Dr. Thomas Graeber's group is working to understand cancer signaling from a systems viewpoint. They focus on developing genome- and proteome-wide detection assays, applying these assays to measuring and computationally modeling aberrant cancer signaling and translating their discoveries to clinical applications. They have developed a mass-spectrometry based protocol for identifying tyrosine-phosphorylated proteins from cancer cell lysates. They are using this proteome-wide "phosphorylation profiling" assay to identify the signaling pathways activated by various oncogenic initiating events (e.g., kinase mutations), and to elucidate the interconnectedness of classical signaling pathways into a more comprehensive signaling network. In modeling cancer signaling, one of their goals is to identify minimal sets of informative components that best reflect the state of the cell and serve as molecular targets for diagnostics, imaging and patient tailored treatment. As with all of systems biology, their research relies on an interdisciplinary approach that combines biology, chemistry, mathematics and computation.
Selected Cancer-Related Publications:
Skaggs BJ, Gorre ME, Ryvkin A, Burgess MR, Xie Y, Han Y, Komisopoulou E, Brown LM, Loo JA, Landaw EM, Sawyers CL, Graeber TG. Phosphorylation of the ATP-binding loop directs oncogenicity of drug-resistant BCR-ABL mutants. Proc Natl Acad Sci U S A. 2006; 103(51): 19466-71.
Graeber TG, Sawyers CL. Cross-species comparisons of cancer signaling. Nat Genet. 2005; 37(1): 7-8.
Ellwood-Yen K, Graeber TG, Wongvipat J, Iruela-Arispe ML, Zhang J, Matusik R, Thomas GV, Sawyers CL. Myc-driven murine prostate cancer shares molecular features with human prostate tumors. Cancer Cell. 2003; 4(3): 223-38.
Graeber TG, Eisenberg D. Bioinformatic identification of potential autocrine signaling loops in cancers from gene expression profiles. Nature Genetics. 2001 November; 29(3):295-300.
Graeber TG, Osmanian C, Jacks T, Housman DE, Koch CJ, Lowe SJ, Giaccia AJ. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature. 1996 January 4; 379(6560):88-91.