Programme

AFFILIATION:

Joan & Sanford I. Weill Medical College of Cornell University, New York, NY, USA

POSITION TITLE:

Meyer Director, Sandra and Edward Meyer Cancer Center
Professor of Cancer Biology in Medicine

EDUCATION/TRAINING:

 

HONORS:

 

RESEARCH INTERESTS:

The major research objective of Dr. Cantley’s laboratory is to understand the biochemical pathways that regulate normal mammalian cell growth and the defects that cause cell transformation. More than 20 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. In 2014, a BTK inhibitor (Ibrutinib) and PI3K inhibitor (Idelalisib) were approved for treating B cell lymphomas and these drugs are beginning to have a major impact on chronic lymphocytic leukemia and other B cell lineage diseases. In 2019, the first PI3K alpha inhibitor was approved by FDA for cancer therapy. In 2020, the PI3Kalpha inhibitor alpelisib (Piqray) was approved in US and Europe for treating PIK3CA mutant breast cancer. Currently, the Cantley laboratory is 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 (Fruman et al., 1999, 2000; Ueki et al., 2002A, 2002B, 2003; Brachmann et al., 2005A, 2005B; Luo et al., 2005, Yuan et al., 2008; Engelman et al., 2008)

 

Another major focus of Dr. Cantley’s 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 peptide oriented library technique was developed to determine optimal phosphopeptides for binding to various protein domains (Songyang et al., 1993). Subsequently, this technique was 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).

 

 

PUBLICATIONS:

List of published work in Google Scholar:
https://scholar.google.com/citations?hl=en&user=g0s8hgEAAAAJ