OHSU

Michael S. Cohen, PhD

mcohen_pic

 

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
  • 2006-11LSRF Postdoctoral Fellow Weill Cornell Medical College, New York, NY

Research

The long-range goal of my research is to design and develop small molecule modulators of protein function that illuminate cellular processes relevant to human diseases. A current focus is the regulation of cellular signaling by polymeric post-translational modification (PPTM) of proteins, such as glutamylation, ubiquitination, and ADP-ribosylation. PPTMs are implicated in diverse cellular activities, including neuronal survival, long-term potentiation, mitosis, DNA repair, and cell-cycle regulation; as well as a number of pathologies, including cancer and neurodegeneration. Progress in understanding the functional roles of the enzymes that mediate PPTMs has been limited, however, by the absence of specific chemical modulators that can be used to dissect their roles in cellular signal transduction. To overcome this limitation, we are combining the tools of Chemistry and Genetics to develop chemical probes that specifically inhibit their activity. We anticipate that these studies will yield new insights into the role of PPTMs in cellular signal transduction, and will illuminate important molecular targets for therapeutic intervention in a variety of human diseases.

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).