Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=3&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=4&sort=-program_officials", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=2&sort=-program_officials" }, "data": [ { "type": "Grant", "id": "15907", "attributes": { "award_id": "1R01DA061841-01", "title": "TEAM-UP: Tobacco treatment navigators uniting with primary care", "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": 44344, "first_name": "MARCY ESTHER", "last_name": "FITZ-RANDOLPH", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-15", "end_date": "2030-03-31", "award_amount": 823882, "principal_investigator": { "id": 44345, "first_name": "SUSAN A.", "last_name": "FLOCKE", "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": "Tobacco use disorder is the deadliest substance use disorder accounting for nearly half a million premature deaths in the United States each year. Primary care clinics have the potential to reach the majority of the population with tobacco cessation assistance in the context of ongoing care, but uptake of evidence-based strategies is poor. Team-based and electronic health record-supported approaches to promote tobacco assessment and referral to cessation services (e.g. Quitlines) have been successful, but were significantly disrupted by the sequelae of COVID-19. Population outreach approaches using navigators and technologies such as patient portals have been effective in facilitating patient access to and engagement with care services and can improve health outcomes. Important gaps in understanding which outreach approaches effectively reach and engage low-income primary care patients with tobacco cessation support remain. We propose that using an outreach strategy focused on patients who were not assisted during a recent primary care visit will greatly improve the delivery of tobacco cessation support to patients. We examine two outreach strategies: a predominately person-based outreach navigator (ON) vs. a technology-based interactive patient portal (IPP). Patients that are not offered assistance during a primary care visit will be randomized into 3 groups: ON vs. IPP vs. usual care / no outreach group (NOC). Both implementation strategies will use an evidence-based approach to communicate the importance of cessation counseling and tobacco cessation medications for an effective quit strategy, offer patient choice among options, and facilitate referrals to tobacco cessation counseling and orders for medications using EHR tools. This study aims to: 1. Implement a tobacco treatment outreach intervention with ON vs. IPP vs. NOC to compare rates and correlates of receipt of cessation counseling and tobacco cessation medication orders. 2. Evaluate the effectiveness of ON vs. IPP vs. NOC on tobacco quit status. 3. Estimate and compare the costs and cost-effectiveness of ON vs. IPP. These aims will be accomplished with a three-arm randomized trial with 6000 patients (randomization ratio of 1:1:1) from 10 community-based clinics. EHR data and patient surveys will be used to assess the effect of the ON vs. IPP vs. NOC on patient reach and effectiveness outcomes and whether the approaches work equitably across important subgroups of patients. We will also assess the cost to implement and conduct each outreach approach and conduct cost-effectiveness analyses. For each Aim, qualitative methods will complement the hypothesis testing analyses to better inform observed differences in outcomes of the approaches. This study is well aligned with NIDA priorities and fills a critical knowledge gap of identifying effective and scalable strategies to improve tobacco cessation assistance among low-income primary care patients.", "keywords": [ "Abstinence", "Acceleration", "Accounting", "Address", "Adopted", "Adoption", "Adult", "Age", "Behavioral", "COVID-19 pandemic", "COVID-19 sequelae", "Caring", "Cessation of life", "Characteristics", "Clinic", "Communication", "Communities", "Complement", "Control Groups", "Cost Analysis", "Cost Effectiveness Analysis", "Counseling", "Data", "Electronic Health Record", "Equity", "FDA approved", "Health", "Health Care", "Health Care Systems", "Health behavior and outcomes", "Individual", "Intervention", "Intervention Strategies", "Knowledge", "Low income", "National Institute of Drug Abuse", "Office Visits", "Outcome", "Patient Care", "Patients", "Persons", "Pharmaceutical Preparations", "Population", "Prevalence", "Primary Care", "Process", "Protocols documentation", "Qualitative Methods", "Race", "Randomized", "Recommendation", "Reporting", "Research", "Services", "Substance Use Disorder", "Surveys", "System", "Technology", "Testing", "Text Messaging", "Tobacco", "Tobacco Use Cessation", "Tobacco Use Disorder", "Tobacco use", "United States", "Visit", "Work", "arm", "care systems", "comparative cost effectiveness", "cost", "cost comparison", "cost effectiveness", "cost-effectiveness evaluation", "effectiveness evaluation", "effectiveness outcome", "evidence base", "experience", "implementation strategy", "improved", "interest", "outreach", "pandemic disease", "patient population", "patient portal", "patient subsets", "population health", "premature", "primary care clinic", "primary care clinician", "primary care patient", "primary care practice", "primary care team", "primary care visit", "programs", "quitline", "scale up", "sex", "social deprivation", "standard of care", "telehealth", "three-arm trial", "tobacco cessation intervention", "tobacco user", "tool", "treatment as usual", "uptake", "video visit" ], "approved": true } }, { "type": "Grant", "id": "15905", "attributes": { "award_id": "1R01AI192598-01", "title": "Investigating the development and regulation of the extrafollicular B cell response as a programmed response type", "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": 44341, "first_name": "MORIAH JOVITA", "last_name": "CASTLEMAN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-16", "end_date": "2030-06-30", "award_amount": 556843, "principal_investigator": { "id": 44342, "first_name": "REBECCA A", "last_name": "ELSNER", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 848, "ror": "", "name": "UNIVERSITY OF PITTSBURGH AT