responses, which could shift the paradigm for vaccinating immunocompromised individuals. These aims address critical knowledge gaps in CARTx recipients, provide a robust infrastructure for POR training of physician scientists, and will provide the groundwork for future studies to refine infection prevention strategies in the growing population of CARTx recipients.", "keywords": [ "Address", "Adult", "Antibodies", "Antibody Response", "Area", "Award", "B-Lymphocytes", "Bacterial Infections", "Benefits and Risks", "Bolus Infusion", "CAR T cell therapy", "CD19 gene", "Cancer Center", "Cancer Patient", "Cell Therapy", "Clinical", "Clinical Research", "Clinical Trials", "Communicable Diseases", "Cost Effectiveness Analysis", "Cost effectiveness research", "Coupled", "Data", "Dose", "Funding", "Funding Opportunities", "Future", "Grant", "Health Surveys", "Humoral Immunities", "Immune", "Immune response", "Immunocompromised Host", "Immunoglobulin G", "Immunoglobulin M", "Immunoglobulins", "Immunologics", "Immunotherapeutic agent", "Incidence", "Individual", "Infection", "Infection prevention", "Infrastructure", "Infusion procedures", "Institution", "Kinetics", "Knowledge", "Laboratories", "Longitudinal", "Malignant Neoplasms", "Measures", "Mediating", "Mentors", "Multicenter Trials", "Outcome", "Patient-Focused Outcomes", "Patients", "Performance", "Physicians", "Pilot Projects", "Placebos", "Population", "Prevention strategy", "Rabies", "Rabies Vaccines", "Rabies virus", "Randomized", "Readiness", "Relapse", "Replacement Therapy", "Reporting", "Research", "Research Support", "Research Training", "Residual state", "SF-36", "Safety", "Sampling", "Scientist", "Serum", "Severities", "Surveys", "Time", "Toxic effect", "Training", "Transplantation", "Vaccinated", "Vaccination", "Vaccines", "Work", "antigen challenge", "arm", "biobank", "chimeric antigen receptor T cells", "cost", "cost effective", "cytokine release syndrome", "eHealth", "first-in-human", "health care resource utilization", "health related quality of life", "human study", "immune effector cell-associated neurotoxicity syndrome", "immune function", "immune reconstitution", "immune-related adverse events", "immunogenicity", "improved", "in vivo", "infection rate", "innovation", "insight", "neoantigens", "novel strategies", "open label", "pathogen", "patient oriented research", "patient population", "programs", "prophylactic", "randomized trial", "response", "side effect", "skills", "tool", "training opportunity", "vaccination strategy", "vaccine immunogenicity", "vaccine response", "vaccine trial" ], "approved": true } }, { "type": "Grant", "id": "16162", "attributes": { "award_id": "5K22AI179938-02", "title": "Elucidating the Cardioprotective Role of Fetal-derived CD8+ T Cells During Viral-induced Myocarditis", "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": 32556, "first_name": "TIMOTHY A", "last_name": "GONDRE-LEWIS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-01", "end_date": "2027-08-31", "award_amount": 107997, "principal_investigator": { "id": 44253, "first_name": "Zachary T", "last_name": "Hilt", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3536, "ror": "", "name": "UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "/ Abstract In light of the recent pandemic of SARS-COV-2, clinical observations of myocarditis have become a topic of national and scientific concern, particularly among pediatrics. Many viral infections can lead to myocarditis where immune cells infiltrate the heart, such as cytomegalovirus (CMV). CMV seropositivity has been associated with worse cardiovascular disease later in life, however, the mechanism of how this occurs is unknown. The long- term goal of the applicant is to better understand the role the immune response plays in regulating homeostasis in the heart during development. The objective of this proposal is to establish how T cells made early in life that are recruited into the heart during myocarditis regulate the long-term consequences on cardiovascular disease. We know that fetal and adult derived CD8+ T cells are different in their developmental origin and functional capacity. This proposal will build from my previous work showing that based on timing of CMV infection, either fetal or adult CD8+ T cells are recruited to peripheral tissues and form tissue resident memory (TRM). This proposal will test the hypothesis that early-life CMV infection leads to a skewing of fetal-derived CD8+ T cells that form TRMs that results in increased tissue remodeling phenotype that has a functional impact on the development of cardiovascular disease later in life. In Aim1, I will phenotypically and functionally characterize fetal or adult derived TRMs and their physiological impact on cardiovascular disease progression. Aim 2 will investigate the unique molecular signatures of fetal or adult derived TRMs in the heart using single cell RNA- sequencing. Aim 3 will use spatial transcriptomics to analyze the three-dimensional space that fetal- versus adult-derived TRMs occupy in the heart. These findings will help provide fundamental knowledge to the field about the interplay of the immune response in the heart and address whether CMV seropositivity drives cardiovascular disease. The applicant will be combining their unique pre-doctoral training in cardiovascular disease, signal transduction and innate immune response with postdoctoral training in adaptive immune response, developmental immunology, and