Craig Martin Crews

Professor of Chemistry; Pharmacology; Molecular, Cellular, and Developmental Biology
Member of Yale faculty since 1995

E-mail: craig.crews@yale.edu
Web site: http://www.yale.edu/crews/

Figure 1: Time 0, 20x magnification
Figure 2: 25 µM protac, 2 hrs. 20x magnification

Research Each year, many promising natural products are identified as being biologically active in cell culture assays. Despite their proven in vitro efficacies, development of these ‘drug candidates’ into clinically useful therapeutic agents is an arduous procedure, often due to issues unrelated to the compound's mechanism of action (e.g. poor pharmacokinetics, unfavorable side effects, etc.). While many of these compounds have limited therapeutic potential, investigation of their mechanism of action can provide new information about complex intracellular signaling pathways. Through natural product total synthesis, affinity reagent generation and biochemical methodologies, the Crews lab identifies natural product target proteins, which serve as the starting point for the rapid development of additional efficacious compounds. In addition, we have recently developed a new chemical genetic strategy (ProTacs) for the identification of key components of intracellular processes using small molecules.

Education
B.A. University of Virginia, 1986
Ph.D. Harvard University, 1993
Postdoctoral Fellow, Harvard University, 1993-95

Honors
Burroughs Wellcome Young Investigator, 1996-99
Fellow of the Royal Society of Chemistry 2005
Bessel Research Award, Alexander von Humboldt Foundation, 2006
Editor, Chemistry&Biology, 2008

Recent Publications
J.S. Schneekloth, Jr., F. Fonseca, M. Koldobskiy, A. Mandal, R. Deshaies, K. Sakamoto, & C. M. Crews. Chemical Genetic Control of Protein Levels: Selective in vivo Targeted Degradation. J. Am. Chem. Soc. 2004, 126, 3748-54.

J. S. Schneekloth, Jr., & C.M. Crews. Chemical Approaches to Controlling Intracellular Protein Degradation. ChemBioChem 2005, 6, 40-6.

A.K. Mandal, J.S. Schneekloth, Jr., K. Kuramochi, & C.M. Crews. Synthetic studies on amphidinolide B1. Org. Lett. 2006, 8, 427-30.

T.W. Corson, N. Aberle, & C.M. Crews. Design and Applications of Bifunctional Small Molecules: Why Two Heads Are Better Than One. ACS Chem. Biol. 2008, 11, 677-692.

A.R. Schneekloth, M. Pucheault, H.S. Tae, & C.M. Crews. Targeted Intracellular Protein Degradation Induced by a Small Molecule:En Route to Chemical Proteomics Bioorg. Med. Chem. Lett. 2008, 18, 5904-8.

Craig Martin Crews

Research Interests