PITTSBURGH", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "This is a proposal to advance our basic understanding of a critical but understudied aspect of immunity—the extrafollicular (EF) response. Upon activation, B cells enter either the EF response, or the germinal center (GC) response. The GC gives rise to high affinity memory B cells and long-lived plasma cells (PC), crucial elements of vaccine responses. While the GC is highly studied, the role of the EF response and how it is generated is much less well understood. Yet, the biology of the EF response is likely to be highly relevant to human health: Recent studies highlight the importance of the EF response, both in controlling infection and in dysregulated contexts such as Lupus and severe COVID infection. We have recently identified IL-12 as an upstream cytokine switch that directs B cells toward the EF response and suppresses GCs. In B cells, IL-12 induces autocrine feed-forward signaling between IL-12 and IFNg, resulting in distinct transcriptional changes and enhanced PC differentiation. B cells secrete IL-12, which promotes both their own differentiation and surprisingly, early TH1 differentiation. IL-12/IFNg signaling also induced the expression of CXCR3 by B cells, known to facilitate DC:T cell interactions during TH1 responses. DCs have also been shown to enhance PC differentiation in some contexts. EF foci form in locations rich in DCs and T cells, but the significance of this location is unknown. These findings lead to our central hypothesis - that the EF response is a specialized “response type” preferentially supporting rapid expansion and PC differentiation, and that EF foci are a niche with local cell-cell interactions and cytokine production, coordinated by inflammation-induced chemokines. GC B cells facilitate the differentiation of TFH, and though naïve B cells can invade existing GC, the bulk of the GC population is maintained through proliferation with infrequent differentiation. In Aim 1, we will test the role of B cells in enhancing the EF response locally, and test the self-renewal capacity of the undifferentiated “EF B cell” population. In Aim 2, we will isolate the continually proliferating EF B cell population and begin to characterize the EF B cell state transcriptionally and epigenetically. We will examine the effects of IL-12 and IFNg on this gene regulatory network. We will also target transcription factors that are predicted to regulate the EF B cell program and test these findings using human B cells. In Aim 3, we will characterize the EF foci as a niche, much like the GC is thought of, using spatial transcriptomics and genetic approaches to define the roles of DCs, CD4 T cells, and CXCR3 in the EF response. Collectively these studies will provide a significant conceptual advance for our understanding of the EF B cell response and enable the creation of new tools to study EF B cells and their progeny. This is an area of great need as relatively little is known about how the EF response is regulated. These studies are therefore poised to have a significant impact in advancing our understanding of the EF response, with a long-term objective of learning how to both restrain EF responses to treat EF-driven autoimmunity, and exploit the EF response for novel vaccine designs and cancer therapeutics.", "keywords": [ "ATAC-seq", "Adoptive Transfer", "Affinity", "Antibody Affinity", "Antibody Response", "Area", "Autoimmune Diseases", "Autoimmunity", "B Cell Proliferation", "B-Cell Activation", "B-Lymphocytes", "Biology", "CD4 Positive T Lymphocytes", "CD8-Positive T-Lymphocytes", "CXC chemokine receptor 3", "CXCL9 gene", "CXCR3 gene", "CXCR4 gene", "Cell Communication", "Cell secretion", "Cells", "Characteristics", "Data", "Dendritic Cells", "Development", "Disease", "Dose", "Elements", "Environment", "Epigenetic Process", "Feedback", "Foundations", "Genes", "Genetic Transcription", "Health", "Histologic", "Human", "Immune", "Immune system", "Immunity", "In Vitro", "Infection", "Infection Control", "Inflammation", "Interleukin-12", "Invaded", "Lead", "Learning", "Ligands", "Location", "Longevity", "Lupus", "Macrophage", "Malignant Neoplasms", "Maps", "Memory B-Lymphocyte", "Modeling", "Molecular", "Mus", "Output", "Pathway interactions", "Plasma Cells", "Plasma Enhancement", "Plasmablast", "Population", "Predictive Factor", "Production", "Proliferating", "Regulation", "Reporter", "Role", "Route", "SARS-CoV-2 infection", "Salmonella infections", "Signal Transduction", "Small Interfering RNA", "Source", "Structure of germinal center of lymph node", "System", "T-Cell Depletion", "T-Lymphocyte", "Testing", "Therapeutic", "Undifferentiated", "Upregulation", "Vaccine Design", "autocrine", "chemokine", "chemokine receptor", "comparative", "cytokine", "gene regulatory network", "genetic approach", "immune checkpoint blockade", "in vivo", "influenza infection", "knock-down", "monocyte", "multiple omics", "novel", "novel vaccines", "organizational structure", "pathogen", "plasma cell differentiation", "programs", "response", "restraint", "self-renewal", "sensor", "severe COVID-19", "spatial transcriptomics", "synergism", "tool", "transcription factor", "transcriptome sequencing", "vaccine response" ], "approved": true } }, { "type": "Grant", "id": "15929", "attributes": { "award_id": "1R21AI188112-01", "title": "The role of the mRNA-based or Newcastle disease virus (NDV)-based vaccine platform in mucosal B cell priming and recirculation", "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": 44341, "first_name": "MORIAH JOVITA", "last_name": "CASTLEMAN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-23", "end_date": "2027-06-30", "award_amount": 464750, "principal_investigator": { "id": 44374, "first_name": "Weina", "last_name": "Sun", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "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": "The experiences and lessons learned from the COVID-19 pandemic geared our interests towards investigating the mechanism of action of different vaccine platforms and vaccination strategies that aim to induce long-lasting protective systemic and mucosal immune responses to prevent disease and transmission via the mucosal route. Dr. Weina Sun co-developed a Newcastle