Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1406&sort=end_date
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=end_date", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1424&sort=end_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1407&sort=end_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=end_date" }, "data": [ { "type": "Grant", "id": "15320", "attributes": { "award_id": "1R01HS030271-01", "title": "Understanding and Addressing Community Health Center Burden, Resiliency, and Burnout - Systems Engineering Analyses and Approaches", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Agency for Healthcare Research and Quality (AHRQ)" ], "program_reference_codes": [], "program_officials": [ { "id": 22658, "first_name": "David", "last_name": "Rodrick", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-30", "end_date": "2029-07-31", "award_amount": 399999, "principal_investigator": { "id": 25614, "first_name": "JAMES C", "last_name": "BENNEYAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 184, "ror": "https://ror.org/04t5xt781", "name": "Northeastern University", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "An estimated 31% of physicians and 54% of nurses experience professional burnout, at a cost of ~$4.6 billion annually, in part due to significant time burden, poor system resiliency, and process inefficiencies. Declared a national emergency by the U.S. Surgeon General’s Office – a staggering 76% of healthcare professionals re- ported exhaustion, burnout, and excessive work burden during the COVID-19 pandemic – burnout significantly affects care quality, medical error, occupational injury, workforce attrition, depression, and suicide contempla- tion. Work burden, personnel burnout, staff shortages, and strained resources are complex issues, deeply in- tertwined, and especially prevalent in practices serving disadvantaged populations, yet remain both signifi- cantly understudied, as a system, and increasingly common. The encouraging broad adoption of asynchronous care (patient portals, EHR email, text messaging) fortunately can significantly improve care and patient experi- ence, but also contribute significantly to time stresses, work-after-work, and burnout, further exacerbated by (and contributing to) staff shortages, inefficient processes, and non-resilient systems. It is not surprising that a National Academy of Medicine report (Taking Action Against Provider Burnout: A Sys- tems Approach) thus recommended greater use of systems engineering to optimize technology use workflows, reduce endemic inefficiencies, develop resilient processes, and apply complex adaptive systems ideas. This project directly responds to 4 of the 8 NAM report recommendations, uniquely incorporating systems science and systems engineering approaches to better understand and address the relative impacts of these issues by: (Aim 1) Understanding the nature, extent, issues, and exemplars of system resiliency, efficiency, and optimized workflows in asynchronous care processes; (Aim 2) Investigating relationships between work burden, system resiliency, inefficiency, and burnout and their impact on care quality and safety; and (Aim 3) Estimating the rel- ative impacts and generalizability to other settings of various types of interventions effective interventions. Notably, (1) analytic process simulation and system dynamics models will be integrated with other methods to help understand these issues, identify insights, estimate effect and relationship sizes, and evaluate potential interventions, and (2) system resiliency analysis and design methods will be applied to develop more robust adaptive processes – both hallmarks of systems engineering. This research will be conducted by a multidisci- plinary team of engineering, qualitative, and health service researchers working with 4 varied community health centers (in complexity, rurality, ethnicity) and validated through statewide CHC and primary care organizations for generalizability, since burnout affects some demographics more than others. Results will be evaluated through a combination of process, resiliency, burnout, and safety measures, with expected impacts including more efficient and resilient processes, reduced burden and burnout, and better care that, if scaled to 20% of primary care across the US, could benefit 209,000 practices serving 133 million patients.