virology, making them uniquely qualified to answer these novel and clinically relevant questions. This K22 will be an invaluable asset to the applicant to formation of their own future NIH-funded research on the complex interplay between the immune response and cardiovascular disease.", "keywords": [ "3-Dimensional", "Activities of Daily Living", "Acute", "Acute Disease", "Address", "Adoptive Transfer", "Adult", "Antibodies", "Atherosclerosis", "Bioinformatics", "Biology", "Birth", "Blood Pressure", "Bone Marrow", "CD8-Positive T-Lymphocytes", "CD8B1 gene", "COVID-19 pandemic", "Cardiovascular Diseases", "Cardiovascular Manifestation", "Cardiovascular system", "Cell Physiology", "Cells", "Cellular Indexing of Transcriptomes and Epitopes by Sequencing", "Cessation of life", "Childhood", "Chronic", "Clinical", "Communicable Diseases", "Complex", "Congestive Heart Failure", "Consensus", "Cytomegalovirus", "Cytomegalovirus Infections", "Cytotoxic T-Lymphocytes", "Development", "Disease Progression", "Elderly", "Fetal Liver", "Fire - disasters", "Friends", "Funding", "Future", "Gene Expression Profile", "Genes", "Goals", "Heart", "Heart Diseases", "Heart failure", "Hematopoietic stem cells", "Heterogeneity", "Homeostasis", "Human", "Immune response", "Immunologics", "Infection", "Inflammatory Response", "Injections", "Innate Immune Response", "Knowledge", "Life", "Light", "Link", "Literature", "Maps", "Memory", "Microanatomy", "Modeling", "Molecular Profiling", "Mus", "Myocarditis", "Myocardium", "Neonatal", "Outcome", "Pathogenesis", "Patients", "Pediatrics", "Peripheral", "Phase", "Phenotype", "Physiological", "Play", "Population", "Positioning Attribute", "Qualifying", "Research", "Resolution", "Resources", "Role", "Shapes", "Signal Transduction", "Slide", "T-Lymphocyte", "Techniques", "Testing", "Thymectomy", "Time", "Tissues", "Training", "United States National Institutes of Health", "Viral", "Virus Diseases", "Virus Replication", "Work", "adaptive immune response", "cardioprotection", "chronic myocarditis", "clinically relevant", "cytotoxic CD8 T cells", "developmental immunology", "fetal", "fetus cell", "frailty", "heart function", "immune cell infiltrate", "imprint", "later life", "mortality", "mouse model", "neonatal infection", "neonate", "novel", "pathogen", "post-doctoral training", "pre-doctoral", "recruit", "response", "seropositive", "single-cell RNA sequencing", "spatial transcriptomics", "transcriptome sequencing", "viral myocarditis", "virology" ], "approved": true } }, { "type": "Grant", "id": "16178", "attributes": { "award_id": "5K23AI185318-02", "title": "Defining vaccine immunogenicity and adoptive transfer in hematopoietic stem cell transplant recipients", "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": 32556, "first_name": "TIMOTHY A", "last_name": "GONDRE-LEWIS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-15", "end_date": "2029-08-31", "award_amount": 194400, "principal_investigator": { "id": 44302, "first_name": "Amy Caryn", "last_name": "Sherman", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3545, "ror": "", "name": "BRIGHAM AND WOMEN'S HOSPITAL", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Allogeneic hematopoietic stem cell transplant (HCT) recipients are at high risk of severe morbidity and mortality due to respiratory viral illnesses, including COVID-19. Despite two mRNA SARS-CoV-2 vaccines that are highly effective for the general population, HCT recipients have reduced immune responses to vaccines and remain at risk. This population’s ongoing risk is amplified by the emergence and circulation of SARS-CoV- 2 variant strains, relaxation of mask mandates and other public health measures, and waning effectiveness of SARS-CoV-2 monoclonal antibodies. New vaccination strategies are urgently needed for patients with hematologic malignancies, both to protect these patients and to reduce viral reservoirs that otherwise would allow for generation of new variants. To inform these strategies, we will evaluate the unique role of adoptive transfer of humoral and cellular immunity in HCT recipients, which will simultaneously use vaccine response as a mechanism to evaluate immune reconstitution. These studies will test our overarching hypothesis that these patients have distinct and altered immune responses to mRNA SARS-CoV-2 vaccination, resulting from their underlying disease, past immunomodulatory therapies, and the unique donor-to-recipient immune dynamics. The Specific Aims of this proposal are: Aim 1: Characterize the relationship between donor and recipient SARS-CoV-2 immunity in matched-related donor allogeneic HCT patients through analysis of humoral responses and transfer of immunity post-transplant from banked samples; Aim 2: Describe the correlation between donors’ pre-harvest cellular responses and recipients’ post-transplant humoral SARS-CoV-2 vaccine responses through creation of a prospective study of HCT recipients and their matched-related donors; and Aim 3: Evaluate donor v. recipient Ag-specific T and B cells and SARS-CoV-2 clonal breadth and depth after re-vaccination post-transplant to assess immune reconstitution, using T and B cell receptor repertoire analyses methods. We expect that completion of these aims and the associated training objectives will generate clinically applicable preliminary data to inform vaccine development and policy for patients with hematologic malignancies. My long-term career goal is to become an independently