Center for Alcohol Research in Epigenetics

表观遗传学酒精研究中心

基本信息

批准号：
10380645
负责人：
SUBHASH C. PANDEY
金额：
$ 25.97万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10380645
关键词：
Abstinence Administrator Advisory Committees Alcohol consumption Alcohol dependence Alcohol withdrawal syndrome Alcoholism Alcohols Amygdaloid structure Animal Model Anxiety Area Autopsy Behavioral Behavioral Mechanisms Biological Markers Brain Brain region Cells Chemicals Clinical Clinical Research Communication Communities Community Outreach DNA DNA Methylation Data Data Analyses Development Doctor of Philosophy Ensure Epigenetic Process Ethanol Ethanol dependence Evaluation Funding Future Gene Expression General Population Genomics Goals Head High-Throughput Nucleotide Sequencing Hippocampus (Brain)Histone Deacetylase Histone Deacetylase Inhibitor Histones Human Individual Institution Interdisciplinary Study International Leadership Maintenance Medical Students Medicine Mental Depression Modeling Modification Molecular Monitor Motivation National Institute on Alcohol Abuse and Alcoholism Neurosciences Occupational activity of managing finances Peripheral Pharmaceutical Preparations Pilot Projects Play Post-Traumatic Stress Disorders Prefrontal Cortex Progress Reports RNA Rattus Research Research Personnel Research Project Grants Resources Rodent Role Scientist Services Testing Training Programs Traumatic Brain Injury United States National Institutes of Health Ventral Tegmental Area Vorinostat Work alcohol effect alcohol research alcohol use disorder behavioral phenotyping brain circuitry brain tissue chromatin remodeling collaborative environment college comorbidity data repository demethylation design doctoral student drinking epigenome epigenomics epitranscriptome epitranscriptomics genome-wide high standard histone modification interest meetings member molecular targeted therapies multidisciplinary negative emotional state neural circuit novel novel therapeutics outreach program prevent programs stem transcriptome transcriptomics whole genome

Abstinence Administrator Advisory Committees Alcohol consumption Alcohol dependence Alcohol withdrawal syndrome Alcoholism Alcohols Amygdaloid structure Animal Model Anxiety Area Autopsy Behavioral Behavioral Mechanisms Biological Markers Brain Brain region Cells Chemicals Clinical Clinical Research Communication Communities Community Outreach DNA DNA Methylation Data Data Analyses Development Doctor of Philosophy Ensure Epigenetic Process Ethanol Ethanol dependence Evaluation Funding Future Gene Expression General Population Genomics Goals Head High-Throughput Nucleotide Sequencing Hippocampus (Brain)Histone Deacetylase Histone Deacetylase Inhibitor Histones Human Individual Institution Interdisciplinary Study International Leadership Maintenance Medical Students Medicine Mental Depression Modeling Modification Molecular Monitor Motivation National Institute on Alcohol Abuse and Alcoholism Neurosciences Occupational activity of managing finances Peripheral Pharmaceutical Preparations Pilot Projects Play Post-Traumatic Stress Disorders Prefrontal Cortex Progress Reports RNA Rattus Research Research Personnel Research Project Grants Resources Rodent Role Scientist Services Testing Training Programs Traumatic Brain Injury United States National Institutes of Health Ventral Tegmental Area Vorinostat Work alcohol effect alcohol research alcohol use disorder behavioral phenotyping brain circuitry brain tissue chromatin remodeling collaborative environment college comorbidity data repository demethylation design doctoral student drinking epigenome epigenomics epitranscriptome epitranscriptomics genome-wide high standard histone modification interest meetings member molecular targeted therapies multidisciplinary negative emotional state neural circuit novel novel therapeutics outreach program prevent programs stem transcriptome transcriptomics whole genome

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项目摘要

Project Summary: The Administrative Core of the P50 application on “Center for Alcohol Research in Epigenetics (CARE)” will coordinate multiple research and pilot projects and the Epigenetics and Behavioral Cores comprising of multidisciplinary research teams. The goal of the CARE to evaluate ethanol-induced epigenetic mechanisms (histone modifications and DNA methylation/demethylation) of transcriptomic and epitranscriptomic (RNA modifications) changes in specific brain circuitries during the development of alcohol use disorder (AUD). The overall hypothesis is that ethanol induces transcriptomic changes due to chromatin remodeling (histone & DNA chemical modifications) in specific neurocircuitries, and that these drive behavioral phenotypes including anxiety, depression, motivation, and escalated ethanol intake. To test this hypothesis, we have selected four interrelated research projects and two pilot projects on epigenetics and epitranscriptomics and set-up two resource cores i.e., Epigenetics and Behavioral Cores utilizing a rat model of alcohol dependence and human postmortem brains to discover integrated and functional facets of the epigenome in AUD. Our approach takes into consideration that both negative and positive effects of ethanol contribute to the initiation and maintenance of AUD. Research projects #1, #2, #3 and #4 will evaluate the status of the epigenome and its role in the altered transcriptome in the ventral tegmental area (VTA), amygdala, hippocampus, and prefrontal cortex (PFC). We will examine these in relation to both the euphoric and dysphoric (negative emotional state) aspects of ethanol dependence and withdrawal. We also propose two pilot projects; one on ethanol-induced epigenetic changes in peripheral cells in humans and rodents serving as biomarkers of active drinking and abstinence. A second pilot project will examine the novel area of the epitranscritome in AUD. The Administrative Core will provide administrative leadership, overall management, and oversight in order to enhance our understanding of the genomic and epigenomic basis of AUD. This Core will also manage community outreach and training programs within CARE. Overall, the Administrative Core will maintain a productive and interactive environment to enhance epigenetic research in AUD. This multidisciplinary endeavor will help us identify novel therapeutic molecular targets to prevent and treat AUD. !

项目摘要： P50申请的行政核心在“表观遗传学中心（CARE）”上的申请协调多个研究和试点项目，以及完成的表观遗传学和行为核心完成多学科研究团队。评估乙醇引起的表观遗传机制的目的（组蛋白的修饰和DNA甲基化/脱甲基化）转录组和表面参考（RNA）修改）在饮酒障碍（AUD）发展过程中特定脑回路的变化。总体假设是乙醇诱导由于染色质重塑引起的转录组变化（组蛋白和DNA 化学修饰）在特定的神经记录中，并且这些驱动行为表型，包括动画，抑郁，动机和升级的乙醇摄入量。为了检验这一假设，我们选择了四个相互关联研究项目和两个有关表观遗传学和表面见解组学的试点项目，并设置了两个资源核心，即使用酒精依赖大鼠模型和人类后大脑对表观遗传学和行为核心在AUD中发现表观基因组的集成和功能性方面。我们的方法考虑到乙醇的负和积极影响有助于AUD的主动性和维护。研究项目＃1，＃2，＃3和＃4将评估表观基因组的状态及其在更改的转录组中的作用腹侧对盖区（VTA），杏仁核，海马和前额叶皮层（PFC）。我们将检查这些关于乙醇依赖的欣快感和烦躁不安（负面情绪状态）方面以及提取。我们还提出了两个试点项目。一个关于乙醇诱导的外周细胞的表观遗传变化在人类和啮齿动物中，作为活跃饮酒和戒酒的生物标志物。第二个试点项目将检查AUD中上皮转运的新区域。行政核心将提供管理领导，整体管理和监督，以增强我们对基因组和 AUD的表观基因组基础。该核心还将在护理中管理社区外展和培训计划。总体而言，行政核心将保持富有成效的互动环境以增强表观遗传 Aud的研究。这项多学科的努力将有助于我们确定新型的热分子靶标预防和治疗aud。呢