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Ray-Chang Wu Professor of Biochemistry and Molecular Medicine Office Phone: 202-994-1891 Email: Email Department: Biochemistry and Molecular Medicine |
Education
- BS, National Yang-ming University, 1989
- PhD, University of Southern California, 1999
Biography
Dr. Ray-Chang Wu is an Associate Professor in the department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, the George Washington University. Dr. Wu received his Ph.D. degree from the University of Southern California, and his post-doctoral training in a world-renowned nuclear hormone receptor biology lab at Baylor College of Medicine, Houston, Texas. Dr. Wu’s research focuses on understanding the molecular mechanism by which nuclear hormone receptors and co-regulators regulates gene transcription, effects cellular function, and contributes to development and progression of cancer.
Research
Epigenetics play an important role in human health and diseases. Disruption of epigenetic modifications leads to dysregulation of gene function without altering the DNA sequence. Epigenetics is a reversible process that is subject to regulation by environmental exposure. Many transcriptional co-regulators, including coactivators and corepressors, are chromatin remodeling proteins that regulate gene expression in response to environmental stimuli by virtue of the ability to alter chromatin modifications. The ongoing research in Wu's lab focuses on understanding the physiological and patho-physiological functions of these important factors in health and disease.
Biological function of chromatin remodeling protein ARID4B
ARID4B belongs to the AT-rich interaction domain (ARID) family, and is a component of the SIN3A/HDAC1 chromatin remodeling complex. However, the exact role of ARID4B in transcriptional regulation and its biological functions remain largely unknown due to the early embryonic lethality of Arid4b null mutants. To overcome the embryonic lethality, working with Dr. Mei-Yi Wu, Associate Profefssor of the Department of Medicine, the labs generated tissue-specific Arid4b knockout and knockin (over-expression) mice to investigate the in vivo function of Arid4b. Using these novel genetically modified mouse models, we are investigating how loss- or gain-of-ARID4B effects cancer initiation and development of endocrine resistance in breast and prostate cancers. By integrating biochemical, proteomic, and bioinfomatics approaches, our study will also provide insight into the molecular mechanism underpinning the biological function of ARID4B.
Steroid receptor coactivator-3 (SRC-3) and Cancer Stem Cells
Cancer stem cells (CSC) are the major driving force behind aggressive and lethal breast cancer. Understanding how the function of CSC is regulated is important as it may identify molecular signature to distinguish indolent cancers from aggressive and therapy resistant ones, and is the essential first step for development of potential anti-CSC therapies.
SRC-3 is the second most overexpressed oncogene that plays a significant role in breast cancer. Despite its importance as an oncogene, whether and how SRC-3 promotes CSC activity to drive aggressive cancer development remains unknown. One objective of this project is to exaime the role of SRC-3 in CSC and to elucidate the molecular mechanism which dictates the function of SRC-3 in CSC. Another objective is to explore the SRC-3/CSC pathway as a potential therapeutic target to reduce therapy resistance in breast cancer.
Grants
Active
R01CA188471 PI: Wu, RC
Corepressor Function of Steroid Receptor Coactivator-3 in Breast Cancer
R01AA023146 PI: Mishra, L
Role of Beta Spectrin and Smad in Alcohol Induced Liver and GI Cell Proliferation
Completed in the past three years
R21CA187857 PI: Wu, RC
Steroid Receptor Coactivator-3 and Cancer Stem Cells
Awards
2001 Annual Endocrine Society Meeting Travel Award
2001 - 2004 US Department of Defense Postdoctoral Fellowship Award
2007 - 2010 Susan G. Komen, Basic, Clinical and Translational Research Award
Teaching
BIOC 6227 (Director)
Student Seminar Series
BIOC 6224 (Co-Director)
Laboratory Techniques in Protein Biochemistry
BIOC 6222
Biochemical Genetics and Medicine
Centers and Institutes
GW Cancer Center
Publications
Young IC, Wu B, Andricovich J, Chuang ST, Li R, Tzatsos A, Wu RC*, Wu MY*. Differentiation of Fetal Hematopoietic Stem Cells Requires ARID4B to Restrict Autocrine KITLG/KIT-Src Signaling. Cell Reports. 2021 Nov 23;37(8):110036. doi: 10.1016/j.celrep.2021.110036. PMID: 34818550 PMCID: PMC8722094 *Co-corresponding authors.
Wu RC*, Young IC, Chen, YF, Chuang ST, Toubaji, A, and Wu MY*. Identification of the PTEN-ARID4B-PI3K pathway reveals the dependency on ARID4B by PTEN-deficient prostate cancer. Nature Communications. 2019 Sep 24;10(1):4332. doi: 10.1038/s41467-019-12184-8.2019 PMID: 31551414 PMCID: PMC6760172 *Co-corresponding authors
mani S, Wu RC, Fu J. MicroRNA-34 family in breast cancer: from research to therapeutic potential. J Cancer. 2018 Sep 28;9(20):3765-3775. doi: 10.7150/jca.25576. eCollection 2018.
