- Professor of Molecular Neuroscience
- (312) 413-4577
School of Public Health / Psychiatric Institute (SPHPI)
1601 W. Taylor St.
SPHPI MC 912
Chicago IL 60612
- Room #:257
Dr. Grayson is interested in epigenetic mechanisms associated with psychiatric disease. We study DNA methylation and other repressive epigenetic marks. In addition, we are currently investigating abnormal patterns of gene expression following chronic alcohol use and withdrawal. The overall goals are to identify new drug targets in each paradigm to establish new therapeutic approaches for treatment. He graduated from Michigan State University with a BS in Biochemistry and obtained the PhD in Biochemistry from Wayne State School of Medicine. After post-doctoral work at The Rockefeller University, he joined the faculty at Georgetown School of Medicine and the Fidia Georgetown Institute for the Neurosciences as an Assistant Professor in 1988. In 1995, Dr. Grayson moved to the Department of Psychiatry at the Allegheny University of the Health Sciences in Pittsburgh, PA. In 1998, he relocated to the Department of Psychiatry at the University of Illinois Chicago where he currently is a tenured Professor of Molecular Neuroscience. Dr. Grayson is also the Director of the Epigenetic Core of the Center for Alcohol Research in Epigenetics (CARE).
Dr. Grayson’s research interests include understanding the role of DNA methylation in modulating gene expression and the role that this epigenetic regulation may play in the pathophysiology of schizophrenia. While DNA methylating enzymes such as DNMT1 and DNMT3a are abundant in post-mitotic neurons, it is not clear whether methylation acts as a reversible switch to turn on and off genes and how this process varies between functionally distinct neuronal phenotypes. For example, which promoters are affected by changes in methylation in GABAergic interneurons vs. glutamatergic pyramidal neurons. Histone deacetylases (HDACs) are a class of histone modifying proteins associated with chromatin remodeling and gene silencing. HDAC inhibitors reverse this process and differentially activate gene expression in cell-type specific patterns. What determines whether a specific promoter will be expressed in response to different inhibitors and in which type of neuron? These questions are relevant to cognitive performance and behaviors relevant to psychiatric disease.
Identification of HDAC inhibitors that might prove therapeutically efficacious in the treatment of cognition in schizophrenia and Alzheimer’s disease; generation of a conditional mutant mouse that overexpresses DNMT1 and DNMT3a in GABA neurons of the brain; role of DNA methylation in the regulation of genes down-regulated in schizophrenia.
Dr. Grayson’s h-index is 58 and his i10-index is 124.
Grayson DR, Guidotti A (2018) DNA methylation in animal models of psychosis. Progress in Mol Biol & Trans Sci 157, in press.
Zhubi A, Chen Y, Guidotti A, Grayson DR (2017) Epigenetic regulation of RELN and GAD1 in the frontal cortex (FC) of autism spectrum disorder (ASD) subjects. Int J Dev Neurosci 62:63-72.
Gatta E, Auta J, Gavin DP, Bhaumik DK, Grayson DR, Pandey SC, Guidotti A (2017) Emerging Role of One-Carbon Metabolism and DNA Methylation Enrichment on δ-Containing GABAA Receptor Expression in the Cerebellum of Subjects with Alcohol Use Disorders (AUD). Int J Neuropsychopharmacol 20:1013-1026.
Gavin DP, Grayson DR, Varghese SP, Guizzetti M (2017) Chromatin Switches during Neural Cell Differentiation and Their Dysregulation by Prenatal Alcohol Exposure. Genes (Basel) 8: 137.
Grayson DR, Guidotti A (2016) Merging data from genetic and epigenetic approaches to better understand autistic spectrum disorder.
Dong E, Dzitoyeva SG, Matrisciano F, Tueting P, Grayson DR, Guidotti A (2015) Brain-derived neurotrophic factor epigenetic modifications associated with schizophrenia-like phenotype induced by prenatal stress in mice. Biol Psychiatry 77:589-596.
Guidotti A, Dong E, Kundakovic M, Satta R, Grayson DR, Costa E (2009) Characterization of the action of antipsychotic subtypes on valproate-induced chromatin remodeling TiPS 30:55-60.
Grayson DR, Kundakovic M, Sharma RP (2010) Is there a future for histone deacetylase inhibitors in the pharmacotherapy of psychiatric disorders? Mol Pharmacol 77:126-135.
Sharma RP, Gavin DP, Grayson DR (2010) CpG methylation in neurons: message, memory, or mask? Neuropsychopharmacol 35, 2009-2020. (PMID: 20631690)
Grayson DR (2010) Schizophrenia and the epigenetic hypothesis. Epigenomics 2:341-344 (invited editorial).
