pavla-brachova@uiowa.edu
Mentor: Kimberly Leslie, M.D.
Lab Room: 3234 MERF
Lab Phone: 319-335-8212

Overcoming resistance to chemotherapy in gynecologic cancers by inhibiting PLK1.

Tumors of advanced gynecologic origin frequently have poor prognosis. Ovarian cancer is the most lethal gynecologic malignancy, and endometrial cancer is the most common. To achieve long term survival with advanced endometrial and ovarian cancer, we must enhance sensitivity to frontline therapy.

For my thesis work, I will be investigating the ability of PLK1 inhibition to overcome taxane resistance. Work in the Leslie lab has shown that PLK1 inhibition abrogates the G2/M checkpoint and causes cancer cells to entire mitosis prematurely. These cells die by a mechanism similar to mitotic catastrophe. We hypothesize that PLK1 inhibition can overcome taxane resistance by blocking multiple arms of mitosis compared to taxanes, which only affect mitotic spindle formation. I will use patient tumor samples as well as ascites fluid as modes for these studies.

Publications:

Meng X, Zhu D, Yang S, Wang X, Xiong Z, Zhang Y, Brachova P, Leslie KK. Cytoplasmic Metadherin (MTDH) provides survival advantage under conditions of stress by acting as RNA-binding protein. J Biol Chem. 2012 Feb 10;287(7):4485-91. Epub 2011 Dec 23. PubMed PMID: 22199357; PubMed Central PMCID: PMC3281628.

Meng X, Brachova P, Yang S, Xiong Z, Zhang Y, Thiel KW, Leslie KK. Knockdown of MTDH sensitizes endometrial cancer cells to cell death induction by death receptor ligand TRAIL and HDAC inhibitor LBH589 co-treatment. PLoS One. 2011;6(6):e20920. Epub 2011 Jun 8. PubMed PMID: 21687633; PubMed Central PMCID:PMC3110819.

Abstracts:

Meng X, Brachova P, Yang S, Xiong Z, Zhang Y, Leslie KK. Knockdown of Metadherin sensitizes cell death induction by death receptor ligand TRAIL and HDAC inhibitor LBH589 co-treatment. AACR meeting, Orlando Florida, 2011.