Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1385&sort=principal_investigator
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=principal_investigator", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1419&sort=principal_investigator", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1386&sort=principal_investigator", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1384&sort=principal_investigator" }, "data": [ { "type": "Grant", "id": "15347", "attributes": { "award_id": "1R01NR021666-01", "title": "Designing for sustainability: Co-designing and testing the efficacy of a web-based toolkit to improve cancer-related emotional distress and anxiety for rural older cancer survivors", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Nursing Research (NINR)" ], "program_reference_codes": [], "program_officials": [ { "id": 6036, "first_name": "Karen", "last_name": "Kehl", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-23", "end_date": "2029-05-31", "award_amount": 827872, "principal_investigator": { "id": 31943, "first_name": "Marquita W.", "last_name": "Lewis-Thames", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 924, "ror": "", "name": "NORTHWESTERN UNIVERSITY AT CHICAGO", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "PROJECT SUMMARY: From 2019-2022, telehealth uptake in rural health clinics surged by 73%. This rapid acceleration in telehealth uptake was driven by COVID-19 precautions, the permanent closure of rural hospitals, a massive shortage of mental health professionals, and $1.5 billion in federal investment in broadband access. However, despite the availability and investment in telehealth, many rural patients, especially rural older adults, lack the digital literacy necessary to fully utilize it, exacerbating barriers to quality healthcare and hindering the potential benefits of telehealth in expanding access to quality healthcare. Increasing rurality and older age are associated with lower digital literacy and telehealth adoption, and rural older cancer survivors (ROCS) face compounded vulnerabilities, which are exacerbated by the reduced access to mental health professionals in rural areas for ROCS experiencing cancer-related distress. Cancer-related distress is stress and anxiety related to a cancer diagnosis and treatment. Telehealth providing support for cancer-related distress is a promising strategy to expand care in rural areas with a shortage of mental health professionals. Still, without interventions to address digital literacy, many ROCS will go without this critical care, thus compromising their overall cancer outcomes. To this end, we developed CONNECT, a web-based toolkit targeting digital literacy and mental health support for ROCS, employing a user-centered design approach and the Designing for Dissemination and Sustainability logic model. CONNECT addresses digital literacy and supports for cancer-related distress management through interactive activities for setting up telehealth visits, accessing educational materials about cancer-related distress, and providing individualized mental health resource recommendations. Feedback from our pilot usability study was positive, reporting high levels of acceptability and usability from users. Yet, additional comments underscored the need to enhance the platform with opportunities to engage caregivers remotely but synchronously to provide additional real-time digital literacy assistance. Building on this pilot, we propose to adapt CONNECT using a co- design process to include recommendations from our pilot, namely, functions that permit synchronous communication with a caregiver (Aim 1). In Aim 2, we will conduct a 2-arm randomized controlled trial to evaluate the efficacy of the adapted CONNECT for improving cancer-related distress among ROCS. We will randomly assign ROCS-caregiver dyads (N=274) to a CONNECT intervention group (N=134) or enhanced standard of care (n=134). Dyads in the intervention group will receive usual care and engage with CONNECT. Participants in the enhanced standard of care group will receive usual care and survivorship care and cancer-related distress literature. Our primary outcome is levels of cancer-related distress. We will secondarily assess digital literacy and healthcare engagement, clinical care, and existing social support networks every 4 months after enrollment for 12 months. In Aim 3, we will use exit interviews in Aims 1 and 2 with a subsample of participants to examine outcomes related to implementation and potential sustainability in the rural multi-level context. Completing these aims will inform future integration of CONNECT across multiple healthcare systems for a multi-site scaled-up effectiveness RCT.