Mass spectrometry-coupled chemical proteomics approaches have been utilized in multiple aspects of small molecule drug research, including identification of drug targets, quantification of drug-to-target interaction affinity, and selectivity profiling. Chemical proteomics has also been used to profile enzyme activity at a systems level across different patient samples.
In the lab we are interested in applying affinity-based chemoproteomics to exploit available kinase-targeted small molecule cancer therapies for the functional interrogation of kinase signaling networks. Our aim is to investigate these targets in cancer cells and eventually tissues in conditions under which native conformations and tertiary structures, protein activity, posttranslational modifications as well as protein-protein interactions are presumed to be largely retained. In particular, we want to use immobilized kinase inhibitors to study expression levels and evaluate enzyme activities under normal and perturbed conditions (e.g. acquired mutations, aberrant activation) using target- and conformation-specific immobilized ligands. Chemical proteomics approaches effectively complement established phosphoproteomics methods to study the molecular basis of tyrosine kinase signaling pathways.