Eric J. Nestler is the Nash Family Professor of Neuroscience, Director of the Friedman Brain Institute, and Dean for Academic Affairs at the Icahn School of Medicine at Mount Sinai and Chief Scientific Officer of the Mount Sinai Health System.[1][2][3] His research is focused on a molecular approach to drug addiction and depression.
He is the co-author of four books and more than 725 peer-reviewed articles, and he serves as principal investigator or co-principal investigator on 8 NIH grants.
Nestler served as Director of the Abraham Ribicoff Research Facilities, as the Founding Director of the Division of Molecular Psychiatry at Yale until 2000, and as Chairman of the Department of Psychiatry at the University of Texas Southwestern Medical Center at Dallas.[1] He joined Mount Sinai in 2008. He has served on the Boards of Scientific Counselors of the National Institute on Drug Abuse and of the National Institute on Alcohol Abuse and Alcoholism, on the National Advisory Mental Health Council for the National Institute of Mental Health, the National Advisory Drug Abuse Council for the National Institute on Drug Abuse,[4] as Council Member of the American College of Neuropsychopharmacology (for which he served as president in 2011) and the Society for Neuroscience (for which he served as president in 2017). He is a member of the Scientific Advisory Board of the Brain & Behavior Research Foundation (BBRF, previously NARSAD) and of One Mind (previously International Mental Health Research Organization),[5] as well as a past member of the Board of Directors of the McKnight Endowment Fund in Neuroscience.[6] He was elected to the Institute of Medicine (now National Academy of Medicine) in 1998 and the American Academy of Arts and Sciences in 2005.[6][7]
Research
The Nestler laboratory's focus in neuropsychopharmacology and molecular neuroscience concentrates on forming a molecular approach to psychiatry and furthering the understanding of the molecular basis of both depression and drug addiction, using animal models to study the way drug use or stress affects the brain.[1] His addiction research largely centers around several transcription factors, including ΔFosB and CREB (master control proteins that induce addiction or depression in vulnerable individuals or resistance to these syndromes in resilient individuals) and the associated epigenetic remodeling that occurs in specific neuronal or glial cell types in the brain. A major goal is to identify the ‘chromatin scars’—long lasting epigenetic changes at specific genomic loci—that mediate lifelong changes in disease vulnerability. Among the prominent targets of this work are medium spiny neurons of the nucleus accumbens and pyramidal neurons in prefrontal cortex and ventral hippocampus.[3][8][9] The Nestler laboratory has driven innovative use of viral-mediated gene transfer, inducible, cell-type specific mutations in mice, and locus-specific epigenome editing to establish causal links between molecular and behavioral phenomena in animal models.[8][9][10] The laboratory also makes creative use of advanced machine learning approaches to derive novel biological insight from large sequencing datasets.
Awards
Dr. Nestler's awards and honors include the Pfizer Scholars Award (1987), the Sloan Research Fellowship (1987), the McKnight Scholar Award (1989), the Jordi-Folch-Pi Memorial Award from the American Society of Neurochemistry (1990), the Efron Award of the American College of Neuropsychopharmacology (1994), the Pasarow Foundation Award for Neuropsychiatric Research (1998), the NARSAD Distinguished Investigator Award (1996), the Bristol-Myers Squibb Freedom to Discover Neuroscience Research Grant (2004), the Patricia S. Goldman-Rakic Award and the Falcone Prize both from NARSAD (2008, 2009),[11] and the Rhoda and Bernard Sarnat International Prize in Mental Health from the Institute of Medicine (2010). He received an honorary doctorate from Uppsala University in Sweden in 2011, and the Anna Monika Prize in Depression Research (2012).[12][13]
In 2017, he was awarded the Wilbur Cross Medal by Yale University[14] for distinguished alumnus from the graduate school, and the Paul Hoch Distinguished Service Award from the American College of Neuropsychopharmacology.[15] In 2019, he received the Redelsheimer Distinguished Award in Biological Psychiatry from the Society for Biological Psychiatry. In 2020, Dr. Nestler received an honorary degree from Concordia University in Montreal as “a pioneer in depression and drug-addiction research and institutional advocacy for equity, diversity and inclusion. He is also the recipient of the Barbara Fish Memorial Award in 2021 for outstanding contributions to the field of neuroscience from the American College of Neuropsychopharmacology and the Peter Seeburg Integrative Neuroscience Prize in 2023 from the Schaller-Nikolich Foundation and Society for Neuroscience.
