Cancer Institute

  • Wael M. ElShamy

    Associate Professor of Biochemistry
    Director, Molecular Cancer Therapeutics Program
    PhD, Molecular Neurobiology, 1998, The Royal
    Karolinska for Medical Research, Stockholm, Sweden
    Postdoc, Cancer Biology, 1999-2002, Dana Farber
    Cancer Institute, Boston, MA,
    Instructor 2002-06, Medicine, Harvard Medical School, Boston, MA,

    Contact information
    2500 N. Jackson State St., G362
    Jackson, MS 39216
    Phone:(601) 815-6814
    E-mail: welshamy@umc.edu

     elshamy_wael.jpg

    Research interests

    • Translational Research in breast and ovarian cancer
    • Molecular biology study of BRCA1-IRIS and Geminin in breast and ovarian cancer metastases
    • Development of drugs and/or drug regimens to target breast and ovarian cancer metastases

    Research synopsis

    Recently, we discovered the novel oncogene, BRCA1-IRIS. Overexpression of BRCA1-IRIS in mammary or ovarian epithelial cells triggers aggressive traits, suggesting that BRCA1-IRIS is involved in the induction of metastasis in breast and ovarian cancer. The goal of our lab is to understand the cellular and molecular basis for BRCA1-IRIS' effects on mammary and ovarian epithelial cells, and to use this information to develop a BRCA1-IRIS-specific inhibitor for clinical use in preventing metastasis in cancer patients. We also rediscovered Geminin as an oncogene. Besides being an endogenous DNA-replication inhibitor, we found that Geminin is also involved in promoting cytokinesis and cell division when expressed at normal levels. In cancer cells, e.g. breast and ovarian cancer cells, Geminin overexpression causes cytokinesis to skip, resulting in tetraploid/aneuploid cells. Increasing amounts of evidence point to aneuploidy as a major cause of cancer metastasis. During the cell cycle, Geminin solubility oscillates, with soluble protein during S phase and insoluble protein in G2/M phase, in a phosphorylation -dependant manner. In G2/M, Geminin is bound to chromatin, centromeres and centrosomes and at the midbody during cytokinesis. When overexpressed, Geminin inhibits the function of several important mitotic-inducing proteins, such as Topoisomerase IIα and Aurora B kinase, leading to cytokinesis-skipping and the formation of tetraploid/aneuploid cells, and most likely metastatic cells in vivo. Our broader goals are to map these interactions on a molecular level, and use this information to find drugs or drug regimes that can inhibit Geminin or any of its interacting partners in cancer cells. Again, the ultimate goal is to find a drug to prevent the metastatic effects of Geminin in a clinical setting, saving patient lives.

    Recent accomplishments and honors

    • 2010 - Session Chair, BIT 3rd Annual World Cancer Congress-2010; Health Science without borders
    • 2009 - American Cancer Society scholar; Dr. Lawrence and Mrs. Bo Hing Chen Tsue American Cancer Society Scholar

    Selected publications

    • Chock K, Allison JM, ElShamy WM. BRCA1-IRIS overexpression abrogates UV-induced p38MAPK/p53 and promotes proliferation of damaged cells. Oncogene. 2010;29(38):5274-85.
    • Chock KL, Allison JM, Shimizu Y, ElShamy WM. BRCA1-IRIS overexpression promotes cisplatin resistance in ovarian cancer cells. Cancer Res. 2010;70(21):8782-91.
    • Hao L, ElShamy WM. BRCA1-IRIS activates cyclin D1 expression in breast cancer cells by downregulating the JNK phosphatase DUSP3/VHR. Int J Cancer. 2007;121(1):39-46.
    • Nakuci E, Xu M, Pujana MA, Valls J, ElShamy WM. Geminin is bound to chromatin in G2/M phase to promote proper cytokinesis. Int J Biochem Cell Biol. 2006;38(7):1207-20.
    • ElShamy WM, Livingston DM. Identification of BRCA1-IRIS, a BRCA1 locus product. Nat Cell Biol. 2004;6(10):954-67.