Systems and Circuits Systems and Circuits
Areas of Research: Systems and Circuits
Neurodevelopment, stress, and transcriptomic regulation
My laboratory studies the neurobiological mechanisms through which early environmental experiences are encoded and maintained into adulthood to have long-lasting impact on behavior. In particular, we are interested in understanding how early life stress increases risk for depression, addiction, and other psychiatric syndromes. This research is translationally motivated by the robust clinical finding that child maltreatment and other forms of early life stress increase the lifetime risk of depression and other mood, anxiety, and drug disorders by 2-4 -fold. Studies in humans and animals suggest that early life stress sensitizes individuals to exposures such as stress encountered later in life. To understand the neurobiological mechanisms underlying this latent behavioral vulnerability, we are integrating a range of technical approaches including rodent behavior, RNA and chromatin sequencing and bioinformatic analysis, in vivo cell-specific gene manipulation, and high-resolution imaging. By understanding how early life stress affects brain development at multiple levels - epigenetic and molecular, neuroendocrine, cells and circuits - we ultimately hope to apply such knowledge towards innovative therapies relevant to individuals who experienced childhood stress and trauma.
- Peña CJ, Kronman HG, Walker DM, Cates HM, Bagot RC, Purushothaman I, Issler O, Loh YE, Leong T, Kiraly DD, Goodman E, Neve RL, Shen L, Nestler EJ. (2017) Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2. Science, 356(6343):1185-1188
- Bagot RC, Cates HM, Purushothaman I, Vialou V, Heller EA, Yieh L, LaBonté B, Peña CJ, Shen L, Wittenberg GM, Nestler EJ. (2017) Ketamine and Imipramine Reverse Transcriptional Signatures of Susceptibility and Induce Resilience-Specific Gene Expression Profiles. Biological Psychiatry, 81(4):285-295.
- Heller EA, Cates HM, Peña CJ, Sun H, Shao N, Feng J, Golden SA, Herman JP, Walsh JJ, Mazei-Robison M, Ferguson D, Knight S, Gerber MA, Nievera C, Han MH, Russo SJ, Tamminga CS, Neve RL, Shen L, Zhang HS, Zhang F, Nestler EJ. (2014) Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors. Nature Neuroscience, 17(12):1720-7.
- Peña CJ and Nestler EJ. (2018) Progress in Epigenetics of Depression. Progress in Molecular Biology and Translational Science.