Wu RC, Zeng Y, Chen YF, Lanz RB, and Wu MY. Temporal-spatial establishment of initial niche for the primary spermatogonial stem cells is determined by an ARID4B regulatory network. Stem Cells, 2017, Jun;35(6):1554-1565. doi: 10.1002/stem.2597. Epub 2017 Mar 16. PMID:28207192 (Featured article)
Mei-Yi Wu, Junjiang Fu, Xiuli Xiao, Jingbo Wu, and Ray-Chang Wu. MiR-34a Regulates Therapy Resistance by Targeting HDAC1 and HDAC7 in Breast Cancer. Cancer Letters, 2014 (in press).
Yi P., Xia W, Wu R.C., Lonard D.M., Hung M.C. and O'Malley B.W. (2013) SRC-3 coactivator regulates cell resistance to cytotoxic stress via TRAF4-mediated p53 de-stabilization. Genes & Development. (in press)
Wu R.C. *, Jiang M., Beaudet A.L., and Wu M.Y. (2013) ARID4A and ARID4B regulate male fertility, a functional link to the AR and RB pathways. Proc Natl Acad Sci U S A. (in press) *corresponding author
Wu, M.Y., Fu, J., Xu, J., O’Malley, B.W., and Wu R.C. Steroid receptor coactivator 3 regulates autophagy in breast cancer cells through macrophage migration inhibitory factor. Cell Research. 2012, in press.
Wu, M.Y, Jiang, M., Zhai, X., Beaudet, A., Wu, R.C. An Unexpected Function of the Prader-Willi Syndrome Imprinting Center in Maternal Imprinting in Mice. PLoS One, in press. 2012.
Liu Y, Tong Z, Li T, Chen Q, Zhuo L, Li Q, Wu RC, Yu C. Hepatitis B virus X protein stabilizes AIB1 protein and cooperates with it to promote human hepatocellular carcinoma cell invasiveness. Hepatology. 2012 Apr 2. doi: 10.1002/hep.25751. [Epub ahead of print] PMID: 22473901.
Sarachana T, Xu M, Wu R.C., Hu VW. Sex hormones in autism: androgens and estrogens differentially and reciprocally regulate RORA, a novel candidate gene for autism. PLoS One. 2011 Feb 16;6(2):e17116.
York B., Yu C., Sagen J.V., Liu Z., Nikolai B.C., Wu R.C., Finegold M., Xu J., O'Malley B.W. Reprogramming the posttranslational code of SRC-3 confers a switch in mammalian systems biology. Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):11122-7. PMID: 20534466
Xu J., Wu R.C., O'Malley B.W. (2009) Normal and cancer-related functions of the p160 steroid receptor co-activator (SRC) family. Nat. Rev. Cancer, 9(9):615-30. PMID: 19701241
Li C., Wu R.C., Amazit L., Tsai S.Y., Tsai M.-J., and O’Malley B.W. (2007) Specific amino acid residues in the bHLH domain of SRC-3 are essential for its nuclear localization and proteasome-dependant turnover. Mol. Cell. Biol., 27(4):1296-308. PMID: 17158932
Wu R.C., Feng Q., Lonard D.M. and O’Malley B.W. (2007) SRC-3 coactivator functional lifetime is regulated by a phospho-dependent ubiquitin time clock. Cell, 129(6):1125-40. PMID: 17574025
Wu R.C., Smith C.L., O’Malley B.W. Transcriptional regulation by steroid receptor coactivator phosphorylation. Endocrine Reviews. 2005 26 (3): 393-399. PMID: 15814849
Zheng F.F., Wu R.C., Smith C.L. and O’Malley B.W. Rapid estrogen-induced phosphorylation of SRC-3 coactivator occurs in an extranuclear complex containing estrogen receptor. Mol. Cell. Biol. 2005 Sep;25(18):8273-84. PMID: 16135815
Wu R.C., Qin J., Yi P., Wong J., Tsai S. Y., Tsai M.-J., and O’Malley B.W. (2004) Selective phosphorylations of the SRC-3/AIB1 coactivator integrate genomic responses to multiple cellular signaling pathways. Mol. Cell, 24;15(6):937-49. PMID: 15383283
Wu R.C., Qin J., Hashimoto Y., Wong J., Xu J., Tsai S.Y., Tsai M.-J., O'Malley B.W. (2002) Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator activity by I kappa B kinase. Mol. Cell. Biol., 22(10):3549-61. PMID: 11971985
Industry Relationships and Collaborations
This faculty member (or a member of their immediate family) has reported a financial interest with the health care related companies listed below. These relations have been reported to the University and, when appropriate, management plans are in place to address potential conflicts.
- None