Assistant 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
Lab Home Page
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
Zhu, Y., Zhu, Y., and Xu, W. EzArray: A Web-based Highly Automated Affymetrix Expression Array Data Management and Analysis System. BMC Bioinformatics, 9:46, 2008.
Higashimoto, K., Kuhn, P., Desai, D., Cheng, X., and Xu, W. Phosphorylation-mediated Inactivation of Coactivator-associated Arginine Methyltransferase 1. Proc. Natl. Acad. Sci. USA, 104: 12318-12323, 2007.
Powell, E., Kuhn, P., and Xu, W. Nuclear Receptor Cofactors in PPARg-Mediated Adipogenesis and Adipocyte Energy Metabolism. PPAR Res., 2007:53843, 11 pages, 2007.
Yao, T., Song, L., Xu, W., DeMartino, G. N., Florens, L., Swanson, S. K., Washburn, M. P., Conaway, R. C., Conaway, J. W., and Cohen, R. E. Proteasome Recruitment and Activation of the Uch37 Deubiquitinating Enzyme by Adrm1. Nat. Cell Biol., 8: 994-1002, 2006.
Xu, W. Nuclear Receptor Coactivators: the Key to Unlock Chromatin. Biochem. Cell Biol., 83: 418-428, 2005.
Xu, W., Cho, H., Kadam, S., Banayo, E. M., Anderson, S., Yates III, J. R., Emerson, B. M., and Evans, R. M. A Methylation-Mediator Complex in Hormone Signaling. Genes Dev., 18: 144-156, 2004.
Louie, M. C., Yang, H. Q., Ma, A.-H., Xu, W., Zou, J. X., Kung, H.-J., and Chen, H.-W. Androgen-induced Recruitment of RNA Polymerase II to a Nuclear Receptor-p160 Coactivator Complex. Proc. Natl. Acad. Sci. USA, 100(5): 2226-2230, 2003.
Xu, W., Cho, H., and Evans, R. M. Acetylation and Methylation in Nuclear Receptor Gene Activation. Methods Enzymol., 364: 205-223, 2003.
Demarest, S. J., Martinez-Yamout, M., Chung, J., Chen, H., Xu, W., Dyson, H. J., Evans, R. M., and Wright, P. E. Mutual Synergistic Folding in Recruitment of CBP/p300 by p160 Nuclear Receptor Coactivators. Nature, 415: 549-553, 2002.
Xu, W., Chen, H., Du, K., Asahara, H., Tini, M., Emerson, B. M., Montminy, M., and Evans, R. M. A Transcriptional Switch Mediated by Co-Factor Methylation. Science, 294: 2507-2511, 2001.