disease virus vector (NDV)-based COVID-19 vaccine that can be used either as an injectable inactivated whole virion vaccine or a live intranasal vaccine, the latter of which can elicit mucosal immune responses as a “stand-alone” vaccine platform. In naïve mice, a 2-dose regimen of intranasal NDV-based vaccine induced a high level of mucosal IgA antibodies. In mice that were pre- vaccinated with mRNA-LNP COVID-19 vaccines via the intramuscular route, a third intranasal NDV booster also substantially enhanced nasal wash antigen-specific IgA. By closely examining samples obtained from different anatomical mucosal sites in mRNA-LNP vaccinated mice without the NDV booster, spike-specific IgA were detected in nasal wash, intestinal lavage as well as vaginal lavage, among which Intestinal lavage contained the highest levels of IgA. Dr. Jennifer Gommerman is an immunologist with special interests studying mucosal B lymphocytes. In humans, she developed methods to detect salivary antibodies. While SARS-CoV-2 infection induces high levels of spike-specific salivary IgG and IgA, salivary IgG are also abundantly found after intramuscular 2-dose mRNA vaccinations. Intriguingly, some of the mRNA-vacccinated individuals developed and maintained modest salivary secretory-IgA that were resistence to decay after a 2-dose mRNA vaccine. Given that both in mice and humans, mucosal antigen-specific IgA were detected after mRNA-LNP vaccination, we hypothesize that mRNA-LNP vaccines can prime de novo mucosal B cells that are close to the administration sites, which are able to recirculate to other mucosal surfaces. Consequently, a further mucosal booster vaccine, such as the intranasal live NDVvaccine, would be able to recall pre-exisiting memory B cell responses. We will follow two specific aims to test our hypothesis, utilizing mRNA-LNP vaccine and NDV vaccine encoding the spike of Beta variant as a proof of concept: (Aim 1) To examine temporal and spatial dynamics of antigen-specific IgA and IgG secreting B cells in the mucosa-associated lymphoid tissues after mRNA and NDV vaccination in mice. (Aim 2) To track circulation of antigen-specific mucosal B cells in photoconvertible Kikume mice after mRNA prime followed by NDV vaccination or infection by flowcytometry. The proposed work entails innovative approaches and mouse models to test our hypothesis. We believe the outcomes of the study can inform the mechanism of action of not only mRNA-based and NDV-based SARS-CoV-2 vaccines, but also the same types of vaccines against other respiratory or enteric viral pathogens, in which mucosal antibody responses plays a critical role to mitigate virus infection and transmission.", "keywords": [ "Anatomy", "Animals", "Antibodies", "Antibody Response", "Antigens", "B-Cell Development", "B-Lymphocytes", "Biological Assay", "C57BL/6 Mouse", "COVID-19 pandemic", "COVID-19 vaccine", "Cells", "Cessation of life", "Circulation", "Conceptions", "Disease", "Dose", "Enteral", "Flow Cytometry", "Future", "Genetic", "Human", "Immunize", "Immunoglobulin A", "Immunoglobulin G", "Immunoglobulin M", "Immunologist", "Individual", "Infection", "Inguinal lymph node group", "Injectable", "Intestines", "Intramuscular", "Lavage", "Left", "Lymphoid", "Measures", "Memory B-Lymphocyte", "Messenger RNA", "Methods", "Mucosal Immune Responses", "Mucous Membrane", "Mus", "Nasal Lavage Fluid", "Newcastle disease virus", "Oncolytic", "Outcome Study", "Phase I Clinical Trials", "Plasma", "Plasma Cells", "Play", "RNA vaccination", "RNA vaccine", "Regimen", "Research", "Resistance", "Respiratory System", "Role", "Route", "SARS-CoV-2 B.1.351", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "Safety", "Salivary", "Sampling", "Secondary Immunization", "Secretory Immunoglobulin A", "Shapes", "Site", "Spleen", "Surface", "Testing", "Transgenic Organisms", "Upper respiratory tract", "Vaccinated", "Vaccination", "Vaccines", "Vagina", "Vaginal Douching", "Variant", "Viral Vector", "Virion", "Virus Diseases", "Wild Type Mouse", "Work", "animal data", "antigen binding", "booster vaccine", "breakthrough infection", "enzyme linked immunospot assay", "experience", "human data", "innovation", "interest", "mRNA lipid nano particle vaccine", "mouse model", "mucosa-associated lymphoid tissue", "mucosal site", "mucosal vaccine", "pathogenic virus", "pre-clinical", "prevent", "receptor", "research clinical testing", "respiratory", "response", "spatiotemporal", "success", "tool", "transmission process", "urogenital tract", "vaccination strategy", "vaccine development", "vaccine platform", "vector", "vector vaccine", "vector-based vaccine", "viral transmission" ], "approved": true } }, { "type": "Grant", "id": "15900", "attributes": { "award_id": "1UG3DA063344-01", "title": "Telehealth-Delivered tDCS for Cannabis Addiction Recovery: The C.A.R.E.S. (Cannabis Addiction Recovery Enhancement Stimulation) Initiative", "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": 44337, "first_name": "JIA BEI", "last_name": "WANG", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-15", "end_date": "2027-06-30", "award_amount": 684694, "principal_investigator": { "id": 22511, "first_name": "Leigh", "last_name": "Charvet", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 832, "ror": "", "name": "NEW YORK UNIVERSITY SCHOOL OF MEDICINE", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 27548, "first_name": "Giuseppina", "last_name": "Pilloni", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 44338, "first_name": "Abhishek", "last_name": "Datta", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 832, "ror": "", "name": "NEW YORK UNIVERSITY SCHOOL OF MEDICINE", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Cannabis use in the U.S. has surged, driven by widespread legalization and accelerated by the COVID-19 pandemic. Over 55 million U.S. adults are current users, and approximately 30% will develop cannabis use disorder (CUD). Despite the urgent need for effective treatments, no FDA-approved options exist, and current interventions have proven insufficient, underscoring the necessity for innovative and accessible solutions. We propose a novel, home-based intervention combining transcranial direct current stimulation (tDCS) with