My laboratory has studied liver regeneration with the goal of using that knowledge gained from such investigation to improve the treatment of children with liver disease. The remarkable regenerative capacity of the liver has probably been recognized for millennia, based on its inclusion in the legend of Prometheus from Greek mythology. This response permits structural and functional recovery from the deficits that follow hepatic injury. The best characterized experimental paradigm for studying liver regeneration is the rodent partial hepatectomy model. Analyses using this system, as well as toxin- and genetically-induced models of liver regeneration, have identified many signals that are regulated during and necessary for normal liver regeneration. Nevertheless, an integrated understanding of the mechanistic regulation of liver regeneration remains incomplete. Indeed, the nature and identities of the most proximal signals that initiate regeneration are still largely unknown.
We use partial hepatectomy and other models of liver regeneration in pharmacologically- and genetically-manipulated mouse models, together with genomic, proteomic, and metabolomic analytical platforms, to investigate the signals required during normal regeneration. Our studies implicate the metabolic response to hepatic insufficiency as a critical regulator of such regeneration. In related analyses, we are pursuing the discovery of novel, non-invasively detectable biological markers of liver regeneration, and investigating the utility of such markers for predicting outcomes and informing treatment decisions in human liver diseases, including pediatric acute liver failure. Our hope is that the results of these studies will lead to the development of novel diagnostic and therapeutic strategies for treating, preventing, and even reversing the complications of acute and chronic liver diseases.
David Rudnick MD-PhD
Assistant Professor of Pediatrics, Developmental Biology
Washington University School of Medicine
Department of Pediatrics and Developmental Biology and Genetics Unit
660 South Euclid Avenue
Campus Box 8208
St. Louis, MO 63110
314-454-6173 (clinical office)
314-286-2832 (research office)
314-286-2839 (research lab)