Signal computation and signaling defect hetereogeneity in cancers
Most human cancers are very difficult or impossible to cure, in no small part because each human cancer essentially presents a unique disease at the molecular level. We are using advanced chemoproteomic technologies and cell biology methods to gain insight into the diversity of cancer-driving kinomes of cancers, since kinases can be effectively targeted using existing drug discovery technology. A second focus of our research is on understanding how complex signals in these cancer cells are computed to drive important cell actions like proliferation, migration and invasion. For this we employ various biophysical tools, as well as biochemical and cell biological assays. We have recently developed an entirely novel and internationally much recognized hypothesis of how complex signal computation is accomplished on large and structurally disordered platform proteins, and how it may potentially be targeted by novel types of drugs.
Simplified model of signal computation in Gab1 protein complexes (Lewitzky et al. 2012, FEBS Lett 586, 2740)
Dividing squamous cell carcinoma cell visualized by confocal microscopy
Crystal structure of a trimer of the Helicobacter pylori protease HtrA catalytic domain