Member of Yale faculty since 1995.
Contact Info
Yale University
P.O. Box 208103
New Haven, CT 06520-8103
Office: 203-432-9364
Lab: 203-432-6553
Research
Enzyme inhibition has proven to be a successful paradigm for pharmaceutical development, however, it has several limitations. As an alternative, for more than 20 years, the Crews 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. A wide variety of targets (kinases, transcription factors, epigenetic readers) have been shown to be degradable with PROTACs at picomolar concentrations. Moreover, the PROTAC technology has been demonstrated with multiple E3 ubiquitin ligases, included pVHL, MDM2, and cereblon.
Education
B.A. University of Virginia, 1986
Ph.D. Harvard University, 1993
Postdoctoral Fellow, Harvard University, 1993-95
Honors
- Fellow of the Royal Society of Chemistry, 2005-
- Bessel Research Award, Alexander von Humboldt Foundation, Germany, 2005
- Editor, Cell Chemical Biology (formerly Chemistry & Biology), 2008-2018
- UCB-Ehrlich Award for Excellence in Medicinal Chemistry, 2014
- Outstanding Investigator Award (R35), National Cancer Institute (NIH), 2015
- Award for Outstanding Achievement in Chemistry in Cancer Research, American Association for Cancer Research (AACR), 2017
- Khorana Prize, Royal Society of Chemistry, 2018
- Pierre Fabre Award for Therapeutic Innovation, 2018
- American Cancer Society Professorship, 2019
- Pharmacia-ASPET Award for Experimental Therapeutics, 2019
- John C. Malone Professor of Molecular, Cellular, & Developmental Biology, 2019-
- Heinrich Wieland Prize, Boehringer Ingelheim Foundation, 2020
- Scheele Prize, Swedish Pharmaceutical Society, 2021
- Honorary Doctoral Degree, Technische Universität Dortmund, Germany, 2021
- Connecticut Medal of Technology, CT Academy of Science and Engineering, 2022
- Bristol Myers Squibb Award in Enzyme Chemistry, American Chemical Society, 2023
- Jacob and Louise Gabbay Award in Biotechnology and Medicine, Brandeis University, 2023
- Emanuel Merck Lectureship Award, Technical Uni. of Darmstadt and Merck, KGaA, 2024
- Kimberly Prize, Northwestern School of Medicine and the Simpson Querrey Institute for Epigenetics, 2024
- IUPAC-Richter Prize in Medicinal Chemistry, International Union of Pure and Applied Chemistry, 2024