Charles J. Sherr
St. Jude Children's Research Hospital
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Primary Section: 41, Medical Genetics, Hematology, and Oncology Secondary Section: 22, Cellular and Developmental Biology Membership Type:
Member
(elected 1995)
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Biosketch
Charles J. Sherr pioneered studies of oncogenes and tumor suppressors, the mechanics of cell division cycle control, and how key cell cycle regulators are perturbed in cancer. Sherr’s laboratory discovered the FMS oncogene and demonstrated that it encoded the colony-stimulating factor-1 receptor (CSF-1R). His identification of growth factor-responsive mammalian D-type cyclins and cyclin-dependent kinase-4 (CDK-4), and the demonstration that cyclin D-CDK4 complexes triggered phosphorylation of the retinoblastoma protein (RB), helped to reveal how mammalian cells respond to extracellular cues in regulating their cell division cycle. Investigations of inhibitory CDK4 (“INK4”) proteins, including the canonical tumor suppressor p16INK4A (CDKN2A), confirmed that inhibition of cyclin D-CDK4 activity prevented entry into S phase and arrested cell proliferation in an RB-dependent manner. These studies also led also to the discovery of the genetically linked, CDKN2A-encoded alternative reading frame (ARF) tumor suppressor protein, an oncogene-activated arbiter of the p53 transcriptional response. Mutations affecting D-type cyclins, CDK4, and INK4A/ARF affect the activities of RB and p53 and are among the most frequently observed events in human cancer. As predicted, drugs targeting CDK4, now FDA-approved for breast cancer, are currently in advanced clinical trials for treatment of many other major malignancies.
Research Interests
Mechanisms of action of cyclin D-dependent CDK4 and CDK6 inhibitors, as monotherapy or in combination with other drugs, in cancer treatment.
