Lewis C. Cantley
Department of Cell Biology, Harvard Medical School Dana Farber Cancer Center
Professor and Member
5/1971 B.S. Chemistry Wesleyan College Buchannan, W. Va.
7/1975 Ph.D. Biophysical Chemistry (Gordon Hammes) Cornell University Ithaca, NY
1998 ASBMB Avanti Award for Lipid Research
1999 American Academy of Arts and Sciences
2000 Heinrich Wieland Preis for Lipid Research, Munich, Germany
2001 National Academy of Sciences
2002 Caledonian Prize, Royal Society of Edinburgh
2005 Pezcoller/AACR International Award for Cancer Research
2009 Rolf Luft Award for Diabetes and Endocrinology Research, Karolinska Institute, Stockholm
2011 Pasarow Award for Cancer Research
2013 Breakthrough in Life Sciences Prize
2013 H. C. Jacobaeus Prize, Stockholm
2014 Fellow of the AACR Academy
2014 National Academy of Medicine
2015 Ross Prize
2015 Gairdner Award
2015 Elected to European life sciences academy EMBO
2015 The Association of American Cancer Institutes Distinguished Scientist Award
2015 AACR Princess Takamatsu Memorial Lectureship
2016 Wolf Prize in Medicine
2016 The Hope Funds Award of Excellence in Basic Science
2017 OncLive Giants of Cancer Care
2019 Louisa Gross Horwitz Prize
2020 National Academy of Inventors
2020 Dr. Paul Janssen Award for Biomedical Research
The major research objective of this laboratory is to understand the biochemical pathways that regulate normal mammalian cell growth and the defects that cause cell transformation. More than 25 years ago this laboratory discovered phosphoinositide 3-kinase (PI3K) as an enzyme that co-purified with a variety of oncoproteins (Whitman et al., 1988). Subsequent research from this laboratory and other laboratories showed that PI3K activation is critical for oncogene-mediated cell transformation, as well as for insulin-dependent stimulation of glucose uptake and metabolism. Further work from this laboratory and other laboratories revealed that lipid products of PI3K directly activate the AKT/PKB protein kinase to provide a cell survival signal (Franke et al., 1997). This discovery, as well as subsequent discoveries from other laboratories that human cancers frequently have activating mutations in PI3K genes and/or inactivating mutations in the PTEN gene (encoding a phosphatase that degrades PI3K lipid products) stimulated pharmaceutical companies to develop PI3K pathway inhibitors for cancer therapy. The Cantley laboratory is currently utilizing mouse models, genetically engineered with mutations in the PI3K pathway, to investigate opportunities for therapeutic intervention in diseases that result from defects in the PI3K pathway.
Further studies from this laboratory have revealed that growth factors, through activation of PI3K and other signaling pathways, cause major changes in cellular metabolism that are critical for the growth of cancer cells. Of particular interest, cancer cells invariably utilize an embryonic form of pyruvate kinase (PKM2) to channel glucose metabolites for optimal cell growth (Christofk et al., 2008A, 2008B, Anastasiou et al., 2011). In some cases mutations or amplifications in genes encoding metabolic enzymes can alter cell metabolism and drive tumor formation (Dang et al., 2009; Locasale et al., 2011). Ongoing studies are defining how oncogene transformation of cells alters the flux of metabolites such as glucose and glutamine and how these changes enhance cell growth and cell survival.
Another major focus of this laboratory is the structural basis for specificity in protein/protein interactions in signal transduction cascades that control cell growth and survival. In particular, this laboratory has focused on the mechanism by which protein phosphorylation can control the assembly of signaling complexes. A novel oriented peptide library technique was developed to determine optimal phosphopeptides for binding to various protein domains (Songyang et al., 1993). This technique was subsequently modified to determine optimal substrates for protein kinases (Songyang et al., 1994, 1995, 1996; Hutti et al., 2004). The identification of optimal peptides has facilitated the determination of the structure of protein-peptide complexes and explained how specificity in signaling is maintained (Yaffe et al., 1997A, 1997B; Elia et al., 2003A, 2003B; Benes et al., 2005). These studies have also led to a bioinformatics approach (Scansite) for predicting sites of protein phosphorylation and protein interaction from primary sequences (Yaffe et al., 2001; Obenauer et al., 2003; Johnson et al., 2021 submitted).
List of Published Work in Google Scholar