Craig Crews, PhD

  • Lewis B. Cullman Professor of Molecular, Cellular, and Developmental Biology and Professor of Chemistry
  • Executive Director, Yale Center for Molecular Discovery

Dr. Crews is the Lewis B. Cullman 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. Dr. Crews has a foothold in both the academic and biotech arenas; on the faculty at Yale since 1995, his laboratory has pioneered the use of small molecules to control intracellular protein levels. In 2003, he co-founded Proteolix, Inc., whose proteasome inhibitor, Kyprolis™ recently received FDA approval for the treatment of multiple myeloma. Since Proteolix’s purchase by Onyx Pharmaceuticals in 2009, Dr. Crews has focused on a new drug development technology, which served as the founding intellectual property for his latest New Haven-based biotech venture, Arvinas, LLC. Currently, Dr. Crews serves on several editorial boards and is Editor of Cell Chemical Biology. In addition, he has received numerous awards and honors, including the 2013 CURE Entrepreneur of the Year Award, 2014 Ehrlich Award for Medicinal Chemistry, 2015 Yale Cancer Center Translational Research Prize and a NIH R35 Outstanding Investigator Award (2015).

Research interests
Biochemistry; Biology; Chemistry; Cell Biology; Neoplasms; Pharmacology; Drugs, Investigational; Proteasome Endopeptidase Complex; Proteasome Inhibitors
Research summary

We use a combination of biochemistry, molecular biology, and bio-organic chemistry to explore different aspects of developmental and cell biology. Different projects include 1) the exploration of how biologically active compounds from nature work in order to identify new probes for cell biology as well as identify novel drug targets and 2) the development of novel small molecules to control intracellular protein homeostasis.

Education
  • PhD, Harvard University, 1992
  • BA, University of Virginia, 1986
Publications
  • Nature Reviews Drug Discovery. 2017 Feb;16(2):101-114
  • Toure, M, and Crews CM (2016) All "Small Molecule" PROTACS: New Members of a Degrading Family. Angewandte Chemie Int. Ed. Engl 55(6):2-10
  • Lai, AC, Toure, M, Hellerschmied, D, Salami, J, Jaime-Figueroa, S, Ko, E, Hines, J, Crews, CM (2015) Accessing Oncogenic BCR-ABL for Degradation by Modular PROTAC Design. Angewandte Chemie Int. Ed. Engl. 55: 807–810
  • Lu J, Qian Y, Altieri M, Dong H, Wang J, Raina K, Himes J, Winkler JD, Crew AP, Coleman K, Crews CM (2015) Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4. Chemistry & Biology 22: 1-9
  • Bondeson DP, Mares A, Smith IED, Ko E, Campos S, Miah AH, Mulholland KE, Routly N, Buckley DL, Gustafson JL, Zinn N, Grandi P, Shimamura S, Bergamini G, Faelth-Savitski M, Bantscheff M, Cox C, Gordon DA, Willard RR, Flanagan JJ, Casillas LN, Votta BJ, den Besten W, Famm K, Sruidenier L, Carter PS, Harling JD, Churcher I, & Crews CM (2015) Catalytic in vivo protein knockdown by small-molecule PROTACs. Nature Chemical Biology. 2015 Aug;11(8):611-7.
  • Gustafson JL, Neklesa TK, Cox CS, Roth AG, Buckley DL, Tae HS, Sundberg TB, Stagg B, Hines J, McDonnell DP, Norris JD, Crews CM. (2015) Small-Molecule-Mediated Degradation of the Androgen Receptor Through Hydrophobic Tagging. Angewandte Chemie Int. Ed. Engl. 10;54(33):9659-62
  • Hines J, Gough JD, Corson TW, Crews CM. Posttranslational protein knockdown coupled to receptor tyrosine kinase activation with phosphoPROTACs. Proc Natl Acad Sci U S A. (2013), May 28; 110(22):8942-7.
  • Neklesa TK, Crews CM. Chemical biology: Greasy tags for protein removal. Nature. (2012) Jul 18;487(7407):308-9.
  • Neklesa TK, Tae H-S, Schneekloth AR, Stulberg MJ, Corson TW, Sundberg TB, Holley SA, and CM Crews. (2011) Small-molecule hydrophobic tagging-induced degradation of HaloTag fusion proteins. Nature Chemical Biology, 7(8):538-43
  • Raina K and CM Crews. (2010) Chemical Inducers of Targeted Protein Degradation. J. Biol. Chem, 285(15):11057-60.
  • Kim KB, Crews CM. (2013) From epoxomicin to carfilzomib: chemistry, biology, and medical outcomes. Nat Prod Rep. 30(5):600-4.
  • Neklesa TK, Noblin DJ, Kuzin AP , Lew S, Seetharaman J, Acton TB, Kornhaber GJ, Xiao R, Montelione GT, Tong L, Crews CM. (2013) A Bidirectional System for the Dynamic Small Molecule Control of Intracellular Fusion Proteins. ACS Chemical Biology 8(10);2293-2300.
  • Buckley DL, and Crews CM. (2014) Small Molecule Control of Intracellular Protein Levels Through Modulation of the Ubiquitin Proteasome System. Angewandte Chem. Int. Ed. 53(9);2312-2330.
  • Raina K, Noblin DJ, Serebrenik YV, Adams A, Zhao C, Crews CM. (2014) Targeted Protein Destabilization Reveals an Estrogen-mediated ER Stress Response. Nature Chemical Biology, 10(11):957-962.
  • Buckley DL, Raina K, Darricarrerre N, Hines J, Gustafson JL, Smith IE, Miah AH, Harling JD, Crews CM. (2015) HaloPROTACS: Use of Small Molecule PROTACs to Induce Degradation of HaloTag Fusion Proteins. ACS Chem. Biol. 10(8):1831-7
  • Molineaux, C, and CM Crews. (2008) Proteasome Inhibitors in Cancer Chemotherapy, Cancer: Principles and Practice of Oncology, 8th Ed. V.T DeVita, T.S. Lawrence, S.A. Rosenberg, editors. Chapter 25., pp.486-490.
  • Flowers GP, Timberlake AT, Mclean KC, Monaghan JR, Crews CM. (2014) Highly Efficient Targeted Mutagenesis in the Axolotl using Cas9 RNA-guided Nuclease. Development, 141(10):2165-71.
  • Crews CM. (2010) Targeting the Undruggable Proteome: The Small Molecules of My Dreams. Chemistry & Biology, 17:551-555.
International activities
  • Visiting Professor- University of Konstanz
    Konstanz, Germany (2010-2013)
    Guest Professor, University of Konstanz