funded clinician-scientist and leader in translational vaccinology with a focus on developing precision vaccines for immunocompromised adults. I will achieve this through: 1) investigation of immunologic pathways that promote or inhibit vaccine-induced responses for patients with hematological malignancies, and 2) translation of these findings into novel vaccines via early-phase clinical trials. Brigham and Women’s Hospital and the Precision Vaccines Program at Boston Children’s Hospital are highly collaborative research environments within the broader Harvard Medical School community that will provide abundant resources and institutional support to complete the described aims.", "keywords": [ "2019-nCoV", "Adoptive Transfer", "Adult", "Affinity", "Allogenic", "Antibodies", "Antibody Response", "Antigens", "B cell clonality", "B cell reconstitution", "B-Cell Antigen Receptor", "B-Lymphocytes", "Bioinformatics", "Biometry", "Blood specimen", "Boston", "COVID-19", "COVID-19 vaccination", "COVID-19 vaccine", "Cell Physiology", "Cells", "Cellular Immunity", "Centers for Disease Control and Prevention (U.S.)", "Childhood", "Chimerism", "Circulation", "Clinical", "Clinical Research", "Cohort Studies", "Communicable Diseases", "Communities", "Data", "Defect", "Development", "Disease", "Dissection", "Dose", "Effectiveness", "Environment", "Evolution", "Fostering", "Frequencies", "Funding", "Gene Amplification", "General Population", "Generations", "Goals", "Guidelines", "Harvest", "Hematologic Neoplasms", "Hematopoietic Stem Cell Transplantation", "Histocompatibility Antigens", "Hospitals", "Humoral Immunities", "Immune", "Immune response", "Immunity", "Immunocompromised Host", "Immunoglobulin G", "Immunologics", "Immunology", "Impairment", "Individual", "Infection", "Influenza", "Institution", "Investigation", "K-Series Research Career Programs", "Kinetics", "Laboratories", "Laboratory Study", "Learning", "Link", "Longitudinal", "Longitudinal cohort", "Masks", "Measures", "Memory B-Lymphocyte", "Mentors", "Mentorship", "Methods", "Modeling", "Monoclonal Antibodies", "Morbidity", "Mutate", "Pathway interactions", "Patients", "Pediatric Hospitals", "Phenotype", "Plasma", "Policies", "Population", "Predisposition", "Prevention", "Prevention Guidelines", "Prospective Studies", "Prospective cohort", "Public Health", "RNA vaccine", "Recommendation", "Recording of previous events", "Relaxation", "Research", "Research Design", "Resources", "Risk", "Role", "SARS-CoV-2 antigen", "SARS-CoV-2 exposure", "SARS-CoV-2 immunity", "SARS-CoV-2 mRNA vaccination", "SARS-CoV-2 mRNA vaccine", "SARS-CoV-2 variant", "Sampling", "Scientist", "Seasons", "Series", "Serum", "Stem cell transplant", "T-Cell Receptor", "T-Cell Receptor Genes", "T-Lymphocyte", "Technology", "Testing", "Training", "Translations", "Transplant Recipients", "Transplantation", "Vaccinated", "Vaccination", "Vaccines", "Variant", "Viral", "Viral reservoir", "Virus", "Vulnerable Populations", "Woman", "Work", "antigen-specific T cells", "career", "chemotherapy", "clinical application", "clinical translation", "early phase clinical trial", "e" ], "approved": true } }, { "type": "Grant", "id": "15695", "attributes": { "award_id": "1R21AI192087-01A1", "title": "PET to Assess Post-TB Lung Disease in TB Patients with / without HIV coinfection", "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": 32558, "first_name": "BARBARA E", "last_name": "LAUGHON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-01", "end_date": "2027-06-30", "award_amount": 427000, "principal_investigator": { "id": 21010, "first_name": "Sanjay", "last_name": "Jain", "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": "Mycobacterium tuberculosis remains the second leading cause of death from a single infectious agent globally, after COVID-19. The risk of developing tuberculosis (TB) is substantially higher in human immunodeficiency virus (HIV) coinfected individuals, with TB and HIV potentiating each other, causing substantial declines in immune function. Globally in 2022, there were an estimated 1.3 million deaths and 10.6 million new cases due to TB. Importantly, it is estimated that more than 58 million patients have survived TB in this century alone. However, unlike other respiratory infections, many patients with TB have permanently damaged tissues and successful TB treatments only transition these patients from harboring a communicable infectious disease, to a syndrome of chronic pulmonary morbidity. This syndrome, commonly referred as post- TB lung disease, affects ~50% of patients with pulmonary TB, who develop chronic adverse outcomes beyond the TB treatments, including bronchiectasis, poor lung function and respiratory symptoms. Although post-TB lung disease remains poorly characterized, it is primarily mediated by M. tuberculosis-induced tissue destruction (necrosis) and subsequent adverse lung tissue remodeling and fibrosis, which in addition to causing pulmonary disease, also impairs vascular supply and reduces antibiotic access to the infected TB lesions. Currently, there are no approved treatments to prevent post-TB lung disease. We have characterized lung disease in animal models of TB to develop adjunctive treatments that prevent post-TB lung disease. Importantly, we have also developed and utilized novel, clinically translatable positron emission tomography (PET)-based imaging to longitudinally profile lesional characteristics in animal models and TB patients: 