Dr. John Porter, professor and biology graduate programs director at University of the Sciences, is hoping that unlocking the structure of compounds in red pigweed will lead to a mechanism and cure for biliary atresia, a bile duct disease that affects about 1 in every 10,000 infants and in most cases leads eventually to liver transplant.
Working in conjunction with a team from University of Pennsylvania, Dr. Porter received a four-year grant from National Institutes of Health (NIH) on October 1, 2011, for isolation, identification, and characterization of a toxin that can cause a syndrome similar to biliary atresia.
The project started in 2007 when gastroenterologist Dr. Rebecca G. Wells of the Perelman School of Medicine at University of Pennsylvania wanted to read more about the 1964 and 1989 epidemics of biliary atresia in Australian lambs, which were attributed to consumption of unusual plants by pregnant ewes during severe droughts. Dr. Wells and her colleague Dr. Michael Pack, also a gastroenterologist at the Perelman School of Medicine, began studying biliary atresia as members of the Biesecker Pediatric Liver Center Center, at the Children’s Hospital of Philadelphia. To her surprise, Dr. Wells learned that there had been a third biliary atresia epidemic in the Australian lambs in 2007. She was able to contact the Australian veterinarian involved, Dr. Steve Whittaker, and learned that pigweed was believed to be the most likely culprit.
Since it would not be feasible to grow the plant in the United States, the US group collaborated with Dr. Whittaker to provide a quantity of the plant for study. Dr. Porter and Dr. Kyung A. Koo, a postdoctoral researcher on the project, fractionated the plant into multiple components, and Dr. Pack’s group identified the toxic fractions using a novel assay his lab devised to monitor bile flow and bile duct morphology in larval zebrafish. Dr. Pack’s group uses the zebrafish to study the pathogenesis of heritable bile duct disorders, thus he was uniquely prepared to collaborate on the pigweed project. Dr. Porter and his research team are now working to determine the structure of the compounds responsible for the toxicity.
“Understanding the cause of the disease in humans is an ultimate goal,” said Dr. Porter.
Once the structures are identified, he will be able to work with Dr. Wells and Dr. Pack to study the new zebrafish model of biliary atresia and develop other animal models of the disease.
“It’s not the highest incidence disease in the world, but it is one that is pretty devastating,” said Dr. Porter. Biliary atresia is the major reason for liver transplants in the pediatric population.