Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1391&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=1392&sort=program_officials", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1390&sort=program_officials" }, "data": [ { "type": "Grant", "id": "15210", "attributes": { "award_id": "1G08LM014406-01", "title": "Long COVID Health Literacy Project: Bringing Health Information to Patients and Providers with Health Disparities in Rural Northern New England", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Library of Medicine (NLM)" ], "program_reference_codes": [], "program_officials": [ { "id": 31790, "first_name": "CRISTAN", "last_name": "SMITH", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-01", "end_date": "2027-07-10", "award_amount": 150000, "principal_investigator": { "id": 31791, "first_name": "Jeffrey", "last_name": "Parsonnet", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2072, "ror": "", "name": "DARTMOUTH-HITCHCOCK CLINIC", "address": "", "city": "", "state": "NH", "zip": "", "country": "United States", "approved": true }, "abstract": "The purpose of this project is to address health disparities in the care of patients with post-acute COVID syndrome (PACS) due to the rural nature of northern New England and its shortage of medical services. We will develop useful, understandable and relatable information for patients and providers, in partnership with rural and biomedical libraries. The foundation for our project is the Dartmouth-Hitchcock PACS Clinic, an established, comprehensive clinic serving patients in Vermont and New Hampshire. The rural nature of northern New England poses a challenge to delivery of comprehensive care to PACS patients. Most parts of VT and NH are characterized as being “small town/isolated rural” or “large rural town.” The debilitating nature of PACS threatens job security, financial stability, and the ability to function normally, and there is limited access to primary care, physical therapy, occupational therapy, and mental health services that can accept and are familiar with the complex nature of PACS. Furthermore, the Area Deprivation Index (ADI), based on a measure created by HRSA, shows that at least half of the two states have ADI scores of >50, indicating that they are “disadvantaged” in relation to national standards. A large percentage of the 1300 patients referred to our PACS clinic report difficulties in accessing reliable information about managing their condition and finding locally based services. Affordable, high-speed internet service is often limited in rural settings, and many rely on local libraries to meet those needs. Above all, patients express a sense of isolation, both physical and emotional. Our experience has taught us that bridging that sense of isolation is often the greatest service we can provide. Our goal is to “reach more people in more ways through enhanced engagement pathways.” Our aims are: To improve the care of patients with PACS in rural VT and NH by disseminating useful, usable, and understandable information to this health-disparity population. To promote a better understanding of PACS for patients and providers by means of new, appropriately targeted resources. We will create an online archive of “digital stories” that highlight lived experiences of patients with PACS and create an independent website and monthly newsletter with content about PACS that is responsive to the emerging science and meets the needs of our patients and providers. To raise awareness about PACS in rural communities and promote community access to information about PACS and post-COVID care. We will partner with rural libraries, which are often a primary hub of information-sharing in rural communities, to assist in deploying computer and information technology that is otherwise unavailable or difficult to use for many of our patients. We will tailor information to meet the needs of our population. Our efforts should be generalizable to other rural communities in the US.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15213", "attributes": { "award_id": "1R21DK138863-01A1", "title": "Effect of Ubiquitin D variants upon APOL1-mediated kidney injury", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)" ], "program_reference_codes": [], "program_officials": [ { "id": 31793, "first_name": "DEEPAK", "last_name": "Nihalani", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-01", "end_date": "2026-06-30", "award_amount": 252000, "principal_investigator": { "id": 31794, "first_name": "MICHAEL J", "last_name": "ROSS", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 741, "ror": "https://ror.org/05cf8a891", "name": "Albert Einstein College of Medicine", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Despite the success of antiretroviral therapy in improving