Faculty: Wei Xu
|Dept:||Associate Professor, Oncology|
|Contact:|| 421A McArdle
|Training Areas:||Molecular & Cellular Pharmacology|
Cellular & Molecular Biology
Cancer Biology Graduate Training Program
|Lab Page:||Click Here|
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
- 2010: DOD Era of Hope Scholar Award
- 2010: Markos Family Breast Cancer Research Grant
- 2008: Wei Xu features in Susan Komen Grantees
- 2008: Shaw Scientist Award (description)
- Zeng H, Wu J, Bedford MT, Sbardella G, Hoffman FM, Bi K, Xu W. A TR-FRET-Based Functional Assay for Screening Activators of CARM1. Chembiochem. 2013 May 10;14)7_:827-35. doi: 10.1002/cbic.201300029. Epub 2013 Apr 12. PMID: 2358185
- Yarger JG, Babine RE, Bittner M, Shanle E, Xu W, Hershberger P, Nye SH. Structurally similar estradiol analogs uniquely alter the regulation of intracellular signaling pathways. J Mol Endocrinol. 2012 Dec 31;50(1):43-57. doi: 10/1530/JME-12-0083. Print 2013 Feb. PMID: 23132914
- Kohns, C., Shanle, E. K., Bradfield, C., and Xu, W. Differential Action of Monohydroxylated Polycyclic Aromatic Hydrocarbons with Estrogen Receptors and β. Toxicol. Sci., in press, 2012 [Epub ahead of print Sep 18 2012].
- 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.
- Al-Dhaheri, M., Wu, J., Skliris, G. P., Li, J., Higashimato, K., Wang, Y., White, K. P., Lambert, P., Zhu, Y., Murhpy, L., and Xu, W. CARM1 Is an Important Determinant of ERα-Dependent Breast Cancer Cell Differentiation and Proliferation in Breast Cancer Cells. Cancer Res., 71: 2118-2128, 2011.
- Chumanov. R. S., Kuhn, P. A., Xu, W., and Burgess, R. R. Expression and Purification of Full-Length Mouse CARM1 from Transiently Transfected HEK293T Cells Using HaloTag Technology. Protein Expr. Purif., 76: 145-153, 2011.
- Kuhn P, Chumanov, R., Wang, Y., Ge, Y., Burgess, R. R., and Xu, W. Automethylation of CARM1 Allows Coupling of Transcription and mRNA Splicing. Nucleic Acids Res., 39: 2717-2726, 2011.
- Shanle, E. K., and Xu, W. Endocrine Disrupting Chemicals Targeting Estrogen Receptor Signaling: Identification and Mechanisms of Action. Che,. Res. Toxicol., 24: 6-19, 2011.
- Shanle, E. K., Hawse, J. R., and Xu, W. Generation of Stable Reporter Breast Cancer Cell Lines for the Identification of ER Subtype Selective Ligands. BIochem. Pharmacol., 82: 1940-1949, 2011.
- Charoensuksai, P., and Xu, W. PPARs in Rhythmic Metabolic Regulation and Implications in Health and Disease. PPAR Res., 2010:243643, 2010.