What we do
Redox-depenendent regulation of protein synthesis
Our previous work revealed that depletion of a master regulator of redox regulation, NRF2, compromises the growth and viability of PDA cells (Chio et al, Cell 2016). In particular, we observed that genetic ablation of Nrf2 in PDA cells led to increased hydrogen peroxide levels, reversible cysteine oxidation of translation regulatory proteins, functional inactivation of the protein synthesis machinery, these oxidative changes indicates that, in the pathobiology of pancreatic cancer, ROS likely function as specific signaling molecules. Elucidating this aspect of redox biochemistry in PDA should also illuminate the biology of cancer in general, where ROS is of clear importance yet its mode of action remains a focus of much contention. In particular, our work identified oxidative cysteine modification as a novel mode of regulation of the translation apparatus. Since dysregulation of mRNA translation is a prominent feature of many tumor types, a deeper understanding of redox-dependent translational regulation should have broader implications beyond PDA.