Erica A. Golemis, PhD
Office Phone: 215-728-2860
In disease states such as cancer, tumors reprogram their signaling to support abnormal growth processes. 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. Our laboratory studies the activity of a signaling scaffold, NEDD9, and interacting proteins such as the oncogenic kinase Aurora-A, to understand the requirement for their action in normal cells, tumors, and in a genetic condition, polycystic kidney disease, that conserves many features of cancer. Our laboratory also focuses on improving the use of preclinical and clinically approved drugs that target signaling in these pathways, with a growing emphasis on the use of HSP90-targeted agents to allow general blockade of signaling pathways. Increasingly, these studies incorporate analysis of underlying genetic features of tumors, through use of next generation sequencing and bioinformatic interpretation. 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.Description of research projects
Fox Chase Programs
- Nikonova, A.S., Serzhanova, V., Plotnikova, O.V., Efimov, A., Bogush, I., Cai, K.Q., Egleston, B.L., Klein-Szanto, A.S., Seeger-Nukpezah, T.N., and Golemis, E.A. Nedd9 restrains renal cystogenesis in Pkd1-/- mice. Proc Nat Acad Sci 111:12859-64, 2014.
- Little, J.L., Serzhanova, V., Izumchenko, E., Egleston, B.L., Parise, E., Klein-Szanto, A.J., Loudon, G., Shubina, M., Seo, S., Kurokawa, M., Ochs, M.F., and Golemis, E.A. A requirement for Nedd9 in luminal progenitor cells prior to mammary tumorigenesis in MMTV-HER2/ErbB2 mice. Oncogene, 33:411-420, 2014.
- Seeger-Nukpezah, T., Proia, D.A., Egleston, B.L., Nikonova, A.S., Kent, T., Cai, K.Q., Hensley, H.H., Ying, W., Chimmanamada, D., Serebriiskii, I.G., and Golemis, E.A. A novel Hsp90 inhibitor slows cyst growth in a mouse model of autosomal dominant polycystic kidney disease (ADPKD). Proc. Nat. Acad Sci. 110:12786-91, 2013.
- Sukhanova, A., Gorin, A., Serebriiskii, I.G., Gabitova, L., Zheng, H., Restifo, D., Egleston, B., Cunningham, D., Bagnyukova, T., Liu, H., Nikonova, A., Adams, G.P., Zhou, Y., Yang, D., Mehra, R., Burtness, B., Cai, K.Q., Klein-Szanto, A., Kratz, L.E., Kelley, R.I., Weiner, L.M., Herman, G.E., Golemis, E.A., and Astsaturov, I. Targeting C4-demethylating genes in the cholesterol pathway sensitizes cancer cells to EGFR inhibitors via increased EGFR degradation. Cancer Discovery, Jan;3(1):96-111. doi: 10.1158/2159-8290.CD-12-0031, 2013.
- Plotnikova, O.V., Nikonova, A.S., Pugacheva, E.N., and Golemis, E.A. Calmodulin activation of Aurora-A (AURKA) is required during ciliary disassembly and in mitosis. Mol Biol Cell 23:2658-70, 2012.
- 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 31(10):1217-27, 2012 Epub Jul 25, 2011.
- 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.
- Astsaturov, I., Ratushny, V., Sukhanova, A., Einarson, M., Bagnyukova, T., Zhou, Y., Devarajan, K., Silverman, J.S., Tikhmyanova, N., Skobeleva, N., Pecherskaya, A., Nasto, R., Jablonski, S.J., *Serebriiskii, I.G., *Weiner, L.M., and *Golemis, E.A. Synthetic lethal screen of an EGFR-centered signaling network defines clusters of proteins contributing to drug resistance. Science Signaling, 3(140):ra67, 2010.