11C-rifampin (chemically identical to rifampin) PET to measure tissue antibiotic area under the curve exposures (Ordonez . . . Jain. Nat Med. 2020) and 18F-FAPI-74 PET for monitoring fibrosis. Our central hypothesis is that 18F-FAPI-74 PET could be used as a noninvasive biomarker to assess post-TB lung disease and fibrosis in TB patients. Additionally, we hypothesize that lesions with significantly reduced 11C-rifampin exposures in TB patients within 6-weeks of treatment initiation (early time-point) will develop post-TB lung disease sequelae at those sites after 6-months of TB treatments. Here, we will leverage our expertise in TB pathogenesis and molecular imaging to conduct longitudinal, observational studies to visualize lesional rifampin exposures and lung fibrosis in patients with recently diagnosed pulmonary TB, with or without HIV coinfection, within 6-weeks and after 6-months of initiating TB treatments. Our goals are to better characterize post-TB lung disease sequelae and identify key factors, such as lesional antibiotic exposures in TB patients that could subsequently lead to post-TB lung disease. In the future, we anticipate that these imaging approaches could be used to noninvasively characterize post TB-lung disease and evaluate novel treatments that prevent or mitigate post TB-lung disease.", "keywords": [ "3-Dimensional", "Affect", "Aftercare", "Animal Model", "Animals", "Antibiotics", "Apoptotic", "Area Under Curve", "BCL2 gene", "Biological Availability", "Biological Markers", "Biological Sciences", "Bronchiectasis", "COVID-19", "Cause of Death", "Cessation of life", "Characteristics", "Chemicals", "Chronic", "Clinical Trials", "Communicable Diseases", "Data", "Diagnosis", "Fibrosis", "Future", "Goals", "HIV", "HIV/TB", "Human", "Image", "Imaging technology", "Impairment", "Individual", "Infectious Agent", "Laboratories", "Lead", "Lesion", "Ligands", "Longitudinal observational study", "Lung", "Lung Diseases", "Measures", "Mediating", "Molecular", "Monitor", "Morbidity - disease rate", "Morphologic artifacts", "Multimodal Imaging", "Mycobacterium tuberculosis", "Necrosis", "Necrosis Induction", "Observational Study", "Oral", "Parents", "Pathogenesis", "Patient Recruitments", "Patients", "Penetration", "Physiology", "Positron-Emission Tomography", "Process", "Pulmonary Fibrosis", "Pulmonary Tuberculosis", "Recommendation", "Research", "Respiratory Signs and Symptoms", "Respiratory Tract Infections", "Rifampin", "Risk", "Safety", "Sampling Biases", "Site", "Spirometry", "Structure of parenchyma of lung", "Syndrome", "Testing", "Time", "Tissues", "Tuberculosis", "Vascular blood supply", "Visualization", "X-Ray Computed Tomography", "adverse outcome", "cancer clinical trial", "cancer therapy", "clinical translation", "co-infection", "early phase clinical trial", "fibroblast-activating factor", "fibrotic lung", "human subject", "idiopathic pulmonary fibrosis", "imaging approach", "imaging biomarker", "immune function", "improved", "inhibitor", "lung injury", "molecular imaging", "novel", "prevent", "pulmonary", "pulmonary function", "research clinical testing", "small molecule", "tool", "tuberculosis treatment" ], "approved": true } }, { "type": "Grant", "id": "15696", "attributes": { "award_id": "1R13TR005695-01", "title": "2025 Nucleosides, Nucleotides and Oligonucleotides Gordon Research Conference and Gordon Research Seminar", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Center for Advancing Translational Sciences (NCATS)" ], "program_reference_codes": [], "program_officials": [ { "id": 32559, "first_name": "PJ", "last_name": "BROOKS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-01", "end_date": "2025-10-31", "award_amount": 13390, "principal_investigator": { "id": 7349, "first_name": "ERIKS", "last_name": "ROZNERS", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 890, "ror": "", "name": "STATE UNIVERSITY OF NY,BINGHAMTON", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 226, "ror": "https://ror.org/05rad4t93", "name": "Gordon Research Conferences", "address": "", "city": "", "state": "RI", "zip": "", "country": "United States", "approved": true }, "abstract": "This proposal seeks funding to support the 2025 Nucleosides, Nucleotides and Oligonucleotides (NNO) Gordon Research Conference (GRC) and the associated Gordon Research Seminar (GRS). This will be the 22nd edition of this conference, initiated in 1976. Throughout its history, NNO GRC has addressed topics directly related to the fundamental science of human biology and the treatment of disease. Modified nucleosides have been extremely effective drugs, most notably antivirals such as AZT and Harvoni, for the treatment of HIV/AIDS and hepatitis C, respectively. Meanwhile, the field has undergone transformative changes to include oligonucleotides as therapeutics for metabolic and genetic diseases, for example Spinraza, which treats spinal muscular atrophy. The recent invention of mRNA vaccines to prevent COVID is another compelling example of the transformative impact of modified nucleosides. The 2025 NNO GRC, entitled “Challenges at the Interface of Structure, Function and Chemistry of Nucleosides and Nucleic Acids” will cover the fundamental science that enabled the recent success of nucleic acid therapeutics while focusing on cutting-edge, current research in novel and emerging technologies. The specific aims for the conference are to: (1) facilitate discussions of the latest research in the