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15322", "attributes": { "award_id": "1R35GM155224-01", "title": "Observational causal inference with infectious disease outcomes", "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": 31916, "first_name": "Guoqin", "last_name": "Yu", "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": 382852, "principal_investigator": { "id": 31917, "first_name": "Alyssa", "last_name": "Bilinski", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 222, "ror": "https://ror.org/05gq02987", "name": "Brown University", "address": "", "city": "", "state": "RI", "zip": "", "country": "United States", "approved": true }, "abstract": "Infectious disease is a leading cause of global morbidity and mortality. Transmission dynamic models have played a critical role in guiding interventions related to many infectious pathogens, including HIV, influenza, SARS-CoV-1, ebolaviruses, SARS-CoV-2, and mpox. Models project how potential interventions (e.g., non- pharmaceutical measures, therapeutics, and vaccines) may affect disease future transmission. However, they often rely on small scale studies to project effects, and there have been growing concerns that models may produce inaccurate, overly optimistic estimates of population-level intervention effectiveness. Observational causal inference models, which measure intervention effectiveness in real-world settings, could help address this limitation, but applying these to infectious disease is not straightforward. Observational approaches, such as difference-in-differences and synthetic control methods, estimate the impact of an intervention based on empirical counterfactuals: comparing outcomes of interest between treated units or places and similar untreated units. While well-understood with linear outcomes, they can produce biased and misleading results in the context of nonlinear transmission dynamics. Even where observational models perform well, it further remains challenging to transport estimates to new settings to project the impact of future interventions. To address these issues, this project will develop comprehensive theoretical architecture for synthesizing transmission dynamic models with observational causal inference models – employing empirical counterfactuals while accounting for complex biological and population dynamics. In the retrospective workstream, I will propose robust specifications for observational causal inference models that can estimate unbiased treatment effects in policy evaluations using infectious disease outcomes. I will also develop model selection and decision-analytic methods to address potentially significant parameter uncertainty. In the prospective workstream, I will develop approaches to generalize estimates from observational causal inference models to new settings using transmission dynamic models and update projected effects in real-time based on local surveillance indicators. I will illustrate the implications of our methods by re-analyzing prior studies on COVID-19 as well as applying them to answer new questions about respiratory illness control, in collaboration with partners in state and local public health institutions. Across both workstreams, I will develop and disseminate open-source public tools and software to facilitate adoption of these methods. Overall, this work will produce a suite of methodological innovations to improve understanding of the impact of past policies and the accuracy of future projections, while also supporting their implementation in public health institutions to guide planning and priority setting.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15323", "attributes": { "award_id": "1R24GM154040-01", "title": "DIALS: supporting structural biology through open source diffraction processing software", "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": 11852, "first_name": "Anne", "last_name": "Gershenson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-20", "end_date": "2029-07-31", "award_amount": 1204713, "principal_investigator": { "id": 31918, "first_name": "Aaron Samuel", "last_name": "Brewster", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2533, "ror": "", "name": "UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "X-ray crystallography is a powerful tool for determining the atomic positions of proteins, used by researchers at synchrotrons and X-ray free electron lasers. Typically, the crystal is exposed to X-rays, which diffract and are collected on a detector to create diffraction patterns. These patterns are processed by software designed to seek out weak signal on the images and create datasets from which the protein structure can be solved. The DIALS diffraction data processing package is a mature product produced in collaboration between LBNL and Diamond Light Source (UK) that has primarily been supported in the US by research funding. DIALS is used at a number of synchrotrons world-wide for regular processing of user datasets and has been used at X- ray free electron lasers for fast processing of large datasets collected at hundreds to thousands of images per second. The program allows fast feedback of data quality when incorporated into automated processing that allows users to quickly make decisions about beamline operation and experimental direction. This has allowed researchers to produce high-impact structures in general biological fields, including human diseases such as COVID-19 and malaria, and energy research such as photosynthesis. This proposal would create a US R24 National Resource for the DIALS diffraction data processing package. The Resource would move DIALS funding in the US from primarily R01 research funding to a combination of separate research funding and operational funding from this proposal. The operational funding would be to support codebase optimization, maintenance, and refactoring, a build-and-release schedule, and new robust and adaptable user interfaces. Further, it would provide user outreach and training, both for general users, and through on-site training for beamline scientists to help with software integration into existing pipelines. The end result will be a well-maintained and documented software package used at synchrotrons and XFELs for routine data analysis without user intervention, and robust support for difficult cases.