mortality, persons with HIV (PWH) have shortened lifespan and increased prevalence of non-infectious diseases including chronic kidney disease (CKD). HIV- associated nephropathy (HIVAN) occurs almost exclusively in persons of African ancestry and variants of the APOL1 gene, which confer resistance to trypanosomal disease, markedly increase risk of progressive CKD. 14% of African Americans have APOL1 high risk (HR) genotypes, which confer a 29-89-fold increased risk of HIVAN among PWH, likely by predisposing glomerular podocytes to HIV-induced injury. Since most persons with APOL1 HR genotypes never develop kidney disease, additional “hits”, including viral infection (HIV, SARS-coV-2), exposure to high levels of interferon, and/or additional genetic factors, are necessary to initiate progressive CKD. Our group was the first to identify a role for the ubiquitin-like protein Ubiquitin D (UBD) in the pathogenesis of kidney disease (HIVAN). We reported roles for UBD in promoting HIV-induced kidney epithelial cell injury and innate immune activation. A role for UBD in modulating kidney injury in APOL1- mediated kidney disease is supported by recently published studies demonstrating increased UBD expression in glomeruli in humans and mice with APOL1 HR genotypes and kidney disease and a recent report that UBD increases APOL1 degradation in vitro. Our analysis of the UBD gene locus identified a haplotype comprised of four missense mutations with an allele frequency of 0.43 in African Americans but only 0.02 in Europeans. Our preliminary data demonstrate that this haplotype (UBDb) is associated with a 5.8-fold increased risk of HIVAN in persons with APOL1 HR genotypes. Further, data from our laboratory indicate that there are important functional differences in the UBDb protein compared to UBDa (reference allele). However, the mechanism by which the UBDb variant synergizes with APOL1 risk alleles to promote kidney injury is unknown. Since UBD can covalently and non-covalently interact with cellular proteins and increase/decrease degradation or alter protein function, we will test our hypothesis that the UBDb variant increases the risk of HIVAN via changes in interactions with APOL1 and other proteins, leading to podocyte injury. We will test our hypothesis and address critically important questions in two Specific Aims. In Aim 1, we will determine the effects of the UBDa and UBDb alleles upon HIV-induced injury and inflammatory responses in novel human podocyte lines with APOL1 HR and non-risk genotypes. In Aim 2, we will use high throughput proteomics and targeted in vitro assays to delineate differences in covalent and non-covalent protein-protein interactions of UBD variants and effects of UBD variants on APOL1 protein ubiquitination and degradation in human podocytes with APOL1 HR and non- risk genotypes. These innovative and important studies will delineate novel mechanisms underlying the increased risk of CKD in PWH, allowing us to devise new strategies to prevent and treat CKD this population.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15214", "attributes": { "award_id": "1R01MH133070-01A1", "title": "Airway inflammation and fear: elucidating immune mediators and neural substrates", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Mental Health (NIMH)" ], "program_reference_codes": [], "program_officials": [ { "id": 31795, "first_name": "Leonardo H", "last_name": "Tonelli", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-01", "end_date": "2029-06-30", "award_amount": 463425, "principal_investigator": { "id": 31796, "first_name": "Ian Paul", "last_name": "Lewkowich", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 31797, "first_name": "RENU", "last_name": "SAH", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1446, "ror": "https://ror.org/01e3m7079", "name": "University of Cincinnati", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "PROJECT SUMMARY: Fear regulation is essential for optimal mental health. Maladaptive fear is a hallmark of posttraumatic stress disorder (PTSD), a debilitating condition afflicting 22% of combat veterans. Impaired functioning of infralimbic (IL) prefrontal cortex (PFC) contributes to fear dysregulation in PTSD, however factors contributing to IL deficits are unclear. Not all trauma-exposed individuals develop PTSD, suggesting that predisposition factors may contribute to IL dysfunction and PTSD risk. Elucidating the nature of such factors will help identify novel therapeutics. Growing evidence supports a strong association between severe asthma and PTSD. Mechanisms and cellular substrates whereby severe asthma associated factors regulate PTSD-relevant fear and IL-PFC deficits remain unknown. Using unique mouse paradigms of aeroallergen house dust mite (HDM)-driven inflammation we observe: 