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Wei Xu, Ph.D.

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Wei Xu photoProfessor of Oncology

B.S., 1991, Chemistry, Beijing University, China
1994, Biophysics, Institute of Biophysics, Beijing, China
, 1999, Biochemistry, University of Iowa
Postdoctoral research: The Salk Institute for Biological Studies,
La Jolla, CA

Office: 7459 Wisconsin Institutes for Medical Research
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


Brinkman AM, Chen G, Wang Y, Hedman CJ, Sherer NM, Havighurst TC, Gong S, Xu W. Aminoflavone-loaded EGFR-targeted unimolecular micelle nanoparticles exhibit anti-cancer effects in triple negative breast cancer. Biomaterials. 2016 Sep;101:20-31. doi: 10.1016/j.biomaterials.2016.05.041. Epub 2016 May 27. PubMed PMID: 27267625; PubMed Central PMCID: PMC5030715.

Liu JT, Do TJ, Simmons CJ, Lynch JC, Gu W, Ma ZX, Xu W, Tang W. Total synthesis of diptoindonesin G and its analogues as selective modulators of estrogen receptors. Org Biomol Chem. 2016 Sep 26;14(38):8927-8930. PubMed PMID: 27714255. [Policy exempt – non-NIH funding]

Wisinski KB, Xu W, Tevaarwerk AJ, Saha S, Kim K, Traynor A, Dietrich L, Hegeman R, Patel D, Blank J, Harter J, Burkard ME. Targeting Estrogen Receptor Beta in a Phase 2 Study of High-Dose Estradiol in Metastatic Triple-Negative Breast Cancer: A Wisconsin Oncology Network Study. Clin Breast Cancer. 2016 Aug;16(4):256-61. doi: 10.1016/j.clbc.2016.03.005. Epub 2016 Mar 31. PubMed PMID: 27133732; PubMed Central PMCID: PMC4969205.

Zeng H, Xu W. Gene expression profiling of Ctr9-regulated transcriptome in ERα-positive breast cancer. Genom Data. 2016 Dec 17(2015);7:103-4. doi: 10.1016/j.gdata.2015.12.006. eCollection 2016 Mar. PubMed PMID: 26981377; PubMed Central PMCID: PMC4778656.

Zeng H, Lu L, Chan NT, Horswill M, Ahlquist P, Zhong X, Xu W. Systematic identification of Ctr9 regulome in ERα-positive breast cancer. BMC Genomics. 2016 Nov 9;17(1):902. PubMed PMID: 27829357; PubMed Central PMCID: PMC5103509.


Charoensuksai P, Kuhn P, Wang L, Sherer N, Xu W. O-GlcNAcylation of co-activator-associated arginine methyltransferase 1 regulates its protein substrate specificity. Biochem J. 2015 Mar 15;466(3):587-99. doi: 10.1042/BJ20141072. PubMed PMID: 25585345; PubMed Central PMCID: Policy Exempt – non-U.S. gov’t. research support.

Shanle EK, Onitilo AA, Huang W, Kim K, Zang C, Engel JM, Xu W, Wisinski KB. Prognostic significance of full-length estrogen receptor beta expression in stage I-III triple negative breast cancer. Am J Transl Res. 2015 Jul 15;7(7):1246-59. eCollection 2015. PubMed PMID: 26328009; PubMed Central PMCID: PMC4548317.

Shlensky D, Mirrielees JA, Zhao Z, Wang L, Mahajan A, Yu M, Sherer NM, Wilke LG, Xu W. Differential CARM1 Isoform Expression in Subcellular Compartments and among Malignant and Benign Breast Tumors. PLoS One. 2015 Jun 1;10(6):e0128143. doi: 10.1371/journal.pone.0128143. eCollection 2015. PubMed PMID: 26030442; PubMed Central PMCID: PMC4451767. Correction: PLoS One. 2015 Jun 25;10(6):e0131955. doi: 10.1371/journal.pone.0131955. eCollection 2015. PubMed PMID: 26110850; PubMed Central PMCID: PMC4482405.

Wang L, Zeng H, Wang Q, Zhao Z, Boyer TG, Bian X, Xu W. MED12 methylation by CARM1 sensitizes human breast cancer cells to chemotherapy drugs. Sci Adv. 2015 Oct 9;1(9):e1500463. eCollection 2015 Oct. PubMed PMID: 26601288; PubMed Central PMCID: PMC4646802.

Xu D, Zhan Y, Qi Y, Cao B, Bai S, Xu W, Gambhir SS, Lee P, Sartor O, Flemington EK, Zhang H, Hu CD, Dong Y. Androgen Receptor Splice Variants Dimerize to Transactivate Target Genes. Cancer Res. 2015 Sep 1;75(17):3663-71. doi: 10.1158/0008-5472.CAN-15-0381. Epub 2015 Jun 9. PubMed PMID: 26060018; PubMed Central PMCID: PMC4558376.

Zeng H, Xu W. Ctr9, a key subunit of PAFc, affects global estrogen signaling and drives ERα-positive breast tumorigenesis. Genes Dev. 2015 Oct 15;29(20):2153-67. doi: 10.1101/gad.268722.115. PubMed PMID: 26494790; PubMed Central PMCID: PMC4617979.

Zhao Z, Wang L, James T, Jung Y, Kim I, Tan R, Hoffmann FM, Xu W. Reciprocal Regulation of ERα and ERβ Stability and Activity by Diptoindonesin G. Chem Biol. 2015 Dec 17;22(12):1608-21. doi: 10.1016/j.chembiol.2015.10.011. Epub 2015 Dec 3. PubMed PMID: 26670079; PubMed Central PMCID: PMC4767166.

Zhao Z, Wang L, Xu W. IL-13Rα2 mediates PNR-induced migration and metastasis in ERα-negative breast cancer. Oncogene. 2015 Mar 19;34(12):1596-607. doi: 10.1038/onc.2014.53. Epub 2014 Apr 21. PubMed PMID: 24747967; PubMed Central PMCID: PMC4321963.


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.  [ERRATUM published in Cancer Cell 2016 Jul 11;30(1):179-180]


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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