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15342", "attributes": { "award_id": "1R01DA060210-01", "title": "The role of norepinephrine transporter phosphorylation in amphetamine reward", "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": 21768, "first_name": "PAUL", "last_name": "HILLERY", "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": 587162, "principal_investigator": { "id": 31937, "first_name": "LYNETTE C", "last_name": "DAWS", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 31938, "first_name": "LANKUPALLE D", "last_name": "JAYANTHI", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 31939, "first_name": "SAMMANDA", "last_name": "RAMAMOORTHY", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 672, "ror": "https://ror.org/02nkdxk79", "name": "Virginia Commonwealth University", "address": "", "city": "", "state": "VA", "zip": "", "country": "United States", "approved": true }, "abstract": "Substance use disorder (SUD), including use of the psychostimulant amphetamine (AMPH) and its congeners, is on the rise, especially in the Covid-19 pandemic era. There are no effective medications available for psychostimulant SUD, likely because of the lack of thorough understanding of the complex neurobiology underlying the disease. Noradrenergic neurotransmission in the mesolimbic circuit plays a critical role in SUD. AMPH inhibits norepinephrine (NE) transporter (NET) activity promoting its behavioral effects. NET, a principal mediator of NE signaling, is regulated by post-translational modifications, such as phosphorylation and protein- protein interactions. These regulators of NET are impacted by psychostimulants, including amphetamine, in turn impacting the stimulant and rewarding effects of these drugs. However, to date, post-translational modifications have not been a focus of investigation in the SUD field. Our published studies over several years demonstrate that the The258/Ser259 motif, a phospho-site in the NET, plays a pivotal role in regulating AMPH-evoked behaviors. In this proposal, we explore this novel finding using cutting-edge techniques, including a phosphorylation-defective NET-Thr258Ala/Ser259Ala mutant mouse model (NET-T258A/S259A), a viral- mediated brain region-specific blockade of NET-T258/S259 phosphorylation, and recordings of extracellular NE dynamics in vivo using high-speed chronoamperometry and microdialysis. With these new models and tailored biochemical, neurochemical, and behavioral studies, the current proposal aims to fill critical gaps in our understanding of the central role of NET phosphorylation in AMPH-evoked NE dynamics and animal behavior. As a key mechanism, we have discovered that NET-T258A/S259A mice exhibit genotype- and sex-specific alterations in AMPH sensitivity in addition to brain-region specific variations in NET function and expression. Here, we will expand and test our overarching hypothesis that brain region-specific T258/S259-dependent NET phosphorylation and regulation contributes to sex-specific AMPH-induced behaviors relevant to addiction and reward. Aim 1 will investigate NET regulatory phenomena including NET phosphorylation and NET subcellular distribution and protein-protein interactions in the prefrontal cortex and nucleus accumbens to determine the relationship between T258A/S259A mutant-dependent dysfunction in AMPH-mediated NET regulation and in AMPH-evoked behaviors. Aim 2 will evaluate brain-region specific roles of T258/S259-dependent NET regulation in AMPH reward using adult DBH-Cre mice expressing the NET-T258/S259 motif in a NE-terminal specific manner. Aim 3 will examine the impact of T258/S259-dependent NET phosphorylation and regulation on NE dynamics (release and clearance as well as extracellular levels) modulated by AMPH in vivo. Outcomes from proposed studies will provide novel insights into the mechanisms of SUD, open new avenues for examining T258/S259-phosphorylation dependent NET regulation as an underlying mechanism of AMPH’s actions and provide new molecular therapeutic intervention points.