Organic Seminar - Dustin Maly

Numerous cellular processes depend on signaling enzymes that respond to stimuli with high spatial and temporal precision. As central regulators of numerous processes that control cell fate and frequent dysregulation in human disease, signaling enzymes are common molecular targets for the development of new therapies. The Maly Lab uses chemical genetic, chemoproteomic, and parallel functional profiling methods to study the molecular wiring and druggability of these enzymes. I will highlight our efforts to understand how active site-directed inhibitors modulate regions distal to their binding sites through allosteric regulatory networks. I will also describe LABEL-seq, a new protein profiling method that enables parallel functional analysis of thousands of protein variants. I will explain how the multiple functional properties measured with LABEL-seq reveal the allosteric wiring of mammalian signaling enzymes. Additionally, I will discuss how we've used LABEL-seq profiling to provide insight into drug sensitivity and resistance, as well as potential new mechanisms for drugging signaling enzymes.