1) compromised fear extinction only in mice with allergen-induced Th2/Th17 expansion, an effect dependent on IL-17A and IL-17RA signaling and accompanied by reduced neuronal activation in the IL-PFC; 2) significant upregulation of microglial Il17ra expression in blood-brain-barrier compromised subfornical organ (SFO) inTh2/Th17 mice (but not in SFO non-microglial cells or PFC microglia); 3) IL-17A-induced activation of SFO neurons, and, 4) direct SFO►IL projections that modulate parvalbumin interneurons that regulate IL excitability and fear. Collectively these observations inform our hypothesis: IL-17A engages microglial IL-17RA and SFO-to-IL projections to modulate IL excitability and fear. This hypothesis will be tested in 2 aims. Aim 1 will determine if SFO►IL PFC projections regulate compromised fear extinction and IL neuronal excitability in mice with HDM-induced mixed Th2/Th17 inflammation. Using a retroCre- dependent chemogenetic strategy, we will inhibit or activate SFO►IL projections to assess effects on fear extinction in mice with Th2 versus Th2/Th17 responses. AAV-ChR2 transduction of SFO neurons and patch- clamp recordings in IL neurons will be undertaken. Aim 2 will determine if microglial IL-17RA signaling in the SFO drives HDM-induced fear extinction deficits. Using SFO targeted cell-specific AAV-Cre in Il17rafl/fl mice, we will assess the necessity of IL17RA signaling in HDM-induced extinction deficits. The transcriptional profile of SFO-derived microglia and non-microglial cells will be generated for cell-type specific gene expression signatures to identify DEGs and downstream signaling pathways in Th2/Th17 mice. Finally, the impact of IL-17A on IL-projecting SFO neurons will be assessed using patch-clamp electrophysiology in slices of brains Th2/Th17 mice, +/- targeted microglial IL-17RA ablation, inhibition of previously identified modulators of SFO microglia- neuron signaling and other transcriptomic-identified targets. Impact: Our studies will inform on how adaptive immune mediators modulate brain function and behavior and identify novel risk factors and therapeutic targets for fear-associated pathologies. Beyond asthma, our findings have implications for other conditions where IL- 17A is elevated in response to pulmonary pathologies (e.g. bacterial pneumonia, ARDS, COVID-19).", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15624", "attributes": { "award_id": "1R01MH135862-01A1", "title": "The neuroimmune mechanism of SARS-CoV-2 on synaptic transmission and plasticity", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Mental Health (NIMH)" ], "program_reference_codes": [], "program_officials": [ { "id": 31795, "first_name": "Leonardo H", "last_name": "Tonelli", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-01-10", "end_date": "2028-11-30", "award_amount": 384772, "principal_investigator": { "id": 32123, "first_name": "Jianyang", "last_name": "Du", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 847, "ror": "", "name": "UNIVERSITY OF TENNESSEE HEALTH SCI CTR", "address": "", "city": "", "state": "TN", "zip": "", "country": "United States", "approved": true }, "abstract": "Given the current global COVID-19 pandemic, as well as documented challenges in long-COVID health burdens among people of lower socioeconomic backgrounds, understanding the cellular and molecular mechanisms responsible for SARS-CoV-2-induced neurological disorders is of fundamental importance. We recently developed a mouse SARS-CoV-2 infection model (SARS2-N501YMA30) showing alteration in mice behaviors fourteen days post-infection, allowing us to study long-term behavioral changes caused by SARS-CoV-2. Four days after the virus infection, we detected SARS-CoV-2 genomic RNA in brain tissues. In addition, SARS-CoV-2 dsRNA was detected exclusively within neurons, along with vigorous microglia activation. These data together with previous works might implicate the involvement of brain immune cells, such as microglia. Also, these preliminary data suggest a novel mechanism of SARS-CoV-2 infection- induced behavioral changes in mice. Thus, the goal of this proposal is to elucidate the mechanisms by which SARS-CoV-2 modulates neuronal activity in mice. This proposal describes three distinct aims to reach this goal. The first aim focuses on determining whether SARS2-N501YMA30 infection induces neuronal hyperactivity in mice. The second aim will determine how SARS2-N501YMA30 activates microglia via microglia-neuron interaction. The third aim will determine how microglia activation excites surrounding excitatory neurons in response to SARS2-N501YMA30 infection. Uncovering the cellular and molecular mechanisms by which SARS-CoV-2 alters neuronal activity through regulating neuron-microglia interaction will facilitate the development of therapeutic