Liver Regeneration & Pathologies

I had the good fortune to interact with John Lambris at the University of Pennsylvania, arguably the biggest expert on the Complement System and he was investigating the role of complement in the regeneration of the liver. We collaborated on this project and identified the complement-IL4 regulatory circuit as a key module that regulates liver regeneration. Subsequently, we have carried out extensive transcriptional and recently lipid measurements on longitudinal changes in the mouse liver during regeneration. This has given us deep insights and exciting mechanisms and further investigations are in progress. The regeneration problem also helped me learn about pathologies of the liver and it became clear that the mechanisms of progression of liver disease from NAFLD to NASH to hepatocarcinoma are not well-understood and that our arsenal of experimental and computational methods would be excellent for the study of this problem. I am engaged in two projects involving NASH. In the first large-scale collaborative project, we are investigating using transcriptomics and lipidomics liver from human patients characterized in the four distinct phases of liver disease (normal, NAFLD, NASH and hepatocarcinoma). In a companion project, in collaboration with Jorge Moscat a distinguished cancer biologist, we are investigating mouse models, wild-type and P62 knockout, liver pathologies with systematic and longitudinal “omics” measurements. We are looking forward to developing quantitative network models of progression of liver disease and identifying potential therapeutic agents. We have now entered into an exceptionally interesting collaboration with Dr. Sindhi in CHOP, where his laboratory has one of the largest collections of patient tissues from biliary atresia. We are now investigating the GWAS studies in combination with the RNA seq data from these patient tissue samples. Recently, we have been fortunate to have an excellent collaborator, the Director of our Liver Center, Rohit Loomba with whom we have profiled human liver samples to find markers of NAFLD.

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