Psychiatry, American Board of Psychiatry and Neurology
Addiction, Behavior, Depression, Epigenetics, Molecular Biology, Neuroscience, Synapses, Synaptic Plasticity, Synaptogenesis
Biophysics and Systems Pharmacology [BSP], Neuroscience [NEU]
MD, Yale University School of Medicine
PhD, Yale University
Yale University School of Medicine
Yale University School of Medicine
Yale University School of Medicine
Sarnat Prize, Institute of Medicine
American Academy of Arts and Science
Institute of Medicine
Nestler Lab, Laboratory of Molecular Psychiatry
Specific Clinical/Research Interest: Molecular neurobiology of drug addiction and depression; transcriptional and epigenetic regulation in the brain.
Our research focuses on identifying the neurobiological basis of drug addiction and depression in rodent models. We study the molecular and cellular changes that occur in regions of the brain important for reward and motivation in response to chronic administration of a drug of abuse or chronic exposure to stress. We are particularly interested in long-lasting changes that are mediated via alterations in gene expression and chromatin remodeling. The result of the research will guide future efforts toward the development of more effective treatments for addiction and depression.
For a complete list of publications, please visit Selected Publications.
For more, please visit the Nestler Lab.
Bagot RC, Cates HM, Purushothaman I, Lorsch ZS, Walker DM, Wang J, Huang X, Schlüter OM, Maze I, Peña CJ, Heller EA, Issler O, Wang M, Song WM, Stein JL, Liu X, Doyle MA, Scobie KN, Sun HS, Neve RL, Geschwind D, Dong Y, Shen L, Zhang B, Nestler EJ. Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility. Neuron 2016 Jun; 90(5).
Heller EA, Hamilton PJ, Burek DD, Lombroso SI, Peña CJ, Neve RL, Nestler EJ. Targeted Epigenetic Remodeling of the Cdk5 Gene in Nucleus Accumbens Regulates Cocaine- and Stress-Evoked Behavior. The Journal of neuroscience : the official journal of the Society for Neuroscience 2016 Apr; 36(17).
Sun H, Martin JA, Werner CT, Wang ZJ, Damez-Werno DM, Scobie KN, Shao NY, Dias C, Rabkin J, Koo JW, Gancarz AM, Mouzon EA, Neve RL, Shen L, Dietz DM, Nestler EJ. BAZ1B in Nucleus Accumbens Regulates Reward-Related Behaviors in Response to Distinct Emotional Stimuli. The Journal of neuroscience : the official journal of the Society for Neuroscience 2016 Apr; 36(14).
Nestler EJ. Transgenerational Epigenetic Contributions to Stress Responses: Fact or Fiction?. PLoS biology 2016 Mar; 14(3).
Cahill ME, Bagot RC, Gancarz AM, Walker DM, Sun H, Wang ZJ, Heller EA, Feng J, Kennedy PJ, Koo JW, Cates HM, Neve RL, Shen L, Dietz DM, Nestler EJ. Bidirectional Synaptic Structural Plasticity after Chronic Cocaine Administration Occurs through Rap1 Small GTPase Signaling. Neuron 2016 Feb; 89(3).
Calipari ES, Bagot RC, Purushothaman I, Davidson TJ, Yorgason JT, Peña CJ, Walker DM, Pirpinias ST, Guise KG, Ramakrishnan C, Deisseroth K, Nestler EJ. In vivo imaging identifies temporal signature of D1 and D2 medium spiny neurons in cocaine reward. Proceedings of the National Academy of Sciences of the United States of America 2016 Mar; 113(10).
Wook Koo J, Labonté B, Engmann O, Calipari ES, Juarez B, Lorsch Z, Walsh JJ, Friedman AK, Yorgason JT, Han MH, Nestler EJ. Essential Role of Mesolimbic Brain-Derived Neurotrophic Factor in Chronic Social Stress-Induced Depressive Behaviors. Biological psychiatry 2015 Dec;.
Nestler EJ. Reflections on: . Brain research 2015 Dec;.
