OHSU

Michael S. Cohen, PhD

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Primary Affiliation

Assistant Professor of Physiology and Pharmacology

Program Affiliation

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

Research Summary

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.

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Meet the Lab

Publications

 

Contact Information


L334/BRB621
3181 SW Sam Jackson Park Rd.
Portland, OR 97239-3098
ph: (503) 418-1363
fax: (503) 494-4352


Selected Publications

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).

 Cohen, M.S., Ghosh, A.K., Kim, H.J., Jeon, N.L., and Jaffrey, S.R. “Chemical Genetic-Mediated Spatial Regulation of Protein Expression in Neurons Reveals an Axonal Function for WldS,” Chemistry and Biology, 19, 179 (2012).

Cohen, M.S., Bas Orth, C., Kim, H.J., Jeon, N.L., and Jaffrey, S.R. “Neurotrophin-mediated dendrite to nucleus signaling revealed by microfluidic compartmentalization of dendrites,” PNAS, 108, 11246 (2011).

Cohen, M.S., Hadjivassiliou, H., and Taunton, J.  “A Clickable inhibitor reveals Context-dependent RSK autoactivation,” Nature Chemical Biology, 3,156 (2007).

Cohen, M.S., Zhang, C., Shokat, K.M., and Taunton, J.  “Structural bioinformatics-based design of selective, irreversible kinase inhibitors,” Science, 308, 1318 (2005).

Open Positions

Graduate students: The Cohen lab is open to graduate students with diverse interests, including chemical synthesis, drug design, pharmacology, cell biology, neuroscience, and cancer. Interested students should email Michael Cohen (cohenmic at ohsu.edu).