Signaling pathways regulating liver stem cells and progenitor cells during liver organogenesis and regeneration and cholestatic liver diseases.
Biliary atresia and other cholestatic liver diseases in children such as Alagille's Syndrome and PFIC requiring biliary diversion.
Biliary atresia is a disease of infants where the bile ducts are damaged due to unclear causes such that bile is unable to flow from the liver and progressive liver damage occurs. Even surgical drainage, which is effective only approximately 60% of the time, does not necessarily prevent progression towards liver failure. As such, biliary atresia is the most common indication for pediatric liver transplantation, which is both costly and associated with significant changes in life style. Efforts to understand the underlying causes of biliary atresia and the progression towards cirrhosis are critical to impacting the outcome of infants and children with this disease.
Bilary Atresia Research
Dr. Wang is the Principal Investigator for an NIH-funded grant at Children's Hospital Los Angeles focusing on biliary atresia and other liver diseases of infants and children within the Childhood Liver Disease Research and Education Network (ChiLDREN), which is a consortium of 15 of the top children's hospitals in the U.S. and Canada, joined to study rare, but lethal pediatric liver diseases. To date, nearly 1,500 patients with biliary atresia have been enrolled in a number of studies and clinical trials through ChiLDREN.
Enrollment for one therapeutic trial studying the efficacy of postoperative corticosteroids on survival for biliary atresia is complete and we are awaiting two year follow up to unblind the data. We are about to embark on a phase I clinical trial, as part of the consortium, studying the utility of intravenous gammaglobulin on survival after surgery for biliary atresia.
Additionally, Dr. Wang heads a basic research program focusing on the molecular events involved in biliary atresia at Children's Hospital Los Angeles. His research lab focuses on the signaling pathways regulating liver stem/progenitor cells during liver organogenesis and a variety of liver damage such as that incurred by biliary atresia. The hope is that insight into how liver stem/progenitor cells are regulated normal and how they respond to a variety of injuries in addition to biliary atresia will allow greater understanding of how they contribute to the damage or to the repair processes that occurs in biliary atresia. Notably, the fact that despite successful surgical drainage of bile most children with biliary atresia still experience progression towards liver cirrhosis indicates that events related to fibrosis of the liver are either irreversible or unrelated to bile drainage. The key to improving outcomes of patients with biliary atresia is in understanding why this occurs.
Understanding how liver, stem and progenitor cells are regulated could also accelerate development of a more effective bio-artifical liver, which could be utilized in general in the setting of liver failure both in adults and children. Our lab is also currently undergoing efforts to engineer liver as well as bile ducts.