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Ovarian cancer is the eighth most common cancer in women and ranks first as the cause of death for gynecological cancers. Obviously, there is an urgent need to develop novel prevention and treatment methods for ovarian cancer. To do this, we must better understand key early events associated with ovarian cancer initiation and progression to identify important pathways that can ultimately be targeted with therapeutics.

The main focus of the laboratory is to understand the molecular and cellular basis of ovarian cancer initiation and progression. Specifically, we are interested in the role of cellular senescence, a state of irreversible cell growth arrest, in suppressor of epithelial ovarian cancer development. In addition, we are investigating how alterations in Wnt signaling pathway contribute to ovarian cancer development. The knowledge gained from these studies may ultimately lead to development of novel markers for ovarian cancer early detection and prognosis, and identification of novel therapeutic targets for ovarian cancer treatment.

1. Li H, Bitler BG, Vathipadiekal V, Maradeo ME, Slifker M, Creasy CL, Tummino PJ, Cairns P, Birrer MJ and Zhang R. ALDH1A1 is a novel EZH2 target gene in epithelial ovarian cancer identified by genome-wide approaches. Cancer Prevention Research. In press.
2. Tu Z, Aird KM, Bitler BG, Nicodemus JP, Beeharry N, Xia B, Yen T and Zhang R. Oncogenic Ras regulates BRIP1 expression to induce dissociation of BRCA1 from chromatin, inhibit DNA repair, and promote senescence. Developmental Cell. In press.
3. Bitler BG, Nicodemus JP, Li H, Cai Q, Wu H, Hua X, Li T, Birrer MJ, Godwin AK, Cairns P and Zhang R. Wnt5a suppresses epithelial ovarian cancer by promoting cellular senescence. Cancer Research. 2011 Oct 1;71(19):6184-94. Epub 2011 Aug 4.PubMed
4. Kennedy AL, Morton JP, Manoharan I, Nelson DM, Jamieson NB, Pawlikowski JS, McBryan T, Doyle B, Mckay C, Oien KA, Enders GH, Zhang R, Sansom OJ and Adams PD. Activation of the PIK3CA/AKT pathway suppresses senescence induced by an activated RAS oncogene to promote tumorigenesis. Molecular Cell. 2011 Apr 8; 42(1): 36-49.PubMed
5. Li H, Cai Q, Godwin AK and Zhang R. Enhancer of zeste homolog 2 (EZH2) promotes the proliferation and invasion of epithelial ovarian cancer cells. Molecular Cancer Research. 2010 Dec; 8 (12): 1610-8.PubMed
6. Poleshko A, Einarson MB, Shalginskikh N, Zhang R, Adams PD, Skalka AM, Katz RA. Identification of a functional network of human epigenetic silencing factors. Journal of Biological Chemistry. 2010 Jan 1;285(1):422-33. PubMed
7. Ye X, Zerlanko B, Kennedy A, Banumathy G, Zhang R, Adams PD. Downregulation of Wnt signaling is a trigger for formation of facultative heterochromatin and onset of cell senescence in primary human cells. Molecular Cell. 2007 Jul 20;27(2):183-96. PubMed
8. Zhang R, Chen W, Adams PD. Molecular dissection of formation of senescence-associated heterochromatin foci. Molecular and Cellular Biology. 2007 Mar;27(6):2343-58. PubMed
9. Zhang R, Liu ST, Chen W, Bonner M, Pehrson J, Yen TJ, Adams PD. HP1 proteins are essential for a dynamic nuclear response that rescues the function of perturbed heterochromatin in primary human cells. Molecular and Cellular Biology. 2007 Feb;27:949-62. PubMed
10. Zhang R, Poustovoitov MV, Ye X, Santos HA, Chen W, Daganzo SM, Erzberger JP, Serebriiskii IG, Canutescu AA, Dunbrack RL, Pehrson JR, Berger JM, Kaufman PD, Adams PD. Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Developmental Cell. 2005 Jan;8(1):19-30. PubMed