Wen-Hwa Lee
Biological Chemistry, School of Medicine
Phone: (949) 824-4492
Email: whlee@uci.edu
http://www.ucihs.uci.edu/biochem/whlee/index.html
http://www.faculty.uci.edu/profile.cfm?faculty_id=5007
Wen Hwa Lee
Dr. Lee remains committed to the research of molecular cancer genetics, mainly specializing in the mechanism of tumor suppressor gene functions, cancer progression and novel therapy. He and his laboratory recently demonstrated that BRCA1 forms a repressor complex with CtIP and ZBRK1 at a ZBRK1 responsive element of the angiopoietin-1 promoter in mammary epithelial cells. A defect of this complex formation derepresses ANG1 transcription, promoting endothelial cell survival and vascular enlargement in a paracrine fashion. This enhanced angiogenesis contributes to an exacerbated malignancy of Brca1-deficient breast tumors. Thus, they unveiled a mechanism for how BRCA1 modulates the tumor microenvironment by transcriptional regulation. In addition, Dr Lee demonstrated that CtIP, a novel tumor suppressor, activates a subset of E2F-responsive promoters by releasing RB-imposed repression; and therefore, promotes G1/S progression. This is the major reason that CtIP contributes to tumor formation. Dr. Lee also works on the development of small molecules targeting to novel targets for therapeutic application. These compounds are effective against a broad range of cancer types including leukemia, breast, lung and brain tumors. He is working closely with organic chemists and structural biologists to refine these next generation compounds toward clinical application.
Selected Publications:
Chen, P. L., Liu, F., Cai, S., Lin, X., Li, A., Chen, Y., Gu, B., Lee, E. Y., and Lee, W. H. (2005). Inactivation of CtIP leads to early embryonic lethality mediated by G1 restraint and to tumorigenesis by haploid insufficiency. Mol Cell Biol 25(9), 3535-42.
Furuta, S., Jiang, X., Gu, B., Cheng, E., Chen, P. L., and Lee, W. H. (2005). Depletion of BRCA1 impairs differentiation but enhances proliferation of mammary epithelial cells. Proc Natl Acad Sci U S A 102(26), 9176-81.
Furuta, S., Wang, J. M., Wei, S., Jeng, Y. M., Jiang, X., Gu, B., Chen, P. L., Lee, E. Y., and Lee, W. H. (2006). Removal of BRCA1/CtIP/ZBRK1 repressor complex on ANG1 promoter leads to accelerated mammary tumor growth contributed by prominent vasculature. Cancer Cell 10(1), 13-24.
Poole , A. J., Li, Y., Kim, Y., Lin, S. C., Lee, W. H., and Lee, E. Y. (2006). Prevention of Brca1-mediated mammary tumorigenesis in mice by a progesterone antagonist. Science 314(5804), 1467-70.
Lin, X., Liu, C. C., Gao, Q., Zhang, X., Wu, G., and Lee, W. H. (2007). RINT-1 serves as a tumor suppressor and maintains Golgi dynamics and centrosome integrity for cell survival. Mol Cell Biol 27(13), 4905-16. |
