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Wei Xu, Ph.D.

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Wei Xu photoProfessor 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: 7459 Wisconsin Institutes for Medical Research
Telephone:
Office - (608) 265-5540; Lab - (608) 262-9834
Email: wxu@oncology.wisc.edu

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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

Gao, J., Xu, D., Sabat, G., Valdivia, H., Xu, W., and Shi, N.-Q.  Disrupting KATP Channels Diminishes the Estrogen-Mediated Protection in Female Mutant Mice during Ischemia-Reperfusion.  Clin. Proteomics, 11(1):19, 2014.

Wang, L., Zhao, Z., Meyer, M. B., Saha, S., Yu, M., Guo, A., Wisinski, K. B., Huang, W., Cai, W., Pike, J. W., Yuan, M., Ahlquist, P., and Xu, W.  CARM1 Methylates Chromatin Remodeling Factor BAF155 to Enhance Tumor Progression and Metastasis.  Cancer Cell, 25(1):  21-36, 2014.

Zhao, Z., Wang, L., and Xu, W.  IL-13Ra2 Mediates PNR-Induced Migration and Metastasis in ERa-Negative Breast Cancer.  Oncogene, in press, 2014 [Epub ahead of print Apr 21 2014].

Shanle, E. K., Zhao, Z., Hawse, J., Wisinski, K., Keles, S., Yuan, M., and Xu, W. Research Resource:  Global Identification of Estrogen Receptor β Target Genes in Triple Negative Breast Cancer Cells.  Mol. Endocrinol., 27(10):  1762-1775, 2013.

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., 41(14): 6870-6880, 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.

Zhao, Z., Wang, L., Wen, Z., Ayaz-guner, S., Wang, Y., Ahlquist, P., and Xu, W.  Systematic Analyses of the Cytotoxic Effects of Compound 11a, a Putative Synthetic Agonist of Photoreceptor-Specific Nuclear Receptor (PNR), in Cancer Cell Lines.  PLoS One, 8(9):e75198, 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.

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