Area of Expertise:
Chromatin and histone modifications: In the eukaryotic cell, the precise organization and regulation of chromatin is critical for many cellular processes such as transcription, replication, recombination, repair, and chromosomal segregation. Although chromatin is defined as DNA associated with proteins, the fundamental repeating unit of chromatin is the nucleosome. The nucleosome consists of two copies of each core histone protein (H3, H4, H2A, and H2B) and 146 base pairs of DNA that wraps twice around them. Histone proteins contain a central histone-fold domain and N- and C-terminal tail domains that are subjected to extensive posttransitional modifications. Since posttransitional modifications on histones such as acetylation, phosphorylation, ubiquitination, and/or methylation can influence the chromatin environment and ultimately gene expression, we are interested in studying the enzymes and their associated proteins that mediate these modifications and how misregulation of these enzymes can lead to a disease state.
Histone methyltransferases and Cancer: Many SET domain-containing proteins have been associated with human cancers suggesting that they play an important regulatory roll in the cell. However, only a few have been identified as histone methyltransferases such as MLL1 and EZH2. Many of these SET domain-containing proteins are found either mutated, chromosomal translocated, or over-expressed when isolated from oncogenic cells. Therefore, we are interested in determining how mis-regulation and/or aberrant expression of these methyltransferases can lead to an oncogenic event and how aberrant histone methylation may play a role in oncogenesis.