Pediatric Gastroenterology, Nutrition and Liver Research

Our Lab is a Pediatric Gastroenterology, Nutrition and Liver Research lab. Currently we focus on pediatric liver diseases and specifically, Biliary Atresia (BA) and Primary Sclerosing Cholangitis (PSC). BA is a fibro-obliterative disease of the extrahepatic bile ducts affecting newborns, and is the leading indication for pediatric liver transplant. The etiology remains unknown and there is no effective treatment. In our lab we use a plant toxin, biliatresone, that causes BA outbreaks in Australian livestock as a novel research tool for the study of BA. This method allows us to study the primary events in the disease, define the signaling mechanisms involved in disease progression, and examine the possibilities for recovery. We also study mechanism of bile duct injury and repair in PSC. 

In our lab, we apply a variety of methods including, animal models, cell culture, 3d spheroid culture, growing human organoids originating from patients, real-time PCR, advanced confocal microscopy etc. In addition, by using a unique high oxygenation tissue incubator we have in our lab, we are able to grow and treat whole neonatal mouse bile ducts, and study the process of tissue damage and recovery following toxin treatment. Our research findings may shed light upon the unknown etiology of pediatric liver diseases and provide new potential therapeutic solutions.

1. Define the signaling pathways downstream of biliatresone that lead to cholangiocyte destruction.
   

   

   Biliatresone regulates RhoU/Wrch1, Hey2 and Sox17 expression in cholangiocytes. Primary mouse neonatal extrahepatic cholangiocyte spheroids were treated with biliatresone (2 ug/ml), BSO (100 µM), or DMSO (same volume as biliatresone) for 24 h. Representative images of spheroids immunostained for F-actin (red), and RhoU/Wrch1 or Hey2 (magenta). Nuclei were stained with DAPI (blue). Images are representative of n=4 independent experiments. Scale bar = 10 µm.

2. Develop a mouse model for the biliary atresia and examine the effect of bile acids leakage on extra hepatic bile ducts.
   

   

   Neonatal mice EHBDs were dissected and incubated for 24 hours with (b) and without (a) Glycochenodeoxycholic acid (GCDC). (a) Immunofluorescence staining for the cholangiocyte marker K19 (green) and the myofibroblast marker α-SMA (red). Scale bar, 50 μm.