Rugang Zhang, Ph.D.


It is well known that cancer is a disease caused by oncogene activation and inactivation of tumor suppressor genes. Paradoxically, activation of oncogenes or inactivation of tumor suppressor genes alone in primary mammalian cells often triggers a state of stable cell growth arrest, known as cellular senescence. Overcoming the senescence-associated cell growth arrest is a necessary step during cell transformation. It is therefore critical to understand the mechanistic basis of oncogenic signaling in the context of senescence induction and bypass. This biological process represents an ideal paradigm to examine the role of DNA damage response, epigenetically determined chromatin structure, and metabolic reprogramming during cancer initiation and progression.

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. We will pursue these issues in the coming years by focusing on the epigenetic SWI/SNF and PRC2 complexes as proof of principles in the context of ovarian cancer and melanoma.