11:30 – 12:00
Dr Anna Barnard: Mimicking Protein-Protein Interactions in Persistent Bacteria
12:00 – 13:00
Main Visiting Speaker – Professor Craig Crews: PROTAC-medicated Protein Degradation: A New Therapeutic Modality
Abstract
Enzyme inhibition has proven to be a successful paradigm for pharmaceutical development, however, it has several limitations. As an alternative, for the past 16 years, my lab has focused on developing Proteolysis Targeting Chimera (PROTAC), a new ‘controlled proteolysis’ technology that overcomes the limitations of the current inhibitor pharmacological paradigm. Based on an ‘Event-driven’ paradigm, PROTACs offer a novel, catalytic mechanism to irreversibly inhibit protein function, namely, the intracellular destruction of target proteins. This approach employs heterobifunctional molecules capable of recruiting target proteins to the cellular quality control machinery, thus leading to their degradation. We have demonstrated the ability to degrade a wide variety of targets (kinases, transcription factors, epigenetic readers) with PROTACs at picomolar concentrations. Moreover, the PROTAC technology has been demonstrated with multiple E3 ubiquitin ligases, included pVHL and cereblon.
Biography
Craig Crews is the American Cancer Society Professor of Molecular, Cellular and Developmental Biology and holds joint appointments in the departments of Chemistry and Pharmacology at Yale University. He graduated from the U. Virginia with a B.A. in Chemistry and received his Ph.D. from Harvard University in Biochemistry. Prof Crews has a foothold in both the academic and biotech arenas; on the faculty at Yale since 1995, his laboratory pioneered the use of small molecules to control intracellular protein levels. His first company, Proteolix, developed the proteasome inhibitor, Kyprolis™ for the treatment of multiple myeloma. His second venture, Arvinas, applies his lab’s PROTAC ‘induced protein degradation’ technology to drug development. He has received numerous awards and honors, including the CURE Entrepreneur of the Year Award (2013), Ehrlich Award for Medicinal Chemistry (2014), Yale Cancer Center Translational Research Prize (2015), a NIH R35 Outstanding Investigator Award (2015), the AACR Award for Outstanding Achievement in Chemistry in Cancer Research (2017), the Khorana Prize from the Royal Society of Chemistry ( 2018), the Pierre Fabre Award for Therapeutic Innovation (2018), the Pharmacia-ASPET Award for Experimental Therapeutics (2019) and was named an American Cancer Society Professor in 2018.