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15343", "attributes": { "award_id": "1R01AI180195-01", "title": "Immunological mechanism of muscle-localizing self-replicating RNA vaccines", "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": 12151, "first_name": "AARON MICHAEL", "last_name": "Joffe", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-13", "end_date": "2029-07-31", "award_amount": 864721, "principal_investigator": { "id": 31940, "first_name": "Taishi", "last_name": "Kimura", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1031, "ror": "", "name": "HDT BIO CORPORATION", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "As evident in the ongoing “tripledemic” of severe acute respiratory syndrome-Coronavirus-2, Respiratory Syncytial virus, and Influenza virus, as well as re-emergence of enterovirus D68, virus infection is an important health threat and a huge economic burden. Multivalent RNA vaccination is an effective measure for counteracting virus infections and cancerous threats. However, multivalent vaccines need to inject relatively larger doses of RNA than monovalent vaccines, which can trigger a potent innate immune response in vivo, causing reduced transgene expression and unwanted reactogenicity. We have recently found that high dose RNA vaccination can be safely achieved in mice by delivering self-amplifying replicon RNA (repRNA) with a family of muscle-localizing cationic nanocarriers, LIONTM. In vivo delivery of repRNA by LION restricted the formulation to the muscle and local lymph nodes without inducing unwanted systemic cytokine responses. Systemic blockade of type I IFN signaling increased transgene expression and the subsequent antibody and T cell responses. Notably, we also found that CD11b+ cells [mostly monocyte dendritic cells (DC)] expand over time after intramuscular injection of repRNA/LION. However, the role of the muscle-infiltrating cells in immunogenicity is unknown. Consequently, many questions remain about how repRNA/LION vaccines induce adaptive immune responses and how transgene expression and adaptive immune responses are inhibited by the type I IFN system. So, Aim 1 looks at skeletal muscle DC (SMDC) and characterizes their immunological function both in vitro and in vivo. Aim 2 focuses on type I IFN signaling and seeks to identify how type I IFN signaling limits transgene expression and adaptive immune responses to repRNA vaccines. Aim 3 spotlights the inflammatory responses to muscle damage and their role in inducing adaptive immune responses to repRNA/LION vaccines. The proposed studies will test the following hypotheses that (1) the muscle plays a critical role in eliciting the immune response to intramuscular-based RNA vaccines, and (2) muscle-restricted activation of the immune system is a novel strategy for RNA vaccines to achieve high efficacy with reduced reactogenicity.", "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": "15536", "attributes": { "award_id": "7K25AI177810-02", "title": "Understand the mechanism of SARS-CoV-2 entry by single-molecule approaches", "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": 27781, "first_name": "Mary Katherine Bradford", "last_name": "Plimack", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-11", "end_date": "2029-07-31", "award_amount": 120258, "principal_investigator": { "id": 31574, "first_name": "Prakash", "last_name": "Shrestha", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1162, "ror": "https://ror.org/02k3smh20", "name": "University of Kentucky", "address": "", "city": "", "state": "KY", "zip": "", "country": "United States", "approved": true }, "abstract": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its transmission across the world was the cause of the COVID-19 pandemic. The CoV entry is mainly initiated by the binding of furin cleavage activated spike (S) protein with ACE2 receptor protein on the surface of host cell. Next, S2’ cleavage by transmembrane protease serine 2 (TMPRSS2) on the cell surface induce the conformational change of S2 subunit to activate the membrane fusion and entry of virus genetic material. Therefore, S protein has been the major target to design the vaccines and therapeutics. While a handful of investigations have been reported about the structure of S protein:ACE2 complex, critical questions about the detachment of S1/S2 subunits, structural changes in S2 and their dynamics to activate the membrane fusion remain. These answers will help to improve the current understanding of the mechanism of virus entry and should be highly significant for the development of effective preventions and therapeutics. I propose to combine novel DNA nanoswitch calipers (DNC), single-molecule fluorescence integrated optical tweezers, and high-throughput magnetic tweezers to study the dynamics of the molecular events associated with the membrane fusion process of viral entry and analyze the heterogeneity of neutralizing antibodies (nAbs). Using DNC that I developed, we showed the measurement of multiple distances within a target biomolecule at angstrom level precision. Next, we showed the high-throughput measurements in magnetic tweezers to analyze the heterogeneous mixture of peptides. Therefore, DNCs are useful to study multicomponent protein-protein interactions and simultaneously monitor the structural changes associated with the process. By executing these projects, I will have the following three important answers. First, I will measure binding dynamics of full-length S protein and monomer/dimer ACE2 receptor proteins to understand the entire energy landscape governing the