He is senior vice president of global research at Amgen and a visiting associate at the California Institute of Technology (Caltech).
[5] Upon starting his laboratory at Caltech, Deshaies studied the function of Cdc34 and how it relates to progression through the cell division cycle.
These studies led his laboratory to discover the SCF complex SCFCdc4,[6] which is the progenitor of what is now known to be a large family of ~250 enzymes known as cullin–RING ubiquitin ligases (CRLs) that are conserved throughout eukaryotes and exert a major impact on the regulation of numerous cellular and organismal processes.
In 2001-2002, the Deshaies lab showed that CSN, together with proteasome subunit Rpn11/PSMD14, are the founding members of a novel family of deubiquitinating enzymes.
[14][15] CSN plays a key role in regulating SCF and other CRL enzymes by removing the ubiquitin-like protein NEDD8 from their cullin subunit.
[18] In subsequent work they discovered that the Rpn11 subunit mediates removal of polyubiquitin chains from proteasome substrates as they are being degraded.
This was followed by identifying novel functions for p97, including removal of proteins from chromatin as part of the DNA damage response [21] and extraction of stalled, nascent polypeptides from the ribosome.
[25] In addition, they discovered (in collaboration with Dr. Hugh Rosen of Scripps and Frank Schoenen of University of Kansas) the p97 inhibitors DBeQ [26] and ML240.
Proteolix built on technology invented by Dr. Crews to develop carfilzomib/Kyprolis® through mid-phase 2 clinical trials before being acquired by Onyx in 2009.
Cleave built on technology invented collaboratively by the Deshaies, Rosen (Scripps), and Schoenen (University of Kansas) laboratories to develop CB-5083, which is a potent and selective inhibitor of p97.