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15348", "attributes": { "award_id": "1R21HD115216-01", "title": "Can Successful Early Childhood Interventions Sustain Impacts into Middle Childhood? A test from Kenya", "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": 8605, "first_name": "JAMES", "last_name": "GRIFFIN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-17", "end_date": "2026-08-31", "award_amount": 332000, "principal_investigator": { "id": 31944, "first_name": "Italo", "last_name": "Lopez Garcia", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 152, "ror": "https://ror.org/03taz7m60", "name": "University of Southern California", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "An estimated 43 percent of children under age 5 in low- and middle-income countries (LMICs) will not reach their full developmental potential due to poverty, stunting, or inadequate psychosocial stimulation. Parenting interventions that coach parents on responsive caregiving can effectively improve ECD outcomes in LMICs, at least in the short-term. However, the very few programs that have examined their sustained effects find that early program impacts tend to fade over time. To date, the only parenting interventions demonstrating sustained impacts five or more years after the end of their programs from a LMIC are two small pilot studies, both featuring weekly individual home visits over two years on a total of 134 stunted or low birthweight children from urban Kingston, Jamaica. Such intensive delivery models are prohibitively expensive to scale in rural and resource-poor LMIC settings. Community-based group meetings are a more cost-effective and scalable delivery model, and can also allowforpeer-to-peer learning and the formation of social support networks. Though growing evidence from LMICs shows that group meetings are at least as effective as individual home visits to improve ECD in the short- term, evidence on their ability to sustain impacts over time, and the mechanisms underlying such impacts (e.g., social support), is still very limited. With NICHD support (R01HD090045), we demonstrated that an 8-month, group-based ECD parenting intervention delivered by CHWs in rural Kenya significantly improved short-term ECD outcomes and parenting practices, and the program was highly cost-effective. In complementary work (R21HD098508), immediately after the main intervention, in half of intervention villages, we added 9 bi-monthly “booster” group meetings to reinforce key messages over two years. In a recent two-year follow-up assessment, we found that early impacts from the original 8-month intervention were sustained when children were ages 3.5 to 5, and the poorest families benefited the most. The booster extension, despite being severely disrupted by the COVID- 19 pandemic, had small additive effects on children’s socioemotional outcomes and parenting behaviors. Building on these results, we now propose to follow-up our original study cohort roughly 5 years after the end of the intervention to measure longer-term sustained impacts on our sample of targeted children who will be roughly 6.5 to 8 years old, as well as their younger and older siblings to uncover potential spillover effects. We will re-enroll households from our original sample across 60 villages to collect an additional survey wave to measure children’s cognitive, language, executive function and socio-emotional skills, as well as parenting behaviors, knowledge and beliefs, social networks, and social norms around parenting to examine potential mediating pathways driving any sustained impacts and any spillover impacts onto siblings. The goal of our study is to help fill a gap regarding evidence on the long-term effectiveness of ECD programs on children’s outcomes from a scalable and cost-effective model of delivery to help inform policy.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15349", "attributes": { "award_id": "1R01DA060215-01A1", "title": "Behavioral Pharmacology of Opioid/Xylazine Mixtures", "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": 23333, "first_name": "KIRAN R V", "last_name": "Vemuri", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-15", "end_date": "2029-07-31", "award_amount": 392940, "principal_investigator": { "id": 31945, "first_name": "DAVID Richard", "last_name": "MAGUIRE", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 748, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH SCIENCE CENTER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "The opioid crisis continues despite the availability of several FDA approved medications for treating opioid abuse and overdose. This public health crisis has worsened significantly over the past several years with the COVID-19 pandemic and the increased availability of fentanyl and related ultra-potent analogs. Recently, there has been a marked rise in overdose deaths involving opioids and xylazine, a non-opioid with sedative, analgesic, and muscle relaxant properties and authorized only for veterinary use. It remains unclear why use of opioid/xylazine mixtures has increased so rapidly. Use of xylazine might be intentional in some situations but not others as it is commonly found as an adulterant in other drugs. Having agonist properties at alpha-2 adrenergic receptors, xylazine decreases release of norepinephrine and dopamine, and causes drowsiness, hypotension, bradycardia, hypothermia, respiratory depression, and coma as well as soft tissue damage that can lead to necrotic skin lesions. Xylazine shares many effects with opioids, increasing the risk of adverse effects, including fatal overdose, when combined with an opioid. Anecdotal reports suggest that xylazine enhances the reinforcing and subjective effects of opioids and diminishes the severity of opioid withdrawal which might contribute to increased use; however, these hypotheses have not been tested experimentally. In the