BLRD Research Career Scientist Award Application

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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.