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|Robert J. Trumbly, Ph.D.
Professor of Biochemistry and Cancer Biology
My present research focus is using bioinformatics, genetic, and biochemical approaches to analyze the role of transcriptional regulation in cancer, primarily
prostate and breast cancer.
Bioinformatics analysis of gene expression in prostate and breast cancer.
In collaboration with Dr. Manohar Ratnam, Dr. Trumbly has analyzed the patterns of gene expression from microarray data in prostate and breast cancer cells. In the case of prostate cancer cells, we have discovered a novel mechanism for androgen-independent growth, which involves gene activation by the androgen receptor in the absence of ligand. The set of genes activated by the apo-AR is greatly enriched for genes regulating progression through the cell cycle, allowing cells to proliferate in the absence of androgen. In a parallel result, we have found that gene activation by the unliganded estrogen receptor permits cell cycling in breast cancer cells, providing a mechanism for development of resistance to anti-estrogens.
Role of groucho (TLE) and jmjC (histone demethylase) proteins in cancer. (1) TLE corepressors.
The Groucho (TLE = Transducin-Like Enhancer-of-split) proteins are corepressors for many key developmental and signaling pathways. There are six genes encoding Groucho homologs in humans, TLE1-4, TLE6, and AES1. The focus of Dr. Trumbly’s interest is in the regulation of specificity of TLE function. Different combinations of TLE genes are expressed in different tissues, suggesting that they have specialized functions, such as differential recruitment by different repressor proteins. Dr. Trumbly plans to elucidate the role of TLE specificity, mediated by both TLE gene specific expression and TLE protein phosphorylation, in the regulation of key developmental and signaling pathways, especially in relationship to cancer. (2) Coregulators containing JmjC domains. Dr. Trumbly has also initiated a study of the functional roles of the UTX and UTY proteins, which are the closest human homologs to the Cyc8 corepressor in yeast. The UTX and UTY proteins have an additional domain at the C-terminus not found in Cyc8, a JmjC domain. This domain was very recently found to possess a novel histone demethylase activity. Using a two-hybrid screen, Dr. Trumbly has discovered several promising candidates for transcriptional regulators that interact with UTY. Of particular interest is the interaction of UTY with the androgen receptor (AR), which plays a critical role in prostate cancer. The JmjC histone demethylase activity is a promising target for enzyme inhibitors that could modulate epigenetic regulation in cancer progression.
1975 B.A. University of California, Berkeley, California (Botany)
1980 Ph.D. University of California, Davis, California (Genetics)
1999-present Professor, Biochemistry and Cancer Biology, The University of Toledo Health Science Campus
1992-1998 Associate Professor, Biochemistry and Molecular Biology Medical University of Ohio
1985-1991 Assistant Professor, Biochemistry and Molecular Biology Medical University of Ohio
1983-1985 Research Associate, New York State Dept. of Health, Center for Laboratories and Research
1979-1977 Teaching Assistant, Genetics Univ. of California, Davis
1975-1977 Research Assistant, Genetics Univ. of California, Davis
Gonit, M., Zhang, J., Salazar, M., Cui, H., Shatnawi, A., Trumbly, R., and Ratnam, M. (2011) Hormone depletion-insensitivity of prostate cancer cells is supported by the AR without binding to classical response elements. Mol Endocrinol 25:621-634.
Salazar, M., Ratnam, M., Patki, M., Kosovic, I., Trumbly, R., Iman, M., Ratnam, M. (2011) During hormone depletion or tamoxifen treatment of breast cancer cells the estrogen receptor apoprotein supports cell cycling through the retinoic acid receptor α1 apoprotein. Breast Cancer Res. 13:R18.
Tang, H., Park, S., Sun, S.C., Trumbly, R., Reng, G., Tsung, E., and Yeung, K.C. (2010) RKIP inhibits NF-ΚB in cancer cells by regulating upstream signaling components of the IΚB kinase complex. FEBS Lett. 584:662-668.
Zhang, J., Gonit, M., Salazar, MD, Shatnawi, A., Shemshedini, L., Trumbly, R., and Ratnam, M. (2010) C/EBPα redirects androgen receptor signaling through a unique bimodal interaction. Oncogene 29:723-738.
Davie, J.K., Trumbly, R.J., and Dent, S.Y. (2002) Histone-dependent association of Tup1-Ssn6 with repressed genes in vivo. Mol. Cell. Biol. 22:693-703.
Zhang, Z., Varanasi, U., and Trumbly, R.J. (2002) Functional dissection of the global repressor Tup1 in yeast: dominant role of the C-terminal repression domain. Genetics 161:957-969.
U.S. Varanasi, M. Klis, P.B. Mikesell, and R.J. Trumbly. (1996) The Cyc8(Ssn6)-Tup1 corepressor complex is composed of one Cyc8 and four Tup1 subunits. Mol. Cell. Biol. 16:6707-6714.