Emory University School of MedicineMorgan Lab

The majority of P450 enzymes are down-regulated in the liver during inflammation or infection, and most of these changes are thought to be due to the hepatic actions of proinflammatory cytokines.  Different cytokines regulate different P450s, and limited information suggests that the pattern of P450 regulation, and hence alterations in drug metabolism and clearance, are disease-dependent.

One of the goals of the lab is to further define the complexity of this regulation in different disease models.  We have extensively characterized a model of food poisoning mice infected with Citrobacter rodentium.  Our data show that tumor necrosis factor-a is responsible for the down-regulation of some Cyp3a enzymes.  However, the hepatic CYP enzymes most affected in this disease are Cyp4as, which are more important in fatty acid metabolism than in drug biotransformation.  Interestingly, Cyp4a10 and Cyp4a14 mice show reduced systemic and hepatic inflammation during infection, implicating these enzymes in the host response to infection. Current research is focused on two parasitic infections, malaria and schistosomiasis.