field; (2) introduce early-career and inexperienced scientists to the field; and (3) provide opportunities for new collaborations and networking. These specific aims will contribute to the long-term goal of the conference to have a broad and sustainable impact on both basic science and clinical translation of nucleosides, nucleotides and oligonucleotides into therapeutics to improve human health. The 2025 NNO GRC will include sessions on (1) RNA epigenetics, modification and translation, (2) synthesis and chemistry of modified nucleotides, (3) genome and RNA editing, (4) nucleic acids chemical biology, and (5) oligonucleotide therapeutics. Co-Chairs have solicited nominations from experts in the field, emphasizing the desire to identify young scientists as potential speakers. The affiliated Gordon Research Seminar (GRS) will feature oral presentations by students and postdocs, a panel discussion with established scientists in the field, and the opportunity to create a sense of community prior to the start of the GRC. Thus, while the cutting-edge science described during the oral sessions will undoubtedly inspire others to move their own research forward in new and creative ways, the combined GRS and GRC efforts to support young and early-career scientists in general will strengthen the field and its impact on human health for decades to come.", "keywords": [ "Address", "Anti-viral Agents", "Antibiotics", "Attitude", "Basic Science", "Biology", "COVID-19 vaccine", "Calibration", "Chemicals", "Chemistry", "Clinic", "Collaborations", "Communities", "Creativeness", "Development", "Disease", "Emerging Technologies", "Employment Opportunities", "Environment", "Epigenetic Process", "Funding", "Funding Agency", "Future", "Genetic Diseases", "Goals", "Government", "HIV/AIDS", "Health", "Hepatitis C", "Human", "Human Biology", "Industrialization", "Industry", "Institution", "International", "Knowledge", "Laboratories", "Learning", "Marketing", "Mentors", "Messenger RNA", "Metabolic Diseases", "Modification", "Nucleic Acids", "Nucleosides", "Nucleotides", "Occupations", "Oligonucleotides", "Oral", "Pharmaceutical Preparations", "Postdoctoral Fellow", "Purine Nucleosides", "RNA", "RNA Editing", "RNA vaccine", "Recording of previous events", "Research", "Research Personnel", "Science", "Scientist", "Spinal Muscular Atrophy", "Structure", "Students", "Therapeutic", "Time", "Translations", "Vaccines", "Virus Diseases", "Writing", "Zidovudine", "career", "clinical application", "clinical translation", "drug development", "drug discovery", "effective therapy", "genome editing", "graduate student", "improved", "insight", "interest", "invention", "new technology", "next generation", "nucleic acid-based therapeutics", "oligonucleotide therapeutics", "posters", "professor", "recruit", "remdesivir", "small molecule", "social group", "success", "symposium", "synergism" ], "approved": true } }, { "type": "Grant", "id": "15740", "attributes": { "award_id": "1R43TR005424-01", "title": "A Novel Approach to Eliminate Length Impurities for High-Quality mRNA Production", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Center for Advancing Translational Sciences (NCATS)" ], "program_reference_codes": [], "program_officials": [ { "id": 32559, "first_name": "PJ", "last_name": "BROOKS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2026-07-31", "award_amount": 349746, "principal_investigator": { "id": 32603, "first_name": "Hari", "last_name": "Bhaskaran", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2611, "ror": "", "name": "CISTERNA BIOLOGICS, INC.", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "With the success of mRNA-based Covid vaccines, there is immense interest in leveraging mRNA technology to develop therapeutics for previously untreatable diseases. However, therapeutic applications, such as protein replacement therapy, cardiovascular regeneration, and cancer immunotherapy, require mRNA of exceptional purity to ensure safety and efficacy. Current mRNA production methods often yield mRNA with impurities, such as double-stranded RNA (dsRNA), long RNA (LRNA), and short truncated (stRNA), which can provoke immune responses and compromise therapeutic outcomes. Cisterna has developed an innovative platform capable of synthesizing high-quality, purified mRNA, devoid of product-related contaminants, making it ideal for therapeutic use while ensuring consistency and reproducibility across batches. In this Phase I SBIR, our goal is to demonstrate the efficacy of our technology in eliminating dsRNA, LRNA, and stRNA compared to conventional methods. We will employ sensitive fluorescence-based methods and assays to quantify and eliminate these impurities, enabling the production of highly pure therapeutic mRNA. Furthermore, we will validate our technology by assessing its impact on immunogenic response and protein expression in mice, aiming for minimal to no immune activation while maintaining or enhancing therapeutic efficacy. Successful completion of this project will provide a validated production platform for contaminant-free mRNA synthesis, paving the way for Phase II studies focused on target identification, construct design, and scale-up manufacturing. The mRNA therapeutics market is poised for significant growth, with biotech and pharmaceutical companies actively developing mRNA-based therapeutics. We aim to leverage potential partnerships to position ourselves as a key player in this dynamic field.", "keywords": [ "Address", "Advanced Development", "Affect", "Antibodies", "Biological Assay", "Biological Products", "Biotechnology", "COVID-19 vaccine", "Cardiovascular system", "Catalytic RNA", "Cellulose", "Consumption", "Detection", "Development", "Disease", "Dose", "Dot Immunoblotting", "Double-Stranded RNA", "Engineering", "Ensure", "Enzymes", "Event", "Excision", "Fluorescence", "Gel", "Goals", "Growth", "Hela Cells", "High Pressure Liquid Chromatography", "Immune", "Immune response", "Innate Immune Response", "Legal patent", "Length", "Longevity", "Luciferases", "Malignant Neoplasms", "Marketing", "Measures", "Messenger RNA", "Metabolic", "Methods", "Modeling", "Mus", "Natural regeneration", "Pharmacologic Substance", "Phase", "Positioning Attribute", "Process", "Production", "RNA", "Rare Diseases", "Recovery", "Reference Standards", "Regimen", "Reproducibility", "Safety", "Sepharose", "Small Business Innovation Research Grant", "Technology", "Technology Assessment", "Testing", "Therapeutic", "Therapeutic Uses", "Time", "Treatment Efficacy", "Validation", "Variant", "Work", "cancer immunotherapy", "commercial application", "cost", "cytokine", "design", "design and construction", "detection limit", "dosage", "drug development", "effective therapy", "enzyme replacement therapy", "high standard", "immune activation", "immunogenic", "immunogenicity", "in vivo", "innovation", "interest", "manufacturing scale-up", "mouse model", "multiplex assay", "novel strategies", "oligo (dT)", "phase 2 study", "prophylactic", "protein expression", "research and development", "response", "success", "therapy development", "therapy outcome", "tool", "transcriptome sequencing" ], "approved": true } }, { "type": "Grant", "id": "15697", "attributes": { "award_id": "1R35GM158174-01", "title": "Multifunctionalized lipid derivatives", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 32560, "first_name": "KADIR", "last_name": "ASLAN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-01", "end_date": "2030-06-30", "award_amount": 394214, "principal_investigator": { "id": 32561, "first_name": "Carsten", "last_name": "Schultz", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 765, "ror": "https://ror.org/009avj582", "name": "Oregon Health & Science University", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true }, "abstract": "It is well understood how lipids are synthesized and metabolized in cells and that many lipids exhibit signalling functions to regulate cellular processes in a spatially and temporally defined way. The latter requires the build- up and turnover of lipid species in membranes either in a site-specific fashion or, alternatively, a directed form of lipid transport. This work aims to investigate the intracellular transfer of lipids from one membrane to another by several proteins that we discovered to be involved in lipid transport. In the previous funding period, we synthesized multifunctional lipid derivatives of five phosphoinositides and four common glycerophospholipids. These feature a photo-activatable protecting group (”cage”) to release the lipid derivative by light and a photo-crosslinking diazirine to covalently attach the lipid derivative to binding proteins. An alkyne group for click chemistry is useful for isolating lipid-protein conjugates or for determining the lipid location in cells by fluorescent tagging and microscopy. In published work, we identified specific lipid binding proteins for phosphatidylinositol 3,4,5-trisphosphate (PIP3), phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2], and phosphatidylinositol (PI) via proteomic analysis. We then used siRNAs to block lipid transport and validated two hits that were required for transporting PIP3 and PI(3,4)P2: cytosolic MPP6 and transmembrane ATP11A. This R35 application proposes the continuation of work described in the application of R01 GM127631, namely the characterization of the lipid transport by the two above mentioned proteins (Project 1). This includes the purification and characterization of recombinant proteins and their functional mutants. We will use purified proteins to determine the 3D structure of MPP6 and its mutants by cryo-electron microscopy with and without crosslinked lipid derivatives. In Project 2, we will synthesize lipid derivatives featuring the photo-crosslinking diazirine closer to the membrane interphase to reach more transiently binding proteins such as those with a PH domain. Comparative proteomic analysis of the lipid interactomes will then be used to identify proteins involved in signalling with and without receptor stimulation. In Project 3, we will use multifunctional lipid derivatives to investigate the lipid interactomes of healthy and virus-infected cells. We recently discovered that an RNA virus infection leads to massive changes in the host cell lipidome. One exciting aspect is that one group of cellular phosphoinositides featuring a particular fatty acid composition is strongly up regulated. We will measure the lipid interactomes of flavivirus- and COVID-infected cells and identify targets crucial for viral infection and replication. Hits will be validated by protein knock-down and the effect on virus infection will be studied. Our unique lipid tools will help to better understand the lipid and lipid binding components of a viral infection.", "keywords": [ "Alkynes", "Binding Proteins", "COVID-19", "Carrier Proteins", "Cell Physiology", "Cells", "Chemistry", "Cryoelectron