strategies to minimize long-COVID suffering, health disparity, and mortality from the COVID-19 pandemic.", "keywords": [ "2019-nCoV", "ACE2", "Affect", "American", "Animal Model", "Animals", "Anxiety", "Astrocytes", "Behavior", "Behavioral", "Biological Assay", "Brain", "C57BL/6 Mouse", "COVID-19", "COVID-19 burden", "COVID-19 detection", "COVID-19 mortality", "COVID-19 pandemic", "Cells", "Central Nervous System", "Data", "Death Rate", "Double-Stranded RNA", "Electrophysiology (science)", "Excitatory Postsynaptic Potentials", "Exhibits", "Foundations", "Goals", "Health Care Systems", "Human", "Hyperactivity", "Immune", "Infection", "Inflammatory", "Long COVID", "Long-Term Effects", "Longitudinal Studies", "Mental Depression", "Microglia", "Modeling", "Molecular", "Mus", "Natural Resistance", "Nervous System Disorder", "Neuroimmune system", "Neuroimmunomodulation", "Neurons", "Neurotropism", "Outcome", "Perfusion", "Persons", "Play", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Process", "Production", "Proteins", "Recombinants", "Recovery", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "Scientist", "Serial Passage", "Slice", "Symptoms", "Synaptic Transmission", "Synaptic plasticity", "Syndrome", "Tail Suspension", "Time", "Virulent", "Virus Diseases", "Work", "behavior test", "brain tissue", "current pandemic", "cytokine", "excitatory neuron", "forced swim test", "genomic RNA", "glial activation", "health disparity", "improved", "in vivo", "mortality", "mouse model", "novel", "novel therapeutic intervention", "overexpression", "patch clamp", "response", "socioeconomics", "therapeutic development", "therapeutic target" ], "approved": true } }, { "type": "Grant", "id": "15222", "attributes": { "award_id": "7R01AA030529-03", "title": "Improving alcohol and substance use care access, outcomes, and equity during the reproductive years: A Type 1 Hybrid Trial in Family Planning Clinics", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Alcohol Abuse and Alcoholism (NIAAA)" ], "program_reference_codes": [], "program_officials": [ { "id": 31802, "first_name": "Damiya Eve", "last_name": "Whitaker", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-01", "end_date": "2027-08-31", "award_amount": 704512, "principal_investigator": { "id": 31803, "first_name": "HEATHER J", "last_name": "GOTHAM", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 26578, "first_name": "Kelli Stidham", "last_name": "Hall", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 26579, "first_name": "Justine Wittenauer", "last_name": "Welsh", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 265, "ror": "https://ror.org/03czfpz43", "name": "Emory University", "address": "", "city": "", "state": "GA", "zip": "", "country": "United States", "approved": true }, "abstract": "Rates of risky alcohol and drug use and alcohol and substance use disorders (AUDs/SUDs) are highest among women during their reproductive years compared to other periods of the life course. AUDs and SUDs are associated with significant and lifelong behavioral, mental, physical, and sexual and reproductive health (SRH) consequences for women and disproportionately for racially and ethnically minoritized women and those living in poverty. There is an urgent need for innovative methods to address alcohol and substance use in preventive healthcare settings. Family planning (FP) clinics are a trusted care source and primary point of access for women and serve as a safety net for structurally marginalized groups in the U.S. FP clinics are uniquely well- suited, but entirely understudied, contexts for implementing and scaling integrated alcohol/drug use services. While screening, brief intervention, and referral to treatment (SBIRT) is a widely accepted, evidence-based intervention for alcohol use in primary care and mental health settings, little is known about the facilitators and barriers to the uptake and sustainment of SBIRT in FP clinics. Even less is understood about telemedicine, which has been rapidly rolled out for COVID-19, as a SBIRT delivery platform. Further, virtually no evidence exists on effective organizational level implementation strategies to accelerate SBIRT’s adoption in FP. We propose an explanatory, sequential, mixed methods study to evaluate SBIRT in an expansive FP clinic network of a national SRH organization – a novel and highly impactful setting with a reach of a diverse and largely socially disadvantaged population of reproductive-aged women at greatest risk for AUDs/SUDs. Our integrated study draws upon the evidence-based implementation approach, Implementation and Sustainment Facilitation (ISF), guided by the Consolidated Framework for Implementation Research and Reach, Effectiveness, Adoption, Implementation and Maintenance models. In Aim 1, to identify specific