mindfulness meditation, targeting the dorsolateral prefrontal cortex—a key region in the neural circuitry underlying the addiction cycle. Delivered via the ElectraRx telehealth portal, this approach is both cost-effective and widely accessible. Our extensive preliminary data, involving over 600 patients and 17,000 home-based tDCS sessions, along with our pilot study of this intervention in CUD, demonstrate its feasibility and potential. However, further development and testing are required to advance it to clinical use. The initial UG3 phase (Years 1-2) will involve developing a tDCS home-based administration system by Soterix Medical Inc. (SMI), tailored specifically for the intended population and environment (\"ElectraRx-CARES\"). We will then refine and validate the tDCS-mindfulness intervention through a double-blind, sham-controlled feasibility trial with n = 46 adults with CUD. If at least 50% of participants complete 70% of the sessions, we will advance to the UH3 phase, where a large-scale RCT enrolling n = 192 participants with CUD to assess the intervention's efficacy in reducing cannabis use and withdrawal symptoms. Follow-up assessments at three months will evaluate the persistence of these effects. FDA guidance on device development and data collection will be obtained throughout. Finally, we will optimize intervention delivery, iterate the device, and advance the regulatory process, including pursuing Breakthrough Device Designation. This scalable intervention addresses a critical public health need and represents a promising step forward in treating the rapidly growing problem of CUD.", "keywords": [ "Acceleration", "Address", "Adult", "Affect", "Anodes", "Back", "Behavior Therapy", "Breakthrough device", "COVID-19 pandemic", "Cannabis", "Clinical", "Clinical Trials", "Data", "Data Collection", "Data Reporting", "Development", "Device or Instrument Development", "Devices", "Double-Blind Method", "Drug Screening", "Enrollment", "Ensure", "Environment", "Equipment and supply inventories", "FDA approved", "Feedback", "Frequencies", "Goals", "Health", "Health Services Accessibility", "Home", "Individual", "Intervention", "Intervention Studies", "Left", "Legal", "Marijuana", "Marijuana Dependence", "Measures", "Medical", "Medical Device", "Monitor", "Outcome", "Outcome Measure", "Participant", "Patient Self-Report", "Patients", "Pharmacotherapy", "Phase", "Pilot Projects", "Population", "Prefrontal Cortex", "Prevalence", "Process", "Public Health", "Randomized", "Recovery", "Risk", "Rural Community", "Safety", "Self Administration", "System", "Systems Development", "Testing", "Time", "Treatment Efficacy", "Urine", "Withdrawal Symptom", "addiction", "arm", "attentional bias", "barrier to care", "cannabis withdrawal", "cost effective", "effective therapy", "efficacy evaluation", "evidence base", "feasibility trial", "follow up assessment", "follow-up", "innovation", "intervention delivery", "marijuana use", "marijuana use disorder", "meetings", "mindfulness", "mindfulness intervention", "mindfulness meditation", "minority communities", "neural circuit", "neuroregulation", "novel", "portability", "predictive marker", "predictive test", "response", "response biomarker", "telehealth", "therapy design", "timeline", "transcranial direct current stimulation", "underserved community" ], "approved": true } }, { "type": "Grant", "id": "15896", "attributes": { "award_id": "1F30AI186615-01A1", "title": "HIV and its impact on Long COVID prevalence and manifestations", "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": 44334, "first_name": "ZUOYU", "last_name": "XU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-22", "end_date": "2028-08-21", "award_amount": 43420, "principal_investigator": { "id": 44335, "first_name": "Skye", "last_name": "Opsteen", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3397, "ror": "", "name": "UNIVERSITY OF ALABAMA AT BIRMINGHAM", "address": "", "city": "", "state": "AL", "zip": "", "country": "United States", "approved": true }, "abstract": "The purpose of this NIH F30 application is to support the PI, Skye Opsteen, and her mentored research and career development for the next three years. The proposed activities will strengthen her potential to become a successful physician scientist. The major goal of this project is to develop her experimental immunology skills to inform the biologic basis of post-COVID syndromes, particularly in people with HIV (PWH) given their increased baseline immune activation. The primary objectives of the research proposal are to investigate if the monocyte and T cell population shifts typical of chronic HIV infection are exacerbated during long COVID, and how the immune features of long COVID in PWH compare to people without HIV. Chronic inflammation has been implicated in long COVID development and is known to drive increased rates of comorbidities in PWH; therefore, studying long COVID in PWH offers a unique opportunity to characterize long COVID phenotypes driven by chronic inflammation. This project will investigate monocyte-mediated inflammation, specifically the role of CD16+ monocytes and inflammatory cytokines IL-1 and TNF in recovery versus long COVID development in PWH, and how these responses contribute to clinical symptoms such as fatigue (Aim 1). The project will also determine the contribution of adaptive immune responses during long COVID in PWH (Aim 2). Our long-term objective is to inform future long COVID studies of potential diagnostic markers and therapeutic targets for patients with long COVID phenotypes driven by persistent inflammation. The proposed training plan for the PI is sponsored by her primary PhD mentor, Dr. Nathan Erdmann, and co- mentor, Dr. Paul Goepfert. Included in the training plan are experiences that will help her develop in three major areas: 1) rigorous immunological research in HIV and SARS-CoV-2, which includes developing familiarity with the existing literature, critically evaluating published studies, and training in principles of scientific integrity and responsible conduct of research; 2) competence in bioinformatic techniques and biostatistical analysis; and 3) career and professional development, including grant writing, manuscript review, clear