Pioneer in the use of small molecules to control intracellular protein turnover, Craig Crews, is also known for exploring cell biology using biologically active natural molecules which has led him to the identification of an FDA approved proteasome inhibitor for the treatment of multiple myeloma. Awarded many times for his research, Craig Crews entrepreneurial activities are also recognized. But who is the person behind this path? Find out through his “portrait of a scientist”!

Why are you active in the field of chemical biology?

I enjoy developing new tools to help with biological discovery.

Describe the most intense moment of your career.

In 2012, while on vacation in Paris, I remember watching the web-stream of the FDA advisory panel debate the merits of our next generation proteasome inhibitor, carfilzomib. After hours of discussion, the vote was unanimous for approval. At that moment, I knew we would be successful in our efforts to translate a Yale compound into a drug to help patients. It was an intense and deeply satisfying feeling and I’m very happy that >80,000 patients have since been treated with it.

Which is the best idea you ever had?

PROTAC-mediated protein degradation. Our idea of hijacking the cell’s own quality control machinery to eliminate disease-causing proteins is changing how drugs are developed today.

Do you have a role-model or a driving force?

My father researched fundamental questions about the fatigue and fracture of composite materials/alloys at NASA. To me, this seemed to be  a very dry subject when I was growing up, but I came to appreciate its significance when he was asked to investigate a plane crash that was a result of a fallen engine due to a failed strut. His work showed me that basic research can have ‘real world’ significance. As my lab has evolved over the years, I’ve always strived to make our research as impactful as possible.

The philosophy along which lines you lead your lab?

Curiosity-driven science. I have the best job in the world – I get paid to be curious and work with great researchers from many different disciplines. There’s never a dull moment and I think that is what attracts people to Yale.

Pick a paper you praise for the elegance of its demonstration.

“RAF inhibitors transactivate RAF dimers and ERK signaling in cells with wild-type BRAF”, Nature, 2010.

My roots are in signal transduction and this paper addresses an odd observation (i.e., “paradoxical activation”) of some BRAF inhibitors. The experiments are well designed and I particularly like the use of the Shokat’s “Bump/Hole” approach to study this question.

Can you shed light on the relevance of inter-disciplinarity for scientific breakthroughs?

Multidisciplinary research works on multiple levels. First, there is the obvious benefit of using tools generated by one discipline to answer questions in another. In addition, too often researchers become too focused on their own very narrow topic. Forcing them to step back and to explain it to someone from another discipline often triggers insights that one would have missed. Finally, it establishes a great community- everyone in the lab knows that they bring something unique to the group, which is valued and appreciated. This serves as the foundation for some great collaborative projects.

Define research with just three words.

Answering questions carefully.

How do you match the words beauty and science?

The human brain is an amazing organ, capable of truly beautiful insights. While computers have impressive raw computation power, I am forever in awe of the elegance with which researchers are able to recognize important questions and design clever experiments to address them. For me, an insightful, clever and well-executed experiment is beautiful.

A piece of advice you’d like to give to the young generation of researchers?

“Be the signal, not the noise”.  Find a topic that excites you, dive deeply into it and make your mark by expanding our knowledge of it.  If you are successful in that, you will stand out from your peers.

A book, song, poem, music or painting that you spot out and get inspiration from?

I have long appreciated Max Beckman’s “Self-Portrait in Tuxedo”.

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Craig 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 since 1995. He graduated from the U. Virginia with a B.A. in Chemistry and received his PhD from Harvard University in Biochemistry. Prof. Crews has a foothold in both the academic and biotech arenas: his laboratory has pioneered the use of small molecules to control intracellular protein turnover and in 2003, he co-founded Proteolix, Inc., whose proteasome inhibitor, Kyprolis™ received in 2012 an FDA approval for the treatment of multiple myeloma. Following Proteolix’s purchase by Onyx Pharmaceuticals in 2009, Prof. Crews has focused on a new drug development technology, the PROTAC protein degradation technology – to develop drugs to treat cancer and other diseases, and which served as the founding intellectual property for his latest New Haven-based biotech venture, Arvinas, LLC. Prof. Crews serves on several editorial boards and is Editor of Cell Chemical Biology. 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, Outstanding Investigator Award (2015) and the AACR Award for Chemistry in Cancer Research (2017).

Photo credit: Robert Lisak