interaction of these proteins. Second, I will measure the detachment kinetics of S1/S2 subunits, induced by TMPRSS2 and determine the change in conformation of S2. These reactions are critical to understand the membrane fusion process. Third, I will utilize the similar approach to measure the binding dynamics of nAbs with S protein. By high-throughput measurements in magnetic tweezers, I will analyze the efficacy and heterogeneity of nAbs to understand the immune response of the patients and vaccinated individuals, and also validate DNC assay with a cell-based pseudovirus neutralization assay. Hence, the proposed work will provide detailed insight into understanding the mechanism of SARS- CoV-2 entry and rapid analysis of immune response of the patients. My quantitative approaches and advanced single-molecule approaches will bring insights, into the field of virology and immunology. This study will also give me firsthand experience in biochemistry, molecular biology, virology, and immunology, enabling me to better apply my quantitative and physical training to more topics in biological research in the future.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15739", "attributes": { "award_id": "1RF1NS144213-01", "title": "SARS-CoV-2 initiation and acceleration of AD pathology in the setting of endogenous and exogenous risk factors", "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": 32579, "first_name": "WILLIAM PATRICK", "last_name": "DALEY", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-15", "end_date": "2029-07-31", "award_amount": 3039032, "principal_investigator": { "id": 8182, "first_name": "Ananth V", "last_name": "Annapragada", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 566, "ror": "https://ror.org/02pttbw34", "name": "Baylor College of Medicine", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 7071, "first_name": "Shannon", "last_name": "Ronca", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 32793, "first_name": "Andrew Arun", "last_name": "Badachhape", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 32794, "first_name": "Parag", "last_name": "Parekh", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2610, "ror": "", "name": "BAYLOR COLLEGE OF MEDICINE", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "The uncertain e,ology of Alzheimer’s disease poses significant obstacles to the development of both therapeu,c and preven,on strategies. At the root of this quandary is the fact that familial disease accounts for a very small frac,on of cases, with the vast majority remaining gene,cally sporadic. The most widely known risk factor, the ApoE4 allele of the gene coding for apolipoprotein E, has been iden,fied, but mechanis,c ,es to disease development are s,ll emerging. Neuroinflamma,on has long been suspected as a contribu,ng factor, and regular exercise documented as a mi,ga,ng factor, with theories to explain their effects being posed, but again with liGle mechanis,c proof. A picture of a very complex process of ini,a,on and progression of Alzheimers disease and related demen,as (AD/RD) including Pick’s disease, fronto-temporal demen,a (FTD) and other tauopathies, is slowly emerging. A key factor in the e,ology of AD/RD that repeatedly crops up is viral infec,on. COVID-19 has brought new aGen,on to this factor, with the observa,on that a frac,on of those infected experience “brain-fog”, a catch-all term that includes cogni,ve dysfunc,on, memory dysfunc,on and mental fa,gue, marked by impaired ability to perform mental tasks compared to before the infec,on. Several factors however, complicate an understanding of the effect of COVID-19 on AD/RD and cons%tute the driving ques%ons for this proposal: These include (1) What are the rela,ve contribu,ons of gene,c risk factors and COVID-19 on ini,a,on and progression of AD/RD? (2) What are the effects of SARS-CoV-2 variants: ex,nct strains e.g. Wuhan, alpha, delta vs. current strains e.g. omicron and its lineage, and their sequen,al infec,on on AD/RD ini,a,on and progression? (3) What are the effects of prior infec,ons with other highly prevalent viruses e.g. HSV-1 on the ini,a,on and progression of AD/RD by SARS-CoV-2? Successful comple,on of this work will probe the rela,onship between COVID-19 and neurodegenera,on, while yielding deep mechanis,c insights into the role of SARS-CoV-2 in combina,on with HSV-1 in triggering/accelera,ng an AD phenotype and focus a search for therapeu,c targets to counteract AD ini,a,on/accelera,on/progression.", "keywords": [ "2019-nCoV", "Acceleration", "Acids", "Alleles", "Alzheimer's Disease", "Alzheimer's disease model", "Alzheimer's disease pathology", "Alzheimer's disease related dementia", "Amyloid", "Amyloid beta-Protein Precursor", "Apolipoprotein E", "Automobile Driving", "COVID-19", "COVID-19 impact", "Code", "Common Cold", "Complex", "Coronavirus", "Coupled", "Development", "Disease", "Exercise", "Familial disease", "Genes", "Herpesvirus 1", "Histopathology", "Image", "Impairment", "Inflammatory", "Interferons", "Interleukin-1", "Interleukin-6", "Link", "MAPT gene", "Magnetic Resonance