Each human chromosome contains 50-250 x 10e6 base pairs of DNA that compacts into an orderly structure by interacting with chromosomal proteins. Together, the DNA and these chromosomal proteins are generically described as chromatin. In eukaryotic organisms, the ability to precisely regulate nuclear processes is hindered by the inherently repressive chromatin environment where DNA is tightly packaged with chromosomal proteins. The fundamental structural unit of chromatin is the nucleosome which consists of the core histone octamer (two each of histone proteins H2A, H2B, H3 and H4) and the associated 146 base pairs of DNA that wraps twice around them. The N-terminal "tails" of the histones protrude from the nucleosome to interact with the nuclear environment. The enzymatic addition or removal of various post-translational modifications on histones generates a "histone code" at specific genomic regions that directly function to regulate specific DNA-templated processes including transcription, replication, repair, recombination and chromosome structure. Importantly, the activities of chromatin-modifying proteins are frequently altered in many human pathologies including developmental and age-related diseases, such as cancer.

The overall goal of my lab is to elucidate the factors that establish and maintain the "histone code" and how their concerted functions regulate essential chromatin-dependent events including transcription, DNA replication and DNA repair. This is accomplished using a combination of conventional biochemical approaches and state-of-the-art technologies. Our long term goal is to translate these fundamental biological insights into novel epigenetic therapies for the treatment of human diseases.