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=1424&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": "15467", "attributes": { "award_id": "5R01GM150187-02", "title": "Biophysical, Structural, and Cellular Dissection of COPI-Dependent Retrograde Trafficking Using a Coronavirus Toolkit", "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": 31765, "first_name": "Thomas Y", "last_name": "Cho", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-30", "end_date": "2028-08-31", "award_amount": 411570, "principal_investigator": { "id": 28219, "first_name": "Syed Saif", "last_name": "Hasan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 793, "ror": "", "name": "UNIVERSITY OF MARYLAND BALTIMORE", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "The secretory pathway is responsible for the biogenesis of soluble and membrane proteins involved in communication, energy transduction, nutrient uptake, and defense. These proteins are synthesized in the endoplasmic reticulum (ER) and then trafficked to Golgi and other organelles such as the plasma membrane. This trafficking causes ER stress by accidental exodus of ER-resident proteins such as UDP-glucuronyl transferases (UGT’s). These are type I membrane proteins (T1MP’s) responsible for modifications of lipid hormones and of analgesics acetaminophen and morphine. These ER-resident T1MP’s display a dibasic sequence (Lys-x-Lys-x-x or Lys-Lys-x-x; x=any amino acid) in their cytosolic tail for ER-retrieval by the coatomer protein I complex (COPI). The α and β’ subunits of this hetero-heptameric complex bind this dibasic sequence to initiate T1MP packaging into vesicles originating from post-ER compartments such as cis-Golgi. These COPI coated vesicles traffic and deliver the T1MP proteins back to ER to restore secretory balance. However, the atomic principles underlying T1MP binding, release, and selective interactions with α and β’COPI subunits are not well understood. This is a critical knowledge-gap as T1MP release and escape from COPI modulate T1MP trafficking, post-translational modifications, and T1MP functions. COPI dysfunction has been implicated in a variety of disorders related to development, auto-immunity, and cancers. Our long-term objective is to gain fundamental insights into COPI-dependent retrograde trafficking of T1MP’s and the underlying atomic-level factors responsible for COPI dysfunction in diseases. In this grant, we will elucidate mechanistic insights into COPI recruitment, release, and T1MP post-translational modifications utilizing the coronavirus (CoV) spike protein, a T1MP with a dibasic Lys-x-His-x-x sequence, as a new model system. This dibasic sequence ensures COPI-dependent retrograde delivery of the spike from Golgi to the viral progeny assembly site in ER-Golgi intermediate compartment (ERGIC). In Aim 1, we will elucidate the atomic details of conformational modulation of COPI-spike interactions. In Aim 2, we will determine the principles that govern release from COPI and subsequent post-translational modifications of the spike. In Aim 3, we will elucidate the atomic basis of COPI subunit selectivity for the spike protein. These investigations will expand on a toolkit of spike mutants with modified COPI interactions, as recently published by our group. We will integrate structural approaches in X-ray crystallography, NMR, and Rosetta modeling with biophysical tools and cellular assays of secretory trafficking to gain unprecedented insights into fine modulation and conformational regulation of COPI-spike interactions. The innovative use of the spike protein as a T1MP model system will yield novel insights into fundamental secretory trafficking. These data will simultaneously opening avenues for the development of targeted therapeutics for COPI-selective disorders and for a deeper understanding of CoV assembly and processing of CoV vaccines.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15188", "attributes": { "award_id": "1R43OH012720-01A1", "title": "ClearWorks Particulate Respirator", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute for Occupational Safety and Health (NIOSH)" ], "program_reference_codes": [], "program_officials": [ { "id": 31768, "first_name": "Eduardo", "last_name": "O'Neill", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-01", "end_date": "2025-08-31", "award_amount": 295924, "principal_investigator": { "id": 31769, "first_name": "Christopher", "last_name": "Estkowski", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2517, "ror": "", "name": "APPLIED DESIGN TECHNOLOGIES", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "The ClearWorks respirator, developed by Applied Design Technologies, addresses the critical need for comfortable and effective respiratory protection for healthcare workers (HCWs) in the face of infectious diseases, like COVID-19. Current respirators often lack both optimal breathability and a secure seal, causing discomfort and increased exposure risk. ClearWorks aims to revolutionize this field with its foam half mask respirator design. The significance of this project lies in protecting HCWs' health and well-being, especially considering the high mortality rates reported among healthcare workers due to COVID-19. ClearWorks respirators offer a range of advantages, including exceptional breathability, a universal fit across different head sizes, transparency for social acceptance and visual speech recognition, lightweight design, reduced CO2 levels, and minimal facial contact pressure. These features are expected to enhance overall comfort and usability, thereby increasing the likelihood of consistent respirator usage during prolonged shifts, a challenge reported by many HCWs. With its unique modular component