Imaging", "Measurement", "Measures", "Memory", "Memory Loss", "Metabolism", "Methodology", "Methods", "Modeling", "National Institute of Neurological Disorders and Stroke", "Neurofibrillary Tangles", "Pathology", "Pathway interactions", "Phenotype", "Pick Disease of the Brain", "Process", "Psyche structure", "Recording of previous events", "Reporting", "Risk", "Risk Factors", "Role", "SARS-CoV-2 B.1.617.2", "SARS-CoV-2 variant", "Severity of illness", "Signal Transduction", "Study models", "Tauopathies", "Testing", "Transgenic Mice", "Viral", "Virus", "Work", "apolipoprotein E-4", "brain fog", "cytokine", "disease model", "experience", "human coronavirus", "hyperphosphorylated tau", "in vivo imaging", "insight", "mouse model", "neuropathology", "novel", "post-COVID-19", "presenilin-1", "response", "tau Proteins", "theories", "transcriptomics" ], "approved": true } }, { "type": "Grant", "id": "15759", "attributes": { "award_id": "1R01AI175536-01A1", "title": "ACE2 immunodecoys for long-lasting immunoprophylaxis against sarbecovirus and merbecoviruses that target human ACE2", "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": 32536, "first_name": "DIPANWITA", "last_name": "BASU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-18", "end_date": "2029-07-31", "award_amount": 2937578, "principal_investigator": { "id": 32825, "first_name": "Samuel", "last_name": "Lai", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32826, "first_name": "RAYMOND J", "last_name": "PICKLES", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2628, "ror": "", "name": "UNIV OF NORTH CAROLINA CHAPEL HILL", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "While vaccines are readily available for SARS-CoV-2, there continues to be significant demand for prophylaxis that are potent and not at risk for viral escape to better protect vulnerable populations. In addition, there is emerging evidence that a number of bat sarbecoviruses and merbecoviruses can use human ACE2 (hACE2) as an entry receptor to infect human cells. Thus, there is also a need to advance effective immunoprophylaxis to protect against such zoonotic coronaviruses with pandemic potential. We have previously advanced an ACE2-immunodecoy as treatment for SARS-CoV-2 infections. Instead of the common approach pursued by many investigators to affinity mature ACE2 to enhance binding to SARS-CoV-2 Spike, we instead sought to optimize the linkage between the extracellular fragment of human ACE2 and IgG1-Fc (ALFc) to promote improved bivalent binding to SARS-CoV-2 Spike. Similar to other ACE2- decoys, ALFc is not susceptible to viral escape. Unlike other ACE2-decoys, the preservation of the full human ACE2 sequence means ALFc is likely active against all ACE2-targeted viruses. We have demonstrated that ALFc maintains picomolar activity (comparable to many of the previous leading monoclonal antibodies that received emergency use authorization) against all variants of SARS-CoV-2, and is highly effective in a hamster challenge model. Importantly, the ALFc has outstanding bioprocessing attributes, including stability at high concentrations and exceptional productivity using cGMP CHO production cell line. These attributes have led the U.S. Army to select ALFc to be advanced into clinical development over other ACE2 decoys; GMP materials for clinical trials and GLP tox studies are currently underway, and a Phase 1 clinical study is planned for 2H 2025. In this proposal, we build on the success of ALFc as an inhaled therapy to establish the efficacy of ALFc as a systemic immunoprophylaxis that can prevent severe pulmonary disease in vulnerable populations. Specifically, the ALFc currently in development possess wildtype IgG1-Fc. For sustained immunoprophylaxis lasting >6-9 months, it is essential to utilize Fc with enhanced affinity to FcRn, such as YTE, LS and DHS mutations. In this proposal, we will first produce and characterize ALFcYTE, ALFcLS and ALFcDHS(Aim 1). We will evaluate their activity against a panel of hACE2-targeting viruses, including emerging bat sarbecoviruses and merbecoviruses, using both pseudotyped alphavirus vectors in cell-lines (BSL-2) and infectious virus clones in well-differentiated cultures of human airway epithelial cells (BSL-3) (Aim 2). Finally, we evaluate the ability of ALFc to protect against infectious clones of SARS-CoV-2 and SHC014-CoV challenge in human ACE2 transgenic mice (Aim 3). Successful completion of these studies will likely advance an intervention for providing immunoprophylaxis against future SARS-CoV-2 variants as well as other hACE2-targeted coronaviruses with pandemic potential.", "keywords": [ "2019-nCoV", "ACE2", "Adult", "Affinity", "Allergic Reaction", "Alpha Virus", "Antibodies", "Binding", "Binding Proteins", "Biodistribution", "Biological Products", "COVID-19 pandemic", "COVID-19 treatment", "Cell Culture Techniques", "Cell Line", "Cells", "Chiroptera", "Circulation", "Clinical Research", "Clinical Trials", "Coronavirus", "Coronavirus Infections", "Cyclic GMP", "Data", "Development", "Dose", "Drug Kinetics", "Engineering", "Epithelial Cells", "Escape