University of Minnesota
MICaB Graduate Program
http://micab.umn.edu
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Current Students

Sexton
Ashley Mooneyham

E-mail:sexto117@umn.edu

Thesis Advisor: Martina Bazzaro

Year entered: 2014

Degrees received:
B.S., University of Wisconsin, Eau Claire, WI, 2014

Research:
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.

Publications:

  • 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.