Pharmacoproteomics: Mass spectrometry based method development for mechanism of action

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The study of drug effects is usually performed using a series of specific assays directed towards the drug target. For example, kinase inhibitors are screened against their targets and a panel of other kinases. The global effect of the drug at the cellular system level is often not studied and in particular not in the early stage of drug development. The cost and time associated with performing such global system studies are limiting factors. This is an interesting aspect of analytical biochemistry that is underdeveloped. Here we propose to develop an integrated analytical system that will allow rapid global study of the proteome in response to drug treatment (pharmacoproteomics). The system will combine technologies developed in the Figeys' laboratory that will allow pharmacoproteomic screening of one compound every six hours. Mass spectrometry will be used to identify and quantify 1000s of proteins while bioinformatics will be used to rapidly classify the proteins that change according to preset criteria. If successful, this pharmacoproteomic system would accelerate the study of the global effect(s) of drugs and be useful to our industrial partner for the rapid screening of their compounds.