Eric J. Nestler

Last updated
Eric J. Nestler
Nestler headshot(39).png
NationalityAmerican
Alma mater
Scientific career
Fields Molecular neurobiology
Molecular neuropharmacology
Clinical neuroscience
Institutions

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.

Contents

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.

Biography

Education

Nestler is a graduate of Herricks High School in New Hyde Park, New York. He received his B.A., his Ph.D. and his M.D. from Yale University, where he performed his doctoral research in the laboratory of Paul Greengard. He completed his residency in psychiatry at both McLean Hospital in Massachusetts and Yale in 1987. [1]

Career

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

RoleSource, TitleIdentifier
Principal InvestigatorNIDA, Transcriptional Mechanisms of Drug Addiction [16] P01 DA047233
Principal InvestigatorNIMH, Pharmacological Actions of Stress & Antidepressants Treatments [17] R01 MH51399
Principal InvestigatorNIDA, Role of Neurotrophic Factors in the Actions of Drugs of Abuse [18] R01 DA14133
Principal InvestigatorNIDA, Molecular Studies of Cocaine Action in Brain [19] R01 DA07359
Principal InvestigatorNIMH, Pharmacological Actions of Stress & Antidepressants TreatmentsR01 MH51399
Principal InvestigatorNIMH, Epigenetic Mechanisms of Chronic Stress ActionR01 MH129306
Co-Principal InvestigatorNIDA, Small Molecule Modulators of ∆FosB FunctionR01 DA040621
Co-Principal InvestigatorNIDA, Glial-Mediated Synaptic Remodeling in Drug AddictionR01 DA040620

Publications (partial list)

Books

Nestler is the author (with Dennis S. Charney, Pamela Sklar and Joseph D. Buxbaum) of Neurobiology of Mental Illness (5th edition; ISBN   0195189809), of Nestler, Hyman and Malenka’sMolecular Neuropharmacology (with Paul J. Kenny, Scott J. Russo and Anne Schaefer); 4th edition; ISBN   978-1-26045-690-5) and two additional books published earlier: Protein Phosphorylation in the Nervous System (with Paul Greengard; ISBN   978-0-47180-558-8) and Molecular Foundations of Psychiatry (with Steven E. Hyman; ISBN   978-0-88048-353-7). He is also the author of more than 725 peer-reviewed publications and reviews. [20] He directs six research projects funded by the National Institute on Drug Abuse and the National Institute of Mental Health. He also serves as director of the Depression Task Force of the Hope for Depression Research Foundation.

Articles

Nestler has been cited more than 134,000 times and has an H-index of 188. [21] [20]

Related Research Articles

The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the forebrain. The ventral striatum includes the nucleus accumbens and the olfactory tubercle.

Dynorphins (Dyn) are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 (PC2), multiple active peptides are released: dynorphin A, dynorphin B, and α/β-neoendorphin. Depolarization of a neuron containing prodynorphin stimulates PC2 processing, which occurs within synaptic vesicles in the presynaptic terminal. Occasionally, prodynorphin is not fully processed, leading to the release of "big dynorphin". "Big dynorphin" is a 32-amino acid molecule consisting of both dynorphin A and dynorphin B.

<span class="mw-page-title-main">Protein c-Fos</span> Mammalian protein found in Homo sapiens

Protein c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It is encoded in humans by the FOS gene. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV. It is a part of a bigger Fos family of transcription factors which includes c-Fos, FosB, Fra-1 and Fra-2. It has been mapped to chromosome region 14q21→q31. c-Fos encodes a 62 kDa protein, which forms heterodimer with c-jun, resulting in the formation of AP-1 complex which binds DNA at AP-1 specific sites at the promoter and enhancer regions of target genes and converts extracellular signals into changes of gene expression. It plays an important role in many cellular functions and has been found to be overexpressed in a variety of cancers.

<span class="mw-page-title-main">Reward system</span> Group of neural structures responsible for motivation and desire

The reward system is a group of neural structures responsible for incentive salience, associative learning, and positively-valenced emotions, particularly ones involving pleasure as a core component. Reward is the attractive and motivational property of a stimulus that induces appetitive behavior, also known as approach behavior, and consummatory behavior. A rewarding stimulus has been described as "any stimulus, object, event, activity, or situation that has the potential to make us approach and consume it is by definition a reward". In operant conditioning, rewarding stimuli function as positive reinforcers; however, the converse statement also holds true: positive reinforcers are rewarding.

<span class="mw-page-title-main">Methamphetamine</span> Central nervous system stimulant

Methamphetamine is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamphetamine was discovered in 1893 and exists as two enantiomers: levo-methamphetamine and dextro-methamphetamine. Methamphetamine properly refers to a specific chemical substance, the racemic free base, which is an equal mixture of levomethamphetamine and dextromethamphetamine in their pure amine forms, but the hydrochloride salt, commonly called crystal meth, is widely used. Methamphetamine is rarely prescribed over concerns involving human neurotoxicity and potential for recreational use as an aphrodisiac and euphoriant, among other concerns, as well as the availability of safer substitute drugs with comparable treatment efficacy such as Adderall and Vyvanse. Dextromethamphetamine is a stronger CNS stimulant than levomethamphetamine.

