Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=4&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=1419&sort=-program_officials", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=5&sort=-program_officials", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=3&sort=-program_officials" }, "data": [ { "type": "Grant", "id": "15886", "attributes": { "award_id": "1R01DA061028-01A1", "title": "Thyroid hormone mediated reprogramming of the basolateral amygdala by adolescent social deprivation", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Drug Abuse (NIDA)" ], "program_reference_codes": [], "program_officials": [ { "id": 44321, "first_name": "DA-YU", "last_name": "WU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-30", "end_date": "2030-05-31", "award_amount": 623650, "principal_investigator": { "id": 44322, "first_name": "Deena M.", "last_name": "Walker", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2648, "ror": "", "name": "OREGON HEALTH & SCIENCE UNIVERSITY", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true }, "abstract": "Social disconnection in humans, particularly during adolescence, is associated with substance use disorder vulnerability. In mice, adolescent social isolation profoundly alters reward processing in adulthood; increasing the preference for drugs of abuse, enhancing associative learning, altering dopaminergic signaling and transcription within the BLA and extended reward circuitry. Intriguingly, these phenomena are all also associated with thyroid hormone signaling. Further, dysregulation of thyroid hormone in early life is associated lifetime risk for reward-related mood disorders and altered development of monoaminergic systems. In adults, thyroid hormone dysregulation is associated with substance- and alcohol use disorders. Therefore, we propose that the persistent impacts of adolescent social isolation result from transient dysregulation of thyroid hormone signaling during the sensitive period of adolescence. Thyroid hormones, when bound to their receptors, are transcription factors that mediate various epigenetic processes and regulate gene expression. Aberrant thyroid hormone signaling at critical developmental periods persistently alters transcription in other tissues through epigenetic reprogramming of thyroid hormone sensitive genes. Despite its critical role in neurodevelopment and its link to substance use disorder, the consequences of thyroid hormone dysregulation in adolescence, a key period for reward circuitry development and substance use disorder vulnerability, is virtually unknown. Our preliminary data suggest that circulating thyroid hormones and expression of its receptors are transiently disrupted in adolescence by social isolation and this is associated with enhanced expression of GABAergic neuronal markers in the adult basolateral amygdala (BLA), a key reward-related brain region Here, we will test the hypothesis that thyroid hormone is critical for development of the basolateral amygdala (BLA) during adolescence and that isolation-induced disruptions to the thyroid hormone system result in lasting epigenetic reprogramming of the reward circuitry to increase cocaine sensitivity. First, we will determine how adolescent social isolation impacts thyroid hormone-mediated transcription in the BLA (Aim 1). Then we will determine if thyroid hormone dysregulation induced by adolescent isolation disrupts cell-type specific transcriptional profiles within the BLA (Aim 2). Finally, we will disrupt thyroid hormone receptor beta levels specifically during adolescence to determine its role in reward-related behavior in (Aim 3). Together, these foundational studies will establish a role for thyroid hormone-mediated programming of the BLA and uncover novel mechanisms of isolation-induced reprogramming of SUD vulnerability during adolescence - an endpoint that has become even more urgent given the known reductions in social interactions due to the mitigation of Covid-19 for the current generation of adolescents.", "keywords": [ "Acute", "Address", "Adolescence", "Adolescent", "Adult", "Agonist", "Amygdaloid structure", "Animals", "Association Learning", "Behavior", "Behavioral", "Binding", "Brain", "Brain region", "COVID-19", "Cell Nucleus", "Cells", "Cleavage Under Targets and Release Using Nuclease", "Cocaine", "Data", "Development", "Environment", "Epigenetic Process", "Exhibits", "Gene Expression", "Gene Expression Profile", "Generations", "Genes", "Genetic Transcription", "Goals", "House mice", "Human", "Individual", "Intervention", "Life", "Link", "Loneliness", "Measures", "Mediating", "Messenger RNA", "Mood Disorders", "Mus", "Neurons", "Peripheral", "Phenocopy", "Positioning Attribute", "Predisposition", "Procedures", "RNA", "Rewards", "Risk Factors", "Role", "Self Administration", "Signal Transduction", "Social Interaction", "Social isolation", "Substance Use Disorder", "System", "Testing", "Thyroid Hormone Receptor", "Thyroid Hormone Receptor β", "Thyroid Hormones", "Time", "Tissues", "Triiodothyronine", "Upregulation", "Work", "addiction", "adolescent brain development", "alcohol use disorder", "cell type", "critical developmental period", "drug of abuse", "drug reward", "experience", "experimental study", "hormonal signals", "knock-down", "later life", "lifetime risk", "mature animal", "molecular phenotype", "neurodevelopment", "new therapeutic target", "novel", "overexpression", "peer", "pre-clinical", "preference", "programs", "receptor", "response", "reward circuitry", "reward processing", "social", "social deprivation", "substance use", "thyroid disruption", "transcription factor", "transcriptional reprogramming", "transcriptome sequencing", "virtual" ], "approved": true } }, { "type": "Grant", "id": "15885", "attributes": { "award_id": "1U48DP006966-01", "title": "BREATHE WELL: Development and Implementation of a Training Program to Increase Vaccination in Early Childcare and Education Centers", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Center for Immunization and Respiratory Diseases (NCIRD)" ], "program_reference_codes": [], "program_officials": [ { "id": 44318, "first_name": "NATALIE", "last_name": "DARLING", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-30", "end_date": "2029-09-29", "award_amount": 499950, "principal_investigator": { "id": 44319, "first_name": "Roshanak", "last_name": "Mehdipanah", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 25237, "first_name": "Marc A", "last_name": "Zimmerman", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [ { "id": 770, "ror": "", "name": "UNIVERSITY OF MICHIGAN AT ANN ARBOR", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true } ] }, { "id": 44320, "first_name": "Abram Luther", "last_name": "Wagner", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 770, "ror": "", "name": "UNIVERSITY OF MICHIGAN AT ANN ARBOR", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT Early childcare and education (ECE) centers