Toogood Laboratory

Our lab uses organic synthesis to prepare molecular tools for exploring important cell signaling and metabolic pathways. The targets and pathways that we choose to explore are strongly biased towards those implicated in cancer. We are particularly focused on cancer cell metabolism. In one project we are seeking inhibitors of pyruvate dehydrogenase kinases. This family of mitochondrial proteins perform an important function in toggling cell metabolism between glycolysis and oxidative phosphorylation. The over-expression of PDHK1 is associated with poor outcomes in patients with ovarian cancer. Inhibition of PDHKs can inhibit tumor growth in preclinical models. We use a variety of computational methods, including virtual screening, molecular docking, and de novo design to identify potential inhibitors for synthesis and testing. In other projects, we are seeking inhibitors of a metabolic enzyme that is implicated in pancreatic cancer and of an RNA target that is important in ovarian cancer.