Research In addition to establishing collaborative drug discovery projects since joining UNC in 2007, Dr. Frye initiated a more basic research program in his lab focused on methyl-lysine (Kme) as a post translational modification (PTM) central to the regulation of chromatin. This research has explored the ligandability of the more than 200 Kme reader domains that occur in several protein families within the human proteome with the goal of discovering the first chemical probes for these domains. The primary intent of a chemical probe is to establish the relationship between a molecular target, usually a protein whose function is somehow modulated by the probe, and the broader biological consequences of that modulation. In order to fulfill this purpose, a chemical probe must be profiled for selectivity, mechanism of action, and cellular activity, as the cell is the minimal system in which ‘biology’ can be explored. Dr. Frye’s published work has begun to define the assays and chemical strategies for probe development in this target-class, as well as new directions required for future progress.