Lewis C. Cantley
Dana-Farber Harvard Cancer Center
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Primary Section: 22, Cellular and Developmental Biology Secondary Section: 41, Medical Genetics, Hematology, and Oncology Membership Type:
Member
(elected 2001)
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Research Interests
My primary work has involved the biochemical signaling pathways that regulate normal mammalian cell growth and the defects that can cause cell transformation. More than a decade ago, my laboratory discovered a phosphoinositide kinase that was activated by growth factor receptors and by oncoproteins. This enzyme catalyzed an unexpected reaction, the phosphorylation of phosphatidylinositol at the D-3 position of the inositol ring, thus leading to the discovery of a new signal transduction pathway. Subsequent research from my laboratory and other laboratories showed that PI 3-kinase activation is critical for oncogene-mediated cell transformation, as well as for insulin-dependent stimulation of glucose uptake and metabolism. This and more recent work on PI 3-kinase as a mechanism of regulated recruitment to cell membranes has led to a better understanding of the importance of this enzyme in development, immunity, and cancers. Another major area of my work has focused on the structural basis for specificity in protein/protein interactions in signal transduction cascades, in particular, on the mechanism by which protein phosphorylation can control the assembly of signaling complexes. Through the work of my laboratory and others, it has been possible to determine structures of protein-peptide complexes and thus explain how specificity in signaling is maintained. These studies have also allowed predictions of intracellular targets of signaling proteins on the basis of primary sequence data banks.