Nestler EJ. Role of the Brain's Reward Circuitry in Depression: Transcriptional Mechanisms. International review of neurobiology 2015; 124.
Nestler EJ, Peña CJ, Kundakovic M, Mitchell A, Akbarian S. Epigenetic Basis of Mental Illness. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry 2015 Oct;.
Sun H, Damez-Werno DM, Scobie KN, Shao NY, Dias C, Rabkin J, Koo JW, Korb E, Bagot RC, Ahn FH, Cahill ME, Labonté B, Mouzon E, Heller EA, Cates H, Golden SA, Gleason K, Russo SJ, Andrews S, Neve R, Kennedy PJ, Maze I, Dietz DM, Allis CD, Turecki G, Varga-Weisz P, Tamminga C, Shen L, Nestler EJ. ACF chromatin-remodeling complex mediates stress-induced depressive-like behavior. Nature medicine 2015 Oct; 21(10).
Vialou V, Thibault M, Kaska S, Cooper S, Gajewski P, Eagle A, Mazei-Robison M, Nestler EJ, Robison AJ. Differential induction of FosB isoforms throughout the brain by fluoxetine and chronic stress. Neuropharmacology 2015 Dec; 99.
Ohnishi YH, Ohnishi YN, Nakamura T, Ohno M, Kennedy PJ, Ohkawa Y, Nishi A, Neve R, Tsuzuki T, Nestler EJ. Correction: PSMC5, a 19S proteasomal ATPase, regulates cocaine action in the nucleus accumbens. PloS one 2015; 10(6).
Bagot RC, Parise EM, Peña CJ, Zhang HX, Maze I, Chaudhury D, Persaud B, Cachope R, Bolaños-Guzmán CA, Cheer JF, Deisseroth K, Han MH, Nestler EJ. Corrigendum: Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression. Nature communications 2015; 6.
Ohnishi YH, Ohnishi YN, Nakamura T, Ohno M, Kennedy PJ, Ohkawa Y, Yasuyuki O, Nishi A, Neve R, Tsuzuki T, Nestler EJ. PSMC5, a 19S Proteasomal ATPase, Regulates Cocaine Action in the Nucleus Accumbens. PloS one 2015; 10(5).
Dias C, Dietz D, Mazei-Robison M, Sun H, Damez-Werno D, Ferguson D, Wilkinson M, Magida J, Gao V, Neve R, Nestler EJ. Dishevelled-2 regulates cocaine-induced structural plasticity and Rac1 activity in the nucleus accumbens. Neuroscience letters 2015 Jun; 598.
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. Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors. Nature neuroscience 2014 Dec; 17(12).
Dias C, Feng J, Sun H, Shao NY, Mazei-Robison MS, Damez-Werno D, Scobie K, Bagot R, LaBonté B, Ribeiro E, Liu X, Kennedy P, Vialou V, Ferguson D, Peña C, Calipari ES, Koo JW, Mouzon E, Ghose S, Tamminga C, Neve R, Shen L, Nestler EJ. β-catenin mediates stress resilience through Dicer1/microRNA regulation. Nature 2014 Dec; 516(7529).
Maze I, Shen L, Zhang B, Garcia BA, Shao N, Mitchell A, Sun H, Akbarian S, Allis CD, Nestler EJ. Analytical tools and current challenges in the modern era of neuroepigenomics. Nature neuroscience 2014 Nov; 17(11).
Bagot RC, Labonté B, Peña CJ, Nestler EJ. Epigenetic signaling in psychiatric disorders: stress and depression. Dialogues in clinical neuroscience 2014 Sep; 16(3).
Dong Y, Nestler EJ. The neural rejuvenation hypothesis of cocaine addiction. Trends in pharmacological sciences 2014 Aug; 35(8).
Mitchell AC, Bharadwaj R, Whittle C, Krueger W, Mirnics K, Hurd Y, Rasmussen T, Akbarian S. The genome in three dimensions: a new frontier in human brain research. Biological psychiatry 2014 Jun; 75(12).
