Molecular Mechanisms of Neurological Disorders
My current research program seeks to translate findings from gene expression studies into hypotheses about the pathological bases of neurological disorders, including schizophrenia and Huntington’s disease, as well as the mechanisms of drugs used to treat these disorders. We have used functional genomics approaches to identify genes that are abnormally expressed in human post-mortem samples from diseased subjects, animal models of disease and in response to drug treatment. The goal of these studies is to achieve a better understanding of dysfunctional systems in these disorders and to provide a basis for new therapeutic approaches and disease prevention.
B.A., Biochemistry, University of California, Berkeley, 1989
Ph.D., Pharmacology, University of California, Irvine, 1994
2009-present Associate Professor, The Scripps Research Institute
2008-2012 Honorary Senior Research Fellow, The Mental Health Research Institute, Melbourne, Australia
2002-2006 Visiting Research Officer, The Mental Health Research Institute of Victoria, Melbourne, Australia
2002-2009 Assistant Professor, The Scripps Research Institute
1998-2002 Senior Research Associate, The Scripps Research Institute
1995-1998 Post-Doctoral Fellow, The Scripps Research Institute
1992/1993 Henry Wood Elliot Memorial Award/Scholarship, The Univ. of California
1992-1994 PMAF Advanced Pre-doctoral Fellowship
1997-1999 NARSAD Young Investigator Fellowship
2001 Young Investigator Award, American Society for Neurochemistry
2002 The International Union of Basic and Clinical Pharmacology (IUPHAR) Young Investigator
Mirendil, H., Thomas, E.A., De Leora, C., Okada, K., Inomata, Y., Chun, J. LPA signaling initiates schizophrenia-like brain and behavioral changes in a mouse model of prenatal brain hemorrhage. Translational Psychiatry 5: e541 (2015)
Jia, H., Morris, C.D., Williams, R., Loring, J.F., Thomas, E.A. Histone deacetylase inhibition imparts beneficial transgenerational epigenetic effects in Huntington's disease transgenic mice via alterations in DNA and histone methylation. Proc. Natl. Acad. Sci. USA 112(1):E56-64 (2015)
Thomas, E.A. Involvement of HDAC1 and HDAC3 in the pathology of polyglutamine disorders: therapeutic implications for selective HDAC1/HDAC3 inhibitors. Pharmaceuticals 7:634-661 (2014)
Tang, B, Jia, H., Kast, R. J., Thomas, E. A. Epigenetic changes at gene promoters in response to immune activation in utero. Brain, Behavior and Immunity. 30:168-75 (2013).
Jia, H., Kast, R. J., Steffan, J. S., Thomas, E. A. Selective histone deacetylase (HDAC) inhibition imparts beneficial effects in Huntington’s disease mice; implications for the ubiquitin–proteasomal and autophagy systems. Human Molecular Genetics, 21:5280-93 (2012).
Tang, B., Becanovic, K., Desplats, P.A., Spencer, B., Hill, A.M., Connolly, C., Masliah, E., Leavitt, B.R., Thomas, E.A. Forkhead box protein p1 is a transcriptional repressor of immune signaling in the CNS; implications for transcriptional dysregulation in Huntington disease. Human Molecular Genetics, 21:3097-111 (2012).
Jia, H., Pallos, J, Jacques, V., Lau, A., Tang, B., Cooper, A., Syed, A., Purcell, J., Chen, Y., Sharma, S., Sangrey, G.R., Darnell, S.B., Plasterer, H., Sadri-Vakili, G., Gottesfeld, J.M., Thompson, L.M., Rusche, J.R., Marsh, J.L., Thomas, E.A. Histone deacetylase (HDAC) inhibitors targeting HDAC3 and HDAC1 ameliorate polyglutamine-elicited phenotypes in model systems of Huntington's disease. Neurobiology of Disease, 46:351-61 (2012).
Tang, B., Dean, B., Thomas, E.A. Disease- and age-related changes in histone acetylation at gene promoters in psychiatric disorders. Translational Psychiatry, 1: e64 (2011). * this article was the #1 downloaded article for Translational Psychiatry in January 2012.
Thomas, E.A., Coppola, G., Tang, B., Kuhn, A., Kim, S., Geschwind, D.H., Brown, T.B., Luthi-Carter, R.,. Ehrlich, M.E. In Vivo Cell-autonomous Transcriptional Abnormalities Revealed in Mice Expressing Forebrain Striatal-restricted Mutant Huntingtin. Human Molecular Genetics, 2010 Dec. 20. * this article was featured on the cover.
Ku, S., Soragni, E., Campau, E., Thomas, E.A., Altun, G., Laurent, L.C., Loring, J.F., Napierala, M., Gottesfeld, J.M. Friedreich's Ataxia Induced Pluripotent Stem cells Model Intergenerational GAA*TTC Triplet-Repeat Instability. Cell Stem Cell 7(5):631-7 (2010).
Torkamani, A., Dean, B., Schork, N.J., Thomas, E.A. Co-Expression Network Analysis of Neural Tissue Reveals Perturbations in Developmental Processes in Schizophrenia. Genome Research, 20:403-12 (2010). * this article was featured on the cover.
Tang, B., Chang, W., Lanigan, C.M., Dean, B., Sutcliffe J.G., Thomas, E.A. Normal Human Aging and Early-Stage Schizophrenia Share Common Molecular Profiles. Aging Cell 8:339-42 (2009).
Thomas, E.A., Coppola, G., Desplats, P.A. Tang, B., Soragni, E. Burnett, R., Gao, F., Fitzgerald, K.M., Borok, J.F., Herman, D., Geschwind, D. H., Gottesfeld, J.M. The Histone Deacetylase Inhibitor, HDACi 4b, Ameliorates the Disease Phenotype and Transcriptional Abnormalities in Huntington's Disease Transgenic Mice. Proc. Natl. Acad. Sci. USA 105:15564-9 (2008).