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

Honors and Awards:

  • Outstanding Performance for Teaching Assistants Finalist, 2016
  • Microbiology, Immunology and Cancer Biology Travel Award, 2016
  • T 32 Cancer Biology Training Grant, 2017
  • Doctoral Dissertation Fellowship, 2017 (awarded but declined)


Research:
Epithelial ovarian carcinoma (EOC) is the most lethal gynecologic cancer in the United States. An estimated 75% of women with EOC present with advanced disease, having already reached stage III or IV at the time of diagnosis.  For these patients, adjuvant therapy with platinum- and taxane- based agents is the standard of care. Unfortunately, although the initial response rate to these 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 5-year survival rate of just 30% for patients with advanced EOC. Thus, to identify novel prognostic markers and therapeutic targets, it is vital to understand the mechanisms underlying chemoresistance.

Our long term goal is to understand the clinical mechanism of resistance to paclitaxel, the most widely prescribed chemotherapy agent for treatment of human cancers. 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. Preliminary data from our lab indicate paclitaxel-resistant ovarian cancer cell lines and clinical specimens have elevated levels of a protein called UNC-45A, or general cell UNC-45. UNC-45A is known to be highly expressed in serous ovarian carcinoma tissue compared to normal ovarian surface epithelium, and UNC-45A expression levels are also associated with ovarian cancer progression. Recently generated data from our laboratory provide strong evidence that UNC-45A additionally acts as a novel microtubule-associated protein (MAP) with potent microtubule (MT) destabilizing properties. My thesis work aims to define mechanisms through which UNC-45A destabilizes MTs and antagonizes the effect of paclitaxel.

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 .May 24; 7(21):30962-76.
  • 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.
  • Mooneyham A, Bazzaro M. Targeting Deubiquitinating Enzymes and Autophagy in Cancer. Cancer Gene Networks. 2017;1513:49-59.
  • Yoshie Iizuka, Ashley Mooneyham, Andrew Sieben, Kevin Chen, Makayla Maile, Raffaele Hellweg, Florian Schütz, Kebebush Teckle, Timothy Starr, Venugopal Thayanithy, Rachel Isaksson Vogel, Emil Lou,  Michael K. Lee, and Martina Bazzaro. UNC-45A is Required for Neurite Initiation and Extension via Controlling NMII activation. Molecular Biology of the Cell. 2017 Mar 29.