are trusted institutions that engage with parents regularly, positioning them as key messengers for childhood immunization and respiratory health promotion. While ECE centers ensure compliance with mandated vaccines, their potential to support uptake of non-mandated immunizations—such as influenza vaccine, COVID-19 vaccine, maternal RSV vaccine, and nirsevimab antibody—remains underutilized. The BREATHE Well (Building Readiness, Engagement, and Trust for Healthy Environments) Toolkit is an evidence-based intervention designed to enhance ECE-originating vaccine communication, training ECE staff to effectively engage parents on immunization topics. This study will evaluate the feasibility, acceptability, and effectiveness of the BREATHE Well toolkit using a cluster- randomized controlled trial (RCT). The project will be guided by three specific aims: (1) Develop and refine the BREATHE Well toolkit through formative research, incorporating input from ECE staff, parents, and public health officials; (2) Assess the acceptability and feasibility of the toolkit through focus groups and surveys with ECE staff and parents in demonstration sites within Michigan; and (3) Evaluate the effectiveness of the toolkit in a cluster-randomized trial of ECE centers, measuring changes in parental vaccine confidence, intent to vaccinate, and staff capacity to serve as trusted messengers. The BREATHE Well toolkit will be designed as a scalable approach usable in different types of ECEs. Findings from this study will inform best practices for integrating vaccine-related education into ECE settings, with the goal of increasing parental vaccine confidence and improving uptake of recommended immunizations.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15882", "attributes": { "award_id": "1K99AI194972-01", "title": "The Role of Tunneling Nanotubes and Mitochondrial programming in HIV-Associated Placental Dysfunction", "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": 44315, "first_name": "UDAY K", "last_name": "SHANKAR", "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": 156744, "principal_investigator": { "id": 44316, "first_name": "Rafael", "last_name": "Tomoya Michita", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2610, "ror": "", "name": "BAYLOR COLLEGE OF MEDICINE", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT HIV is known to be transmissible from mother to the developing fetus during pregnancy, leading to adverse health outcomes for both. Although HIV is linked to placental pathologies, there is still a large gap in knowledge about the mechanisms underlying HIV-associated pregnancy complications, despite four decades of research in general on HIV topics. The objective of this project is to investigate the role of intercellular conduits composed of F-actin microtubules that connect plasma membranes of neighboring cells enabling cytoplasmic continuing and intercellular transfer of cargo. These conduits are known as tunneling nanotubes (TNTs). Recent investigations by the PI and others have demonstrated that other viruses such as Zika and SARS-CoV-2 induce the formation of TNTs in placental trophoblast cells, and there is evidence they serve as a means of mitochondrial transfer and possibly viral transfer that promotes infectious spread. There is evidence that HIV induces TNT formation in neurons, but it is not known whether the virus has this effect on placental cells. Building on prior studies and ongoing work by the PI, the central hypothesis of this project is that HIV uses TNTs to spread infection in trophoblasts, and that TNTs mediate placental dysfunction by transferring damaged mitochondria and adversely reprogramming trophoblast metabolism. This metabolic reprogramming may contribute to placental dysfunction and adverse pregnancy outcomes. Aim 1 of this project will elucidate the molecular mechanisms of TNT formation between HIV-infected immune cells and trophoblasts. Aim 2 will determine the impact of HIV on mitochondrial dynamics and transfer and resulting trophoblast function. These two aims will be pursued during the final postdoctoral training period of the K99 phase. Aim 3 seeks to identify how HIV-exposed mitochondria reprogram trophoblast biology, impairing placental function and affecting fetal development in vivo. This third aim will be pursued during the R00 phase of the project. Successful completion of these aims will provide new insights into the mechanisms underlying HIV infection, identifying potential therapeutic targets to mitigate vertical transmission and placental pathologies caused by HIV and other viruses. During the mentored phase, the PI will gain expertise in primary cell culture, metabolomics, trophoblast organoids, and mitochondrial epigenetics to examine how HIV infects the placenta and disrupts cellular metabolism—establishing a foundation for the R00 phase. With guidance from the advisory team, this training and research will contribute to the identification of therapeutic strategies to improve outcomes for infants and individuals with HIV, while positioning the investigator to establish an independent, competitive R01-funded laboratory at the intersection of HIV, TNTs, placental biology, and mitochondria.", "keywords": [ "2019-nCoV", "Actins", "Advisory Committees", "Affect", "Affinity Chromatography", "Anti-viral Response", "Automobile Driving", "Biology", "Bypass", "Cell Physiology", "Cell Separation", "Cell Survival", "Cell fusion", "Cell membrane", "Cells", "Chronic", "Cloning", "Coculture Techniques", "Confocal Microscopy", "Coupled", "Cytoplasm", "Cytoskeleton", "DNA", "Data", "Deoxyadenosines", "Development", "Disproportionately impacts women", "Epigenetic Process", "F-Actin", "Fetal Development", "Fetus", "Flow Cytometry", "Foundations", "Functional disorder", "Funding", "Genes", "Genetic Transcription", "HIV", "HIV Infections", "HIV-1", "Health", "Image Cytometry", "Immune", "Immune Evasion", "Immune response", "Immunoprecipitation", "Impairment", "In Vitro", "Individual", "Infection", "Inflammation", "Investigation", "Knowledge", "Label", "Laboratories", "Link", "Mass Spectrum Analysis", "Measures", "Mediating", "Mentors", "Metabolic", "Metabolic Pathway", "Metabolic dysfunction", "Metabolism", "Microtubules", "Mitochondria", "Mitochondrial DNA", "Modeling", "Modification", "Molecular", "Mothers", "Mus", "Mutation", "Neurons", "Organoids", "Outcome", "Oxidative Phosphorylation", "Pathology", "Pathway interactions", "Patients", "Perinatal Infection", "Phase", "Placenta", "Placental Biology", "Positioning Attribute", "Pregnancy", "Pregnancy Complications", "Pregnant Women", "Primary Cell Cultures", "Process", "Proteins", "Quantitative Reverse Transcriptase PCR", "Reactive Oxygen Species", "Recombinants", "Regulation", "Research", "Research Personnel", "Risk", "Role", "Site-Directed Mutagenesis", "Study models", "System", "T-Lymphocyte", "Techniques", "Tertiary Protein