targets for implementation, sustainment, and scale-up of SBIRT, we will conduct administrative surveys with clinic stakeholders (clinic directors, providers, and staff n=153) and key informant interviews with stakeholders and patients (n=40) to investigate organizational practices and perspectives on alcohol- and substance-related services. In Aim 2, we will conduct a dual randomized Type 1 Hybrid Effectiveness-Implementation trial testing SBIRT (in-person and telemedicine) vs. usual care, within a large, high-volume Northeastern affiliate of the national organization. We will randomize 600 patients across 4 clinics, collecting patient level data on alcohol and substance use primary effectiveness outcomes, as well as secondary SRH, mental/physical health, quality of life, and wellbeing outcomes at baseline, 30 days, and 3 months. Aim 3 will explore facilitators and barriers to SBIRT adoption and the ISF implementation strategy via surveys and interviews with clinic directors, providers, and staff (n=20) and patients (n=20) electronic medical records. Results will provide new, timely evidence to inform scale-up of alcohol and substance related services in FP settings nationally.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15226", "attributes": { "award_id": "1U01AI184132-01", "title": "Clinical and mechanistic studies defining optimal preparative approaches to infants with IL2RG/JAK3/RAG1/RAG2 SCID: a randomized trial of busulfan dosage", "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": 31806, "first_name": "Margaret A.", "last_name": "Morris Fears", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-08-13", "end_date": "2029-05-31", "award_amount": 1072951, "principal_investigator": { "id": 31807, "first_name": "JEFFERY J", "last_name": "AULETTA", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 31808, "first_name": "Michael A", "last_name": "Pulsipher", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2522, "ror": "https://ror.org/016cke005", "name": "National Marrow Donor Program", "address": "", "city": "", "state": "MN", "zip": "", "country": "United States", "approved": true }, "abstract": "Severe combined immunodeficiency (SCID) is a group of genetic disorders that abrogate T cell development and function. Allogeneic hematopoietic cell transplantation (HCT) is the standard treatment for the disease and can be performed successfully in SCID patients without the high dose pre-HCT busulfan conditioning due to the unique capacity for progenitors to engraft in the empty thymus and reconstitute T cell development. Without conditioning, lineages other than T cells remain of host origin. The CSIDE protocol was funded with an earlier grant to test the efficacy and safety of a regimen of low dose, individualized targeted busulfan compared to moderate dose in SCID patients at risk of poor humoral outcome undergoing non-matched sibling donor HCT. We hypothesize that patients randomized to receive low dose busulfan will achieve similar outcomes compared to those receiving moderate dose (myeloablative) busulfan, achieving both T and B cell immune reconstitution. Due to COVID and competition with gene therapy, accrual slowed, but with 50 centers open and a redesigned approach, additional enrollment facilitated by this grant will ensure that the trial reaches meaningful conclusions. In Aim 1, patients have been randomized to cumulative area-under-the-curve (cAUC) exposure of busulfan of 30 mg*h/L versus 60 mg*h/L. IL2RG/JAK3 patients also receive rATG, while RAG1/2 patients receive rATG, fludarabine, and thiotepa. Stem cell sources include unrelated and haploidentical related donor products that have been TCRαβ+/CD19+ depleted with no post-HCT GVHD prophylaxis. The safety profile of the trial has been excellent to date. The original primary endpoint was protective antibody response to tetanus by 2 years post-HCT. Because of enrollment challenges, we redesigned the primary endpoint into an ordinal ranked win comparison, which allows higher power even if we cannot fully enroll. The primary outcome will center around the IL2RG/JAK3 cohort, which should achieve full accrual, randomizing 32 patients. The RAG1/2 cohort will close once the IL2RG/JAK3 cohort closes, likely accruing up 18-20 patients which we will analyze descriptively. In Aim 2, We hypothesize that donor HSC engraftment measured by the surrogate of myeloid donor chimerism will be associated with superior quality of T cell reconstitution and improved adaptive immune responses to vaccination. We hypothesize that T cell exhaustion and poor T cell receptor (TRB) diversity seen in patients undergoing HCT in the absence of conditioning will be diminished or absent in CSIDE participants due to improvements in thymic output associated with engraftment of donor-derived HSC. We