case of overdose, treatment with naloxone (Narcan®) blocks only the effects of the opioid, thus additional measures are required to successfully treat opioid/xylazine overdose. Repeated exposure to xylazine might also lead to physical dependence and withdrawal, and it remains unclear whether xylazine alters opioid withdrawal. Though medications are approved for reversing effects of xylazine in veterinary care, there are currently no approved medications for treating xylazine overdose or withdrawal in humans. Proposed studies use well- established methods and a highly translational species to improve our understanding of interactions between opioids and xylazine as well as to elucidate factors contributing to the use of opioid/xylazine mixtures, which will help to drive the discovery of safe and effective treatments.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15350", "attributes": { "award_id": "1R01CE003665-01", "title": "RFA-CE-24-030, Social policies to prevent firearm assault", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Center for Injury Prevention and Control (NCIPC)" ], "program_reference_codes": [], "program_officials": [], "start_date": "2024-09-30", "end_date": "2027-09-29", "award_amount": 399939, "principal_investigator": { "id": 31946, "first_name": "Ellicott Colson", "last_name": "Matthay", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "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": "Firearm violence is a persistent public health crisis that disproportionately affects young Black and Brown people. From 2019 to 2021, firearm homicide rates rose an alarming 46% among people aged 10–34 years, peaking at the highest levels seen in 20 years and exacerbating stark racial/ethnic inequities. Policies that address the conditions contributing to persistently high rates of firearm violence are needed. Two major categories of policies have a strong scientific premise but lack rigorous evaluations of their effectiveness in reducing firearm homicide and nonfatal firearm assault injuries (herein referred to as “firearm assault”). First, alcohol control policies (e.g., alcohol outlet density restrictions) are a well-established means of limiting alcohol availability thereby reducing alcohol-related harms. No studies have clearly established whether alcohol control policies prevent firearm assault. Second, economic support policies (e.g., income supplements) influence upstream causes of firearm assault including poverty and income inequality, but the impacts of these policies on racial/ethnic inequities in firearm assault are unknown. Local (city and county) policies, in particular, are likely to shape the environments in which firearm assault unfolds. Further, research assessing the synergy between these sets of policies is absent but essential to identify multifaceted solutions that maximize impact. This will be the first quasi-experimental study to test the impacts of a range of local alcohol control and economic support policies on overall rates and racial/ethnic inequities in firearm assault among young people. The study will leverage heterogenous policy changes introduced by county governments during the COVID-19 pandemic, which provide an unprecedented opportunity to rigorously assess impacts on firearm assault. The investigators will establish a cohort of ~90% of California residents ages 10-32 years, and construct a longitudinal hierarchical database by individually linking birth records, emergency department encounters, inpatient hospitalizations, and deaths, combined with comprehensive legal epidemiologic research on county policies from 1/1/2018 to 12/31/2022. The Specific Aims are to evaluate the impacts of county 1) alcohol control policies, 2) economic support policies, and 3) their interaction, on firearm assault, overall and by race/ethnicity among California young people. This study will provide critical evidence that local governments are urgently seeking on which policies they could enact or avoid to reduce firearm assault and promote health equity in communities. This project addresses Objectives 2 and 3 of RFA-CE-24-030 as it entails effectiveness research to evaluate alcohol control policies as place-based prevention approaches and economic support polices as structural approaches to reduce firearm assault. It also addresses NCIPC’s Cross Cutting Violence Prevention priority to “evaluate the effectiveness… of policies or community-level change strategies designed to enhance the economic and social environment to reduce multiple forms of violence throughout the lifespan.”", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15351", "attributes": { "award_id": "1R21AG081823-01A1", "title": "Comprehensive Determination of Isoprostanoid Metabolism", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Aging (NIA)" ], "program_reference_codes": [], "program_officials": [ { "id": 31947, "first_name": "YI-PING", "last_name": "Fu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-23", "end_date": "2026-08-31", "award_amount": 478765, "principal_investigator": { "id": 31948, "first_name": "Ginger Lohr", "last_name": "Milne", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 456, "ror": "https://ror.org/05dq2gs74", "name": "Vanderbilt University Medical Center", "address": "", "city": "", "state": "TN", "zip": "", "country": "United