Structure", "Testing", "Therapeutic", "Training", "Validation", "Vertical Transmission", "Viral", "Virion", "Virus", "Virus Diseases", "Visualization", "Western Blotting", "Work", "ZIKA", "Zika Virus", "adverse pregnancy outcome", "antiretroviral therapy", "experimental study", "fetal", "global health", "heteroplasmy", "improved outcome", "in vivo", "infant outcome", "insight", "knock-down", "live cell imaging", "metabolomics", "mitochondrial dysfunction", "mouse model", "mutant", "placental trophoblasts", "post-doctoral training", "pregnant", "programs", "protein protein interaction", "reproductive age", "single molecule real time sequencing", "single-cell RNA sequencing", "stem cells", "therapeutic target", "transmission process", "tropho" ], "approved": true } }, { "type": "Grant", "id": "15879", "attributes": { "award_id": "1R01HD120113-01", "title": "DISSECTING MECHANISMS OF INFLAMMATORY SIGNALING ACROSS THE MATERNAL FETAL INTERFACE", "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": 44310, "first_name": "DENISE", "last_name": "RUSSO", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-15", "end_date": "2028-05-31", "award_amount": 2255352, "principal_investigator": { "id": 44311, "first_name": "Christiana Elizabeth", "last_name": "Smith-Anderson", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3385, "ror": "", "name": "UNIVERSITY OF COLORADO DENVER", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true }, "abstract": "Infants exposed in utero to maternal inflammatory disorders are at risk of long-lasting health impacts, such as altered neurodevelopmental outcomes or dysregulated immune responses. When maternal infections are the inflammatory stimulus, these adverse neonatal outcomes can occur in the absence of congenital infection. Our preliminary data show that infants who are HIV-exposed, but uninfected experience high rates of morbidity and mortality that are associated with maternal inflammation in a dose-dependent fashion. Early reports suggest that acute maternal infection with COVID-19 can have profound impacts on fetal immune development. Inflammatory signaling across the maternal-fetal interface during a critical fetal developmental window is likely to be responsible for these adverse neonatal outcomes. However, critical gaps exist in our understanding of how inflammatory signals are transferred across the placenta. The overarching goal of this proposal is to determine the cellular and molecular mechanisms involved in the transfer of inflammatory signals across the maternal-fetal interface in the setting of acute or chronic viral infection. We will capitalize upon access to samples from pregnancies complicated by either HIV, which results in chronic inflammation, or SARS-CoV-2, which causes severe acute inflammation, to address the following Specific Aims: 1) to profile the transcriptomic signatures of heterogenous maternal and fetal cell types in their in situ environment within placentas from pregnancies affected by HIV or SARS-CoV-2 versus healthy pregnancies; 2) to compare concentrations of inflammatory and regulatory biomarkers in maternal and infant peripheral blood, cord blood and placentas from term pregnancies affected by HIV or SARS-CoV-2 versus healthy pregnancies and determine their association with placental gene expression; and 3) to characterize inflammatory signaling across the maternal-fetal interface using a 3- dimensional in vitro model that incorporates key placental cell types. This proposal includes several innovative components, including the use of advanced bioinformatics to directly correlate placental gene expression data from a single-cell spatial transcriptomics assay to the peripheral concentrations of inflammatory biomarkers within the same participants, and the development of a novel Transwell-based model of the human placenta that can be used to mechanistically interrogate the role of each cell type in the transfer or inflammatory signals. Disentangling the mechanisms responsible for the transfer of inflammation across the maternal-fetal interface will ultimately allow for the identification of therapeutic agents to modulate inflammation in pregnancy, thereby preventing adverse neurodevelopmental and/or immunologic consequences to the fetus.", "keywords": [ "2019-nCoV", "3-Dimensional", "Acute", "Address", "Affect", "Amniotic Fluid", "Animals", "Architecture", "Bioinformatics", "Biological Assay", "Biological Markers", "COVID-19", "COVID-19 diagnosis", "Cells", "Chronic", "Circulation", "Coculture Techniques", "Data", "Decidua", "Decidual Cell Reactions", "Development", "Disease", "Dose", "Endometrial Stromal Cell", "Endothelial Cells", "Environment", "Equilibrium", "Exposure to", "Fetal Growth Retardation", "Fetal Tissues", "Fetus", "Fibroblasts", "Future", "Gene Expression", "Geography", "Goals", "HIV", "HIV-exposed uninfected infant", "HIV/HBV", "Health", "Human", "Hypertension", "Immune", "Immune response", "Immunologics", "Impairment", "In Situ", "Infant", "Infant Health", "Infection", "Inflammation", "Inflammatory", "Innate Immune Response", "Insulin-Dependent Diabetes Mellitus", "Interleukin-1 alpha", "Interleukin-6", "Leukocytes", "Macrophage", "Malaria", "Maternal-Fetal Exchange", "Measures", "Mediator", "Mesenchymal Stem Cells", "Modeling", "Molecular", "Morbidity - disease rate", "Mothers", "Neonatal", "Obesity", "Outcome", "Participant", "Pathway interactions", "Peripheral", "Placenta", "Plasma", "Pregnancy", "Pregnancy Complications", "Pregnant Women", "Premature Labor", "Proteomics", "Reporting", "Respiratory Tract Infections", "Risk", "Role", "Sampling", "Second Pregnancy Trimester", "Signal Transduction", "Source", "Spontaneous abortion", "Stimulus", "TNF gene", "Testing", "Therapeutic Agents", "Tissues", "Umbilical Cord Blood", "Umbilical vein", "Villous", "Virus Diseases", "adverse pregnancy outcome", "cell type", "chemokine", "congenital infection", "cytokine", "differential expression", "ex vivo perfusion", "experience", "fetal", "fetus cell", "healthy pregnancy", "human-based research", "immunoregulation", "in vitro Model", "in vivo", "inflammatory milieu", "innovation", "maternal inflammation", "mortality", "neonatal outcome", "novel", "offspring", "peripheral blood", "pregnant", "prenatal exposure", "prevent", "spatial transcriptomics", "transcriptomics", "trophoblast" ], "approved": true } }, { "type": "Grant", "id": "15878", "attributes": { "award_id": "1R01AI189484-01", "title": "Role of norovirus capsid dynamics in adaptive immune evasion", "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": 44307, "first_name": "RODOLFO M", "last_name": "ALARCON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-01", "end_date": "2029-08-31", "award_amount": 2920356, "principal_investigator": { "id": 44308, "first_name": "THOMAS JAMES.", "last_name": "SMITH", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 44309, "first_name": "Christiane", "last_name": "Wobus", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 