hypothesize that IL2RG/JAK3 patients receiving moderate dose busulfan and/or with high level donor chimerism will exhibit multiple in vitro biomarkers of IL-21 response, as this cytokine signals via IL2RG/JAK3. We hypothesize that vaccine response will correlate with normalization of IGH CDR3 diversity in RAG1/2 patients with mixed chimerism due to strong selective advantage for antigen-specific B cells. We hypothesize that T cell tolerance will occur by different mechanisms (central deletion versus peripheral regulation) according to donor type. Finally, we hypothesize that analysis of pK samples for elements of our preparative approaches (rATG, thiotepa, and fludarabine) will allow targeted treatment of infants undergoing HCT for SCID or other disorders moving forward.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15228", "attributes": { "award_id": "1R21HD112011-01A1", "title": "Novel Designed Multi-Ligands as Tocolytics for Dysregulated Myometrial Pathways in the Treatment of Preterm Labor", "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": 31810, "first_name": "KATIE MARIE", "last_name": "Vance", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-08-08", "end_date": "2026-07-31", "award_amount": 219592, "principal_investigator": { "id": 31811, "first_name": "Scott Danielson", "last_name": "Barnett", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 953, "ror": "https://ror.org/01keh0577", "name": "University of Nevada Reno", "address": "", "city": "", "state": "NV", "zip": "", "country": "United States", "approved": true }, "abstract": "Preterm birth is a major medical problem resulting in disability and death for very preterm infants. Therapeutic approaches to manage preterm labor are off-label and ineffective. No tocolytic therapy in use today is satisfactory beyond 48 hours, and none is FDA approved. Preterm labor more often impacts African American women than their Caucasian counterparts and is exacerbated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which leads to preterm birth in COVID- 19 affected pregnancies. Our central hypotheses are that designed multi-ligand (DML) drugs to be generated in this research that target dysregulated pathways in preterm myometrium will provide a therapeutic benefit in cases of preterm labor while decreasing fetal exposure to the compounds, and that co-administration of the DML’s ‘constituent single entities’ will exhibit synergistic tocolysis. In addition to providing a potential synergistic benefit, we expect that our DMLs will be poorly transported across the placenta due to favorable pharmacokinetic properties of the DMLs, and thus will protect the fetus from exposure. Decreased placental transfer will improve dose-ranging for clinical benefit to prevent preterm labor. This research will justify novel DMLs as potential new tocolytics to prevent preterm birth. This proposal will generate novel DMLs using advanced Medicinal Chemistry techniques and will make extensive use of ex vivo and in vivo experimentation using both human and mouse tissue. The long term goal of this project is to generate first-in-class tocolytics that will delay or halt early labor and prevent preterm birth.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15233", "attributes": { "award_id": "1R21AI181677-01", "title": "Synergizing neutralization and non-neutralization antibody targets at the HIV/SIV viral spike apex", "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": 31817, "first_name": "Nancy R.", "last_name": "Miller", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-08-09", "end_date": "2026-06-30", "award_amount": 228825, "principal_investigator": { "id": 21421, "first_name": "TIMOTHY J", "last_name": "CARDOZO", "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": [], "awardee_organization": { "id": 832, "ror": "", "name": "NEW YORK UNIVERSITY SCHOOL OF MEDICINE", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "An HIV vaccine remains a critical and as yet unrealized asset in the 40-year fight against the HIV/AIDS pandemic. New insights towards achieving vaccine protection from HIV acquisition may be gained by a comparative case study of COVID-19 vaccines, which achieved nearly 100% efficacy against a similarly enveloped, RNA virus with a similarly architected, trimeric, Class I fusion viral spike mechanism. Neutralization B-cell epitopes exposed at the apex of the SARS-CoV-2 trimeric viral spike correlated clearly and strongly with protection from viral acquisition, both in humans in the real world/circulating virus setting and in non-human primate (NHP) preclinical models. We hypothesized that vaccine immunogens could be improved by focusing antibody responses to two equivalent B-cell epitopes at the HIV/SIV viral spike apex, one an epitope targeted by neutralizing antibodies (V2b) and one a purely non-neutralization epitope (V2c). In preliminary results, we showed that removal of the viral spike apical V1 loop segment (DV1-Env) masking the V2c epitope enhanced protection against viral challenge in both a highly stringent SIV and matched SHIV challenge model, achieving >90% vaccine efficacy. In further preliminary results, we designed an immunogen displaying only this V2c epitope in isolation and proved that it was highly immunogenic as an isolated epitope and indeed elicited purely non-neutralizing antibodies in vivo. The study revealed that V2c contributed to, but was not sufficient on its own, for protection. In this exploratory study, we pursue the new hypothesis that the combination of the two HIV, viral-spike apical, B-cell epitopes in a single vaccine can reconstitute an increased level of protection as observed with COVID-19 vaccines, by synergizing V2c with the V2b neutralization epitope. We will 1) design and validate a V2b-focused immunogen, and 2) test the precise combination of neutralizing, vaccine-elicited anti-V2b antibodies with non-neutralizing, cytotoxic, vaccine-elicited V2c antibodies, along with coordinated cellular immune responses in vivo for their ability to delay viral acquisition as compared to the V2c epitope alone. Successful results in these two aims could justify a research project on the design and translational development of a novel, viral-spike-apex-focused, efficacious HIV vaccine.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15243", "attributes": { "award_id": "1U19AI181968-01", "title": "The UCI Vaccines for Pandemic Preparedness Center (VPPC)", "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": 31830, "first_name": "Genevieve Anne", "last_name": "Holzapfel", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-08-20", "end_date": "2027-07-31", "award_amount": 33116067, "principal_investigator": { "id": 31831, "first_name": "PHILIP Louis", "last_name": "FELGNER", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 971, "ror": "", "name": "UNIVERSITY OF CALIFORNIA-IRVINE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "– Overall: The UCI Vaccines for Pandemic Preparedness Center (VPPC) The Mission: \"To contribute to human health and well-being by developing agile, safe, effective and accessible vaccines that protect the vulnerable against future pathogens of pandemic importance and by educating the next generation of vaccine scientists that will tackle such challenges.” Joshua Lederberg envisioned the world as a battlefield between microbes and man, famously saying, “The future of humanity and microbes likely will unfold as episodes of a suspense thriller that could be titled Our Wits Versus Their Genes” (Lederberg, 2000). Although the genes of the microbial world have been evolving much longer than our wits, we have come up with efficient ways to respond to infectious diseases, but regrettably evolving microorganisms keep managing to challenge and outsmart us. The latest COVID episode in this series sensitized the world again to the importance of learning from the outbreak experience and challenges us to better prepare for the next one. The 100 Days Mission (100DM), endorsed by government and non-government organizations worldwide is a proposed response to the next “Disease X” by making safe, and effective vaccines available within 100 days of the pathogen’s identification. Achieving that goal could defuse the threat of a pathogen with pandemic potential. The International Pandemic Preparedness Secretariate (IPPS), the Coalition for Epidemic Preparedness Innovations (CEPI), the HHS Administration for Strategic Preparedness and Response (ASPR Next) and the NIH/NIAID have embraced the concept of studying prototype pathogens as a critical element of preparedness. By developing vaccines on rapid-response platforms against examples of a given viral genus or family, researchers can address scientific challenges characteristic of that family in advance, providing an important head start on developing vaccines against related threats. Universal programmable vaccine platforms that can be rapidly employed against broad virus families can be evaluated in clinical trials to provide confidence in their safety, and manufacturing, and regulatory considerations can be managed ahead of the next outbreak. The UC Irvine Vaccines for Pandemic Preparedness Center (VPPC) aims to conduct basic and translational research to develop vaccines against prototype members of the Bunyavirus, Paramyxovirus and Picornavirus families with demonstrated immunogenicity and efficacy in animal models. Two universal, programmable, rapid response vaccine platforms will be characterized and compared in this study: the i) Adjuvanted Recombinant Protein (ARP) Vaccine, and ii) mRNA/Lipid Nanoparticle (LNP) Vaccine. Such prototype vaccines will need to be tested in advance, at a minimum, for clinical safety and immunogenicity, and efficacy where possible, so that emerging viruses in the same family can be rapidly and safely deployed. Gathering such data and experience will build confidence in these rapid response platforms and inform regulators as they make decisions about the emergency authorization of vaccines against related pathogens.