communication through presentation and manuscript preparation, and translation of research findings to clinical applications. After completion, this training plan will provide the PI with the foundation necessary for a successful career as a physician scientist. Her ultimate career goal is to one day lead a translational research laboratory that studies human immune responses to emerging and reemerging pathogens in the setting of chronic immune dysregulation to assist in the clinical prevention and treatment of various infectious diseases in at-risk populations.", "keywords": [ "2019-nCoV", "Adipose tissue", "Affinity", "Antibodies", "Antibody Affinity", "Antibody Formation", "Antigen Presentation", "Area", "Automobile Driving", "Binding", "Bioinformatics", "Biological", "Biological Assay", "Biometry", "Blood", "COVID-19 pathogenesis", "COVID-19 prevalence", "Chronic", "Clinical", "Communicable Diseases", "Communication", "Competence", "Development", "Doctor of Philosophy", "Exhibits", "Extravasation", "FCGR3B gene", "Familiarity", "Fatigue", "Foundations", "Frequencies", "Future", "Gene Expression Profile", "Goals", "Grant", "HIV", "HIV Infections", "Hospitalization", "Human", "Immune", "Immune response", "Immunocompetent", "Immunoglobulin G", "Immunologics", "Immunology", "Impairment", "Individual", "Inflammation", "Inflammatory", "Inflammatory Response", "Laboratory Study", "Lead", "Link", "Literature", "Long COVID", "Macrophage", "Manuscripts", "Mediating", "Mentors", "NF-kappa B", "Patients", "Persons", "Phenotype", "Physicians", "Plasma", "Population", "Populations at Risk", "Predisposition", "Preparation", "Prevention", "Production", "Publishing", "Recovery", "Research", "Research Proposals", "Risk", "Role", "Scientist", "Symptom Burden", "Symptoms", "Syndrome", "T-Lymphocyte", "Techniques", "Tissues", "Training", "Translational Research", "United States National Institutes of Health", "Viral", "Writing", "acute COVID-19", "adaptive immune response", "antiretroviral therapy", "career", "career development", "clinical application", "comorbidity", "cytokine", "diagnostic biomarker", "emerging pathogen", "exhaustion", "experience", "immune activation", "insight", "mitochondrial dysfunction", "monocyte", "persistent symptom", "post SARS-CoV-2 infection", "post-COVID-19", "programmed cell death protein 1", "receptor", "research and development", "response", "responsible research conduct", "severe COVID-19", "skills", "therapeutic target" ], "approved": true } }, { "type": "Grant", "id": "15895", "attributes": { "award_id": "3R01AI170564-04S1", "title": "Single arm trial of menstrual cups among economically vulnerable women to reduce Bacterial vaginosis and STIs through reduced harmful sexual and menstrual practices", "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": 44333, "first_name": "ELEANORE JENNIFER", "last_name": "CHUANG", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2027-07-31", "award_amount": 139891, "principal_investigator": { "id": 24638, "first_name": "Supriya Dinesh", "last_name": "Mehta", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 163, "ror": "https://ror.org/02mpq6x41", "name": "University of Illinois at Chicago", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 3396, "ror": "", "name": "RUSH UNIVERSITY MEDICAL CENTER", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "In western Kenya, HIV prevalence is 16% among women in the general population, and 29% among the most economically constrained women. The HIV/STI epidemic overlaps with broader reproductive health concerns. Menstrual hygiene management (MHM) is a pervasive problem across low- and middle-income countries. In Phillips-Howards’ survey of over 3,400 women in rural Kenya, two-thirds of women in impoverished settings state they depend on their sexual partners to provide branded products. Economically vulnerable women at high risk for HIV and STI are uniquely challenged because many continue to have sex during menses, and engage in harmful MHM practices, such as vaginal insertion of sponges and cotton to maintain dryness. Led by co-investigator Phillips-Howard, a cluster-randomized study of 644 girls aged 14-16 years old in western Kenya compared reusable menstrual cups to usual menstrual practice and counseling; after 9 months, menstrual cup use resulted in 35% reduction (p=0.034) in Bacterial vaginosis (BV) prevalence and 56% reduction (p=0.001) in STI prevalence compared to other materials. Among 431 Kenyan secondary schoolgirls aged 14-21, we observed cloth use for menses was associated with a 1.72-fold increased odds of non-optimal vaginal microbiome (CST-IV vs. CST-I: aOR=1.90; 95% CI: 1.03–2.86). Over 18 months of observation prior to COVID-19, girls using menstrual cups to manage menses had 20% higher occurrence of Lactobacillus crispatus dominated CST-I (aRR=1.29; 95% CI: 1.08–1.53, controlling for age, and baseline STI and sexual activity). Menstrual cups designed for use during intercourse may help women prevent BV and STIs through hygienic menstrual practices and avoidance of harmful practices to maintain vaginal dryness during menses. Objective: This single-arm interventional trial seeks to evaluate the preliminary efficacy of menstrual cups on non-optimal vaginal microbiome (VMB), BV, and STIs of economically vulnerable women at high risk for STIs and HIV, assess safety profile, and understand implementation needs. In Aim 1, we will evaluate the impact of menstrual cups on VMB, BV, and STIs among 402 economically vulnerable women in semi-urban Kenya. In Aim 2, we will conduct integrated surveillance for enhanced detection of safety endpoints, risk of cup contamination, and mitigating or facilitating water, sanitation, hygiene (WASH) factors. In Aim 3, we will identify constructs for successful MHM program implementation using an implementation science framework. Future Directions: The biological protection suggested in a randomized setting, and our findings that unhygienic cloth use is associated with non-optimal VMB, while menstrual cup use increases optimal VMB composition, together provide rational justification for this trial, of relevance to economically challenged women globally. Assessing preliminary efficacy signal in