851, "ror": "", "name": "UNIVERSITY OF TEXAS MED BR GALVESTON", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Human noroviruses are responsible for almost a fifth of all cases of gastroenteritis worldwide. Containment of disease is difficult since as few as ten virions are sufficient to infect a normal adult. Noroviruses evolve continuously with new strains arising every 2-4 years that cause worldwide epidemics. Emergence of new strains can increase the number of cases by 50%. In the US alone, there are more than 2 million outpatient clinic visits, ~100,000 hospitalizations, and ~900 deaths (mostly among adults 65 and older) annually. Globally, there are ~200 million cases among children less than 5 years old, leading to ~50,000 deaths every year. However, no vaccines or antivirals are approved to limit infections. Efforts to develop an effective vaccine have been hindered by a lack of detailed structural information about antibody binding and the mechanisms of antibody escape. Understanding these processes has been difficult with human noroviruses because of the lack of a tissue culture system that supports the generation of a cell culture-derived virus stock and small animal model. To this end, we will be using the highly tractable mouse norovirus system where we have a highly efficient cell culture system, infectious clone, and natural mouse model. We have recently shown, for the first-time, that a virus (i.e., mouse norovirus, MNV) can use host metabolites to switch between two ‘faces’: one recognized by antibodies from recovered animals (apo) and one activated for infection. In conditions found in systemic circulation, the protruding domain (P domain) of the apo form floats above the shell by ~16Å and the loops at the tip are splayed apart. It is this conformation to which the antibody response is made. Once the virus enters the alimentary canal, low pH, bile salts, and metal ions individually and synergistically activate the virus whereby the P domain rotates and contracts onto the shell, and the antibody binding epitope at the tip of the P domain closes. This blocks antibody recognition while enhancing receptor binding. Essentially, each time MNV infects the host, the antibody response is naïve for that conformation. Importantly, we propose that this could explain why the antibody response to norovirus infection in both mice and humans appears to be notoriously short-lived. The goal of this proposal is to test our immune evasion model by creating mutant forms of MNV locked into either the apo or activated states and observing how those changes affect the pathogenesis and immune response in the host. These studies will detail the activation process at the molecular level, elucidate the reason why caliciviruses evolved such mobile P domains, and greatly impact the development of norovirus vaccines and therapeutics. Finally, subsequent to our publications, similar host metabolite immune evasion was observed with COVID-19. Therefore, our results will increase awareness of possible similar features in other virus families and may become paradigms in the future.", "keywords": [ "2019-nCoV", "5 year old", "Acute", "Adult", "Affect", "Affinity", "Ambulatory Care Facilities", "Animal Model", "Animals", "Annual Reports", "Anti-viral Agents", "Antibodies", "Antibody Affinity", "Antibody Response", "Awareness", "Bile Acids", "Binding", "Biology", "Blocking Antibodies", "C-terminal", "COVID-19", "Calicivirus", "Capsid", "Capsid Proteins", "Case Study", "Cell Culture System", "Cell Culture Techniques", "Cessation of life", "Characteristics", "Child", "Circulation", "Clinic Visits", "Containment", "Contracts", "Cryoelectron Microscopy", "Crystallography", "Development", "Dimerization", "Disease", "Distal", "Dose", "Environment", "Epidemic", "Epitopes", "Exhibits", "Face", "Failure", "Family", "Future", "Gastroenteritis", "Gastrointestinal tract structure", "Generations", "Genetic Variation", "Genome", "Goals", "Hospitalization", "Human", "Immune", "Immune Evasion", "Immune response", "Immunity", "Immunologic Memory", "Immunologics", "In Vitro", "Individual", "Infection", "Ingestion", "Innate Immune Response", "Intestines", "Invaded", "Ions", "Libraries", "Ligands", "Lymphatic System", "Mediating", "Metals", "Modeling", "Molecular", "Molecular Conformation", "Mus", "Mutagenesis", "Norovirus", "Pathogenesis", "Pathogenicity", "Persons", "Population", "Process", "Property", "Publications", "Retinal blind spot", "Role", "Rotation", "Series", "Site", "Spleen", "Structure", "Support System", "Surface", "Symptoms", "System", "Tertiary Protein Structure", "Testing", "Therapeutic", "Time", "Tissues", "Vaccines", "Viral Pathogenesis", "Virion", "Virus", "Viviparous-1 protein", "Work", "acute infection", "adaptive immune response", "adaptive immunity", "bile salts", "biophysical techniques", "design", "gastrointestinal epithelium", "human old age (65+)", "improved", "in vivo", "in vivo evaluation", "mouse model", "mutant", "oral infection", "receptor", "receptor binding", "recombinant virus", "reverse genetics", "structural biology", "tissue culture", "tool", "vaccine development", "viral RNA", "volunteer" ], "approved": true } }, { "type": "Grant", "id": "15877", "attributes": { "award_id": "1F31DA063126-01", "title": "A statewide examination of the address-level relationships between residential eviction proceedings and overdose events in Rhode Island", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Drug Abuse (NIDA)" ], "program_reference_codes": [], "program_officials": [ { "id": 44305, "first_name": "ERIN MARGARET", "last_name": "PARKER", "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": 49538, "principal_investigator": { "id": 44306, "first_name": "Alexandra", "last_name": "Skinner", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3365, "ror": "", "name": "BROWN UNIVERSITY", "address": "", "city": "", "state": "RI", "zip": "", "country": "United States", "approved": true }, "abstract": "PROPOSAL SUMMARY In the wake of the COVID-19 pandemic, overdose mortality and affordable housing shortages have reached unprecedented levels in Rhode Island and across the United States. Housing insecurity is a known risk factor for overdose, yet the effects of residential eviction—a structural and policy-sensitive cause of housing insecurity—on overdose risks are understudied. Eviction is a complex legal process composed of a series of stages, each of which may impact overdose risk and thus offers opportunity for public health intervention. The objective of this proposal is to pursue a thorough examination of the relationship between residential eviction proceedings (i.e., filing, hearing, and enforcement) and overdose at the address level in Rhode Island, to better inform eviction prevention policies that complement ongoing harm reduction and overdose prevention efforts. The proposed research will leverage the wealth of centralized, high-resolution data