2000 - Charles J. Sherr

Department of Tumor Cell Biology
St.Jude Children’s Research Hospital
Memphis, Tennessee – USA

Motivation:
The AACR-Pezcoller International Award recognizes a scientist of international renown who has made a major scientific discovery in the field of cancer research. Dr. Charles J. Sherr is being recognized for his significant contributions to the understanding of the mechanisms of cell growth control and neoplastic transformation. His initial landmark discovery showed that the FMS oncogene encodes the receptor for colony-stimulating factor-1. Later, he identified the mammalian G1 D-type cyclins as delayed-early response genes too growth factor stimulation, which immediately led to the critical concept that D-type cyclins function as growth factor sensors that couple extracellular signals to cell cycle progression. Dr. Sherr and his group also demonstrated that the three D-type cyclins regulate a novel cyclin-dependent kinase (CDK4) that phosphorylates the retinoblastoma protein (RB), but not the canonical CDK substrate histone H1. Continued studies in this area of tumor biology have helped investigators realize the critical role of the “Rb pathway” in the majority of human cancers.
Dr. Sherr also demonstrated that the INK4a Iocus encodes a second protein (p19ARF), and further research identified ARF to be a tumor suppressor gene that functions upstream of p53. It is now recognized that the INK4a-ARF Iocus encodes two distinct tumor suppressor proteins that interact with RB and p53. Expression of ARF is induced by oncogenes, and it serves to limit potentially harmful hyperproliferative signals by triggering p53-dependent cell cycle arrest or apoptosis. The discoveries by Dr. Sherr of the D-type cyclins, CDK4, CDK inhibitors, and ARF have enlightened us about the key mechanisms that link mammalian cell cycle control to the genesis of cancer. Further, they have clarified our understanding of the signaling pathways that are central to tumor development and have pinpointed novel targets for therapeutic intervention.
Dr. Sherr received both his MD and PhD from New York University in 1972. He served a senior fellowship in the Laboratory of Viral Carcinogenesis, National Cancer Institute, from 1975-77. Dr. Sherr is currently Chairman and Herrick Foundation Chair, Department of Tumor Cell Biology, St. Jude Children’s Research Hospital, and Investigator, Howard Hughes Medical Institute.
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