Shaun K. Olsen, PhD

In broad terms, the research in my laboratory focuses on mechanisms of molecular recognition in protein-protein interactions and on the structural enzymology of proteins essential for cellular function.  The majority of our efforts are focused on understanding how enzymes in the ubiquitin (Ub) conjugation cascade (E1, E2, and E3) function together to conjugate Ub to cellular proteins. Post-translational modification of proteins by Ub is a means of regulating fundamental cellular processes including cell cycle control, DNA repair, signal transduction, and immunity.  The importance of understanding how the Ub system works is underscored by the fact that dysregulation of Ub signaling is implicated in a number of human disorders and that the pathway is a validated target for therapeutic intervention in cancer.  To achieve our goals, we employ a multidisciplinary approach that includes X-ray crystallography, single particle cryo-EM, enzymology, and a variety of biochemical and biophysical techniques.  When appropriate, we use yeast genetics and eukaryotic cell-based functional assays to assess the biological importance of our structural, biochemical, and biophysical findings. We are also involved in collaborative studies with our colleagues at the CPRIT-supported Center for Innovative Drug Discovery (CIDD) to identify small molecule inhibitors of enzymes and PROTACs targeting enzymes involved in Ub signaling and DNA repair.