Lewis C. Cantley, Ph.D.
Harvard Institutes of Medicine
Division of Signal Transduction
4 Blackfan Circle
Boston, MA 02115

Research in the Cantley laboratory is focused on understanding cell signaling pathways important in human diseases. Much of our attention is aimed at elucidating the molecular mechanisms by which aberrant activation of one particular pathway, the phosphoinositide 3-kinase (PI3K)/Akt pathway, leads to tumor formation in a wide variety of human cancers. We are performing screens to identify new protein targets regulated by this pathway using a combination of biochemistry and bioinformatics. The tuberous sclerosis complex-2 (TSC2) gene product, tuberin, was found in one such screen. We have demonstrated that tuberin is a direct biochemical target of Akt and that activation of the PI3K/Akt pathway inhibits tuberin function. We are currently characterizing the molecular nature of this inhibition. This finding directly links the well known oncogenic PI3K/Akt pathway with the less well understood tumor suppressor gene products mutated in the TSC disease. Our research in this area is now aimed at defining the biochemical basis for TSC and the role of the PI3K/Akt pathway in the clinical manifestations of the disease. We are addressing these questions using a diverse set of approaches, including human cell culture and biochemistry, small molecule inhibitor screens, and mouse genetics.

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