Project Grant R21AA031559
- This federal Project Grant award of $657,156.00 from the National Institute on Alcohol Abuse and Alcoholism (CFDA 93.273 - Alcohol Research Programs) to the Scripps Research Institute seeks to investigate the role of BK channels in alcohol-induced dysmyelination. The project aims to use a mouse model of alcohol use disorder to study the structural and functional impacts of chronic alcohol exposure on myelination, oligodendrogenesis, and neurological function. Key goals include assessing...
- The National Institute on Alcohol Abuse and Alcoholism (NIAAA) awarded a $438,375 Project Grant under the Alcohol Research Programs (CFDA 93.273) to Cedars-Sinai Medical Center to establish a human liver-on-a-chip model for studying alcohol-associated liver disease (ALD). The 2-year project, starting September 2023, aims to investigate the roles of liver sinusoidal endothelial cells and acetaldehyde metabolism in regulating ethanol-induced liver damage as well as the contribution of fibrotic...
- The National Institute on Alcohol Abuse and Alcoholism (NIAAA) awarded a $1,376,398.00 Project Grant under CFDA 93.273 Alcohol Research Programs to Yale University. The 5-year grant, with a start date of June 1, 2025 and an ultimate completion date of February 28, 2030, supports the development of a humanized mouse model to study the key features of alcohol-associated hepatitis (AAH), a leading cause of liver-related deaths worldwide. The project aims to create a fully humanized mouse liver...
- The National Institute on Alcohol Abuse and Alcoholism (NIAAA), under the Alcohol Research Programs (CFDA 93.273), awarded a $152,643 Project Grant to Yale University on September 5, 2025 for the project "NOVEL GLUN2BR RADIOLIGAND FOR PET NEUROIMAGING IN ALCOHOL USE DISORDER". The project aims to conduct the first-in-human characterization of a novel positron emission tomography (PET) radioligand, (S)-[18F]OF-NB1, to quantify the role and availability of the GLUN2B subunit-containing...
- This Project Grant award from the National Institute on Alcohol Abuse and Alcoholism (NIAAA), under the Alcohol Research Programs (CFDA 93.273), provides $459,707 to The Medical University of South Carolina to investigate the effects of chronic intermittent ethanol (CIE) exposure on lateral orbitofrontal cortex (LOFC) astrocyte physiology, structure, and gene expression, and how these changes contribute to the excessive drinking observed in alcohol dependence. The research aims to address a...
- This Project Grant award in the amount of $404,508.00 was provided by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) under the Alcohol Research Programs (CFDA 93.273) federal grant program. The award aims to examine interleukin-1β (IL-1β) synaptic regulation and its role in cognitive impairment during early withdrawal and protracted abstinence from chronic alcohol exposure in male and female mice. The overarching goal is to determine the neuroimmune mechanisms by which chronic...
- This Project Grant award of $248,844 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) under the Alcohol Research Programs (CFDA 93.273) will support research to investigate whether blood gene expression profiles can serve as a non-invasive proxy for brain tissue in the development of diagnostic and treatment tools for alcohol use disorder (AUD). The primary objectives are to determine if there is a biological signature of AUD in human blood samples, and whether blood gene...
- This $559,180 Project Grant award from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) under the Alcohol Research Programs (CFDA 93.273) will enable the Research Triangle Institute (RTI International) to conduct multi-omic data integration and translational research on alcohol use disorder (AUD) with and without comorbid cigarette smoking. The key objectives are to identify neurobiological factors underlying AUD with and without cigarette smoking by investigating AUD-associated...
- The National Institute on Alcohol Abuse and Alcoholism (NIAAA), under the Alcohol Research Programs (CFDA 93.273), awarded a $498,002 Project Grant to the University of Illinois to conduct a 3-year study aimed at increasing alcohol abstinence among young adults with alcohol use disorder (AUD). The project, titled "STUDY AIMED AT INCREASING ALCOHOL ABSTINENCE (DEDICATE)", has two primary goals: (1) to test the efficacy of combining contingency management (CM) with problem-solving...
- This federal Project Grant award of $700,000.00 from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859) supports research to investigate the neurophysiological and genetic factors underlying binge drinking and alcohol use disorder. The key objectives are to leverage advanced neurophysiological techniques, including monosynaptic circuit labeling, optogenetic manipulation, and single-nucleus RNA sequencing, to...
