BLRD Research Career Scientist Award Application

BLRD 研究职业科学家奖申请

• 批准号: 10594004
• 负责人: SUBHASH C. PANDEY
• 金额: --
• 依托单位: JESSE BROWN VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2029-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10594004
• 关键词: ATAC-seq; Acute; Adolescence; Adolescent; Adult; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohol withdrawal syndrome; Amygdaloid structure; Animal Model; Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Area; Autopsy; Award; Behavior; Big Data; Brain; Caring; Cell physiology; ChIP-seq; Chemicals; Chronic; Clinical Research; DNA; DNA Methylation; Dependence; Development; Drug Addiction; Drug Design; Drug abuse; Education; Epigenetic Process; Event; Functional disorder; Funding; Future; Gene Expression; General Population; Genes; Genome; Grant; Health; Healthcare; Histone Acetylation; Histones; Human; Individual; Intervention; Laboratories; Laboratory Research; Life; Maintenance; Methylation; Mission; Modification; Molecular; National Institute on Alcohol Abuse and Alcoholism; Neurobiology; Neurosciences; Pathway interactions; Patient Care; Patients; Physiology; Population; Post-Traumatic Stress Disorders; Postdoctoral Fellow; Predisposition; Process; Research; Research Personnel; Research Project Grants; Research Training; Risk Factors; Role; Scientist; Series; Shapes; Symptoms; Synaptic plasticity; Training; Translating; Translations; United States National Institutes of Health; Untranslated RNA; Veterans; Work; adolescent alcohol exposure; adolescent binge drinking; alcohol abuse therapy; alcohol effect; alcohol exposure; alcohol research; alcohol use disorder; alcohol use initiation; anxiety-like behavior; behavioral phenotyping; brain circuitry; career; comorbidity; drinking behavior; experience; experimental study; mature animal; molecular targeted therapies; neural circuit; next generation; novel; pharmacologic; pre-doctoral; preclinical study; programs; substance use; therapeutic development; transcriptome sequencing; transcriptomics; underage drinking; withdrawal-induced anxiety

Abstract Alcohol use disorder is one of the major health concerns for veterans, as well as for the general population. An integral part of the mission of the VA is to provide care for VA patients suffering from alcohol and/or drug abuse problems with and without comorbid anxiety. The overall aim of Dr. Pandey’s research program is to elucidate the epigenetic mechanisms that underlie the pathophysiology of alcohol use disorder (AUD) and co-morbid anxiety disorders. Numerous studies performed by Dr. Pandey’s laboratory have found that ethanol exposure results in epigenetic alterations involving histone acetylation/methylation, DNA methylation, and non- coding RNAs that modulate gene expression in the amygdala. The major focus of his laboratory is the role of these epigenetic mechanisms and non-coding RNAs in transcriptomic changes in specific neural circuitries, particularly in the amygdala, and the subsequent induction of behavioral phenotypes that underlie ethanol withdrawal- induced anxiety and the co-morbidity of anxiety and AUD. His lab investigates the differential epigenetic effects of acute and chronic alcohol exposure and withdrawal in both early-life and adult animal models, as well as in adult animals that were exposed to alcohol in adolescence. These findings are then translated to humans using postmortem brains of individuals with AUD and control subjects. In addition to his own laboratory’s research, Dr. Pandey has programmed several events for the educational enrichment of next- generation and current researchers in the field and is involved in many collaborative studies with VA and UIC researchers. Taken together, these research projects are shaping the field’s understanding of AUD and will inform the development of novel pharmacological interventions for the treatment of AUD, with and without comorbid anxiety, in veterans and in the general population.

摘要 酒精使用障碍是退伍军人和一般人的主要健康问题之一 人口VA的使命的一个组成部分是为患有 酒精和/或药物滥用问题，有或没有共病焦虑。的总体目标 博士Pandey的研究计划是阐明表观遗传机制， 酒精使用障碍（AUD）和共病焦虑障碍的病理生理学。许多 Pandey博士实验室进行的研究发现， 表观遗传学改变涉及组蛋白乙酰化/甲基化、DNA甲基化和非 编码调节杏仁核基因表达的RNA。他的主要重点是 这些表观遗传机制和非编码RNA在 特定神经回路的转录组学变化，特别是杏仁核，以及 随后诱导的行为表型是乙醇戒断的基础- 诱发性焦虑和焦虑与AUD的共病。他的实验室调查了 急性和慢性酒精暴露和戒断在两种情况下的不同表观遗传效应 早期和成年动物模型，以及暴露于酒精的成年动物， 青春期这些发现然后被翻译到人类使用死后的大脑， AUD患者和对照受试者。除了他自己的实验室的研究，博士。 Pandey为下一个教育丰富计划了几个活动- 一代和当前的研究人员在该领域，并参与了许多合作 与VA和UIC研究人员的研究。综合起来，这些研究项目正在形成 该领域对AUD的理解，并将为新型药理学的开发提供信息。 在退伍军人和老年人中治疗AUD（伴或不伴共病焦虑）的干预措施 一般人口。