Research Associate Professor of Physiology
Dr. Bodwell received a B.S. in 1973 from the University of New Hampshire and a Ph.D. in biochemistry from the University of Vermont in 1980. He joined the Department of Physiology in 1980 as a research associate and was appointed to the rank of Research Assistant Professor in 1985 and Research Associate professor in 1996. He was a Senior Scientist at Medarex Inc. from 1988 to 1989 and returned to the department in 1989.
Glucocorticoids exert their action primarily through an intracellular glucocorticoid receptor (GR). The cytosolic GR binds hormone and the complex is transported to the nucleus. These complexes form homodimers on specific DNA sequences called glucocorticoid response elements (GRE) that are located in the promoter region of target genes. While the GR is associated with the GRE it is able to interact with the basal transcription machinery and modulate transcription from these genes. Past research interests include: (I) the role of phosphorylation in receptor function and (II) the interaction of the GR with transcription factors from the cAMP (CREB) and diacylglycerol (Jun and Fos) pathways. Recently initiated studies investigate the mechanism of arsenic (As) disruption of GR (as well as other steroid receptors) mediated gene transcription. Elevated intake of As (primarily from drinking water) has been associated with a number of disease states and at levels of As around the EPA limit, As disrupts transcription in a very complicated fashion. As, within a very narrow concentration range, causes both marked stimulation and inhibition of GR mediated transcription. Current work is aimed at understanding the molecular mechanism involved in this response. Manuscripts are in preparation for these new studies so published abstracts are referenced below.
Richardson, J., Vinson, C., and J. Bodwell. Cyclic adenosine-3',5'-monophsophate-mediated activationof a glutamine synthetase composite glucocorticoid response element. Mol. Endocrinol. 13:546-554, 1999.
Hamilton, J.W., J.E., Bodwell, R.C. Kaltreider, A.M. Davis, J.C. Davey, L.A. Kingsley and J.P. Lariviere. Arsenic is an endocrine disruptor, blocking hormone-mediated gene regulation by the estrogen and glucocorticoid receptors in vivo. Toxicol. Sci. 66(S1):85, 2002.
Bodwell, J. E., Kingsley, L. A. and Hamilton, J. W. (2004) Arsenic at Very Low Concentrations Alters Glucocorticoid Receptor (GR)-Mediated Gene Activation but Not GR-Mediated Gene Repression: Complex Dose-Response Effects Are Closely Correlated with Levels of Activated GR and Require a Functional GR DNA Binding Domain. Chem Res Toxicol 17, 1064-1076.
Bodwell, J. E., Gosse, J. A., Nomikos, A. P. and Hamilton, J. W. (2006) Arsenic disruption of steroid receptor gene activation: Complex dose-response effects are shared by several steroid receptors. Chem Res Toxicol 19, 1619-1629.
Davey, J. C., Bodwell, J. E., Gosse, J. A. and Hamilton, J. W. (2007) Arsenic as an Endocrine Disruptor: Effects of Arsenic on Estrogen Receptor-Mediated Gene Expression In Vivo and in Cell Culture. Toxicol Sci 5, 5.
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