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15251", "attributes": { "award_id": "3OT2OD037636-01S1", "title": "AOU WI Area of Interest 1: Community, Participant and Provider Engagement, Enrollment...", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "NIH Office of the Director" ], "program_reference_codes": [], "program_officials": [ { "id": 31839, "first_name": "Stephanie Melania", "last_name": "Alexander-troupe", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-08-01", "end_date": "2025-07-31", "award_amount": 2000000, "principal_investigator": { "id": 21340, "first_name": "ELIZABETH S", "last_name": "BURNSIDE", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 799, "ror": "", "name": "UNIVERSITY OF WISCONSIN-MADISON", "address": "", "city": "", "state": "WI", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 31438, "first_name": "Lisa Anne", "last_name": "CadmusBertram", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 31441, "first_name": "Scott Joseph", "last_name": "Hebbring", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 31442, "first_name": "Todd A", "last_name": "Mahr", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 31443, "first_name": "SANJAY K", "last_name": "SHUKLA", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 31840, "first_name": "Zeno E", "last_name": "Franco", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2495, "ror": "", "name": "MARSHFIELD CLINIC RESEARCH FOUNDATION", "address": "", "city": "", "state": "WI", "zip": "", "country": "United States", "approved": true }, "abstract": "1. ABSTRACT The All of Us Research Program (AoURP) has experienced dramatic change over the last five years. To list just a few of the many examples: AoURP conducted multiple retention eligible campaigns (e.g., mental health campaign), began distributing genetic results to participants, initiated the first ancillary study (Nutrition for Precision Health), and made available the Research Workbench to scientists. Throughout the many changes that have occurred over the years, the most challenging was the SARS-Cov-2 pandemic which disrupted every facet of society and impacted how AoURP's partnering institutions functioned. But with change comes opportunity, and opportunity is possible for organizations that are highly adaptable and innovative. This includes the All of Us Wisconsin Consortium (AoU-WI). AoU-WI was one of the last RMCs to join the national program. As time progressed, AoUWI matured, strengthened close collaborations across WI and nation, and developed diverse strategies in engagement, enrollment, and retention. The diversity at all levels of AoU-WI is something we are most proud of and has allowed our program to flourish in the ever-changing AoURP. To maintain AoU-WI's momentum, we will leverage lessons learned from the last five years. AoU-WI will constantly reassess, modify, and diversify its strategies to ensure AoURP is available to all. Continued diversity in our program will be essential as AoURP persistently changes over the next five years. In this application, we will describe how AoU-WI will not only maintain successful activities that has allowed our program to be leaders in engagement, enrollment, and retention, but how we intend to innovate. We will conduct outreach and engagement activities to promote the enrollment of communities who are historically underrepresented in biomedical research (Aim 1). AoU-WI will also engage, enroll, and retain participants who reflect the rich diversity of the US (Aim 2). This will be done with both adults and pediatrics (Aim3) while ensuring participants have access to technology for study activities (Aim 4). Lastly, AoU-WI will engage and collaborate with health care providers serving communities that are historically underrepresented in biomedical research to facilitate enrollment and retention (Aim5). We will do this by expanding the AoU-WI consortium to include Advocate Aurora Health, the ninth largest not-for-profit integrated healthcare system in the U.S. By successfully achieving these aims, AoU-WI ensures our continuous contribution to the mission of \"accelerating health research and medical breakthroughs, enabling individualized prevention, treatment, and care for all of us.\"", "keywords": [], "approved": true } } ], "meta": { "pagination": { "page": 1391, "pages": 1419, "count": 14184 } } }