available in Rhode Island—and our team’s established relationship with the state health department—to construct a longitudinal dataset with data linked from several administrative sources. We will first characterize the prevalence and time course of eviction proceedings relative to non-fatal or fatal overdose events by conducting sequence and cluster analyses to operationalize variation in the order, duration, and timing of eviction proceedings before and after a given overdose event (AIM 1). We will then estimate the address-level causal effect of residential eviction proceedings on risk of non-fatal and fatal overdose, both overall and by race and ethnicity of overdose decedents, using a sequential target trial approach (AIM 2). The proposed research will be among the first of its kind to link eviction records with address-level health data to characterize heterogeneity in the duration and timing of eviction proceedings, to examine a causal link between eviction and overdose, and to explore differential impacts of eviction on overdose death by race and ethnicity. Because eviction is an intervenable mechanism of housing vulnerability that may be associated with overdose risk, findings from this work may elucidate novel avenues for addressing the intersecting housing and overdose crises in tandem. The proposed research will be completed by the principal investigator with support and mentorship from collaborators with substantial expertise in advanced quantitative methods for life course epidemiology and causal inference. The training activities detailed in this application, focused on advancing skills in epidemiologic study design and longitudinal data analysis and developing a deep contextual knowledge of the social and legal implications of eviction proceedings, will prepare the principal investigator for a career as an independent social epidemiologist and academic researcher.", "keywords": [ "Acute", "Address", "Alaska Native population", "American Indian Population", "Applied Skills", "Black race", "COVID-19 pandemic", "Censuses", "Characteristics", "Cluster Analysis", "Complement", "Complex", "County", "Data", "Data Analyses", "Data Linkages", "Data Set", "Discrimination", "Dose", "Drug user", "Economics", "Epidemiologist", "Epidemiology", "Ethnic Origin", "Event", "Exposure to", "Funding", "Goals", "Harm Reduction", "Health", "Hearing", "Heterogeneity", "Hispanic", "Housing", "Individual", "Intervention", "Knowledge", "Learning", "Legal", "Life Cycle Stages", "Life course epidemiology", "Link", "Mentorship", "Methodology", "Methods", "Neighborhoods", "Overdose", "Patients", "Policies", "Prevalence", "Prevention", "Principal Investigator", "Process", "Race", "Records", "Research", "Research Design", "Research Personnel", "Resolution", "Rhode Island", "Risk", "Risk Factors", "Sequence Analysis", "Series", "Shapes", "Source", "Structural Models", "Time", "Training", "Training Activity", "United States", "United States National Institutes of Health", "Variant", "Work", "career", "data management", "epidemiology study", "health data", "housing insecurity", "legal implication", "longitudinal dataset", "marginalized community", "mortality", "neglect", "novel", "overdose death", "overdose prevention", "overdose risk", "psychosocial", "public health intervention", "residence", "response", "risk prediction", "segregation", "skills", "social", "social implication", "stressor", "structural health determinants" ], "approved": true } }, { "type": "Grant", "id": "15872", "attributes": { "award_id": "1U01AI189332-01A1", "title": "Molecular determinants of vaccine-induced antibody durability", "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": 44300, "first_name": "AMY COLLEEN", "last_name": "PALIN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-20", "end_date": "2030-07-31", "award_amount": 777495, "principal_investigator": { "id": 44301, "first_name": "George K", "last_name": "Lewis", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 24795, "first_name": "Mohammad Mohseni", "last_name": "Sajadi", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1532, "ror": "https://ror.org/036a0e562", "name": "Baltimore VA Medical Center", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 793, "ror": "", "name": "UNIVERSITY OF MARYLAND BALTIMORE", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "This research proposal aims to define the molecular determinants of durable versus non-durable antibody responses in vaccinated individuals. Given the critical role of antibodies in combating infectious diseases, it is essential to understand why some antibody responses are long-lasting while others are transient. This distinction is pivotal for improving vaccine development and enhancing protection against pathogens such as HIV-1, Influenza, and SARS-CoV-2, where current vaccines either fail to induce long-term immunity or require frequent re-administration. The primary objective is to investigate the cellular and molecular mechanisms underpinning the longevity of antibody responses post-vaccination. The study will focus on the dynamics of antibody-secreting cells (ASCs) including plasmablasts, short-lived, and long-lived plasma cells, which are believed to be central to maintaining long-term antibody levels. We propose a benchmark prospective human study to characterize ASC populations and their antibody production over time in response to vaccines that induce varying durations of antibody responses. This involves a clinical trial with vaccine-naïve volunteers using the licensed HPV vaccine, GARDASIL 9, for long-term responses, and an investigational HIV vaccine, IHV01, for short-lived responses. The study will span all zones of antibody dynamics post-vaccination, with comprehensive sampling from peripheral blood, lymph nodes, and bone marrow. Aim 1- A clinical trial will be carried out by vaccinating healthy volunteers intramuscularly with the HPV vaccine on the right thigh and IHV01 on the left thigh, three times at 0, 1, and 6 months with scheduled collections of peripheral blood, lymph node fine needle aspirations (FNA), and bone marrow for 42 months to generate specimens spanning all phases of circulating antibody dynamics. Aim 2- The goal of Aim 2 is to quantify and characterize B cell responses the HPV capsid protein and gp120 epitopes in IHV01 over the course of the clinical trial described above in the following specimens: 1) circulating antibodies; 2) circulating and LN memory B cells; 3) follicular and germinal center B cells; 4) circulating and LN plasmablasts; and 5) bone marrow plasma cell subsets. The specimens/populations will be queried with state-of-the-art methods including cellular phenotyping, transcriptomics, VH/VL lineage analyses, antigen-binding cell frequencies. Aim 3- The goal of Aim 3 is to develop mathematical models relating the molecular and cellular signatures from Aim 2 to the dynamics of the durable and non-durable antibody responses generated