My scientific interest centers on chemical biology, targeted drugs, drug-protein interaction networks, synergy and molecular mechanisms of action in the context of cancer research, particularly lung cancer research. I am pursuing a multi-layered chemical biology/systems pharmacology strategy based on the systematic screening for drug synergy and subsequent identification of the molecular basis underlying the observed synergy by for instance combining chemical proteomics, phosphoproteomics and transcriptomics approaches. This integrated strategy can identify on one hand novel synergistic drug combinations, which due to the focus on clinical drug candidates will have high potential for translation into clinical settings. In addition, the mechanistic understanding will help to further dissect complex oncogenic signaling networks, as well as providing potential mechanism-based biomarkers that can guide patient stratification for future clinical trials of the respective drug combinations.
My core expertise lies in chemical proteomics, which is a postgenomic adaptation of classical drug-affinity chromatography that is powered by downstream mass spectrometry and bioinformatics analysis. This technology is optimally suited to support systematic investigations of cellular drug activities and mechanisms of action by characterizing in an unbiased fashion the cell-specific native drug-target interaction profiles, which are important starting points for identifying the engaged signaling pathways and networks. By applying this strategy, we have been able to identify a large number of new drug-protein interactions, predict drug side effects, characterize circuitries of oncogenic signaling and identify novel synergistic drug combinations.