CHIMERA-BONCAT: A NOVEL IN VIVO MODEL FOR IN-DEPTH CHARACTERIZATION OF THE HUMAN MICROGLIAL RESPONSE TO ALCOHOL - ABSTRACT ALCOHOL USE DISORDER (AUD) IS A SIGNIFICANT HEALTH CRISIS IN THE U.S., WHICH CAN RESULT IN NUMEROUS DAMAGING EFFECTS ON MULTIPLE ORGAN SYSTEMS INCLUDING THE BRAIN. ALTHOUGH VARIOUS CELL-TYPE-SPECIFIC AND ASSOCIATED MOLECULAR MECHANISMS UNDERLIE THESE NEGATIVE EFFECTS OF ALCOHOL IN THE BRAIN, THE NEUROIMMUNE RESPONSE, MODULATED IN PART BY MICROGLIA, HAS BEEN CONSIDERED A KEY PATHOLOGICAL DRIVER DURING ALCOHOL MISUSE. MICROGLIA, THE RESIDENT IMMUNE CELLS OF THE BRAIN, EXHIBIT A BROAD RANGE OF REACTIVITY FROM ALCOHOL EXPOSURE THAT IS CONTEXT- DEPENDENT; HOWEVER, THE FULL MOLECULAR LANDSCAPE OF THIS PHENOTYPIC SPECTRUM HAS YET TO BE FULLY CHARACTERIZED. ADDITIONALLY, MOST STUDIES THAT HAVE INVESTIGATED ALCOHOL-INDUCED MICROGLIAL REACTIVITY UTILIZE RODENT ANIMAL MODELS, WHICH HAVE LIMITED TRANSLATIONAL RELEVANCE TO NEUROIMMUNE-SPECIFIC OUTCOMES RELATED TO AUD IN HUMANS. TO ADDRESS THESE LIMITATIONS, WE PROPOSE A NOVEL IN VIVO MODEL CALLED CHIMERA-BIOORTHOGONAL NON- CANONICAL AMINO ACID TAGGING (BONCAT), WHICH WILL ALLOW COMPREHENSIVE, UNBIASED, AND CELL-TYPE-SPECIFIC CHARACTERIZATION OF THE HUMAN MICROGLIAL RESPONSE TO ALCOHOL IN AN IN VIVO ENVIRONMENT. IN ORDER TO RIGOROUSLY TEST THE UTILITY OF THIS INNOVATIVE MODEL TO STUDY HUMAN MICROGLIAL REACTIVITY TO ALCOHOL AT THE PROTEOME LEVEL, WE HAVE DEVELOPED THE FOLLOWING SPECIFIC AIMS: 1) CHARACTERIZATION OF HUMAN MICROGLIA DERIVED FROM INDUCED PLURIPOTENT STEM CELLS (IPSCS) BEARING MUTANT METRS (AN ENZYME NECESSARY TO CARRY OUT THE BONCAT APPROACH) AND DETERMINE IN VITRO REACTIVITY TO ALCOHOL AND 2) CHARACTERIZATION OF THE HUMAN MICROGLIAL RESPONSE TO ALCOHOL IN VIVO USING CHIMERA-BONCAT, WHICH WILL UTILIZE A CHIMERIC MOUSE MODEL WITH HUMAN MICROGLIA THAT ARE ENGINEERED FOR BONCAT LABELING. THIS PROJECT WILL BE THE FIRST OF ITS KIND TO INVESTIGATE ALCOHOL-INDUCED REACTIVITY OF HUMAN MICROGLIA USING AN IN VIVO CHIMERIC MODEL AS WELL AS A NOVEL APPROACH TO SELECTIVELY ENRICH HUMAN MICROGLIA FROM THE CHIMERIC MOUSE BRAIN FOR DOWNSTREAM PROTEOMIC ANALYSIS. THE RESULTS FROM THIS STUDY WILL PROVIDE KEY INSIGHTS INTO ALCOHOL-INDUCED PHENOTYPIC CHANGES THAT OCCUR IN HUMAN MICROGLIA WITH POTENTIALLY HIGHER TRANSLATIONAL VALUES COMPARED TO CONVENTIONAL MODELS.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $176.7k | 7/31/25 | ||
| Not listed | $214.4k | 8/7/24 |