to the HPV capsid and the HIV-1 gp120 protein, respectively. The anticipated outcomes include a predictive model of antibody response durability, which will inform future vaccine design and the development of dose-predictive strategies. Successful completion of this study will also provide a valuable resource to the scientific community by archiving and sharing the biological specimens collected, facilitating further research into vaccine-induced immunity.", "keywords": [ "2019-nCoV", "Antibodies", "Antibody Formation", "Antibody Response", "Antibody-mediated protection", "Antigens", "Archives", "B-Lymphocytes", "Benchmarking", "Biological", "Blood", "Bone Marrow", "Capsid", "Capsid Proteins", "Cells", "Characteristics", "Clinical Trials", "Collection", "Communicable Diseases", "Communities", "Data", "Development", "Dose", "Epitopes", "Fine needle aspiration biopsy", "Frequencies", "Future", "Goals", "HIV", "HIV Envelope Protein gp120", "HIV vaccine", "HIV-1", "HIV-1 vaccine", "Human", "Immunity", "Immunization", "Immunize", "Immunoglobulin-Secreting Cells", "Infectious Agent", "Influenza", "Influenza vaccination", "Intramuscular", "Left", "Licensing", "Longevity", "Memory B-Lymphocyte", "Methods", "Molecular", "Mus", "Outcome", "Phase", "Phenotype", "Plasma", "Plasma Cells", "Plasmablast", "Play", "Population", "Prospective Studies", "Proteins", "Reaction", "Research", "Research Design", "Research Proposals", "Resources", "Role", "SARS coronavirus", "Sampling", "Schedule", "Serology", "Specimen", "Structure of germinal center of lymph node", "Thigh structure", "Time", "Vaccinated", "Vaccination", "Vaccine Design", "Vaccinee", "Vaccines", "Work", "antigen binding", "comparative", "design", "draining lymph node", "healthy volunteer", "human study", "improved", "in silico", "lymph nodes", "mathematical model", "pathogen", "peripheral blood", "predictive modeling", "prospective", "response", "time interval", "transcriptomics", "vaccine development", "vaccine response", "vaccine-induced antibodies", "vaccine-induced immunity", "volunteer" ], "approved": true } }, { "type": "Grant", "id": "15870", "attributes": { "award_id": "1R01CA303579-01", "title": "Advancing next-generation CAR-NK therapies targeting CD5 positive T cell malignancies to the clinic", "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": 44297, "first_name": "LORI A", "last_name": "HENDERSON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-19", "end_date": "2029-08-31", "award_amount": 1847485, "principal_investigator": { "id": 44298, "first_name": "Rafet", "last_name": "Basar", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 23208, "first_name": "Katy", "last_name": "Rezvani", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1420, "ror": "", "name": "UNIVERSITY OF TX MD ANDERSON CAN CTR", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true } ] }, { "id": 44299, "first_name": "May", "last_name": "Daher", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1420, "ror": "", "name": "UNIVERSITY OF TX MD ANDERSON CAN CTR", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Summary: Patients with relapsed/refractory (R/R) T cell malignancies have poor outcomes and novel therapies are urgently needed. While CAR-T cells have shown remarkable efficacy in patients with B-cell malignancies and multiple myeloma, targeting T-cell malignancies presents unique challenges. One of the major issues is fratricide due to the shared expression of target antigens on both malignant and normal T cells, leading to self-targeting. Additionally, there is a risk of product contamination with malignant T cells during the manufacturing process, and the prolonged life-span of CAR-T cells poses the risk of long-term T-cell aplasia. In contrast, CAR- engineered natural killer (NK) cells offer several advantages. Unlike T-cells, NK cells do not express T cell target antigens such as CD5, eliminating the risk of fratricide. CAR-NK cells also avoid the issue of product contamination with malignant cells, as they can be derived from healthy donors rather than the patient’s own cells. Their shorter life-span reduces the likelihood of prolonged T-cell aplasia. Moreover, CAR-NK cells retain their innate cytotoxicity while also providing tumor specificity against the target antigen through engineering, without the concerns of graft-versus-host disease in the allogeneic setting, cytokine release syndrome or neurotoxicity. Building on our successful first-in-human trial of cord blood (CB) derived CAR19/IL-15 NK cells in patients with relapsed/refractory B-cell malignancies (published in NEJM 2020; Nature Medicine 2024), we now propose a clinical trial targeting CD5 in T cell malignancies. Our engineered CAR-NK cells express an scFv against CD5, IL-15 to enhance persistence, and an inducible caspase-9 (iC9) safety switch (collectively termed iC9/CAR5-28ζ/IL-15 NK cells). A key innovation in this proposal is our novel ex vivo expansion protocol for CAR- NK cells, incorporating IL-12, IL-18, TGF-β and Rapamycin to enhance the metabolic fitness of the cells. Preclinically, iC9/CAR5-28ζ/IL-15 NK cells generated using this novel expansion strategy demonstrated potent activity against T-cell lymphoma models. The clinical protocol has received IRB and FDA (protocol #2021-0526, IND 30087) and is currently enrolling patients. In parallel, we will conduct state-of-the-art correlative studies to comprehensively characterize the infused CAR-NK cells, tracking their persistence, trafficking, and immune modulation in patients. Additionally, we have developed a robust genome-wide CRISPR screening platform to identify novel regulators of CAR-NK cell function and mechanisms of resistance in T cell malignancies. Insights from these studies will inform the development of next-generation CAR-NK cells, optimized to overcome immune evasion strategies and improve patient outcomes. In Aim 1 we will conduct a Phase I/II clinical trial to test the safety and efficacy of iC9/CAR5-28ζ/IL-15 NK cells in patients with CD5+ T cell malignancies. In Aim 2 we will apply comprehensive correlative studies. In Aim 3, we will perform genome-wide CRISPR screens in both our iC9/CAR5-28ζ/IL-15 NK cells and T cell malignancy cell lines to uncover novel mechanisms of resistance and inform the design of next-generation CAR-NK cell therapies.", "keywords": [ "Adoptive Transfer", "Allogenic", "Antigen Targeting", "Antigens", "Autologous", "B lymphoid malignancy", "Biology", "Blood", "Blood donor", "Bone Marrow", "CAR T cell therapy", "CASP9 gene", "CRISPR screen", "Cell Line", "Cell Physiology", "Cell Therapy", "Cells", "Clinic", "Clinical", "Clinical Protocols", "Clinical Trials", "Clustered Regularly Interspaced Short Palindromic Repeats", "Collection", "Correlative Study", "Cryopreservation", "Data", "Development", "Disease", "Donor Selection", "Dose", "Engineering", "Event", "Future", "Home", "Hour", "IL18 gene", "Immune Evasion", "Immune response", "Institutional