Rugang Zhang, Ph.D.

faculty photo
Department: Genetics
Graduate Group Affiliations

Contact information
The Wistar Institute
3601 Spruce Street
Room 308
Philadelphia, PA 19104
Office: 215-495-6840
Education:
B.Sc.
Anhui Normal University, Anhui, China, 1997.
Ph.D.
Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China, 2002.
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Description of Research Expertise

Research Interests:

To understand the basic mechanisms underlying oncogene-induced senescence, an important tumor suppression mechanism.
To identify novel intervention strategies for epithelial ovarian cancer (EOC), the most lethal gynecological malignancy in the developed world.

Key Words:

Cellular Senescence, Tumor Suppression, Chromatin Structure, Metabolism, Epithelial Ovarian Cancer, Epigenetic Cancer Therapy, Wnt signaling, Targeted Cancer Therapy Resistance, Tissue Aging

Research Details:

The Zhang laboratory studies the mechanisms that underlie how normal mammalian cells age and how tumor cells evade the process and become transformed. In particular, his laboratory is interested in how alterations in epigenetics—heritable changes that affects gene expression without changes in the underlying DNA sequence—lead to the evasion of the aging process during tumor development. Understanding these mechanisms could lead to novel strategies for developing cancer therapeutics by forcing tumor cells into the aging process. His laboratory primarily focuses on ovarian cancer, which ranks first as the cause of death for gynecological cancers in the developed world.

Rotation Projects for 2013-2015

1. Molecular mechanism that reconciles the tumor-suppressing role of oncogene-induced senescence with the tumor-promoting nature of oncogene.
2. Molecular basis underlying oncogene-induced senescence-associated stable cell growth arrest.
3. Novel epigenetic combinational therapeutic strategies for ovarian cancer.
4. PARP inhibitors resistance mechanism in "BRCAness" ovarian cancer.
5. Role of Wnt signaling in epithelial ovarian cancer.
6. Targeting polycomb repressive complex 2 in epithelial ovarian cancer.
7. Role of chromatin remodeling factors such as SWI/SNF complex components ARID1A and ARID2 in epithelial ovarian cancer and melanoma.

Lab personnel:

Benjamin Bitler, Ph.D., Postdoctoral Fellow (Supported by NIH/NCI K99/R00 Award)
Katherine Aird, Ph.D., Postdoctoral Fellow (Supported by NIH/NCI K99/R00 Award)
Hengrui Zhu, Ph.D., Postdoctoral Associate
Yuki Yokoyama, Ph.D., Postdoctoral Associate
Sergey Karakashev, Ph.D., Postdoctoral Associate
Linh Le, B.S., Predoctoral Student, CB/CAMB (Supported by T32GM007229 Fellowship)
Nail Fatkhutdinov, M.S., Predoctoral Student
Pyoung Hwa (Peace) Park, B.S., Technician

Selected Publications

Aird KM, Worth AJ, Snyder NW, Lee JV, Sivanand S, Liu Q, Blair IA, Wellen KE, Zhang R.: ATM couples replication stress and metabolic reprogramming during cellular senescence. Cell Reports 11(6): 893-901, 2015.

Zhao B, Zhang WD, Lu YQ, Cun YX, Li CH, Guo K, Nie WH, Li L, Zhang R, Zheng P. : ESC-specific protein Filia is a master regulator of DNA damage response and safeguards genomic stability of mouse ESCs. Cell Stem Cell 16(6): 684-98, 2015.

Bitler BG, Garipov A, Amatangelo M, Kossenkov A, Schultz DC, Shih IM, Conejo-Garcia JR, Speicher DW, Zhang R. : Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers. Nature Medicine 21(3): 231-238, 2015.

Rutkowski MR, Stephen TL, Svoronos N, Allegrezza MJ, Perales-Puchalt A, Tesone AJ, Escovar-Fadul X, Nguyen JM, Cadungog MG, Zhang R, Salatino M, Rabinovich GA, Tchou J, Conejo-Garcia JR. : Microbially driven TLR-dependent signalling governs distal malignant progression through tumor-promoting inflammation. Cancer Cell 27: 27-40, 2015.

Aird KM, Zhang G, Li H, Tu Z, Bitler BG, Garipov A, Wu H, Wei Z, Wagner SN, Herlyn M, Zhang R.: Suppression of Nucleotide Metabolism Underlies the Establishment and Maintenance of Oncogene-Induced Senescence. Cell Reports 3: 1252-1265, 2013.

Tu Z, Zhuang X, Yao YG, Zhang R.: BRG1 is required for formation of senescence-associated heterochromatin foci (SAHF) induced by oncogenic RAS or BRCA1 loss. Molecular and Cellular Biology 33: 1819-1829, 2013.

Tu, Z., Aird, K. M., Bitler, B. G., Nicodemus, J. P., Beeharry, N., Xia, B., Yen, T. J., Zhang, R.: Oncogenic RAS regulates BRIP1 expression to induce dissociation of BRCA1 from chromatin, inhibit DNA repair, and promote senescence. Developmental Cell 21(6): 1077-91, 2011.

Bitler, B. G., Nicodemus, J. P., Li, H., Cai, Q., Wu, H., Hua, X., Li, T., Birrer, M. J., Godwin, A. K., Cairns, P., Zhang, R.: Wnt5a suppresses epithelial ovarian cancer by promoting cellular senescence. Cancer Research 71(19): 6184-94, 2011.

Kennedy, A. L., Morton, J. P., Manoharan, I., Nelson, D. M., Jamieson, N. B., Pawlikowski, J. S., McBryan, T., Doyle, B., McKay, C., Oien, K. A., Enders, G. H., Zhang, R., Sansom, O. J., Adams, P. D.: Activation of the PIK3CA/AKT pathway suppresses senescence induced by an activated RAS oncogene to promote tumorigenesis. Molecular Cell 42(1): 36-49, 2011.

Li, H., Cai, Q., Godwin, A. K., Zhang, R.: Enhancer of zeste homolog 2 promotes the proliferation and invasion of epithelial ovarian cancer cells. Molecular Cancer Research 8(12): 1610-8, 2010.

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Last updated: 08/26/2015
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