conjunction with implementation characteristics and adverse events, will generate a comprehensive and necessary foundation for definitive assessment of effectiveness of menstrual cups as a multipurpose intervention for MHM, and to reduce BV and STIs.", "keywords": [ "16 year old", "Acceleration", "Address", "Adverse event", "Age", "Bacterial Vaginosis", "Behavioral", "Biological", "COVID-19", "Characteristics", "Chlamydia", "Counseling", "Data", "Decision Making", "Detection", "Discrimination", "Dryness", "Education", "Eligibility Determination", "Epidemic", "Extravasation", "Financial Support", "Focus Groups", "Foundations", "Future", "General Population", "Gonorrhea", "Gossypium", "Guidelines", "HIV", "HIV/STD", "Health Care", "High Risk Woman", "Hygiene", "Individual", "Intervention", "Intervention Trial", "Interview", "Investigation", "Kenya", "Knowledge", "Lactobacillus", "Life", "Location", "Medical", "Menstruation", "Odors", "Participant", "Phase", "Policies", "Porifera", "Poverty", "Practice Management", "Prevalence", "Privacy", "Randomized", "Reporting", "Reproductive Health", "Research Personnel", "Risk", "Rural", "Safety", "Sanitation", "Secondary Schools", "Secrecy", "Sex Behavior", "Sexual Partners", "Signal Transduction", "Soaps", "Surveys", "Taboo", "Technology", "Time", "Training", "Trichomonas Infections", "UNESCO", "Vagina", "Water", "Woman", "Wool", "Work", "aged", "arm", "biobehavior", "contextual factors", "cost", "cost effective", "cost effective intervention", "design", "diverse data", "effectiveness evaluation", "girls", "global health", "implementation context", "implementation determinants", "implementation evaluation", "implementation framework", "improved", "low and middle-income countries", "microbiome composition", "pandemic disease", "pharmacovigilance", "prevent", "primary outcome", "programs", "safety assessment", "scale up", "sex", "sexual and reproductive health", "social", "social stigma", "stem", "treatment arm", "trial design", "vaginal dryness", "vaginal microbiome", "women's reproductive health" ], "approved": true } }, { "type": "Grant", "id": "15893", "attributes": { "award_id": "1U18FD008634-01", "title": "Increased Extraction Capacity for Molecular Section", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [ { "id": 44330, "first_name": "MEGAN", "last_name": "MILLER", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-20", "end_date": "2026-08-31", "award_amount": 31722, "principal_investigator": { "id": 44331, "first_name": "YAN", "last_name": "ZHANG", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3378, "ror": "", "name": "UNIVERSITY OF ARIZONA", "address": "", "city": "", "state": "AZ", "zip": "", "country": "United States", "approved": true }, "abstract": "Vet-LIRN Network Capacity-Building Project and Equipment Grants (U18) PAR-23-202 Increased Extraction Capacity for Arizona Veterinary Diagnostic Laboratory Molecular Section Project Summary/Abstract- The Arizona Veterinary Diagnostic Laboratory (AZVDL) is seeking funding to purchase an Indical IndiMag2 to enhance its nucleic acid extraction capability and capacity, thereby strengthening its emergency surge testing for significant animal food/feed emergency events. Veterinary diagnostic laboratories play a critical role in protecting both animal and public health, especially during large-scale foodborne disease outbreaks or contamination incidents. Funding through the Vet-LIRN Network Capacity-Building Project and Equipment Grants (U18) is essential to expand AZVDL’s ability to respond effectively to such emergencies. This support will enable AZVDL to improve its diagnostic capabilities by acquiring advanced equipment. The COVID-19 pandemic has demonstrated that veterinary laboratories are uniquely positioned to provide high-throughput testing during public health crises, as they routinely handle large- scale diagnostic procedures for zoonotic and animal diseases. By enhancing its capacity, AZVDL will be better equipped to provide real-time detection of pathogens or contaminants in animal food and feed, helping to prevent outbreaks that threaten food safety, public health, and economic stability. This funding initiative also aligns with the goals of the Food Safety Modernization Act (FSMA), which emphasizes proactive measures to detect and prevent foodborne illnesses. Upgrading AZVDL’s infrastructure will not only improve its response to emerging threats but also contribute to the broader national network of veterinary laboratories dedicated to safeguarding both animal and human populations.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15892", "attributes": { "award_id": "7R35GM124918-08", "title": "How the endocytic network mediates specificity of cell signaling", "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": 44328, "first_name": "KALYNDA K", "last_name": "STOKES", "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": 419850, "principal_investigator": { "id": 44329, "first_name": "Yan", "last_name": "Yu", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 827, "ror": "", "name": "WASHINGTON UNIVERSITY", "address": "", "city": "", "state": "MO", "zip": "", "country": "United States", "approved": true }, "abstract": "Abstract: How the Endocytic Network Mediates Specificity of Cell Signaling Receptor crosstalk – the cooperation between two or more receptors to modulate cell responses – is a key signaling mechanism. It enables cells to generate a large combinatorial repertoire of specific signaling with a limited variety of receptors. Receptor crosstalk plays an essential role in cell physiology. Consequently, dysfunctions in receptor crosstalk are associated with many human diseases, such as infectious diseases (including COVID-19), cancer, and cardiovascular diseases. To understand the physical mechanisms by which signals from different receptors are integrated in crosstalk, studies have exclusively focused on receptor interactions at the plasma membrane. In contrast, how the crosstalk signals are transduced with high fidelity from the plasma membrane to the nucleus is poorly understood and scarcely explored. The overall goal of this research is to establish the functional role of the endocytic network in transducing and regulating