Low-input profiling of brain-region and cell-type specific epigenomic dynamics to understand gene-environment interactions in opioid addiction

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Project Summary Addiction is a physiological process that involves changes in neural plasticity in response to drugs of abuse. Although genetic factors have been recognized as a strong influence on the susceptibility to addition, environmental stimuli and life experiences also form important risk factors. There has been increasing evidence that epigenetic mechanisms mediate the influence of environmental factors on gene activities in the CNS and therefore are likely involved in brain development and pathology of drug abuse. Furthermore, DNA sequence variation is known to impact epigenetic landscape, chromatin structures and molecular phenotypes via influencing the cis-regulatory elements such as promoters and enhancers. In this project, we are interested in probing how epigenomic mechanisms mediate environmental factors such as adolescent drug exposure during addiction development and how a genetic variant affects such mediation. We will use the state-of-the-art omic and bioinformatic technologies to decipher the links among genetics, epigenetics and environmental factors involved in opioid addiction. The low-input approaches will allow us to characterize epigenomic and transcriptomic dynamics with cell-type and brain-region specificity.