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Rugang Zhang, Ph.D.

Rugang Zhang, Ph.D.

Laboratory

The Zhang Laboratory

Contact

215-495-6840
rzhang@wistar.org

Deputy Director, The Wistar Institute Cancer Center

Professor & Co-Leader, Gene Expression & Regulation Program

About the Scientist

Zhang is committed to finding a cure for epithelial ovarian cancer, the most lethal gynecological malignancy in the developed world. In addition, he investigates the aging process of normal mammalian cells and its role in both tissue aging and cancer development for the discovery of therapeutic applications.

Born and educated in China, Zhang received his Ph.D. degree from the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences in 2002. He completed his post-doctoral training at the Institute for Cancer Research, Fox Chase Cancer Center, where he later became an Assistant Professor in 2008. Zhang joined The Wistar Institute as an Associate Professor in 2012 and was promoted to the rank of Full Professor in 2015. He is also an adjunct faculty at University of Pennsylvania.

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The Zhang Laboratory

The Zhang laboratory studies ovarian cancer biology with the goal of developing novel therapeutic approaches to combat the disease with precision. In particular, the lab investigates how alterations in epigenetics— or the heritable changes that affects gene expression without alterations in the underlying DNA sequence—contribute to epithelial ovarian cancer. The ultimate goal of this line of investigation is to leverage these newly gained mechanistic insights for developing new therapeutics in a personalized manner based on one’s unique genetic and/or pathway signatures.

The Zhang laboratory also investigates the mechanisms that underlie aging in normal mammalian cells and how this process is implicated in tissue aging or evaded by tumor cells during malignant transformation. In particular, the lab focuses on epigenetic and metabolic pathways that regulate the aging process. The overarching goal for identifying such mechanisms is the development of novel strategies to promote healthy aging and combat cancer.

Staff

Postdoctoral Fellows

Takeshi Fukumoto, M.D., Ph.D.
Sergey Karakashev, Ph.D.
Jianhuang Lin, Ph.D.
Pingyu Liu, Ph.D.
Timothy Nacarelli, Ph.D.
Shuai Wu, Ph.D.
Bo Zhao, Ph.D.

Graduate Students

Nail Fatkhutdinov
Joseph Zundell

Research Assistant

Elizabeth Magno

Research

Epigenetics of epithelial ovarian cancer

A major discovery in recent cancer genome-wide sequencing is the identification of significant genetic changes in chromatin-modifying genes. However, despite great strides in identifying the various epigenetic enzymes/factors involved in cancer, the translational application of these findings in cancer intervention remains to be explored. The Zhang lab will pursue these issues in the coming years by focusing on the epigenetic SWItch/Sucrose Non-Fermentable (SWI/SNF) and Polycomb repressive complex 2 (PRC2) complexes as proof of principles in the context of ovarian cancer.

a. Mechanism-guided therapeutic strategies for genetic alterations that affect the SWI/SNF chromatin remodeling complex in epithelial ovarian cancer (such as ARID1A mutation in clear cell and endometrioid subtypes of ovarian cancer, and CARM1 amplification/overexpression in high-grade serous ovarian cancer).

b. Epigenetic approaches to chemotherapy resistance and cancer stemness in epithelial ovarian cancer.

c. Epigenetic approaches to primer for and/or synergize with immunological therapy in epithelial ovarian cancer.

d. PARP inhibitors resistance mechanism and approaches to sensitizing BRCA-proficient ovarian cancer to PARP inhibitors.

 

Epigenetic and metabolic basis of cellular senescence

Cellular senescence is a state of stable cell growth arrest that is accompanied by drastic molecular and phenotypic changes. Cellular senescence is a major contributor to tissue aging and plays a context-dependent role in tumor development. For example, cellular senescence is tumor suppressive and overcoming the senescence-associated cell growth arrest is a necessary step during cell transformation. In contrast to its tumor suppressive function, senescent cells can also promote cancer by acquiring a secretory phenotype and create a pro-tumorigenic microenvironment. The biological process of cellular senescence represents an ideal paradigm to examine the role of the DNA damage response, epigenetically determined chromatin structure, and metabolic reprogramming during tissue aging and cancer development.

a. Chromatin basis of the senescence-associated secretory phenotype.

b. Targeting senescence-associated metabolic vulnerability to develop cancer therapeutics.

c. Targeting senescence-associated immunological vulnerability to develop cancer therapeutics.

Selected Publications

Karakashev, S., Zhu, H., Zhang, R., et al. " CARM1-expressing ovarian cancer depends on the histone methyltransferase EZH2 activity." Nat Commun. 2018 Feb 12;9(1):631. doi: 10.1038/s41467-018-03031-3.

Bitler, B.G., Wu, S., Zhang, R., et al. "ARID1A-mutated ovarian cancers depend on HDAC6 activity." Nat Cell Biol. 2017 Aug;19(8):962-973. doi: 10.1038/ncb3582. Epub 2017 Jul 24.

Aird, K.M., Iwasaki, O., Zhang, R., et al. "HMGB2 orchestrates the chromatin landscape of senescence-associated secretory phenotype gene loci." Cell Biol. 2016 Nov 7;215(3):325-334. Epub 2016 Oct 31.

Zhu, H., Bengsch, F., Zhang R., et al. "BET Bromodomain Inhibition Promotes Anti-tumor Immunity by Suppressing PD-L1 Expression." Cell Rep. 2016 Sep 13;16(11):2829-2837. doi: 10.1016/j.celrep.2016.08.032.

Bitler, B.G., Aird, K.M., Zhang, R., et al. "Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers." Nat Med. 2015 Mar;21(3):231-8. doi: 10.1038/nm.3799. Epub 2015 Feb 16.

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