Dong E, Chen Y, Gavin DP, Grayson DR, Guidotti A (2010) Valproate induces DNA demethylation in nuclear extracts from adult mouse brain. Epigenetics 5:730-735. (PMID: 20716949)
Chen Y, Dong E, Grayson DR (2011) Analysis of the GAD1 promoter: trans-acting factors and DNA methylation converge on the 5' untranslated region. Neuropharmacology 60:1075-1087. (PMID: 20869372)
Guidotti A, Auta J, Chen Y, Davis JM, Dong E, Gavin DP, Grayson DR, Matrisciano F, Pinna G, Satta R, Sharma RP, Tremolizzo L, Tueting P (2011) Epigenetic GABAergic targets in schizophrenia and bipolar disorder. Neuropharmacology 60:1007-1016. (PMID: 21074545)
Redmond LC, Dumur CI, Archer KJ, Grayson DR, Haar JL, Lloyd JA (2011) Krüppel-like factor 2 regulated gene expression in mouse embryonic yolk sac erythroid cells. Blood Cells Mol Dis 47:1-11. (PMID: 21530336)
Guidotti A, Grayson DR (2011) A neurochemical basis for an epigenetic vision of psychiatric disorders (1994-2009). Pharmacol Res 64:344-349. (PMID: 21699980)
Grayson DR (2011) Laboratory of molecular neurobiology (1988-1994). Pharmacol Res 64:339-343. (PMID:21708255)
Kadriu B, Chen Y, Guidotti A, Grayson DR (2012) The DNA methyltransferases1 (DNMT1) and 3a (DNMT3a) co-localize with GAD67-positive neurons in the GAD67-GFP mouse brain. J Comp Neurol 520:1951-1964. (PMID: 22134929)
Matrisciano F, Tueting P, Dalal I, Kadriu B, Grayson DR, Nicoletti F, Guidotti A. Epigenetic modifications of GABAergic interneurons are associated with the schizophrenia-like phenotype induced by prenatal stress in mice. Neuropharmacology, epub ahead of print. (PMID: 22564440)
Guidotti A, Dong E, Gavin DP, Veldic M, Zhao W, Bhaumik DK, Pandey SC, Grayson DR (2012) DNA Methylation/demethylation network expression in psychotic patients with a history of alcohol abuse. Alcohol Clin Exp Res, epub ahead of print. (PMID: 22958170)
Grayson DR, Guidotti A (2013) DNA-methylation dynamics in schizophrenia and related psychiatric disorders. Neuropsychopharmacol 38:138-66. (PMID: 22948975)
|Better DNA Methyltransferase (DNMT) Inhibitors Correct the Behavioral and Molecular Endophentoypes of an Animal Model of Psychosis||Progress in developing new, more effective, and less toxic drugs to treat the complex symptomatology of schizophrenia and bipolar disorder has been hampered by the lack of objective diagnostic tools to assess prodromes, progression severity, and therapeutic responses to drugs.||Laboratory of Molecular Neuroscience||On-going|
|DNA Methylation and Hydroxymethylation in Autism Spectrum Disorders (ASD)||The role of methylcytosine (5mC) and hydroxymethylcytosine (5hmC) in the brain of ASD is largely underexplored. We have examined the epigenetic marks 5mC and 5hmC at selected promoters of several genes that are down-regulated in ASD prefrontal cortex and cerebellum.||
||Laboratory of Molecular Neuroscience||On-going|
|DNA Methylation in the Etiopathogenesis of Schizophrenia (SZ)||DNA methylation is an important epigenetic mark that plays a prominent role in regulating gene expression during development of the brain. For the last twenty years, we have been investigating the role of DNA methylation in regulating candidate genes that are down-regulated in SZ.||Laboratory of Molecular Neuroscience||On-going|
|Epigenetic mechanisms Operative in Psychotic Disorders||As part of our ongoing studies on the etiopathogenesis of schizophrenia and psychosis-related disorders, we have developed an animal model that mimics some of the behavioral and molecular endophenotypes associated with these disorders.||Psychiatric Institute||On-going|
|Expression and Methylation of HPA Axis Genes in Adult Suicide Brain||The goal of this project is to study the expression and methylation of genes related to HPA axis in postmortem brain of adult suicide victims and normal control subjects to determine if abnormalities in the HPA axis genes, of their methylation are associated with suicide.||Mood Disorders and Suicide Research||On-going|
|The Effects of Chronic Alcohol Administration and Withdrawal on Epigenetic Marks in the Rat Brain||As part of the NIAAA-funded Center for Alcohol, Dr. Grayson is the Director of the Epigenetic Core. The Core prepares RNA, DNA and Chromatin from multiple brain regions (frontal cortex, hippocampus, amygdala and ventral tegmental area) of rats chronically treated with ethanol, chronically treated rats subjected to a 24 hour withdrawal period and non-treated control rats.||Laboratory of Molecular Neuroscience||On-going|