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 silencing of tumor suppressor genes in cancer cells and help to find novel therapeutics for prevention and treatment of tumors. Toward this goal, we have chosen yeast as a eukaryotic model system to study molecular mechanisms of epigenetic silencing. Moreover, we are also interested in translating what we have learned in yeast to the study of silencing of tumor suppressor genes in cancer cells. 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. Determining the role of histone H3 and H4 chaperones such as chromatin assembly factor 1 (CAF-1), Asf1, and Rtt106 in epigenetic silencing.
2. Regulating genome stability by a novel histone acetyltransferase Rtt09 that we have recently discovered.
3. Profiling epigenetic alterations, especially alterations on histone modifications in gliomas.