Review Boards", "Interleukin-12", "Interleukin-15", "Life", "Malignant - descriptor", "Malignant Neoplasms", "Medicine", "Modeling", "Multiple Myeloma", "NK cell therapy", "Natural Killer Cells", "Natural Killer T cell", "Nature", "Outcome", "Pathway interactions", "Patient-Focused Outcomes", "Patients", "Phase I/II Clinical Trial", "Phase I/II Trial", "Prognosis", "Progression-Free Survivals", "Proliferating", "Protocols documentation", "Publishing", "Recruitment Activity", "Refractory", "Relapse", "Resistance", "Risk", "Role", "Safety", "Sampling", "Selection Criteria", "Sirolimus", "Site", "Source", "Survival Rate", "T-Cell Lymphoma", "T-Lymphocyte", "Therapeutic", "Therapeutic Uses", "Time", "Toxic effect", "Transforming Growth Factor beta", "Treatment outcome", "Tumor Cell Line", "Umbilical Cord Blood", "biobank", "cancer cell", "cellular transduction", "chimeric antigen receptor", "chimeric antigen receptor T cells", "chimeric antigen receptor natural killer cells", "cost", "cytokine release syndrome", "cytotoxicity", "design", "engineered NK cell", "exhaustion", "extend lifespan", "first-in-human", "follow-up", "genome-wide", "graft vs host disease", "immunodeficiency", "immunoregulation", "improved", "improved outcome", "in vivo", "innovation", "insight", "leukemia/lymphoma", "life span", "lymph node biopsy", "manufacturing process", "metabolic fitness", "multiple omics", "neurotoxicity", "next generation", "novel", "novel therapeutic intervention", "novel therapeutics", "participant enrollment", "peripheral blood", "pharmacologic", "pre-clinical", "preclinical study", "resistance mechanism", "response", "safety testing", "spatial transcriptomics", "success", "targeted treatment", "tool", "trafficking", "tumor", "tumor specificity" ], "approved": true } }, { "type": "Grant", "id": "15868", "attributes": { "award_id": "1R43NR021082-01A1", "title": "Development of an accessible Cognitive Behavioral Therapy digital therapeutic for individuals with Long COVID", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Nursing Research (NINR)" ], "program_reference_codes": [], "program_officials": [ { "id": 44294, "first_name": "JOSHUA R", "last_name": "WOLFF", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-16", "end_date": "2026-08-30", "award_amount": 383159, "principal_investigator": { "id": 44295, "first_name": "Laura", "last_name": "Randa", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3387, "ror": "", "name": "TOIVOA, INC", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true }, "abstract": "The over 100 million cases of COVID-19 that have occurred in the US since 2019 have spurred a ‘pandemic within a pandemic’ as up to 70% of COVID survivors experience long-term medical conditions and 10-20% develop post-acute sequelae of SARS-CoV-2 infection (PASC) or ‘Long COVID’. Strikingly, 6 weeks after diagnosis, 30% of Long COVID patients require assistance for daily activities and over 75% report impaired ability to work. Symptoms of Long COVID include both physical and psychological impairments. 30% of COVID patients develop vision issues that can persist into Long COVID, and over two-thirds of Long COVID patients present with serious mental health symptoms. Thus, there is a critical need for accessible digital mental health interventions to serve the growing population of Long COVID patients. Cognitive behavioral therapies (CBTs) are a known effective treatment for depression, anxiety and other mental health disorders, and the rise of digital health offers a new opportunity to provide large-scale, cost-effective, accessible CBT services to patients in populations where access to mental health care is difficult to obtain. In the case of Long COVID, access to effective mental health care is complicated by the heterogenous nature of the population and a current lack of consensus guidelines for management of Long COVID and related mental health impacts. Despite the enormous negative impact of Long COVID on mental health, patients describe gaining access to appropriately personalized treatment as ‘complex, difficult, and exhausting’. A readily accessible, highly personalized, and cost-effective means of CBT digital health services would be ideally positioned to meet the critical and rapidly growing mental health needs of Long COVID patients. At Toivoa, Inc., we are closing this treatment gap with the first FDA-authorized, accessible, highly personalized digital mental health therapeutic – Rauha – which integrates the digital delivery of expert CBT from licensed clinical psychologists with personalized support and guidance mediated via National Health and Wellness Board Certified (NHWBC) certified mental health coaches. Our Rauha platform is currently designed for adults with hearing loss and mobility disabilities, and this project will seek to optimize Rauha to meet the unique accessibility needs of Long COVID patients. The overarching goals of this Phase I SBIR project are to gather peer-review on Rauha from a panel of clinical experts and advisory boards of patients, caregivers, and mental health coaches to reach a consensus opinion on digital therapeutic content for Long COVID patients addressing their mental health needs (Aim 1), customize Rauha to best serve Long COVID patients and their caregivers (Aim 2), and conduct a human factors study with Long COVID patients to evaluate the usability and acceptability of Rauha’s personalized CBT digital therapeutic content with an integrated mental health coach with shared life experiences for addressing their mental health needs (Aim 3). Successful completion of Phase I will position Toivoa for a Phase II program to conduct a powered randomized control clinical trial to evaluate the efficacy of Rauha among Long COVID patients.", "keywords": [ "3-Dimensional", "Address", "Adult", "Affect", "Agreement", "American", "Anxiety", "Authorization documentation", "Behavioral", "Board Certification", "COVID-19", "COVID-19 patient", "COVID-19 survivors", "Caregivers", "Caring", "Cellular Phone", "Certification", "Chronic Disease", "Clinical", "Cognitive", "Cognitive Therapy", "Communities", "Complex", "Consensus", "Data", "Development", "Diagnosis", "Dimensions", "Disabled Persons", "Distress", "Dose", "Educational process of instructing", "Enrollment", "Evaluation", "Family", "Fatigue", "Feedback", "General Population", "Goals", "Guidelines", "Health", "Health Services", "Home", "Human", "Impairment", "Individual", "Internet", "Intervention", "Interview", "Licensing", "Life", "Life Experience", "Long COVID", "Long-term disability", "Mediating", "Medical", "Mental Depression", "Mental Health", "Mental Health Services", "Mental disorders", "Mission", "Mobility disability", "Nature", "Needs Assessment", "Outcome", "Patient Care", "Patient Preferences", "Patient Self-Report", "Patients", "Peer Review", "Persons", "Phase", "Population", "Positioning Attribute", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Psyche