Wei Xu, Ph.D.
Associate Professor of
Oncology
B.S., 1991, Chemistry, Beijing
University, China
M.S., 1994, Biophysics, Institute of Biophysics,
Beijing, China
Ph.D., 1999, Biochemistry, University of
Iowa
Postdoctoral research: The Salk
Institute for Biological Studies,
La Jolla, CA
Office: 421A McArdle
Laboratory
Telephone: Office - (608) 265-5540; Lab - (608)
262-9834
Email: wxu@oncology.wisc.edu
Research Interests: Epigenetic transcriptional control in breast cancer
Research Description: My laboratory is focused on the transcriptional regulation of estrogen receptor (ER) signaling pathways by nuclear receptor co-factors. Estrogen receptors regulate cell proliferation, differentiation and cell cycle control in a cell- and tissue-specific manner. The effect of estrogen in etiology and progression of breast cancer is ascribed to ER-promoted cell proliferation. We have discovered that some ER co-regulatory proteins regulate ER-mediated growth inhibition rather than proliferation. We are in the process of exploring the molecular mechanisms by which nuclear receptor coactivators regulate ER-mediated growth inhibition and attempting to develop novel chemotherapy strategies to treat ER-positive breast cancer. Furthermore, we aim to understand the crosstalk between ER pathways and other growth factors and kinase networks, as these mechanisms account for the intrinsic or acquired tamoxifen resistance in endocrine therapy.
An important epigenetic route to carcinogenesis involves the aberrant patterns of histone modifications in chromatin, leading to alterations in gene expression and transformation from normal to cancer cells. The second focus of our lab is to explore the functional roles of histone arginine methylation in the epigenetic control of cancer cells. Our major interest is on a protein arginine methyltransferase CARM1/PRMT4, a nuclear hormone receptor co-activator. Histone H3 methylation by CARM1 potentiates target gene activation by ER. Our ongoing studies include combining biochemical and functional genomic approaches to understand the role and regulation of histone R methylation in the transcriptional control of ER. In addition to learning about how CARM1 regulates ER in cancer cells, we will employ mice genetics to decipher the significance of histone arginine methylation in tumor prevention, thereby facilitating the rational design of novel chemotherapy drugs by targeting the epigenome in breast cancer.
Selected recent publications
Sievers, C. K., Shanle, E. K., Bradfield, C. A., and Xu, W. Differential Action of Monohydroxylated Polycyclic Aromatic Hydrocarbons with Estrogen Receptors a and β. Toxicol. Sci., 132(2): 359-367, 2013.
Wang, L., Charoensuksai, P., Watson, N. J., Wang, X., Zhao, Z., Coriano, C. G., Kerr, L. R., and Xu, W. CARM1 Automethylation Is Controlled at the Level of Alternative Splicing. Nucleic Acids Res., in press, 2013 [Epub ahead of print May 30 2013].
Yarger, J. G., Babine, R. E., Bittner, M., Shanle, E., Xu, W., Hershberger, P., and Nye, S. H. Structurally Similar Estradiol Analogs Uniquely Alter the Regulation of Intracellular Signaling Pathways. J. Mol. Endocrinol., 50(1): 43-57, 2013.
Zeng, H., Wu, J., Bedford, M. T., Sbardella, G., Hoffmann, F. M., Bi, K., and Xu, W. A TR-FRET-Based Functional Assay for Screening Activators of CARM1. ChemBioChem, 14(7): 827-835, 2013.
Powell, E., Shanle, E., Brinkman, A., Li, J., Keles, S., Wisinski, K. B., Huang, W., and Xu, W. Identification of Estrogen Receptor Dimer Selective Ligands Reveals Growth-Inhibitory Effects on Cells That Co-Express ERa and ERβ. PLoS One, 7(2):e30993, 2012.
Wen, Z., Pyeon, D., Wang, Y., Lambert, P., Xu, W., and Ahlquist, P. Orphan Nuclear Receptor PNR/NR2E3 Stimulates p53 Functions by Enhancing p53 Acetylation. Mol. Cell. Biol., 32: 26-35, 2012.
Wu, J., and Xu, W. Histone H3R17me2a Mark Recruits Human RNA Polymerase-Associated Factor 1 Complex to Activate Transcription. Proc. Natl. Acad. Sci. USA, 109: 5675-5680, 2012.
Al-Dhaheri, M., Wu, J., Skliris, G. P., Li, J., Higashimato, K., Wang, Y., White, K. P., Lambert, P., Zhu, Y., Murphy, L., and Xu, W. CARM1 Is an Important Determinant of ERα-Dependent Breast Cancer Cell Differentiation and Proliferation in Breast Cancer Cells. Cancer Res., 71: 2118-2128, 2011.
Chumanov, R. S., Kuhn, P. A., Xu, W., and Burgess, R. R. Expression and Purification of Full-Length Mouse CARM1 from Transiently Transfected HEK293T Cells Using HaloTag Technology. Protein Expr. Purif., 76: 145-153, 2011.
Kuhn, P., Chumanov, R., Wang, Y., Ge, Y., Burgess, R. R., and Xu, W. Automethylation of CARM1 Allows Coupling of Transcription and mRNA Splicing. Nucleic Acids Res., 39: 2717-2726, 2011.
Shanle, E. K., and Xu, W. Endocrine Disrupting Chemicals Targeting Estrogen Receptor Signaling: Identification and Mechanisms of Action. Chem. Res. Toxicol., 24: 6-19, 2011.
Shanle, E. K., Hawse, J. R., and Xu, W. Generation of Stable Reporter Breast Cancer Cell Lines for the Identification of ER Subtype Selective Ligands. Biochem. Pharmacol., 82: 1940-1949, 2011.