Microscopy", "Diazomethane", "Exhibits", "Fatty Acids", "Flavivirus", "Funding", "Glycerophospholipids", "Interphase", "Light", "Lipid Binding", "Lipids", "Location", "Measures", "Membrane", "Microscopy", "Modification", "PH Domain", "Phosphatidylinositols", "Proteins", "Proteomics", "Publishing", "RNA Virus Infections", "Recombinant Proteins", "Signal Transduction", "Site", "Small Interfering RNA", "Virus", "Virus Diseases", "Virus Replication", "Work", "comparative", "crosslink", "knock-down", "lipid transport", "lipidome", "mutant", "phosphatidylinositol 3 4 5-triphosphate", "phosphatidylinositol 3 4-diphosphate", "protein purification", "receptor", "three dimensional structure", "tool" ], "approved": true } }, { "type": "Grant", "id": "15698", "attributes": { "award_id": "4R44AI179588-02", "title": "3STEP: A swab-seal-read assay for tuberculosis and RIF resistance enabled by autonomous extraction technology", "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": 32562, "first_name": "KAREN A", "last_name": "LACOURCIERE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-03", "end_date": "2027-06-30", "award_amount": 1000000, "principal_investigator": { "id": 31601, "first_name": "Jay Wyatt", "last_name": "Warrick", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2509, "ror": "", "name": "SALUS DISCOVERY, LLC", "address": "", "city": "", "state": "WI", "zip": "", "country": "United States", "approved": true }, "abstract": "In 2021 there were 10.6 million new cases of Mycobacterium tuberculosis (TB) and 1.6 million TB-related deaths, making TB the second leading infectious cause of death worldwide behind only COVID-19. Standard TB diagnostic methods are insufficient in that they either 1) utilize challenging sample types and are often invasive (e.g., sputum, gastric aspiration, lymph node biopsy), 2) lack sufficient sensitivity and/or specificity (e.g., culture, reliance on clinical observation alone), or 3) cannot be widely implemented in community point-of-care (POC) settings. As a result, there remains a significant unmet need for affordable POC technologies that can be used at local or temporary clinics, urgent care facilities, pharmacies, and school health clinics with easier to acquire samples (e.g., urine or oral swabs). In addition, TB is notoriously difficult to lyse adding another challenge to the creation of a POC solution. Salus Discovery has developed 3STEP, a new LAMP-based POC NAT for TB that directly overcomes the above mentioned challenges. 3STEP provides lab-quality, PCR sensitivity (<10 CFU/swab analytical sensitivity) with the speed and simplicity of a lateral flow assay (LFA), (i.e., a simple tongue swab, 3 user steps, no liquid transfers, and results within ~30 minutes). 3STEP also addresses challenges of spectral multiplexing in LAMP reactions by enabling spatial multiplexing for integrated detection of drug-resistant infections. Importantly, our novel stabilized interface technology (SIFT) used to create 3STEP enables both an ultra-cheap disposable and an affordable isothermal instrument design. In this SBIR Fast Track Phase I/Phase II proposal we will continue developing 3STEP for the detection of TB and rifampin resistant (RR) TB from tongue swabs by: In Aim 1 (Phase I), optimizing 3STEP for TB oral swabs using contrived samples, including designing and implementing RR testing into the spatial multiplexing capabilities of 3STEP; In Aim 2 (Phase I), prototyping and testing a POC lysis module; In Aim 3 (Phase I), assessing clinical sensitivity in a small pilot study using bio-banked samples collected through FIND’s FEND-TB program; In Aim 4 (Phase II), finalizing the 3STEP assay and consumable for an expanded clinical evaluation; And in Aim 5 (Phase II), performing a larger scale clinical evaluation of the multiplexed 3STEP TB/RR assay. Results will be important to subsequent funding efforts for 3STEP commercial development (assay and reader) and to demonstrate field-readiness for participation in TB diagnostic evaluation studies similar to R2D2, DriveDx4TB, SMART4TB, and FEND-TB.", "keywords": [ "Address", "Benchmarking", "Binding", "Biological Assay", "Budgets", "COVID-19", "Cause of Death", "Cessation of life", "Chemistry", "Clinic", "Clinical", "Clinical Sensitivity", "Closure by clamp", "Collection", "Communities", "Consultations", "Cytolysis", "DNA", "Detection", "Development", "Devices", "Diagnostic Procedure", "Diagnostic tests", "Disease", "Drug resistance", "Dryness", "Ensure", "Evaluation", "Evaluation Studies", "Freeze Drying", "Funding", "Future", "Health Care Facility", "Infection", "Injections", "Learning", "Liquid substance", "Manufacturer", "Methods", "Molds", "Molecular", "Mutation", "Mycobacterium tuberculosis", "Oral", "Oral Tuberculosis", "Organism", "Patients", "Performance", "Pharmacy facility", "Phase", "Pilot Projects", "Point of Care Technology", "Polymorphism Analysis", "Preparation", "Reaction", "Reader", "Readiness", "Recommendation", "Rifampicin resistance", "Sampling", "Single Nucleotide Polymorphism", "Small Business Innovation Research Grant", "Specificity", "Speed", "Sputum", "Stomach", "Swab", "Technology", "Testing", "Time", "Tongue", "Tube", "Tuberculosis", "Ultrasonics", "Urine", "Validation", "aspirate", "assay development", "biobank", "commercialization", "cost", "design", "drug testing", "feasibility testing", "instrument", "instrumentation", "lateral flow assay", "lymph node biopsy", "novel", "point of care", "point-of-care