Protein CoAlation and antioxidant functions of Coenzyme A in health and disease
The main focus of research in my laboratory is to study molecular mechanisms of protein CoAlation and antioxidant functions of Coenzyme A (CoA) in health and disease. We recently discovered a novel unconventional function of CoA in redox regulation mediated by covalent attachment of CoA to cellular proteins and termed it protein CoAlation. Protein CoAlation was shown to be a reversible and widespread post-translational modification induced in prokaryotic and eukaryotic cells by oxidising agents and metabolic stress. We have developed range of new research tools and methodologies which have been instrumental in uncovering protein CoAlation, including: a) unique anti-CoA mAbs which work efficiently in various immunological assays; b) in vitro protein CoAlation and deCoAlation assays; c) a reliable strategy for the identification of CoAlated proteins by LC-MS/MS. These advances put us into a unique position to leverage our existing research strengths on the evolving topic of protein CoAlation. We propose that under physiological conditions CoA is mainly used for producing metabolically-active CoA thioesters (acetyl-CoA, malonyl-CoA, succinyl-CoA etc), but when cells are exposed to oxidative and/or metabolic stress CoA may also function to protect cellular proteins from overoxidation by CoAlation. Our research will focus on providing fundamentally important information on the mechanisms of protein CoAlation/deCoAlation and the role of CoA in balancing redox state and cellular metabolism in health and pathologies, such as cancer and neurodegeneration. The development of novel diagnostic and therapeutic approaches is the ultimate goal of our research, which we pursue through collaboration with academic and industrial partners.