receptor crosstalk. During the past 6 years, our group has made pioneering discoveries in support of the central hypothesis that the endocytic network is where extracellular chemical and physical stimuli intertwine to regulate receptor crosstalk. Specifically, we reported a new model in which receptors can crosstalk by forming overlapping interfaces between discrete signaling clusters, challenging the prevailing view that receptors oligomerize to crosstalk. Importantly, such spatially organized interaction between receptors at endosomes and plasma membranes is modulated by extracellular physical cues, and directly regulates cell inflammatory responses. These prior discoveries and the plethora of new approaches we developed for studying endosome functions laid a critical and unique foundation for us to address the knowledge gap: how does the endocytic network mediate receptor crosstalk? We will address how the endocytic network orchestrates chemical cues from receptor crosstalk (Direction 1) and transduces extracellular physical cues to refine the specificity of crosstalk signaling (Direction 2). To address the first direction, we will define the physical mechanisms by which endocytic sorting, collective endosome-organelle interactions, and endosome-specific activation modulate crosstalk signaling originated from the plasma membrane. To address the second direction, we will integrate experiments with computational modeling to determine the feedback loop between the endocytic network and cell-matrix interactions that regulate receptor crosstalk. This project will establish a mechanistic and predictive understanding of how the endocytic network mediates the spatiotemporal specificity of receptor crosstalk and cell signaling in general; a topic that is poorly understood. It will also lower the technical barrier that has impeded research on this topic, by establishing novel quantitative toolsets for dissecting the dynamics and function of the endocytic network on multiple length scales. Ultimately, a better understanding of endosome functions in receptor crosstalk will facilitate the development of new therapeutic strategies for diseases.", "keywords": [ "Address", "Autoimmune Diseases", "Biological Process", "COVID-19", "Cancer Vaccines", "Cardiovascular Diseases", "Cell Nucleus", "Cell Physiology", "Cell membrane", "Cells", "Chemicals", "Communicable Diseases", "Computer Models", "Cues", "Development", "Disease", "Endocytosis", "Endosomes", "Feedback", "Foundations", "Functional disorder", "Goals", "Immunologic Adjuvants", "Inflammatory Response", "Knowledge", "Length", "Malignant Neoplasms", "Mediating", "Mission", "Modeling", "Organelles", "Pathogenesis", "Play", "Prevention", "Public Health", "Receptor Cross-Talk", "Reporting", "Research", "Role", "Signal Transduction", "Sorting", "Specificity", "Stimulus", "United States National Institutes of Health", "cancer therapy", "combinatorial", "disease diagnosis", "endosome membrane", "experimental study", "extracellular", "human disease", "novel", "novel strategies", "novel therapeutic intervention", "receptor", "response", "spatiotemporal" ], "approved": true } }, { "type": "Grant", "id": "15890", "attributes": { "award_id": "1R43HL176305-01A1", "title": "Development of a tissue-targeted non-thrombotic EPO derivative", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 44326, "first_name": "NITIN", "last_name": "AGRAWAL", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-09-20", "end_date": "2026-08-31", "award_amount": 306658, "principal_investigator": { "id": 44327, "first_name": "Robert Rogers", "last_name": "Yocum", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3394, "ror": "", "name": "GENERAL BIOLOGICS, INC.", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "“Development of a tissue-targeted non-thrombotic EPO derivative.” Chronic obstructive pulmonary disease (COPD) affects 16 million people in the US and is the third leading cause of death in the world, with an estimated 500 million cases worldwide. In the US the primary cause is cigarette smoking, but in most of the world the cause is air pollution. In this disease, the airways (bronchioles) are constricted and the alveoli are distended and never fully contract. Current treatments use drug inhalers that open up the airways, but these treatments are only partially effective. In addition, about 2 million of the US COPD patients are also anemic, so that oxygen delivery is particularly poor. Erythropoietin (EPO) is a hormone that mediates the body’s response to massive blood loss (hemorrhage). EPO is used to treat anemia in kidney failure, cancer, etc., based on its stimulation of red blood cell production. EPO also has a useful tissue-protective activity that can reduce effects of oxygen limitation that damage the heart, brain, and other tissues. However, EPO also enhances blood clotting and increases frequency of heart attacks, strokes and deep vein thrombosis when given to anemic patients. To address COPD and other problems of oxygen delivery, General Biologics is developing an engineered protein, termed “EPO-H” (EPO for Hypoxia), that retains the red blood cell producing and tissue-protective activities of EPO, but lacks the blood clotting side effects. EPO-H will also have a long plasma half-life, to allow for infrequent dosing, patient convenience, and reduced burden on the health care system. The net effect should be that, compared to current commercial versions of EPO, our protein (“EPO-H”) will maintain production of red blood cells, show increase neuroprotection, and have significantly reduced or eliminated blood-clotting site effects. Natural EPO is not currently given to COPD patients or patients with disorders such as cystic fibrosis or extreme Covid-19 requiring hospitalization and mechanical ventilation. Our experimental aims are: (1) General Biologics will produce engineered protein for all of the experiments and will test the proteins for blood-based surrogate markers of hypoxia resistance and blood-clotting, to establish a dose at which the therapeutic effect is expected but side effects are not.; (2) University of Maryland will demonstrate that EPO-H can promote survival of mice in a low- oxygen environment; and also (3) demonstrate that EPO-H does not enhance clot size in a mouse model of deep vein thrombosis, even though natural EPO does increase the size of blood clots in mice with deep vein thrombosis.", "keywords": [ "Address", "Affect", "Air Pollution", "Alveolus", "Anemia", "Antibodies", "Atmosphere", "Binding", "Biological Assay", "Biological Products", "Blood - brain barrier anatomy", "Blood Platelets", "Blood Proteins", "Blood coagulation", "Blood flow", "Blood specimen", "Brain", "Bronchioles", "C57BL/6 Mouse", "COVID-19", "COVID-19 patient", "Cause of Death", "Cell Survival", "Cells", "Chimeric Proteins", "Chronic Obstructive Pulmonary Disease", "Coagulation Process", "Collaborations", "Contracts", "Core Facility", "Cystic Fibrosis", "Deep Vein Thrombosis", "Development", "Disease", "Dose", "Dose Limiting", "Drug Kinetics", "Drug usage", "Elements", "Environment", "Epoetin Alfa", "Erythrocytes", "Erythropoietin", "Erythropoietin Receptor", "Flow Cytometry", "Frequencies", "Glycophorin", "Goals", "Half-Life", "Health Care Systems", "Hematopoiesis", "Hematopoietic stem cells", "Hemorrhage", "Hormones", "Hospitalization", "Hypoxia", "Inferior vena cava structure", "Inhalators", "Kidney Failure", "Lead", "Malignant Neoplasms", "Maryland", "Measures", "Mechanical ventilation", "Mediating", "Medical", "Modeling", "Mus", "Mutate", "Mutation", "Myocardial Infarction", "Needles", "Oxygen", "Patients", "Persons", "Pharmaceutical Preparations", "Plasma", "Production", "Protein Engineering", "Proteins", "Reagent", "Research", "Resistance", "Reticulocyte count", "Reticulocytes", "Signal Transduction", "Site", "Stroke", "Surrogate Markers", "Testing", "Therapeutic", "Therapeutic Effect", "Thrombus", "Time", "Tissues", "Universities", "Ventilator", "analytical tool", "cigarette smoking", "constriction", "deprivation", "drug testing", "experimental study", "heart damage", "humanized antibody", "improved", "in vivo", "loss of function", "medical schools", "mouse model", "nanobodies", "neuroprotection", "novel", "preclinical development", "professor", "promote resilience", "resilience", "response", "side effect", "success", "thrombotic" ], "approved": true } }, { "type": "Grant", "id": "15897", "attributes": { "award_id": "7R01DA059176-02", "title": "Multimodal Analysis of Gestational Health and Placental Injury in Opioid-Affected Pregnancies", "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": "2025-08-15", "end_date": "2026-07-31", "award_amount": 1247483, "principal_investigator": { "id": 22880, "first_name": "Elizabeth E", "last_name": "Krans", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 848, "ror": "", "name": "UNIVERSITY OF PITTSBURGH AT PITTSBURGH", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 28076, "first_name": "Yingshi", "last_name": "Ouyang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 28077, "first_name": "Yoel", "last_name": "Sadovsky", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1167, "ror": "", "name": "CHILDREN'S RESEARCH INSTITUTE", "address": "", "city": "", "state": "DC", "zip": "", "country": "United States", "approved": true }, "abstract": "Opioids are medically used for safe pain relief and management. However, illicit opioid use has substantially increased across the US in the past decade, with further worsening during the COVID-19 pandemic, leading to a profound impact on human health. Specifically, opioid use disorder (OUD) during pregnancy poses an increased risk of pregnancy-associated maternal morbidity and mortality, fetal growth restriction (FGR) and related complications, neonatal opioid withdrawal syndrome, and long-term neurobehavioral effects. Some of these risks persist despite the use of safer opioids, such as buprenorphine and methadone, medications for OUD (MOUD) patients. Whereas current studies center mainly on transplacental opioid transport to the fetus and the adverse effects of opioids on infants, the direct impact of illicit and prescription opioids on placental development, differentiation, and function are largely unexplored. The placental floating villi mediate maternal- fetal gas exchange, nutrient uptake, waste release immune defense and the production of hormones and extracellular vesicles (EVs). These villi are covered by a layer of multinucleated, terminally differentiated syncytiotrophoblasts (STBs), which forms the feto-placental frontline that is directly exposed to opioids in the maternal blood. Subjacent to this layer are mononucleated, progenitor cytotrophoblasts (CTBs), which replenish the STB layer through the process of differentiation and fusion. Importantly, injuries to the STB and CTB layers are implicated in pregnancy-associated complications, including FGR and stillbirth. Here we seek to investigate opioid-dependent placental injury, focusing on the most critical and unique layer of placental trophoblasts. We will enroll participants with OUD, including illicit opioids and MOUD (buprenorphine, methadone), examine their pregnancy course and their children’s health through the first year postpartum. Using biospecimens from each participant, including maternal plasma and urine across the three trimesters, placental biopsies and fetal cord blood at delivery, we will employ multimodal cutting-edge technologies, including single-cell RNAseq, spatial transcriptomics, protein chip cytometry and placenta EV RNA profiling, and explore the molecular and cellular processes affected by opioids in the maternal-placental-fetal trio- ecosystem. To gain mechanistic insights into the functional changes in gene expression and EV cargo, we will use an array of model systems, including human trophoblast stem cells and cultured primary human trophoblasts, and mechanistically interrogate pathways underlying opioid injury. We will further correlate key molecular signatures with clinical assessment, including maternal gestational disorders, perinatal and infant neurodevelopmental outcomes. Together, our strategic plan, bolstered by our transdisciplinary team, enables us to address critically important knowledge gaps related to human placenta biology in opioid-affected pregnancies.", "keywords": [], "approved": true } } ], "meta": { "pagination": { "page": 3, "pages": 1419, "count": 14184 } } }