structure", "Psychologist", "Public Health", "Randomized Controlled Clinical Trials", "Recording of previous events", "Reporting", "Risk Factors", "Schools", "Services", "Sleeplessness", "Small Business Innovation Research Grant", "Structure", "Surveys", "Symptoms", "Syndrome", "Testing", "Therapeutic", "Therapeutic Intervention", "Training", "Underserved Population", "Viral", "Vision", "Visual", "Wellness coaching", "Work", "biopsychosocial", "brain fog", "care outcomes", "cost effective", "design", "digital", "digital delivery", "digital equity", "digital health", "digital mental health", "digital platform", "digital treatment", "effective therapy", "efficacy evaluation", "exhaust", "experience", "hearing disability", "hearing impairment", "improved", "pandemic disease", "patient engagement", "patient population", "personalized care", "personalized medicine", "physical symptom", "programs", "psychoeducation", "psychologic", "psychological distress", "psychological symptom", "skills", "sleep onset", "social", "success", "usability" ], "approved": true } }, { "type": "Grant", "id": "15866", "attributes": { "award_id": "1R21AI182913-01A1", "title": "Verification of pigs as an appropriate model for the development of human vaccines targeting the entero-mammary pathway to elicit a robust secretory IgA response in human milk", "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": 44292, "first_name": "MERCY R", "last_name": "PRABHUDAS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-03", "end_date": "2027-08-31", "award_amount": 477406, "principal_investigator": { "id": 20577, "first_name": "Rebecca", "last_name": "Powell", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [ { "id": 625, "ror": "https://ror.org/04a9tmd77", "name": "Icahn School of Medicine at Mount Sinai", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 3386, "ror": "", "name": "ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Secretory Immunoglobulin A (sIgA) is the dominant immunoglobulin (Ig) in human mucosae and their fluids and is critical in protecting these surfaces from infection [1, 2]. sIgA is most often comprised of dimeric IgA linked by joining (j) chain. This dimer is secreted by the B cell, with j-chain marking it for transport by polymeric Ig receptor (pIgR) on epithelial cells into mucosal fluids [3]. pIgR is cleaved as it transports, leaving a domain known as secretory component (SC) attached, creating sIgA [4, 5]. SC renders it highly resistant to degradation in harsh mucosal environments [6, 7]. Human milk Ig is ~90% sIgA [8-10]. B cells that produce human milk sIgA originate from the gut associated lymphoid tissue (GALT), via the entero-mammary pathway [5, 11-13]. This pathway is evident in humans in that mammary B cells display adhesion receptors similar to GALT B cells, and milk sIgA exhibits strong reactivity for enteric microbes [14-20]. Our work analyzing the milk antibody response to SARS-CoV-2 infection found robust sIgA is elicited that is exceptionally long-lasting, a critical finding that is likely representative of any mucosal infection where immunogens ultimately present in the GALT [21-23]. In contrast, after COVID-19 vaccination, the response is IgG-dominant with low or undetectable sIgA, all waning within 3-6 months. We have also shown that influenza-specific milk sIgA is poorly boosted after seasonal vaccination [24]. Certainly, intramuscular (IM) vaccines do not elicit significant milk sIgA [24, 25]. Intranasal live-attenuated influenza vaccine is not better than IM vaccine for eliciting milk sIgA or IgG [26]. There is a true need to design vaccines aimed to elicit potent, specific sIgA responses in milk to protect breastfed infants. We expect such vaccines would be best designed to target the GALT of a lactating woman. However, animal models for such targeted vaccine design do not exist. The entero-mammary pathway is not universal; for example, little evidence has been found for this pathway in sheep or cows, who’s milk contains mainly serum IgG [27]. Early studies in mice and pigs suggested IgA-secreting GALT B cells traffic to the mammary gland, and in these species, sIgA predominates in milk [27]. Mice are not a good model animal for our work, given the paucity of milk produced and, unlike humans, their milk IgG is actively transported from the infant gut into the systemic circulation during the neonatal period [6, 28]. Pigs are likely more ideal. As such, this exploratory project aims to verify that pigs are an appropriate pre-clinical model for the human entero- mammary pathway and therefore, our future vaccine work. Using state-of-the-art single cell RNA sequencing, we will determine if, compared to other immune compartments, the cellular adhesion marker profiles of GALT and mammary gland (and/or milk) B cells destined to produce/producing sIgA are most similar; and the expressed Ig of these B cells are also highly related. The overall goal of this foundational work is to use pigs as a model for the development of targeted vaccines for lactating women that elicit robust, long-lasting milk sIgA to protect the breastfed infant. This work is focused on the unique needs of lactating women.", "keywords": [ "2019-nCoV", "Active Biological Transport", "Alveolar", "Animal Model", "Antibodies", "Antibody Formation", "Antibody Response", "Antigens", "Attenuated", "B-Lymphocytes", "Blood", "Breast Feeding", "Breastfed infant", "COVID-19 vaccination", "Cattle", "Cell Adhesion", "Cell Count", "Child", "Circulation", "Collaborations", "Colon", "Data", "Discipline of Nursing", "Distal part of ileum", "Enteral", "Environment", "Epithelial Cells", "Exhibits", "Family suidae", "Future", "Goals", "Gut associated lymphoid tissue", "Human", "Human Milk", "Immune", "Immunoglobulin A", "Immunoglobulin G", "Immunoglobulins", "Immunologics", "Infant", "Infection", "Influenza", "Intramuscular", "J-Chain Immunoglobulins", "Knowledge", "Lactation", "Lavage", "Life", "Link", "Liquid substance", "Mammary gland", "Measurable", "Mediating", "Microbe", "Milk", "Mucous Membrane", "Mus", "Newborn Infant", "Pathway interactions", "Pattern", "Permeability", "Play", "Polymeric Immunoglobulin Receptors", "Polymers", "Pre-Clinical Model", "Reagent", "Research Personnel", "Resistance", "Role", "SARS-CoV-2 infection", "Sampling", "Seasons", "Secretory Component", "Secretory Immunoglobulin A", "Serum", "Sheep", "Site", "Small Intestines", "Surface", "Testing", "Vaccination", "Vaccine Design", "Vaccines", "Virginia", "Woman", "Work", "adhesion receptor", "design", "dimer", "gastrointestinal epithelium", "ileum", "immunoglobulin B", "infancy", "influenza virus vaccine", "jejunum", "lactation period", "live attenuated influenza vaccine", "mammary", "medical schools", "milk production", "model development", "neonatal period", "respiratory", "response", "single-cell RNA sequencing" ], "approved": true } } ], "meta": { "pagination": { "page": 4, "pages": 1419, "count": 14184 } } }