diagnostics", "programs", "prototype", "research clinical testing", "resistant strain", "resistant tuberculosis", "school based health center", "seal", "stability testing", "tuberculosis diagnostics", "urgent care" ], "approved": true } }, { "type": "Grant", "id": "15781", "attributes": { "award_id": "1R01AI183979-01A1", "title": "Expanding access and impact of tuberculosis preventive therapy: Community-friendly delivery and monitoring of TPT to improve uptake and reduce TB transmission", "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": 32562, "first_name": "KAREN A", "last_name": "LACOURCIERE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-19", "end_date": "2030-07-31", "award_amount": 690538, "principal_investigator": { "id": 28321, "first_name": "ADRIENNE E", "last_name": "SHAPIRO", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2645, "ror": "", "name": "UNIVERSITY OF WASHINGTON", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "Enter the text here that is the new abstract information for your application. International and Kenyan guidelines recommend TB preventive therapy (TPT) for people with HIV (PWH) and other people at high risk for TB, including close contacts of people with TB. Despite the evidence for reduced morbidity and mortality for people with HIV (PWH) who receive TPT, and guidelines recommending use, there remains a substantial gap between people recommended to receive and people who actually receive and complete a course of TPT. The 2022 WHO Global TB Report highlighted the growing gap in access and provision of TPT, which has been aggravated by the COVID-19 pandemic. Bridging this gap is a Kenyan and global priority. With the recent availability and evidence for newer, shorter regimens of TPT, a transformation of HIV care delivery models (in part forced by the COVID-19 pandemic) and evolving national guidelines for TPT, it is increasingly urgent to explore new person-friendly models of TPT delivery to inform programmatic guidance that results in greater uptake, adherence, and completion of TPT. HIV care transformed to adopt “differentiated service delivery” (DSD) models, which encourage community-delivered care, infrequent clinic/facility visits, multi- month dispensing, limited laboratory monitoring, and task-shifted treatment models to deliver comprehensive HIV care to stable adults in community settings. These successful models for differentiated HIV care delivery may be able to be adapted to include TPT. The availability of safe, effective, short-course TPT (i.e. 3HP, 3HR) with limited monitoring requirements suggests that similar community-based and multi-month dispensing models may be adapted to scale essential TPT to populations who most need it, including PWH, young child contacts, and all household contacts of people with TB. We will explore two approaches of adapting HIV differentiated services to TB prevention. We hypothesize that people who receive differentiated TPT delivery have higher rates of completion of a course of TPT than people who receive standard-of-care clinic-based TPT. We will 1) conduct a randomized controlled trial of DSD care (multi-month dispensing) vs. clinic standard-of-care TPT delivery in two priority populations for TPT in Kenya: household contacts of people with TB and PWH, 2) investigate the impact of DSD TPT on household and community TB transmission with follow-up testing and mathematical modeling, and 3) examine preferences, barriers and facilitators of TPT completion and TPT implementation using qualitative research. Together, this research will establish the foundation for implementation studies of optimized patient and community-friendly, differentiated TPT delivery approaches to increase TPT uptake and completion in Kenya and ultimately decrease morbidity, transmission, and mortality from TB.", "keywords": [ "Adherence", "Adopted", "Adult", "Adverse effects", "Biological Assay", "COVID-19 pandemic", "Caring", "Cessation of life", "Child", "Client", "Clinic", "Clinical", "Communicable Diseases", "Communities", "Dose", "Drug resistance in tuberculosis", "Eligibility Determination", "Focus Groups", "Foundations", "Friends", "Goals", "Guidelines", "HIV", "HIV/TB", "Health system", "Home", "Household", "Incidence", "Individual", "Interferon Type II", "International", "Interview", "Kenya", "Laboratories", "Measures", "Methodology", "Methods", "Modeling", "Monitor", "Morbidity - disease rate", "Patients", "Persons", "Pharmaceutical Preparations", "Population", "Prevention", "Preventive therapy", "Qualitative Research", "Randomized", "Randomized Controlled Trials", "Recommendation", "Regimen", "Reporting", "Research", "Schedule", "Service delivery model", "Services", "Testing", "Text", "Time", "Toxic effect", "Travel", "Treatment Protocols", "Tuberculosis", "Tuberculosis diagnosis", "Visit", "World Health Organization", "care delivery", "community setting", "cost", "experience", "follow-up", "gaps in access", "health care delivery", "high risk", "immunoreactivity", "implementation strategy", "implementation study", "improved", "informant", "innovation", "isoniazid", "mathematical model", "mortality", "person centered", "pill", "preference", "prevent", "preventable death", "rifapentine", "scale up", "screening", "service delivery", "standard of care", "supply chain", "transmission process", "treatment as usual", "trial comparing", "uptake" ], "approved": true } } ], "meta": { "pagination": { "page": 1405, "pages": 1442, "count": 14420 } } }