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Our laboratory is interested in defining the changes in cell signaling that occur as tumors initiate, progress, and develop resistance to drugs, with the ultimate goal of inhibiting these processes. Part of our research focuses on study of NEDD9, a member of the Cas protein family. NEDD9 acts as a scaffold for signaling proteins that play essential roles in cancer progression and normal organismal development.  Part of the laboratory also addresses the biological functions of NEDD9-interacting proteins, including particularly an oncogenic kinase, Aurora-A.  Complementary projects use computer-based bioinformatic approaches to look for genes that sensitize cells to therapies targeted against cancer-promoting proteins such as EGFR. We hope through these studies to better define the interactions of signaling pathways in malignant versus normal cells, allowing improvements in cancer diagnosis and treatment.

1. Ratushny, V., Pathak, H.B., Beeharry, N., Tikhmyanova, N., Li, T., Litwin, S., Yen, T.J., Weiner, L.M., Godwin, A.K., and Golemis, E.A. Dual inhibition of SRC and Aurora kinases induces post-mitotic attachment defects and cell death. Oncogene, in press 2011.
2. Plotnikova, O.V., Pugacheva, E.P., and Golemis, E.A., Aurora-A kinase activity influences calcium signaling in kidney cells. J. Cell Biol 193:1021-1032, 2011. Pubmed
3. Astsaturov I, Ratushny V, Sukhanova A, Einarson M, Bagnyukova T, Zhou Y, Devarajan K, Silverman JS, Tikhmyanova N, Skobeleva N, Pecherskaya A, Nasto R, Jablonski SJ, Serebriiskii IG, Weiner LM, and Golemis EA. Synthetic lethal screen of an EGFR-centered signaling network defines clusters of proteins contributing to drug resistance. Science Signaling, 3(140):ra67, 2010. Pubmed
4. Plotnikova OV, Pugacheva EN, Dunbrack RL, Jr., and Golemis EA. Rapid calcium-dependent activation of Aurora-A kinase. Nature Commun. 1 : 64 doi: 10.1038/ncomms1061 Epub September 7, 2010. Pubmed
5. Singh, M.K., Izumchenko, E., Klein-Szanto, A., Egleston, B.L., Wolfson, M., Golemis, E.A. Enhanced genetic instability and dasatinib sensitivity in mammary tumor cells lacking Nedd9. Cancer Research 70:8907-8916, 2010. Pubmed
6. Izumchenko E, Singh MK, Plotnikova OV, Tikhmyanova N, Little JL, Serebriiskii IG, Seo S, Kurokawa M, Egleston BL, Klein-Szanto A, Pugacheva EN, Hardy RR, Wolfson M, Connolly DC, Golemis EA. HEF1/CAS-L/NEDD9 null status limits mouse mammary tumor progression. Cancer Res. 2009 Sep 15;69(18):7198-206. Pubmed
7. Singh MK, Dadke D, Nicolas E, Serebriiskii IG, Apostolou S, Canutescu A, Egleston BL, and Golemis EA. A novel Cas-family member, HEPL, regulates FAK and cell spreading. Mol Biol Cell, 19:1627-1636, 2008. Pubmed
8. Pugacheva EN, Jablonski SA., Hartman TR, Henske EP, and Golemis EA. HEF1-dependent Aurora A activation induces disassembly of the primary cilium. Cell 2007 Jun 29;129(7):1351-63. Pubmed