Department of Biology
Breaking Bad: Lysine Methyl Signaling in Chromatin and Disease Regulation
My laboratory is interested in understanding the molecular mechanisms by which chromatin signaling networks effect nuclear and epigenetic programs, and how disruption in these mechanisms contribute to cancer and other pathologic states. Our work centers on the biology of protein lysine methylation, a principal chromatin-regulatory mechanism thought to be involved in directing epigenetic processes. We study how lysine methylation events are generated, sensed, and transduced, and how these chemical marks integrate with other modification and signaling systems to govern diverse functions. We previously identified the PHD finger and the BAH domain as methyl lysine-binding domains and provided evidence that disrupting the read-out of histone modifications can cause inherited human diseases. Another focus of the lab has aimed to characterize lysine methyltransferase (KMTs) and to identify novel methylation events on histone and non-histone proteins, including developing a proteome-wide strategy for quantitative analysis of methyl lysine. New results suggest that lysine methylation occurs widely across the proteome and that it may regulate the function of hundreds of proteins. I will discuss this work and new studies investigating KMTs in the regulation of cancer pathways.