We are interested in modulating the activity of chromatin reader proteins with small-molecule ligands, specifically potent and selective chemical probes, in order to open new avenues of research in the field of epigenetics. Our work has pioneered the biochemical assays and medicinal chemistry strategies for high quality probe development for methyl-lysine (Kme) reader proteins, as well as the means by which to evaluate probe selectivity, mechanism of action, and cellular activity. Using a variety of approaches, we utilize such chemical tools to improve our understanding of their molecular targets and the broader biological consequences of modulating these targets in cells. We are also interested in developing novel methods and screening platforms to discover hit compounds to accelerate Kme reader probe discovery, such as affinity-based combinatorial strategies, as well as innovative techniques utilizing our developed antagonists to more fully understand the dynamic nature of chromatin regulation.