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B.S., University of Wisconsin, Eau Claire, WI, 2014
Epithelial ovarian carcinoma (EOC) is the most lethal gynecologic cancer in the United States. Although initial response rate to platinum- and taxane- based chemotherapeutic agents is over 80%, progression-free survival after treatment is only 18 months. Moreover, the response rate to currently available chemotherapeutic agents diminishes with each relapse, leading to a 5-year survival rate of just 30%. Our long term goal is to understand the clinical mechanism of resistance to paclitaxel, which is a cornerstone of first-line treatment and also recommended for single-agent use upon recurrence. Paclitaxel targets rapidly dividing cancer cells by binding to and stabilizing beta-tubulin subunits of polymerized microtubules. This stabilization causes detrimental effects on the cell cycle, leading to cell death. It has been suggested that the quantity of stable microtubules within a cell impacts paclitaxel-mediated cytotoxicity. Therefore, it is important to elucidate the details of microtubule modulation within a cell as a potential mechanism of paclitaxel resistance. Preliminary data from our lab suggests UNC-45A, a conserved member of the UCS protein family, is a key modulator of microtubule stability and has an impact on paclitaxel sensitivity. We aim to mechanistically define how UNC-45A is regulating microtubule stability and investigate the translational potential of UNC-45A as a predictor of paclitaxel resistance in patients.
Vogel, R. I., T. Pulver, W. Heilmann, A. Mooneyham, S. Mullany, X. Zhao, M. Shahi, J. Richter, M. Klein, L. Chen, R. Ding, G. Konecny, S. Kommoss, B. Winterhoff, R. Ghebre, M. Bazzaro. 2016. USP14 is a predictor of recurrence in endometrial cancer and a molecular target for endometrial cancer treatment. Oncotarget.
Griffin, P., A. Sexton, L. Macneill, Y. Iizuka, M. K. Lee, and M. Bazzaro. 2015. Method for measuring the activity of deubiquitinating enzymes in cell lines and tissue samples. J Vis Exp. 10;(99):e52784.