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Articles

Dennis R. Grayson

Dgrayson
CONTACT INFORMATION

University of Illinois at Chicago
Department of Psychiatry
1601 W. Taylor St. (R-257)
Chicago, IL 60612

Office Phone: (312) 413-4577
E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Assistant:
Dr. Ying Chen

KEY PUBLICATIONS (from a list of over 115 publications)

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)

Access the recommendation on F1000Prime Grayson DR, Guidotti A (2013) DNA-methylation dynamics in schizophrenia and related psychiatric disorders. Neuropsychopharmacol 38:138-66. (PMID: 22948975)



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Dennis R. Grayson

Professor of Molecular Neuroscience

Dr. Grayson has been interested in mechanisms associated with gene expression for over 20 years.  He joined the laboratory of Dr. James E. Darnell, Jr. at the Rockefeller University on 1984 to study cell-type specific transcription factors. This led to the identification of HNF3A as a hepatocyte nuclear factor important for activating the expression of multiple genes in hepatocytes. In 1988, Dr. Grayson joined the Fidia-Georgetown Institute for the Neurosciences and with the support of Dr. Erminio Costa, initiated a program in studying gene expression in neurons. From 1994-1998, he moved to the Allegheny University of the Health Sciences in Pittsburgh and developed a program in molecular psychiatry. He continued his interests in psychiatry and joined the Psychiatric Institute in 1998.  This represented a unique opportunity to join his long time collaborators, Drs. Costa and Guidotti to pursue molecular underpinnings of schizophrenia. Dr. Grayson has received NRSA post-doctoral support, R01 and K04 funding from the NIH over the years. He has published over 100 papers in peer-reviewed journals and actively reviews NIH grants and post-doctoral fellowships. In addition, Dr. Grayson has been invited to speak at numerous national and international meetings.

Interests:

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.

Affiliations/Memberships:

Society for Neuroscience, Society for Biological Psychiatry, American Society for Biochemistry and Molecular Biology

Projects:

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.

 

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