Mutant", "Evolution", "Excipients", "FDA Emergency Use Authorization", "Future", "Hamsters", "Human", "IgG1", "Immunocompromised Host", "Individual", "Infant", "Infection", "Inhalation", "Inhalation Therapy", "Intervention", "Length", "Link", "Literature", "Lung", "Lung Diseases", "Macaca", "Macaca mulatta", "Marketing", "Measures", "Merbecovirus", "Modeling", "Molecular Conformation", "Monoclonal Antibodies", "Mus", "Mutate", "Mutation", "Nebulizer", "Nose", "Parents", "Passive Immunization", "Phase", "Prevention", "Production", "Productivity", "Prophylactic treatment", "Proteins", "RNA vaccine", "Recording of previous events", "Research Personnel", "Risk", "SARS coronavirus", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "SARS-CoV-2 variant", "Sarbecovirus", "Serum", "Temperature", "Testing", "Therapeutic", "Transgenic Mice", "Transgenic Organisms", "Vaccines", "Variant", "Viral", "Virus", "Virus Diseases", "Vulnerable Populations", "Work", "Zoonoses", "aerosolized", "airway epithelium", "bioprocess", "clinical development", "clinical material", "design", "extracellular", "flexibility", "immunoprophylaxis", "improved", "in vitro Model", "in vivo", "manufacture", "melting", "mutant", "neonatal Fc receptor", "pandemic coronavirus", "pandemic potential", "preservation", "prevent", "pulmonary", "receptor", "receptor binding", "success", "vector", "zoonotic coronavirus" ], "approved": true } }, { "type": "Grant", "id": "15763", "attributes": { "award_id": "1RF1NS138437-01A1", "title": "Impact of SARS-CoV-2 on the cerebrovasculature as a risk factor for VCID: Role of Wnt/beta-catenin", "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": 32579, "first_name": "WILLIAM PATRICK", "last_name": "DALEY", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-11", "end_date": "2029-07-31", "award_amount": 2549080, "principal_investigator": { "id": 31999, "first_name": "Sarah Elizabeth", "last_name": "Lutz", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2631, "ror": "", "name": "UNIVERSITY OF ILLINOIS AT CHICAGO", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "COVID-19 increases the risk of vascular contributions to cognitive impairment and dementia (VCID). VCID is one of the most prevalent forms of dementia, so the potential public health impact of the COVID-19 pandemic on future VCID is substantial. However, the mechanisms by which COVID-19 modifies VCID are unknown. Identifying mechanisms that regulate how prior COVID-19 influences the brain endothelial cell response to vascular stress is important. Here, we provide preliminary evidence that COVID-19 decreases resistance to VCID by weakening the blood-brain barrier (BBB). This is accompanied by cerebrovascular inflammation. This grant will test the novel mechanism that SARS-CoV-2 infection accelerates VCID by suppressing cerebrovascular Wnt/β-catenin signaling. In Aim 1, we determine how prior SARS-CoV-2 infection influences BBB permeability and cognition upon subsequent vascular insult, by genetic and epigenetic modification. In Aim 2 we use endothelial-targeted genetic interventions to assess the contribution of Wnt/β- cat targets to resistance to post-infectious VCID. In Aim 3, we ask whether established post-infectious VCID can be reversed by increasing cerebrovascular Wnt/β-catenin. These studies could lead to novel approaches to identify individuals at high risk for VCID and novel potential therapeutic strategies to mitigate the impact of prior infection on the development of dementia.", "keywords": [ "2019-nCoV", "ATAC-seq", "Acceleration", "Acute", "Blood - brain barrier anatomy", "Blood Vessels", "Blood brain barrier dysfunction", "COVID-19", "COVID-19 pandemic effects", "Cells", "Cerebrovascular system", "Clinic", "Cognition", "Critical Pathways", "Data", "Dementia", "Development", "Endothelial Cells", "Endothelium", "Engineering", "Epigenetic Process", "Extravasation", "Functional disorder", "Future", "Genes", "Genetic", "Goals", "Grant", "High Fat Diet", "Human", "Hypertension", "Impaired cognition", "Individual", "Infection", "Inflammation", "Inflammatory", "Knowledge", "Ligands", "Modification", "Mus", "Pathogenicity", "Pathway interactions", "Pattern", "Pericytes", "Permeability", "Phenotype", "Prevention", "Public Health", "Recording of previous events", "Recovery", "Research", "Resistance", "Respiratory Tract Infections", "Risk", "Risk Factors", "Role", "SARS-CoV-2 infection", "Signal Transduction", "Testing", "Therapeutic", "Translating", "Vascular Dementia", "Viral", "beta catenin", "blood-brain barrier permeabilization", "brain endothelial cell", "cerebrovascular", "gene therapy", "high risk", "in vivo", "inhibitor", "macromolecule", "mouse model", "neuroinflammation", "neurotoxic", "novel", "novel strategies", "post SARS-CoV-2 infection", "post-pandemic", "prevent", "programs", "promote resilience", "respiratory", "response", "small molecule", "therapeutic target", "transcriptome sequencing", "vascular cognitive impairment and dementia", "vascular stress" ], "approved": true } } ], "meta": { "pagination": { "page": 1406, "pages": 1424, "count": 14236 } } }