Cancer Epigenetics - Zhiguo Zhang

Mission and Overview

Chromatin, an organized structure of proteins including histones and DNA in eukaryotic cells, governs diverse cellular processes including gene transcription, DNA replication and DNA repair. Inappropriate gain or loss of chromatin structure plays a causal role in carcinogenesis. For instance, like genetic mutations in tumor suppressor genes that cause cancer, epigenetic silencing of tumor suppressor genes plays a causal role in development of a variety of tumors. However, in contrast to permanent genetic mutations, epigenetic silencing is reversible. Thus, understanding how epigenetic silencing is achieved in normal cells will help us to control inappropriate gain or loss of tumor suppressor gene silencing in cancer cells and help find novel therapeutics for prevention and treatment of tumors. Toward this goal, we use both yeast and mammalian cells to study molecular mechanisms of epigenetic silencing and epigenetic inheritance. In the long run, we hope to find novel therapeutics to interfere with cancers caused by epigenetic alterations. Current research interests in my laboratory are:

1. Elucidate the molecular mechanisms by which nucleosome assembly is coupled to DNA replication during S phase of the cell cycle in budding yeast.
2. Discover small molecule inhibitors of yeast Rtt109.
3. Elucidate how two major mammalian nucleosome assembly pathways are regulated.
4. Understand how X-chromosome inactivation is maintained in mouse cells.