Distinguished Research Fellow

EDUCATION AND POSITIONS HELD:

• B.S., Biology, National Taiwan Normal University, 1968-1972
• MS, Biochemistry, National Taiwan University, 1975-1977
• Ph.D., Molecular Biology, University of California at Berkeley, 1978-1981
• Postdoctoral, Molecular Biology, University of California at Berkeley, 1981-1982
• Research Scientist, Cetus Corporation at Berkeley, California, 1982-1983
• Visiting Scientist, Lawrence Berkeley Laboratory, Berkeley, 1983-1984
• Assistant Professor, Assoc. Professor, 1984-1990, Professor, 1990-1991, University of California at San Diego
• Professor/Chairman, Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 1991-2003
• Member, NIH Cell Biology & Physiology Study Section II, 1992-1996
• Member, NCI Cancer Center Study Group IRG A, 1998-2002
• Donald Bren Professor, 2003-present, Chairman, 2005- present, Department of Biological Chemistry, University of CA at Irvine

HONORS:

• A.P. McDermott Distinguished University Professor, UTHSC-SA, 1991
• NIH Director Lectureship, 1991
• Outstanding Scientific Achievement, SCBA, 1992
• Alcon Research Award, 1994
• Member, Sinica Academia, ROC, 1994
• F.E. Shideman-Sterling Award, Univ. of Minnesota, 1999
• Presidential Award, SCBA, 2001
• Outstanding Alumni Award, National Taiwan Normal University, 2002
• First Class Medal, Dept. of Health, Taiwan, 2002
• Inducted Member, Texas Hall of Fame for Science, Mathematics and Technology, 2003
• Donald Bren Chair Professorship, Univ. California , Irvine, 2003

RESEARCH INTERESTS:

This lab co-discovered the first human tumor suppressor gene, Retinoblastoma gene (RB), in late 1980 that plays essential roles in maintaining genomic stability and preventing tumor formation. Re-introduction of the wild-type Rb or p53 mediated by viral vectors suppresses tumor formation in animal studies. In addition, we have elucidated RB interaction networks, which modulate RB suppressing activity. One of the RB-interacting proteins, Hec1, is overly expressed in most cancer cells and plays essential roles in chromosome segregation by interacting with several proteins that modulate the G2/M phase. Inactivation of Hec1 led to cell death due to abnormal chromosomal segregation. Importantly, Hec1 is phosphorylated by a mitotic kinase, Nek2, which is essential for Hec1 function in chromosome segregation. We have identified small molecules that disrupt the interaction between Nek2 and Hec1, and may offer a novel agent to treat cancer.

In addition, we worked on two human breast cancer susceptibility genes, BRCA1 & BRCA2 and have established their dual participation in transcription regulation and DNA damage repair. BRCA1 has been shown to associate directly with the RAD50/MRE11/NBS1 complex, which functions in both non-homologous end-joining and homologous recombination repair of DNA double-strand breaks. The BRCA2 via its BRC repeats binds to RAD51, which catalyzes homologous DNA pairing and DNA strand exchange in an in vitro recombination reaction. Expression of a wild-type BRC repeat disrupted this interaction and rendered cells hypersensitive to gamma-irradiation and failed to activate the G2/M checkpoint. Small molecules that disrupt the interaction between BRC repeat and Rad51 have been isolated. These small compounds offer a potential to develop new combinatorial treatment with chemotherapy or radiation therapy.

SELECTED PUBLICATIONS

• Wei PC, Wang ZF, Lo WT, Su MI, Shew JY, Chang TC, Lee WH*., 2013, “A cis-element with mixed G-quadruplex structure of NPGPx promoter is essential for nucleolin-mediated transactivation on non-targeting siRNA stress.”, Nucleic acids research, 1;41(3):1533-43. (SCI)
• Zhu J, Zhou L, Wu G, Konig H, Lin X, Li G, Qiu XL, Chen CF, Hu CM, Goldblatt E, Bhatia R, Chamberlin AR, Chen PL, Lee WH, 2013, “A novel small molecule RAD51 inactivator overcomes imatinib-resistance in chronic myeloid leukaemia.”, EMBO molecular medicine, 2013 Jan 22. doi: 10.1002/emmm.201201760. [Epub ahead of print]. (SCI)
• Chang PH, Hwang-Verslues WW, Chang YC, Chen CC, Hsiao M, Jeng YM, Chang KJ, Lee EY, Shew JY*, Lee WH*, 2012, “Activation of Robo1 signaling of breast cancer cells by Slit2 from stromal fibroblast restrains tumorigenesis via blocking PI3K/Akt/beta-catenin pathway.”, Cancer research, 72(18), 4652-61. (SCI)
• Tyan SW, Hsu CH, Peng KL, Chen CC, Kuo WH, Lee EY, Shew JY, Chang KJ, Juan LJ*, Lee WH*, 2012, “Breast cancer cells induce stromal fibroblasts to secrete ADAMTS1 for cancer invasion through an epigenetic change.”, PloS one, 7(4), e35128. (SCI)
• Wei PC, Hsieh YH, Su MI, Jiang X, Hsu PH, Lo WT, Weng JY, Jeng YM, Wang JM, Chen PL, Chang YC, Lee KF, Tsai MD, Shew JY*, Lee WH*, 2012, “Loss of the Oxidative Stress Sensor NPGPx Compromises GRP78 Chaperone Activity and Induces Systemic Disease.”, Molecular cell, 48(5), 747-59. (SCI)
• Chen PL, Chen CF, Chen Y, Guo XE, Huang CK, Shew JY, Reddick RL, Wallace DC, Lee WH, 2012, “Mitochondrial genome instability resulting from SUV3 haploinsufficiency leads to tumorigenesis and shortened lifespan.”, Oncogene, 2012 May 7. doi: 10.1038/onc.2012.120. [Epub ahead of print]. (SCI)
• Wei PC, Lo WT, Su MI, Shew JY, Lee WH*., 2012, “Non-targeting siRNA induces NPGPx expression to cooperate with exoribonuclease XRN2 for releasing the stress.”, Nucleic acids research, 40(1):323-32. (SCI)
• Hwang-Verslues WW, Chang PH, Wei PC, Yang CY, Huang CK, Kuo WH, Shew JY, Chang KJ, Lee EY, Lee WH, 2011, “miR-495 is upregulated by E12/E47 in breast cancer stem cells, and promotes oncogenesis and hypoxia resistance via downregulation of E-cadherin and REDD1.”, Oncogene, 30(21), 2463-74. (SCI)