Innovation at the Interface of Chemistry and Cancer Bryan Dickinson, PhD, assistant professor of chemistry, is developing small molecule, fluorescent probes to study enzymes in cells responsible for removing a class of protein modifications called palmitoylation. Hundreds of proteins in human cells are tagged by this modification, including some known to play an important role in cancer. In a recent study1 , Dickinson and colleagues showed that they could detect these eraser enzymes in live cells, and the activity of the erasers changed in cancer cells depending on their growth state. Dickinson was recently awarded a five–year, $1.25 million grant from the National Institutes of Health to develop similar fluorescent tools to track the activity of another type of eraser protein, one that removes lysine acetylation, in living cells. Approaches that marry chemistry, biology and physics to study and manipulate biological systems are able to provide resolution in living cells in both space and time. “Chemical biology can answer questions that genetics can’t,” Dickinson said. Also employing synthetic chem- istry approaches, Raymond Moellering, PhD, assistant pro- fessor of chemistry, is developing chemical tools to better under- stand the proteome—the entire complement of proteins in cells, tissues or an organism—and to manipulate target proteins and pathways for cancer treatment. For example, his lab has discov- ered several novel post–transla- tional modifications on proteins that bridge metabolism and cell signaling in cancer cells. This work, which is supported by a Pathways to Independence Award from the National Cancer Institute, has resulted in the dis- covery of new signaling pathways and small molecule probes that regulate metabolism in cancer cells. Additionally, the Mary Kay Foundation funded Moellering’s project on developing precision imaging diagnostics to detect and treat the metastatic spread of breast and ovarian cancer. Finally, to address newly discov- ered cancer pathways, Moellering’s lab is developing novel protein– based drugs to block the activity of proteins important to tumor cells that have proven challenging to disrupt through more conven- tional means. 1 Kathayat et al., Nat Chem Biol 13:150-2, 2017 4 Powered by Innovation