architecture, ClearWorks provides opportunities for cost-effective upgrades and customization, while its innovative foam seal design and pleated filters contribute to comfort and breathability. To validate ClearWorks' effectiveness, the prototype will undergo rigorous testing in this Phase I SBIR, including Fit Factor assessments and resistance testing, adhering to NIOSH standards. These tests will demonstrate the product's superior performance in ensuring a secure seal and minimizing breathing resistance. Additionally, third-party validation by a highly regarded testing provider will provide independent confirmation of the research findings. The ClearWorks respirator project aims to address a significant gap in respiratory protection for healthcare workers and essential personnel. By combining innovation in design, materials, and fit, ClearWorks seeks to reshape the landscape of respiratory protection, ultimately improving the safety and well-being of those on the front lines of infectious disease control. The product's commercial potential is substantial, targeting the healthcare sector, home health nurses, and broader essential worker categories.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15209", "attributes": { "award_id": "2R44OH012421-02", "title": "Refinement of Very Low Leakage Non-Invasive Ventilation Mask for Infectious Patients", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute for Occupational Safety and Health (NIOSH)" ], "program_reference_codes": [], "program_officials": [ { "id": 31768, "first_name": "Eduardo", "last_name": "O'Neill", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-01", "end_date": "2026-08-31", "award_amount": 643238, "principal_investigator": { "id": 26332, "first_name": "Daniel", "last_name": "Micka", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1508, "ror": "", "name": "CREARE, LLC", "address": "", "city": "", "state": "NH", "zip": "", "country": "United States", "approved": true }, "abstract": "A large number of patients with infectious respiratory diseases such as COVID-19, influenza, and SARS require respiratory support. Noninvasive Positive Pressure Ventilation (NPPV) via a mask is an appropriate treatment for many patients that can lead to better outcomes than intubation. Additionally, the equipment used for NPPV (such as CPAP machines) is widely available, making NPPV well suited for responding to outbreaks and pandemics. Unfortunately, NPPV masks increase the risk of disease transmission by spreading contaminated aerosols leaking from the mask seal. This exposes health care workers and other patients to increased risk and can hamper efforts to contain outbreaks of infectious diseases. The objective of this program is to develop an innovative NPPV patient interface that greatly reduces the leakage of contaminated aerosols through the mask seal. The two key innovations are a purged dual seal and a mask integrated vacuum ejector. The dual seal captures contaminated leakage across the primary mask seal and integrated ejector provides the purge flow required by the dual seal. All the contaminated flow is then passed through to a viral filter before exhausting to the room. Our device is a cost effective drop in replacement for existing masks that integrates easily with NPPV equipment used in hospitals. In a prior program and Phase I, we developed and tested initial PDS mask prototypes. We demonstrated far better sealing performance than a leading commercial mask in laboratory and human subject testing. In the proposed Phase II program we will refine and productize our mask design, extensively test the performance, publicize the results, and prepare for regulatory clearance and commercialization. This will enable our innovative leak-prevention mask technology to be widely deployed in critical care settings—benefiting patients and protecting health care workers.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15199", "attributes": { "award_id": "1UG1EY036346-01", "title": "Village-Integrated Eye Worker Trial II (VIEW II) Extension", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Eye Institute (NEI)" ], "program_reference_codes": [], "program_officials": [ { "id": 31781, "first_name": "DONALD F", "last_name": "EVERETT", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-01", "end_date": "2029-08-31", "award_amount": 1448874, "principal_investigator": { "id": 31782, "first_name": "Jeremy David", "last_name": "Keenan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 768, "ror": "https://ror.org/043mz5j54", "name": "University of California, San Francisco", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The World Health Organization estimates that 80% of blindness worldwide is avoidable. However, in resource-limited settings progressive eye diseases such as glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD) often go undiagnosed until it is too late. New approaches that detect progressive eye diseases before they cause irreversible vision loss could help reduce visual impairment of communities. One such approach is community-based eye disease screening. The Village Integrated Eye Workers Trial II (VIEW II) is an ongoing cluster-randomized trial in which communities in Nepal receive visual acuity screening and are subsequently randomized to receive either a community-based eye disease screening intervention consisting of optical coherence tomography (OCT) and intraocular pressure (IOP) assessment, or to no intervention. The goal of the screening intervention is to detect cases of glaucoma, diabetic retinopathy, and age-related macular degeneration—all of which are progressive and cause irreversible vision loss if left untreated—and refer these cases to the local eye hospital for management. A door-to-door