NIH-Funded Grants and Research
Role
Source, Title
Identifier
Principal Investigator
NIDA, Transcriptional Mechanisms of Drug Addiction[16]
P01 DA047233
Principal Investigator
NIMH, Pharmacological Actions of Stress & Antidepressants Treatments[17]
R01 MH51399
Principal Investigator
NIDA, Role of Neurotrophic Factors in the Actions of Drugs of Abuse[18]
R01 DA14133
Principal Investigator
NIDA, Molecular Studies of Cocaine Action in Brain[19]
R01 DA07359
Principal Investigator
NIMH, Pharmacological Actions of Stress & Antidepressants Treatments
R01 MH51399
Principal Investigator
NIMH, Epigenetic Mechanisms of Chronic Stress Action
R01 MH129306
Co-Principal Investigator
NIDA, Small Molecule Modulators of ∆FosB Function
R01 DA040621
Co-Principal Investigator
NIDA, Glial-Mediated Synaptic Remodeling in Drug Addiction
Labonté B, Engmann O, Purushothaman I, Menard C, Wang J, Tan C, Scarpa JR, Moy G, Loh YE, Cahill M, Lorsch ZS, Hamilton PJ, Calipari ES, Hodes GE, Issler O, Kronman H, Pfau M, Obradovic AL, Dong Y, Neve RL, Russo S, Kazarskis A, Tamminga C, Mechawar N, Turecki G, Zhang B, Shen L, Nestler EJ (2017). "Sex-specific transcriptional signatures in human depression". Nat Med. 23 (9): 1102–1111. doi:10.1038/nm.4386. PMC5734943. PMID28825715.
McClung CA, Nestler EJ (2003). "Regulation of gene expression and cocaine reward by CREB and ∆FosB". Nature Neuroscience. 6 (11): 1208–1215. doi:10.1038/nn1143. PMID14566342. S2CID38115726.
Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ (2006). "Sustained hippocampal chromatin regulation in hippocampus in a mouse model of depression and antidepressant action". Nature Neuroscience. 9 (4): 519–525. doi:10.1038/nn1659. PMID16501568. S2CID21547891.
^ abWhalley K (December 2014). "Psychiatric disorders: a feat of epigenetic engineering". Nat. Rev. Neurosci. 15 (12): 768–769. doi:10.1038/nrn3869. PMID25409693. Chronic exposure to stress or drugs of abuse causes widespread changes in the activity of chromatin remodelling enzymes. However, it has been difficult to determine the relative functional importance of drug- or stress-induced epigenetic modifications of individual genes. Nestler and colleagues have now employed gene- and brain-region-specific chromatin remodelling to examine the role of one particular gene, [ΔFosB], in addiction- and depression-related changes in the brain and behaviour. ... This study shows that single epigenetic modifications can modulate both [ΔFosB] expression and its behavioural effects. A similar approach may be used to target other genes of interest and elucidate further the changes in molecular pathways that underlie psychiatric disorders.
^Dennis S. Charney (2003). "Preface". In Charney, Dennis S. (ed.). Molecular neurobiology for the clinician. Washington, DC: American Psychiatric Pub. pp. xvi–xvii. ISBN9781585627332. Dr. Nestler, in Chapter 4, presents an extremely creative and potentially groundbreaking view of the molecular mechanisms and neural circuitry of reward and how they might relate to vulnerability to addictive behaviors. ... Dr. Nestler focuses on two transcription factors, CREB (cAMP response element binding protein) and ΔFosB
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