Craig M. Crews

Craig M. Crews, Ph.D. (born June 1, 1964) is an American scientist at Yale University. As the Lewis B. Cullman Professor of Molecular, Cellular and Developmental Biology, Crews also holds joint appointments in the departments of Chemistry and Pharmacology. He currently serves as an Editor of Cell Chemical Biology^[1] and is the Executive Director of the Yale Center for Molecular Discovery.^[2] His research interests focus on Chemical Biology, particularly on controlled proteostasis, which has led to the development of the FDA approved anti-cancer drug Carfilzomib (Kyprolis®).^[3]

Education and training

Crews graduated from the University of Virginia in 1986 with a bachelor's degree in Chemistry, after which he performed research at the University of Tübingen as a German Academic Exchange Service (DAAD) Fellow. As a graduate student in the laboratory of Raymond Erikson at Harvard University, Crews purified and cloned the MAP kinase kinase MEK1,^[4][5] a key kinase that controls cell growth. He subsequently worked in the research group of Stuart Schreiber as a Cancer Research Institute Fellow before joining the faculty of Yale University as an assistant professor in Molecular, Cellular, and Developmental Biology.

Research

Crews studies controlled proteostasis, i.e., the small molecule control of protein turnover. His lab’s synthesis and mode of action studies of the natural product epoxomicin revealed that it is a potent and selective proteasome inhibitor.^[6] Subsequent medicinal chemistry efforts produced the epoxyketone containing proteasome inhibitor YU101,^[7] which served as the basis for the multiple myeloma drug Carfilzomib (Kyprolis®). In 2001, Crews developed (in collaboration with Ray Deshaies) PROTACs (Proteolysis Targeting Chimeras),^[8][9] a new technology to induce proteolysis. PROTACs are dimeric molecules that recruit targeted intracellular proteins to the cellular quality control machinery (i.e., an E3 ubiquitin ligase) for subsequent removal by the proteasome.^[10]

Proteolix

In 2003, Crews co-founded the biotechnology company Proteolix to develop YU101, the next generation proteasome inhibitor from his lab, which ultimately became carfilzomib. Marketed under the trade name Kyprolis, carfilzomib was approved by the FDA on June 20, 2012 for use in patients with multiple myeloma who have received at least two prior therapies and have demonstrated disease progression on or within 60 days of completion of the last therapy.^[11] Based on successful Phase II trials of carfilzomib, Onyx Pharmaceuticals acquired Proteolix in 2009 ^[12] and was itself acquired by Amgen in 2013 for $10.4 billion.^[13]

Arvinas

In 2013, Crews founded New Haven-based Arvinas, LLC, which uses the PROTAC protein degradation technology from his lab to develop drugs to treat cancer and other diseases. In 2015, Arvinas partnered with Merck^[14] and Genentech^[15] to develop PROTAC-based drugs.

Awards and recognition

• 2015: Inaugural Recipient of the National Cancer Institute Outstanding Investigator Award(R35)^[16]
• 2015: Yale Cancer Center Translational Research Prize^[17]
• 2014: UCB-Ehrlich Award for Excellence in Medicinal Chemistry (European Federation of Medicinal Chemistry)^[18]
• 2013: Entrepreneur of the Year, Connecticut United for Research Excellence (CURE)^[19]
• 2013: Fellow, American Association for the Advancement of Science^[20]
• 2011: Senior Scholar Award, Ellison Medical Foundation ^[21]
• 2010-2013: Visiting Professor, Universität Konstanz, Germany
• 2009: Gates Foundation Global Grand Challenge Explorations Grant ^[22]
• 2005: Friedrich Wilhelm Bessel Research Award, Alexander von Humboldt Foundation^[23]
• 2005: Fellow of the Royal Society of Chemistry
• 2002: CaP CURE Research Award ^[24]
• 1996: Burroughs Wellcome Fund New Investigator Award^[25]
• 1986: German Academic Exchange Service Fellow (DAAD)

References

External links

1. Crews lab
2. Yale Center for Molecular Discovery
3. Arvinas, LLC.
4. Proteolix, Inc.