Michael S. Cohen, PhD
Primary AffiliationAssociate Professor of Physiology and Pharmacology
SOM-Physiology and Pharmacology Department
Background & Education
2000 B.S. Chemistry, cum laude University of California, Irvine, CA
2006 Ph.D. Chemical Biology University of California, San Francisco, CA
2006-11 LSRF Postdoctoral Fellow Weill Cornell Medical College, New York, NY
2015 Pew Biomedical Scholar
The long-range goal of our research program is understand the role of nicotinamide adenine dinucleotide (NAD+) in cell signaling. In addition to its well-known role as a co-factor in redox metabolism, NAD+ is used as a substrate for posttranslational modifications. One such posttranslational modification is ADP-ribosylation, which is implicated in diverse cellular activities, including transcriptional and translational regulation. ADP-ribosylation was originally thought to be catalyzed by a single enzyme, ARTD1 (ADP-ribosyltransferase 1), but a family of 17 proteins is now recognized in humans that shares structural homology to the ARTD1 catalytic domain. Progress in understanding the specific role of individual ARTDs in cells types has been limited by (i) the lack of selective ARTD inhibitors, and (ii) the inability to identify the direct targets for individual ARTDs in a cellular context. Most ARTD inhibitors are non-selective and do not distinguish among family members due to the highly conserved nature of their catalytic domains. Likewise, ARTDs share the same substrate, NAD+, making the determination of the direct targets of individual ARTDs in a cellular context a major challenge. To overcome these limitations, we are combining chemistry and molecular design to develop selective inhibitors of individual ARTD family members, and NAD+ analogues that are specific substrates for engineered ARTDs and not used by wild-type ARTDs. We are using these novel chemical tools to probe the role of ADP-ribosylation in cell signaling in the brain.
Contact InformationMichael Cohen, PhD
3181 SW Sam Jackson Park Rd.
Portland, OR 97239-3098
ph: (503) 418-1363
fax: (503) 494-4352
Cambronne, X.A.*,Stewart, M.L., Kim, D., Jones-Brunette, A.M., Morgan, R.K., Farrens, D.L.,Cohen, M.S.*, Goodman, R.H. "Biosensor reveals multiple sources formitochondrial NAD+," Science 352, 1474 (2016).
Barrett R.M., Liu H.W., Jin H., Goodman R.H., and Cohen M.S. "Cell-specific Profiling of Nascent Proteomes Using Orthogonal Enzyme-mediated Puromycin Incorporation," ACS Chemical Biology April ASAP (2016).Carter-O'Connell, I.O., Jin H., Morgan, R.K., David, L.L., and Cohen. M.S. "Decoding the MARylome: A Chemical Genetic Strategy for Identifying Family-member Specific Targets of Mono-ARTDs," Cell Reports, 14 (2016). pdf link
Huang, J., Wang, K., Vermehren-Schmaedick, A., Adelman, J., Cohen, M.S. "PARP6 is a regulator of Hippocampal Dendritic Morphogenesis," Scientific Reports (Nature), 6, 18512 (2016). pdf link
Morgan, R.K., Carter-O'Connell, I.O., and Cohen, M.S. "Selective inhibition of PARP10 using a chemical genetics strategy," Bioorganic Medicinal Chemistry Letters, 25, 4770 (2015).
Morgan, R.K. and Cohen, M.S. "A Clickable Aminooxy Probe for Monitoring Cellular ADP-ribosylation," ACS Chemical Biology, 10, 1778 (2015).
Carter-O'Connell, I.O. and Cohen, M.S. "Identifying Direct Protein Targets of Engineered Poly-ADP-ribose Polymerases (PARPs) Using Modified Nicotinamide Adenine Dinucleotide Reporters," Current Protocols in Chemical Biology, (2015).Carter-O'Connell IO, Jin H, Morgan RK, David LL, Cohen MS. "Engineering the substrate specificity of ADP-ribosyltransferases for identifying direct protein targets," Journal of the American Chemical Society, online March (2014). Complete Publication list