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.

抽象的 饮酒障碍是退伍军人的主要健康问题之一，以及一般性的 人口。 VA任务不可或缺的一部分是为VA患者提供护理 从饮酒和/或没有合并焦虑的毒品滥用问题。总体目的 Pandey博士的研究计划是阐明是基于的表观遗传机制 酒精使用障碍（AUD）和合并焦虑症的病理生理。很多的 Pandey博士实验室进行的研究发现，乙醇暴露会导致 涉及组蛋白乙酰化/甲基化，DNA甲基化和非 - 非 - 非遗传学改变 编码在杏仁核中调节基因表达的RNA。他的主要重点 实验室是这些表观遗传机制和非编码RNA的作用 特定神经循环的转录组变化，特别是在杏仁核中， 随后的诱导行为表型是基于乙醇戒断的基础的 诱导动画和动画和aud的合并症。他的实验室调查了 急性和慢性酒精暴露和戒断的差异表观遗传效应 早期生命和成人动物模型以及暴露于酒精的成年动物中 青少年。然后，这些发现使用后尸体大脑转化为人类 除了他自己的实验室研究，博士 潘迪（Pandey 该领域的一代和现任研究人员，并参与了许多协作 与VA和UIC研究人员的研究。综上所述，这些研究项目正在塑造 该领域对AUD的理解，并将告知新型药理的发展 在退伍军人和没有合并焦虑的情况下，对AUD治疗的干预措施 一般人口。