Michael S. Cohen
Dr. Cohen is an Associate Professor in the Department of Physiology and Pharmacology at Oregon Health and Science University. The Cohen lab is developing chemical tools to illuminate the role of protein ADP-ribosylation in cells. ADP-ribosylation is a reversible posttranslational modification that is essential for cellular function, yet little information exists regarding relevant protein substrates and target specificity. ADP-ribosylation is catalysed by a family of 17 ubiquitously expressed enzymes in humans known as ADP-ribosyltransferases (ARTDs1-17 in humans; also known as PARPs), which transfer the ADP-ribose moiety from nicotinamide adenine dinucleotide (NAD+) to amino acids on target proteins. Progress in understanding the specific roles of a given ARTD has been limited by the inability to identify the direct targets for individual ARTDs in a cellular context and the lack of selective inhibitors for individual ARTD family members. My laboratory has designed orthogonal NAD+ analogue-engineered ARTD pairs for the identification of direct protein targets of individual ARTDs. We have successfully applied this approach toward the identification of the direct targets of several ARTD family members. We are also using structure-based design to generate selective inhibitors of individual ARTD family members. Taken together, the chemical tools generated in my laboratory will provide a more complete understanding of the biology of ADP-ribosylation.