The Digestive Diseases Research Program at Cummings School of Veterinary Medicine at Tufts University involves studies to better understand the cellular mechanisms involved in cholestatic liver diseases defined as diseases associated with decreased bile formation. In cholestasis, solutes (endogenous and exogenous) destined for bile accumulate either in the liver or blood because of failure to maintain transhepatic solute transport. This can result in jaundice resulting from the accumulation of bilirubin and hepatocellular damage including hepatocellular death from the accumulation of toxic bile acids.
The long-term goal of this program is to more clearly define cellular mechanisms involved in hepatic solute transport and bile acid-induced hepatocellular death. More specifically, studies are conducted to elucidate the regulatory signaling pathways and the specific kinases and phosphatases that are involved in the regulation and dysregulation of transhepatic solute transport and in the progression of and protection from hepatocellular death. A better understanding of the cellular mechanisms should allow us to devise pharmacological means to ameliorate cholestatic disease syndromes by facilitating transhepatic solute transport and preventing hepatocellular death.
The program is led by a group of scientists with both clinical and basic science research backgrounds. A wide variety of molecular, genetic and pharmacologic techniques are used to elucidate the signaling pathways using various experimental models including isolated perfused livers, primary hepatocyte cultures and hepatoma cell lines.