States", "approved": true }, "abstract": "Oxidative stress (OxS) is a biochemical process that leads to damage of cellular lipids when endogenous redox homeostasis is disrupted. OxS is mechanistically linked with the physiology of aging and age-related diseases, such as cardiovascular disease, neurodegeneration, cancer, frailty, diabetes, and SARS-CoV-2. The identification of biomarkers to measure OxS is thus of significant public health revelance in order to better understand disease mechanisms and target potential therapies. F2-Isoprostanes (F2-IsoPs) are formed from the oxidation of the cellular lipid arachidonic acid and considered to be excellent biomarkers of OxS. Currently, F2- IsoPs are being used as outcome measures in more than 80 active clinical trials worldwide. Further, the NIA- sponsored Interventions Testing Program (ITP) has identified nine agents that significantly increase lifespan, and four of those agents are known to decrease F2-IsoPs. While F2-IsoPs have proven to be useful biomarkers of OxS, our laboratory has obtained evidence to support the hypothesis that metabolites of F2- IsoPs more accurately reflect endogenous OxS than unmetabolized F2-IsoPs in certain biological settings. Yet, F2-IsoP metabolites are rarely quantified in clinical studies. F2-IsoP-like molecules (F-isoprostanoids) are made from the oxidation of other polyunsaturated fatty acids (PUFA), including adrenic, eicosapentaenoic (EPA), and docosahexaenoic acids. These compounds are proving to be useful biomarkers in neurodegenerative conditions and age-related macular degeneration, but their metabolism has never been studied. The central hypothesis of this proposal is that understanding the metabolism of F-isoprostanoids is critical for the accurate and complete quantitation of these urinary biomarkers in aging and OxS-related diseases. In Specific Aim 1, we will use human liver microsomes to identify metabolites of several F- isoprosatnoid isomers generated from the free radical oxidation of PUFA. Metabolites will be identified using mass spectrometry (MS). In Specific Aim 2, we will establish and validate a robust LC/MS method for the quantification of F-isoprostanoid metabolites, from Specific Aim 1, in human urine. For this purpose, we will utilize urine samples from The Fatty Acid Desaturase Activity, Fish Oil, and Colorectal Cancer Prevention Study (FnADAFO), a randomized clinical trial that was completed in 2018 at Vanderbilt. Subjects recruited in this study were supplemented with olive oil or marine fish oil for six months, so these urine samples are ideal for validation of this metabolite quantification. We anticipate that the completion of this application will redefine our understanding F2-IsoP metabolism and, for the first time, define a strategy to comprehensively assess this important biomarker of lipid peroxidation. Overall, these studies will change how the field evaluates endogenous OxS and lipid peroxidation, thus setting the stage for future applications examining the role of isoprostanoids in human physiology and the pathogenesis of disease.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15352", "attributes": { "award_id": "1R01LM014255-01A1", "title": "Evaluation of Impact of EHR Documentation Assistant Modalities on Provider and System Level Outcomes", "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": 31895, "first_name": "Catherine Mary", "last_name": "Farrell", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-17", "end_date": "2028-07-31", "award_amount": 666827, "principal_investigator": { "id": 31949, "first_name": "Vishnu", "last_name": "Mohan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 765, "ror": "https://ror.org/009avj582", "name": "Oregon Health & Science University", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true }, "abstract": "Over the past decade, there has been a growing epidemic of physician burnout, driven most notably, by Electronic Health Records (EHR), and the increasing amount of time providers spend on them. A number of solutions have been developed to untether the provider from the EHR. Prior to the COVID-19 pandemic, the two most widely adopted solutions were Speech Recognition (SR) and Medical Scribes (MS). The pandemic has worsened many of these preexisting issues with EHR, and with the broad adoption of telemedicine, creating new sociotechnical concerns. Fueled in part by this, 2 additional solutions, Virtual Scribes (VS) and Digital Scribes (DS) have begun to be employed for both in-person and telemedicine visits. We have previously performed a mixed methods evaluation of MS documenting significant barriers to successful adoption with significant variance in practice and outcomes. In spite of this rapid expansion of options, there is little information available directly to compare and contrast the ways they are co-opting provider work in the EHR, or their impact on provider activity in the EHR, medical record completion/accuracy, and safety issues. At OHSU, providers who adopt MS have baseline longer times to chart completion and significant greater amount of after-hours record completion, and use of a MS or SR had no impact on these metrics, with many, higher performing providers, worsening with MS adoption. These trends persisted and even