    University of Konstanz, University of Konstanz

Current projects

We develop novel reagents, which will allow us to explore new areas in cell biology. This 'chemical genetic' approach uses biologically active natural products and de novo designed small molecules to identify critical components in intracellular processes. In the past few years, our efforts have focused on anti-angiogenic, antitumor and anti-inflammatory natural products. More recently, we have explored the use of small molecules to control intracellular protein levels, either by inhibiting their degradation or by inducing their proteolysis via the 26S proteasome. A goal of this research is to develop novel methodologies that would allow for small molecule control of the 'undruggable proteome'.

Honors
  • Award for Outstanding Achievement in Chemistry in Cancer Research
  • UCB-Ehrlich Award for Excellence in Medicinal Chemistry
  • Guest Professor
  • Bessel Research Award
  • Fellow
  • Outstanding Investigator Award (R35)
  • Fellow
  • Senior Scholar in Aging
  • New Investigator Award
  • CaPCURE Research Prize
  • Connecticut Academy of Science and Engineering
  • Entrepreneur of the Year 2013
  • New Investigator Award
  • Translational Research Prize
  • Lewis B. Cullman Professor of MCDB
  • Arthur Greer Memorial Prize for Outstanding Junior Faculty Member in the Social or Natural Sciences
Services
  • Yale Center for Molecular Discovery
  • Editorial Board
    Molecular and Cellular Proteomics
    (2001 - 2009)
  • Editorial Board
    Cell Chemical Biology (formerly Chemistry & Biology)
  • Principal Investigator
    NIH Chemistry and Biology Interface Training Grant
  • Editor
    Cell Chemical Biology (formerly Chemistry & Biology)
  • Editorial Advisory Board
    ChemBioChem
  • Founder of a biotech accelerator focused on translating biological and biomedical discoveries into new biopharma ventures.
    PITCH (Program in Innovative Therapeutics for CT's Health)
Languages
German