Giulio Draetta
Professor
The University of Texas MD Anderson Cancer Center
Departments of Genomic Medicine and Molecular & Cellular Oncology
The research in my laboratory focuses on disease mechanisms in pancreatic cancer and glioblastoma. We use classical genetic and biochemical analyses with functional genomics and state-of-the-art technologies to identify novel tumor dependencies and evaluate their potential for therapeutic translation. Focus areas include tumor heterogeneity, oncogenic reprograming of epigenetic and metabolic pathways, and mechanisms of disease ad-aptation and evolution. Our findings have provided the biological rationale for positioning novel therapeutic strat-egies, including identifying actionable vulnerabilities in cancer metabolism and elucidating resistance mecha-nisms, as well as have initiated numerous drug discovery projects within the TDD, including ongoing projects to identify drugs targeting the epigenetic and metabolism machinery. In particular, I am excited about our work identifying a therapeutically exploitable dependency of glioblastoma on mitochondrial fatty acid metabolism. This work focused on medium-chain acyl-CoA dehydrogenase (MCAD), an enzyme that metabolizes medium-chain fatty acids that are, upon accumulation, toxic to glioma cells. Using RNA-interference technology and patient-derived glioblastoma spheroids, we found that inhibiting MCAD in glioma cells induced the accumulation of unmetabolized toxic fatty acids, triggering a cascade of effects that induced irreversible mitochondrial damage and, eventually, glioma cell death. Overall, our work was the first to show that MCAD is a potential therapeutic target in glioblastoma. We are continuing to work on this topic, aiming at discovering MCAD small molecule inhibitors and at elucidating the mechanisms leading to glioma cells becoming dependent on MCAD.
Institute for Applied Cancer Science
Education & Training
MD, University of Naples Medical School, 1981
PhD, University of Naples Medical School, 1985
Research Info
functional genomics; drug discovery and translational medicine; tumor cell metabolism; cancer stem cells