Craig M. Crews

Research Statement

AI generated · 1d ago

Craig M. Crews's research centers on induced protein degradation as a therapeutic strategy, most notably the development of PROTACs, bifunctional molecules that recruit E3 ubiquitin ligases to eliminate disease-relevant proteins. His foundational review of targeted protein degraders (2022) and his earlier framing of induced protein degradation as a drug discovery paradigm (2016) helped establish the field, while work demonstrating catalytic, in vivo protein knockdown by small-molecule PROTACs (2015) showed the approach could function in living systems. Related studies on hijacking the E3 ligase cereblon to degrade BRD4 (2015) and on lessons in PROTAC design from selective degradation with a promiscuous warhead (2017) refined the chemistry and selectivity of these molecules. Earlier contributions include co-authorship on the original chimeric molecules targeting proteins to the Skp1–Cullin–F box complex for ubiquitination and degradation (2001), the conceptual seed of the PROTAC strategy, and first-author work on the primary structure of MEK, a kinase phosphorylating the ERK gene product (1992). His portfolio also includes epoxomicin, a selective proteasome inhibitor with in vivo anti-inflammatory activity (1999). No software, datasets, patents, or grants are indexed beyond these publications. Across these works, the through-line is a sustained effort to convert targeted protein degradation from a chemical curiosity into a broadly applicable therapeutic modality.

Most Cited Works

PROTAC targeted protein degraders: the past is prologue

Miklós Békés, David R Langley, Craig M Crews

Nature Reviews Drug Discovery2022

3,404Citations

Catalytic in vivo protein knockdown by small-molecule PROTACs

Daniel P Bondeson, Alina Mares, Ian E D Smith, Eunhwa Ko, Sebastien Campos, Afjal H Miah, Katie E Mulholland, Natasha Routly, Dennis L Buckley, Jeffrey L Gustafson, Nico Zinn, Paola Grandi, Satoko Shimamura, Giovanna Bergamini

Research Areas

Protein Degradation and InhibitorsUbiquitin and proteasome pathwaysChemical Synthesis and AnalysisProtease and Inhibitor MechanismsProstate Cancer Treatment and Research

Affiliations & Education

Employment

1995–present· now
Yale University(US)
John C. Malone Professor of MCDB · Molecular, Cellular, and Developmental Biology

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