census is performed four years after starting the screening intervention to determine the effectiveness of screening for reducing vision impairment relative to communities not receiving the screening intervention. This is a proposal for the extension of the VIEW II trial, maintaining the original randomization and continuing the same screening intervention in the study clusters except that fundus photography is also included in the screening intervention and that the targeted age group is expanded to those ≥50 years. The specific aims of the proposal are (1) to determine if the screening intervention is effective for preventing vision loss at the community level over 7 years, (2) to compare text messages versus community volunteers for improving linkage to care, and (3) to determine the natural history of OCT measurements over time in a population-based study. Glaucoma, DR, and AMD are slowly progressive diseases, and given interruptions to study activities caused by the COVID-19 pandemic, the originally planned 4-year endpoint in the original VIEW II trial may not be long enough to observe the full effect of the screening intervention. Extending the trial will provide a more accurate assessment of any benefit of screening. Extending the trial also allows for repeated OCTs in a population-based sample, providing much needed data on the natural history of OCT parameters to help clinicians better determine what constitutes progression. This research is significant because it will provide the strongest type of evidence to guide national eye health programs – results from a randomized controlled trial. Ultimately, this trial will benefit blindness prevention programs worldwide in deciding how to allocate limited resources to optimally detect eye disease.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15201", "attributes": { "award_id": "1R43OH012719-01", "title": "Protecting Healthcare Workers Using a Patient-Worn Negative Pressure System to Prevent the Spread of Highly Transmissible Infectious Diseases", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute for Occupational Safety and Health (NIOSH)" ], "program_reference_codes": [], "program_officials": [ { "id": 31783, "first_name": "Marcienne Michele", "last_name": "Wright", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-01", "end_date": "2025-08-31", "award_amount": 295924, "principal_investigator": { "id": 31784, "first_name": "Sridhar", "last_name": "Kota", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2519, "ror": "", "name": "INSPIRE RX LLC", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "The goal of this project is to develop a solution that allows for rapid, safe, and scalable initial treatment and transport of patients with highly transmissible infectious diseases. This is a necessary innovation because resource management and infectious transmission control were two of the greatest challenges healthcare providers faced when fighting the COVID-19 pandemic. When a patient is suffering from highly transmissible respiratory diseases and requires breathing assistance, they are placed in negative pressure rooms. However, given the limited supply of negative pressure rooms available to prevent virus transmission, and the misperception regarding the safety and effectiveness of negative pressure rooms, a new solution is needed. To help prevent the spread of highly transmissible infectious diseases, start-up company Inspire Rx has developed a personal negative pressure device called the AerosolVE™ BioHelmet. The BioHelmet is capable of preventing the spread of aerosolized pathogens while also enabling the use of non-invasive oxygen therapies on patients with respiratory diseases such as COVID-19, influenza, tuberculosis, measles, and chicken pox. The negative pressure AerosolVE™ BioHelmet immediately isolates patients with any highly transmissible respiratory infectious disease and serves as an instant personal negative pressure environment that is more effective than a traditional negative pressure room. The BioHelmet is intended to provide safe transportation via ambulance, airplane, or helicopter, allowing critical EMS and transportation staff to remain safe, and it can also be used in any area of a hospital (including waiting rooms, hallways, imaging facilities, and any patient room). In this project the team will refine and further evaluate the AerosolVE BioHelmet, building on their preliminary data collected during the COVID-19 pandemic. They will first refine the BioHelmet design and fabricate 5 AerosolVE BioHelmets and pump units for follow-on bench testing and obtaining end-user feedback (Aim 1). They will conduct performance and bench testing for the different device components of the BioHelmet to demonstrate that the device performs as expected for its intended use, including particulate testing (Aim 2). Finally, they will obtain end-user feedback from clinicians, hospital administrators, and others to inform final design requirements (Aim 3). In a future Phase II grant, they will conduct performance and bench testing in FDA approved labs to ensure safety and efficacy, as well as clinical testing to ensure the BioHelmet can be comfortably worn for an extended period (several days). They will then submit an FDA 510(k) application to enable commercialization. The BioHelmet will provide a novel, compact, portable, and inexpensive solution that offers a safe negative pressure environment both inside and outside the hospital, which will ultimately save lives by protecting healthcare workers while treating patients.", "keywords": [], "approved": true } }, { "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 } } ], "meta": { "pagination": { "page": 1391, "pages": 1424, "count": 14236 } } }