Drew Feranchak, MD*
Drew Feranchak, MD*
Chief, Division of Pediatric Gastroenterology, Hepatology, and Nutrition
Children's Hospital of Pittsburgh
Associate Director, Pittsburgh Liver Research Center
Children’s Hospital of Pittsburgh
University of Pittsburgh Medical Center
Rangos Research Center – 7th floor
4401 Penn Ave.
Pittsburgh, PA 15224
The focus of the Feranchak laboratory is to understand the cellular mechanisms underlying hepatobiliary transport and bile formation in order to develop new treatment options for chronic cholestatic liver diseases. Chronic cholestatic liver diseases still account for significant morbidity and mortality in both children and adults. In fact, they account for the majority of liver diseases in children and are the leading indication for liver transplantation. Despite this, few medical treatment options exist for the majority of these disorders. Our studies focus on cholangiocytes, the epithelial cells that line the lumen of intrahepatic bile ducts and contribute importantly to the volume and composition of bile. Cholangiocytes are also the cellular site of injury in many cholestatic liver diseases associated with abnormal bile flow. Our studies utilize novel cholangiocyte models including single cells, isolated cell populations, and epithelial monolayers that retain secretory polarity. We apply state-of-the-art technologies to our investigations by combining electrophysiology, molecular biology, and fluorescence imaging techniques. The use of these specialized models, biophysical approaches, and advanced live-cell fluorescence imaging techniques has provided an integrated approach to the study of biliary physiology. The long-term goal of these studies is to define the cellular mechanisms involved in cholangiocyte secretion, and to identify the physiologic factors that contribute to bile formation. While there have been remarkable advances in the treatment of many liver diseases (e.g. viral hepatitis), cholestatic liver disorders continue to represent a significant public health challenge with few successful therapeutic options. Accordingly, the development of targeted choleretic agents that stimulate ductular secretion directly and promote bile flow may prevent bile stasis, plugging, and subsequent toxic injury to liver parenchymal cells in a variety of conditions. It is not only feasible, but likely, that targeting the secretory pathways defined in these studies will result in significant new therapeutic molecules of importance not just to bile flow, but to common disorders such as gallstone formation, cholestasis from drugs or other hepatic insults, and impaired biliary secretion associated with cirrhosis. Thus, these studies are directly relevant to the overall public health by decreasing the burden of liver and biliary diseases.
Special Interest Groups:
Chronic Liver Injury