widened with the use of telemedicine. The goal of this project is to expand upon these initial findings and use a mixed methods approach to determine the impact of EHR documentation assistance solutions on EHR use and provider workflow in ambulatory care. In Aim #1, we will adapt the Rapid Assessment Protocol (RAP) for in-person and virtual evaluation to expand on our prior work with MS to evaluate the impact of MS, VS, SR, and DS on provider workflow in the context of in-person and telemedicine visits. We will then convene a multidisciplinary stakeholder group to review these findings to come up with a series of metrics, both quantitative and simulation based, to allow for assessment of the 4 modalities. In Aim #2, we will use EHR audit logs to determine the impact of adoption of each of these 4 modalities, including data from OHSU and Medstar Health to improve generalizability, control for various EHR systems and allow for anchoring back to the qualitative data in Aim #1. In Aim #3, we will use the data from the first 2 aims, to create a high-fidelity simulation to all for direct head-to-head comparison of the 4 modalities on measures not reliably extracted from EHR audit logs including note accuracy, time-on-task, EHR navigation and patient-provider communication. In Aim #4, we will define and create a success matrix for selection of DA modalities to guide decision making on the use of appropriate DA resources for a given specialty type and location. We will also create a Documentation Assistance Dashboard (DAD) to allow for real-time, longitudinal monitoring of the various modalities across specialties.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15353", "attributes": { "award_id": "1R01AG086245-01", "title": "Molecular Targets Modulating Neuro COVID Sequelae Linked to Tauopathy", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Aging (NIA)" ], "program_reference_codes": [], "program_officials": [ { "id": 21701, "first_name": "Luci", "last_name": "Roberts", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-15", "end_date": "2029-05-31", "award_amount": 749994, "principal_investigator": { "id": 31950, "first_name": "PAULA C", "last_name": "BICKFORD", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 23775, "first_name": "Shyam S", "last_name": "Mohapatra", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1638, "ror": "", "name": "JAMES A. HALEY VA MEDICAL CENTER", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true } ] }, { "id": 24037, "first_name": "SUBHRA", "last_name": "MOHAPATRA", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1638, "ror": "", "name": "JAMES A. HALEY VA MEDICAL CENTER", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 235, "ror": "https://ror.org/032db5x82", "name": "University of South Florida", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true }, "abstract": "The COVID-19 pandemic caused by SARS-CoV-2 (CoV2) virus has left a large cohort of individuals suffering from ongoing neurological sequelae known as neuro-COVID. The condition involves CoV2 neurotropism and long-term inflammatory responses, including increases in neurodegenerative and neurotoxic proteins such as tau. Despite progress made, the molecular mechanisms underlying CoV2-induced tauopathy are unknown. Aging activates innate immune mechanisms and inflammation, and the latter has been linked to tau pathology. Together these observations have provided a strong scientific premise for this proposal, which aims to investigate CoV2-induced molecular changes in the context of aging and tauopathy to identify critical mechanisms underlying the development of neuro-COVID symptoms using mouse models. To this end, data in a mouse- adapted CoV2-MA10 virus infection in C57BL/6 mice show increased expression of genes involved in neuroinflammation and tauopathy risk that increase with age, which models neuro-COVID seen in the patient’s brains. Our preliminary studies led to the identification of two groups of proteins: one involved in protein misfolding/tauopathy (FKBP51) and the other related to innate immune activation including genes involved in IFN regulation (IFI204). Our studies also showed that CoV2-MA10 accelerates tau pathology in PS19 tau transgenic mice, establishing a model to further study tauopathy mechanisms that are accelerated by CoV2. Most notably, intranasal instillation of dendriplexes (DPX) comprising dendrimers and plasmid encoding short hairpin RNA (pshRNA) for the lead target FKBP51 in MA10-infected C57BL6 mice significantly reduced neuroinflammation, and expression of FKBP51 and Tau phosphorylation. These findings lead to the central hypothesis that age-dependent CoV2 neuro-invasion-induced tau pathology is caused by innate immune activation and elevated FKBP51 expression. We further hypothesize that CoV2 infection induces similar inflammation and protein misfolding in PS19 tauopathic mice, accelerating neuropathology and cognitive deficits. These hypotheses will be tested in the following two specific aims. SA #1 will assess age as a primary variable that exacerbates inflammation leading to tauopathy and long-term cognitive decline in C57BL/6 mice following CoV2-MA10 infection. SA #2 will examine the progression of tauopathy in PS19 transgenic mice following CoV2- MA10 Infection. Each of these aims will: i) characterize neuropathology and behavior; ii) identify target mechanisms underlying the pathology and neuro-COVID sequelae using spatial transcriptomic profiling; and iii) validate the role of FKBP51, IFI204 and other novel leads in neuropathological and cognitive consequences, using DPX formulations carrying pshRNA for these leads. This multi-PI and multi-disciplinary approach to understanding the mechanisms leading to neuro-COVID is expected to expand our basic knowledge and identify new mechanistic targets increasing our understanding of the impact of CoV2 on pre-existing age-related or genetically pre-disposed neurodegeneration.