<span class="mw-page-title-main">JunD</span> Protein-coding gene in the species Homo sapiens

Transcription factor JunD is a protein that in humans is encoded by the JUND gene.

<span class="mw-page-title-main">EHMT2</span> Protein-coding gene in the species Homo sapiens

Euchromatic histone-lysine N-methyltransferase 2 (EHMT2), also known as G9a, is a histone methyltransferase enzyme that in humans is encoded by the EHMT2 gene. G9a deposits the mono- and di-methylated states of histone H3 at lysine residue 9 and lysine residue 27. The presence of H3K9me1/2 is usually associated with gene silencing.

<span class="mw-page-title-main">FOSB</span> Protein

Protein fosB, also known as FosB and G0/G1 switch regulatory protein 3 (G0S3), is a protein that in humans is encoded by the FBJ murine osteosarcoma viral oncogene homolog B (FOSB) gene.

<span class="mw-page-title-main">PPAR agonist</span> Drug

PPAR agonists are drugs which act upon the peroxisome proliferator-activated receptor. They are used for the treatment of symptoms of the metabolic syndrome, mainly for lowering triglycerides and blood sugar.

Cocaine addiction is the compulsive use of cocaine despite adverse consequences. It arises through epigenetic modification and transcriptional regulation of genes in the nucleus accumbens.

Behavioral epigenetics is the field of study examining the role of epigenetics in shaping animal and human behavior. It seeks to explain how nurture shapes nature, where nature refers to biological heredity and nurture refers to virtually everything that occurs during the life-span. Behavioral epigenetics attempts to provide a framework for understanding how the expression of genes is influenced by experiences and the environment to produce individual differences in behaviour, cognition, personality, and mental health.

Addiction is a state characterized by compulsive engagement in rewarding stimuli, despite adverse consequences. The process of developing an addiction occurs through instrumental learning, which is otherwise known as operant conditioning.

<span class="mw-page-title-main">Alcino J. Silva</span> American neuroscientist (born 1961)

Alcino J. Silva is a Portuguese-American neuroscientist who was the recipient of the 2008 Order of Prince Henry and elected as a fellow of the American Association for the Advancement of Science in 2013 for his contributions to the molecular cellular cognition of memory, a field he pioneered with the publication of two articles in Science in 1992.

Addiction vulnerability is an individual's risk of developing an addiction during their lifetime. There are a range of genetic and environmental risk factors for developing an addiction that vary across the population. Genetic and environmental risk factors each account for roughly half of an individual's risk for developing an addiction; the contribution from epigenetic risk factors to the total risk is unknown. Even in individuals with a relatively low genetic risk, exposure to sufficiently high doses of an addictive drug for a long period of time can result in an addiction. In other words, anyone can become an individual with a substance use disorder under particular circumstances. Research is working toward establishing a comprehensive picture of the neurobiology of addiction vulnerability, including all factors at work in propensity for addiction.

<span class="mw-page-title-main">Antonello Bonci</span> American physician

Antonello Bonci is an Italian-American neurologist and a neuropsychopharmacologist specialized in the long-term effects of drug exposure on the brain. In August 2019, he became president of Global Institutes on Addictions Miami. Bonci was previously the scientific director of the National Institute on Drug Abuse and a professor at the University of California, San Francisco.

<span class="mw-page-title-main">Yasmin Hurd</span> American neuroscientist

Yasmin Hurd is the Ward-Coleman Chair of Translational Neuroscience and the Director of the Addiction Institute at Mount Sinai. Hurd holds appointments as faculty of Neuroscience, Psychiatry, Pharmacology and Systems Therapeutics at the Icahn School of Medicine at Mount Sinai in New York City and is globally recognized for her translational research on the underlying neurobiology of substance use disorders and comorbid psychiatric disorders. Hurd's research on the transgenerational effects of early cannabis exposure on the developing brain and behavior and on the therapeutic properties of cannabidiol has garnered substantial media attention. In 2017, Dr. Hurd was elected to the National Academy of Medicine and, in 2022, Dr. Hurd was elected to the National Academy of Sciences (NAS).

<span class="mw-page-title-main">Gustavo Turecki</span> Canadian psychiatrist and academic

Gustavo Turecki is a Canadian psychiatrist, suicidologist, neuroscientist who is a professor at McGill University in Montreal, Quebec, Canada. He holds a Tier 1 Canada Research Chair Tier in Major Depressive Disorder and Suicide. He is the sitting Chair of the Department of Psychiatry at McGill University, the Scientific Director of the Douglas Research Centre, and the Psychiatrist-in-Chief of the Centre intégré universitaire de santé et de services sociaux de l’Ouest-de-l’Île-de-Montréal. He works at the Douglas Mental Health University Institute, where he heads both the McGill Group for Suicide Studies and the Depressive Disorders Program, and is the co-director of the Douglas Bell-Canada Brain Bank.

