Cancers employ profoundly altered networks of biosynthetic and catabolic pathways in order to couple rapid growth with available nutrients. This metabolic reprogramming is not only a hallmark of the malignant state, but it can directly drive malignant transformation since many important oncogenes alter cell metabolism and since recurrent oncogenic mutations in metabolic enzymes are being increasingly identified in human cancers. Changes in cell metabolism can be coupled to epigenetic gene regulation due the use of metabolic intermediates as co-factors or substrates for DNA and histone modifying enzymes. The goal of our laboratory is to define the mechanisms by which metabolic pathways become deregulated in cancer cells, and elucidate their resulting impact on epigenetic control, cell differentiation and malignant transformation. Our studies focus on studying these processes in the context of pancreatic cancer and biliary cancer (cholangiocarcinoma).