The Graves lab applies affinity proteomics and mass spectrometry to study the mechanisms of action of emerging and established anti-cancer drugs. Traditionally the focus of the laboratory has been on the application of kinase inhibitors with a particular interest in kinase adaptations in cancer drug resistance. Much of this research has utilized immobilized kinase inhibitor chromatography as a means of enriching and studying the kinome ‘en masse’. This research has lead to important insights into kinome remodeling and cellular mechanisms of acquired resistance in cancer. This same technology has been applied to study the host-kinome response to human cytomegalovirus in collaboration with Dr. Nat Moorman at UNC. These studies illustrated the power of this approach to identify host kinases that could be successfully be targeted as a novel anti-viral approach. More recently, the Graves lab began collaborating with a small biotechnology company (Madera Therapeutics), to investigate the cellular targets for an emerging class of ant-cancer compounds known as the imipridones. Through a drug-affinity chromatography approach, the Graves lab identified the mitochondrial protease ClpP as a major target of regulation by these compounds. Current efforts are directed at investigating the efficacy of these compounds in multiple models of cancer and further investigating how ClpP activation impacts mitochondrial function and cell proliferation.