Professor in Oncology
608-262-9834 or 608-265-5540
7457 Wisconsin Institute for Medical Research
Research Interests: Breast cancer prevention and treatment using environmental and nutritional estrogenic compounds. Mechanism of transcription activation of ERa and ERb by environmental estrogenic ligands.
Our laboratory is exploring the protective roles of environmental and nutritional estrogenic compounds in mammals for breast cancer prevention and treatment. Estrogen receptors (ERs) exist in two forms, ERa and ERb, which have opposing roles in cell proliferation. Estrogenic compounds can control balance between mammary cell proliferation and differentiation via stimulating the formation of different forms of ER dimers. We have developed the Bioluminescent Resonance Energy Transfer (BRET) assays for detecting in vivo homodimerization and heterodimerization of ERa and ERb induced by estrogenic compounds. These assays have been optimized for high throughput screening, which allow us to identify novel estrogenic compounds capable of differentially modulating these dimer forms. Biological functions of these estrogenic compounds are currently being investigated in cell-based and breast cancer mouse models. Furthermore, the compounds will be utilized in gene expression microarrays for identification of clinically relevant ERb-directed biomarkers for breast cancer diagnosis and prognosis. We have also employed biochemical and functional genomic approaches, as well as mouse 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.
- Charoensuksai, P., Kuhn, P., Wang, L., Sherer, N., and Xu, W. O’GlcNAcylation of Coactivator-Associated Arginine Methyltransferase 1 Regulates Its Protein Substrate Specificity. Biochem. J., in press, 2015 [Epub ahead of print Jan 13 2015].
- Zhao, Z., Wang, L., and Xu, W. IL-13Ra2 Mediates PNR-Induced Migration and Metastasis in ERa-Negative Breast Cancer. Oncogene, in press, 2015 [Epub ahead of print Apr 21 2014].
- Brinkman, A. M., Wu, J., Ersland, K., and Xu, W. Estrogen Receptor α and Aryl Hydrocarbon Receptor Independent Growth Inhibitory Effects of Aminoflavone in Breast Cancer Cells. BMC Cancer, 14:344, 2014.
- 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.
- 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.
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Mentor to METC Graduate Students:
- Carlos Coriano (current), Ashley Brinkman (2015),
- Erin Shanle (2013)
Mentor to METC Post-Docs:
- Taryn James, PhD (2011-2013)