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15354", "attributes": { "award_id": "1DP1CA300850-01", "title": "RaceCAR-M immunotherapy for cancer and beyond", "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": 22844, "first_name": "MONICA", "last_name": "Zamisch", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-20", "end_date": "2029-08-31", "award_amount": 1088500, "principal_investigator": { "id": 31951, "first_name": "Denise J.", "last_name": "Montell", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1707, "ror": "", "name": "UNIVERSITY OF CALIFORNIA SANTA BARBARA", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Cellular immunotherapies like Chimeric Antigen Receptor T cells (CAR-T) extend the lives of cancer patients who are otherwise out of options. These therapies represent a leap forward in cancer treatment but suffer from severe limitations because 1) the tumor microenvironment excludes and exhausts T cells including CAR-T cells, 2) some tumor cells escape by downregulating the target antigen, 3) the therapy incites cytokine storms and autoimmune reactions, and 4) cellular therapies are currently complex, time-consuming, and exorbitantly expensive. Here we propose to overcome these limitations and thereby revolutionize, generalize, and democratize cellular immunotherapies. A promising new cellular immunotherapy approach is CAR-M (macrophage). Two Phase 1 clinical trials are in progress and it is clear that the approach is safe though there is substantial room for improvement in efficacy. While CAR-M has many advantages over CAR-T, it is clear that it would be of great value to enhance the capacity of CAR macrophages to attack and kill cancer cells while sparing normal tissue. Based on fundamental cell and developmental biology we have been doing in fruit flies, we discovered how to greatly increase the ability of human macrophages to attack and kill specific whole target cells of our choosing. Inspired by our discovery in fruit flies, we have been able to engineer mouse and human macrophages to avidly and specifically engulf and kill cancer cells. Here we propose to test this approach against the most prevalent solid tumors like breast, lung, and colon, and against hard-to-treat cancers like ovarian, pancreatic, and glioblastoma. Another huge limitation of cellular immunotherapies is their cost and complexity. We propose to overcome this problem by greatly simplifying the production and delivery of CAR-M. We propose to transform CAR-M into an affordable, off-the-shelf therapy. This will enable generalization of the approach to hard-to-treat diseases beyond cancer, such as multidrug resistant bacteria, viral and fungal infections, autoimmune diseases, and more.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15355", "attributes": { "award_id": "1U48DP006882-01", "title": "Community-Based Participatory Research to Enhance Vaccine Uptake Across the Lifespan through Innovative Points of Access and Altering Norms in Border and Rural Regions", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Center for Immunization and Respiratory Diseases (NCIRD)" ], "program_reference_codes": [], "program_officials": [ { "id": 31906, "first_name": "Natalie", "last_name": "Darling", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-30", "end_date": "2029-09-29", "award_amount": 350000, "principal_investigator": { "id": 31952, "first_name": "SCOTT C", "last_name": "CARVAJAL", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 31953, "first_name": "Katherine", "last_name": "Ellingson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 31954, "first_name": "Thomas", "last_name": "Nuno", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 438, "ror": "https://ror.org/03m2x1q45", "name": "University of Arizona", "address": "", "city": "", "state": "AZ", "zip": "", "country": "United States", "approved": true }, "abstract": "Vaccination is a highly effective public health intervention that saves millions of lives per year, yet declination rates for are increasing in the US for a variety of reasons ranging from safety concerns to religious and philosophical objection. In the wake of declining vaccination rates associated with the COVID-19 pandemic, the Chiricahua Community Health Centers, Inc. (CCHCI) in rural southeast Arizona initiated an innovative project to enhance vaccination through placement of an immunization specialist in dental clinics affiliated with the federally qualified health center (FQHC) system. The literature suggests that there are multiple salient and modifiable points to promote vaccine uptake within a multilevel approach that engages adults, adolescents, providers, families and