Our laboratory is focused on the transcriptional regulation of estrogen receptor (ER) signaling pathways by nuclear receptor co-factors. Our major interest is on a protein arginine (R) 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 ER-regulated processes controlled by CARM1 and the mechanism by which histone arginine modification contributes to the epigenetic control of cancer cells.
We will also 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.
- Can histone methylation and chromatin remodeling activity be uncoupled in the differential regulation of ER-target genes?
- Which kinases and pathways mediate the phosphorylation of CARM1?
- What are the downstream cellular events following CARM1-mediated arginine methylation?
- What is the functional role of CARM1 in estrogen-responsive cancers (e.g. breast and ovarian cancer)?
- What are the biological functions of ERa/b heterodimer in breast cancer? Are there natural compounds that promote ERa/b heterodimer formation?
Honors & Awards
- Vilas Distinguished Achievement Professor, 2013-2014
- Society of Toxicology Achievement Award, 2013
- Vilas Associate of University of Wisconsin, 2012
- DOD Era of Hope Scholar, 2010
- Shaw Scientist Award, 2008
- Discover non-histone substrates for CARM1 (paper published in Cancer Cell)
Selected Publications (Find publications on PubMed)
- Shlensky, D., Mirrielees, J. A., Zhao, Z., Wang, L., Mahajan, A., Yu, M., Sherer, N. M., Wilke, L. G., and Xu, W. Differential CARM1 Isoform Expression in Subcellular Compartments and Among Malignant and Benign Breast Tumors. PLoS One, 10(6): e0128143, 2015.
- Charoensuksai, P., Kuhn, P., Wang, L., Sherer, N., Xu, W. (2015) O-GlcNAcylation of co-activator-associated protein arginine methyltransferase 1 regulates its substrate specificity. Biochem J. 466(3): 587-99.
- Brinkman, A.M., Wu, J., Ersland K., Xu, W. (2014) Estrogen receptor a and aryl hydrocarbon receptor independent growth inhibitory effects of aminoflavone in breast cancer cells. BMC Cancer, 14(1): 344.
- Zhao, Z., Wang, L., Xu, W. (2014) IL-13Ra2 mediates PNR-induced migration and metastasis in ERa-negative breast cancer. Oncogene, 34(12): 1596-1607.
- 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., Xu, W. (2014) CARM1 methylates chromatin remodeling factor BAF155 to enhance tumor progression and metastasis. Cancer Cell, 25: 1-16.