Department of Biochemistry

My research has focused on the regulatory mechanisms for CTP:phosphocholine cytidylyltransferase (CCT), the rate-limiting enzyme required for the de novo synthesis of phosphatidylcholine. It has been demonstrated that phosphatidylcholine biosynthesis is inhibited during inflammatory processes, such as in acute lung injury. We hypothesize that this results from elaboration of injurious mediators, such as tumor necrosis factor-a (TNFa, which inhibit PC synthesis by decreasing expression of cytidylyltransferase. Our recent work has discovered that CCT is degraded coordinately by the ubiquitin-proteasome and calpain proteolytic pathways in response to TNFa. Ongoing studies are directed at identifying TNFa-proteolytic attack sites and strategies directed at mutation of these residues within CCT. The long-term goal involves expressing proteinase-resistent CCT mutants in models of acute lung injury.