communities. To enhance vaccine coverage through novel strategies, we propose the following specific aims: 1) Identify barriers and facilitators to vaccine uptake for specific vaccine types and populations in rural and border regions through engagement of individuals, communities, providers, and public health officials; 2) Determine the sustainability of the CCHCI FQHC dental clinic immunization program and scalability of the intervention to dental clinics at the Mariposa Community Health Center (MCHC) FQHC clinics in Santa Cruz County; and 3) Implement and evaluate a multilevel intervention to enhance vaccination uptake in populations unlikely to access FQHC care via an Underserved Population Study Team deployed through the MHU. Our approach will integrate socioecological and health beliefs model framing to understand the roles of socioeconomic factors, trust in health systems and public health authorities, and perceptions of vaccine efficacy and risk. We propose implementation of the dental clinic immunization program at the MCHC and support for the continuation of the program at CCCHCI. We also propose that staff from both CCHCI and MCHC work with the study investigators to author an implementation guide, rooted in Normalization Process Theory and a Dynamic Sustainability Framework, to participate in rigorously evaluating adaptability, effectiveness, and sustainability of this approach in FQHCs. We will develop, pilot, and assess a multilevel intervention strategy aimed at improving vaccination rates within populations that face barriers to healthcare access, particularly those residing in rural and hard-to-reach areas or individuals who do not typically utilize FQHCs. We will leverage the UA College of Public Health Primary Prevention Mobile Health Unit (MHU) program as a strategic platform for delivering vaccinations, utilizing community events as key touchpoints for outreach. At the community level, our focus will be on fostering a supportive environment that promotes vaccination through education, awareness campaigns, and collaboration with local community leaders. Simultaneously, at the individual level, the MHU team will provide personalized education, addressing specific concerns and providing tailored information to encourage vaccine uptake.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15356", "attributes": { "award_id": "1R21AG086855-01", "title": "Mitigating Delirium with Fluvoxamine Treatment for Non-Cardiac Surgery (MD FluNCS): Feasibility Trials & Mechanistic Insights", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Aging (NIA)" ], "program_reference_codes": [], "program_officials": [ { "id": 21701, "first_name": "Luci", "last_name": "Roberts", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-15", "end_date": "2026-05-31", "award_amount": 215425, "principal_investigator": { "id": 31955, "first_name": "Ben Julian", "last_name": "Palanca", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 31956, "first_name": "Robert D", "last_name": "Sanders", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 827, "ror": "", "name": "WASHINGTON UNIVERSITY", "address": "", "city": "", "state": "MO", "zip": "", "country": "United States", "approved": true }, "abstract": "The pathogenesis of postoperative delirium likely involves systemic inflammation, downstream neuroinflammation, and altered synaptic plasticity reflected by elevations in IL-6 and electroencephalographic (EEG) slowing. Furthermore, there are no known pharmacologic interventions for preventing postoperative delirium. Fluvoxamine is an antidepressant that could suppress neuroinflammation through sigma-1 receptor agonism. Fluvoxamine reduces prostaglandin synthesis and cytokine release from human blood. It is concentrates in the brain and neuroprotective via sigma-1 receptors. It improves survival in sepsis animal models and reduces clinical deterioration from COVID-19. Promise in the treatment of delirium is supported by a series of case reports of fluvoxamine treating delirium in older adults and/or intensive care unit. It is not clear whether suppressing neuroinflammation is a viable pathway towards mitigating delirium severity. Furthermore, it is unclear whether fluvoxamine is a feasible pharmacologic intervention for mitigating delirium risk, given societal stigma against antidepressants as well as side effects of nausea and potential drug-drug interactions. To evaluate the safety and feasibility of a multisite investigation on perioperative fluvoxamine, we propose Mitigating Delirium with Fluvoxamine Treatment for Non-Cardiac Surgery (MD FluNCS): Feasibility Trials & Mechanistic Insights. This work will enhance our understanding of core pathogenesis of postoperative delirium in a population at risk for Alzheimer's disease and related dementias. With the rise in the aging population, we hope to provide an intervention to mitigate risk as well as translatable theragnostic biomarkers and approaches for future precision medicine. The investigation will lay the groundwork for a larger scale Phase 3 trial geared toward advancing long-term goal of improving public health and quality of life for those at risk of postoperative delirium and related sequelae.", "keywords": [], "approved": true } } ], "meta": { "pagination": { "page": 1385, "pages": 1419, "count": 14184 } } }