Shen L, Shao N, Liu X, Nestler E. ngs.plot: Quick mining and visualization of next-generation sequencing data by integrating genomic databases. BMC genomics 2014; 15.
Maze I, Noh KM, Soshnev AA, Allis CD. Every amino acid matters: essential contributions of histone variants to mammalian development and disease. Nature reviews. Genetics 2014 Apr; 15(4).
Maze I, Chaudhury D, Dietz DM, Von Schimmelmann M, Kennedy PJ, Lobo MK, Sillivan SE, Miller ML, Bagot RC, Sun H, Turecki G, Neve RL, Hurd YL, Shen L, Han MH, Schaefer A, Nestler EJ. G9a influences neuronal subtype specification in striatum. Nature neuroscience 2014 Apr; 17(4).
Vialou V, Bagot RC, Cahill ME, Ferguson D, Robison AJ, Dietz DM, Fallon B, Mazei-Robison M, Ku SM, Harrigan E, Winstanley CA, Joshi T, Feng J, Berton O, Nestler EJ. Prefrontal cortical circuit for depression- and anxiety-related behaviors mediated by cholecystokinin: role of ΔFosB. The Journal of neuroscience : the official journal of the Society for Neuroscience 2014 Mar; 34(11).
Scobie KN, Damez-Werno D, Sun H, Shao N, Gancarz A, Panganiban CH, Dias C, Koo J, Caiafa P, Kaufman L, Neve RL, Dietz DM, Shen L, Nestler EJ. Essential role of poly(ADP-ribosyl)ation in cocaine action. Proceedings of the National Academy of Sciences of the United States of America 2014 Feb; 111(5).
Feng J, Wilkinson M, Liu X, Purushothaman I, Ferguson D, Vialou V, Maze I, Shao N, Kennedy P, Koo J, Dias C, Laitman B, Stockman V, LaPlant Q, Cahill ME, Nestler EJ, Shen L. Chronic cocaine-regulated epigenomic changes in mouse nucleus accumbens. Genome biology 2014; 15(4).
Koo JW, Mazei-Robison MS, Chaudhury D, Juarez B, LaPlant Q, Ferguson D, Feng J, Sun H, Scobie KN, Damez-Werno D, Crumiller M, Ohnishi YN, Ohnishi YH, Mouzon E, Dietz DM, Lobo MK, Neve RL, Russo SJ, Han MH, Nestler EJ. BDNF is a negative modulator of morphine action. Science (New York, N.Y.) 2012 Oct; 338(6103).
Dietz DM, Sun H, Lobo MK, Cahill ME, Chadwick B, Gao V, Koo JW, Mazei-Robison MS, Dias C, Maze I, Damez-Werno D, Dietz KC, Scobie KN, Ferguson D, Christoffel D, Ohnishi Y, Hodes GE, Zheng Y, Neve RL, Hahn KM, Russo SJ, Nestler EJ. Rac1 is essential in cocaine-induced structural plasticity of nucleus accumbens neurons. Nature neuroscience 2012 Jun; 15(6).
Lobo MK, Covington HE, Chaudhury D, Friedman AK, Sun H, Damez-Werno D, Dietz DM, Zaman S, Koo JW, Kennedy PJ, Mouzon E, Mogri M, Neve RL, Deisseroth K, Han MH, Nestler EJ. Cell type-specific loss of BDNF signaling mimics optogenetic control of cocaine reward. Science (New York, N.Y.) 2010 Oct; 330(6002).
Maze I, Covington HE, Dietz DM, LaPlant Q, Renthal W, Russo SJ, Mechanic M, Mouzon E, Neve RL, Haggarty SJ, Ren Y, Sampath SC, Hurd YL, Greengard P, Tarakhovsky A, Schaefer A, Nestler EJ. Essential role of the histone methyltransferase G9a in cocaine-induced plasticity. Science (New York, N.Y.) 2010 Jan; 327(5962).
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