Chemistry-based strategies for investigating protein ADP-ribosylation: a QBI Online Seminar with Michael Cohen

The QBI Online Seminar Series presents Michael Cohen, an associate professor in the Department of Chemical Physiology and Biochemistry at Oregon Health and Science University (OHSU). Dr. Cohen received his BS in chemistry (cum laude) from UC Irvine and a PhD in chemical biology from UC San Francisco. During his graduate studies under the guidance of Dr. Jack Taunton, he designed and synthesized cysteine-targeted, covalent inhibitors of protein kinases using a structural bioinformatics-based approach. As a Life Sciences Research Foundation postdoctoral fellow in the lab of Dr. Samie Jaffrey at Cornell Medical College, he developed a combined microfluidic and chemical genetic approach for studying spatial signaling in neurons. In 2011 Dr. Cohen started his independent career at OHSU.

The Cohen lab is focused on two main areas:

1. Uncovering new roles for nicotinamide adenine dinucleotide (NAD) regulation in cells.
2. Elucidating the function of post-translational modifications (PTMs) mediated by enzymes that use NAD as a substrate.

A current focus is on the evolutionarily conserved PTM known as ADP-ribosylation. The Cohen lab seeks to understand the impact ADP-ribosylation on cell function as a strategy for therapeutic development. ADP-ribosylation is catalyzed by a family of enzymes known as PARPs, 17 in humans), and involves the transfer of ADP-ribose from NAD to amino acids in target proteins. Despite being called PARPs, most of the family members catalyze mono-ADP-ribosylation (MARylation) and not poly-ADP-ribosylation (PARylation). Over the past eight years they have developed novel chemical tools and approaches, including orthogonal NAD analogue-enzyme pairs and selective PARP inhibitors, which have provided insights into the function of PARP-mediated MARylation in ways not attainable with conventional methods. Dr. Cohen has received several awards and honors, including the Pew Biomedical Scholarship and the International Society for Chemical Biology Young Chemical Biologist Award.