Epigenetics of depression is the study of how epigenetics contribute to depression.

H3K9me2 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the di-methylation at the 9th lysine residue of the histone H3 protein. H3K9me2 is strongly associated with transcriptional repression. H3K9me2 levels are higher at silent compared to active genes in a 10kb region surrounding the transcriptional start site. H3K9me2 represses gene expression both passively, by prohibiting acetylation as therefore binding of RNA polymerase or its regulatory factors, and actively, by recruiting transcriptional repressors. H3K9me2 has also been found in megabase blocks, termed Large Organised Chromatin K9 domains (LOCKS), which are primarily located within gene-sparse regions but also encompass genic and intergenic intervals. Its synthesis is catalyzed by G9a, G9a-like protein, and PRDM2. H3K9me2 can be removed by a wide range of histone lysine demethylases (KDMs) including KDM1, KDM3, KDM4 and KDM7 family members. H3K9me2 is important for various biological processes including cell lineage commitment, the reprogramming of somatic cells to induced pluripotent stem cells, regulation of the inflammatory response, and addiction to drug use.

Mary Kay Lobo is an American psychiatric neuroscientist who is a Professor of Neurobiology at the University of Maryland School of Medicine. Her research considers the molecular mechanisms that underpin drug addiction and depression. She was named a finalist in the 2011 Blavatnik Awards for Young Scientists.

References

  1. 1 2 3 4 "Mount Sinai Hospital Doctor Profile" . Retrieved 9 June 2014.
  2. ↑ "McGraw Hill Medical". Archived from the original on 14 July 2014. Retrieved 9 June 2014.
  3. 1 2 "Mount Sinai's Eric Nestler headlining first of new lecture series hosted by School of Neuroscience". www.neuroscience.vt.edu. Retrieved 2020-05-24.
  4. ↑ "National Institute on Drug Abuse". Archived from the original on 14 July 2014. Retrieved 9 June 2014.
  5. ↑ "International Mental Health Research Organization". Archived from the original on 14 July 2014. Retrieved 9 June 2014.
  6. 1 2 "The McKnight Endowment Fund for Neuroscience" . Retrieved 9 June 2014.
  7. ↑ "Center for Brain Health". Archived from the original on 4 March 2016. Retrieved 9 June 2014.
  8. 1 2 Whalley K (December 2014). "Psychiatric disorders: a feat of epigenetic engineering". Nat. Rev. Neurosci. 15 (12): 768–769. doi: 10.1038/nrn3869 . PMID   25409693. 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.
  9. 1 2 Heller, Elizabeth A; et al. (2014). "Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors". Nature Neuroscience. 17 (12): 1720–1727. doi:10.1038/nn.3871. ISSN   1097-6256. PMC   4241193 . PMID   25347353.
  10. ↑ Dennis S. Charney (2003). "Preface". In Charney, Dennis S. (ed.). Molecular neurobiology for the clinician. Washington, DC: American Psychiatric Pub. pp. xvi–xvii. ISBN   9781585627332. 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
  11. ↑ "NARSAD". Archived from the original on 7 July 2014. Retrieved 9 June 2014.
  12. ↑ "Max Planck Institute of Psychiatry" . Retrieved 9 June 2014.
  13. ↑ "New York Social Diary". 2008-10-23. Archived from the original on 10 July 2014. Retrieved 9 June 2014.
  14. ↑ "Yale Graduate School honors four alumni with Wilbur Cross Medals". Archived from the original on 11 October 2022. Retrieved 3 January 2017.
  15. ↑ "Eric Nestler given the ACNP Paul Hoch Distinguished Service Award". Archived from the original on 4 January 2018. Retrieved 3 January 2017.
  16. ↑ Nestler EJ (2001). "Molecular neurobiology of addiction". Am J Addict. 10 (3): 201–17. doi:10.1080/105504901750532094. PMID   11579619.
  17. ↑ Malberg JE, Eisch AJ, Nestler EJ, Duman RS (December 2000). "Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus". J. Neurosci. 20 (24): 9104–10. doi:10.1523/JNEUROSCI.20-24-09104.2000. PMC   6773038 . PMID   11124987.
  18. ↑ "drugabuse.gov". Archived from the original on 14 July 2014. Retrieved 9 June 2014.
  19. ↑ "Labome". Archived from the original on 14 July 2014. Retrieved 9 June 2014.
  20. 1 2 "PubMed". National Institutes of Health. Retrieved 28 September 2017.
  21. ↑ "Eric Nestler - Google Scholar Citations". scholar.google.com. Retrieved 2020-05-23.
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