My name is Cece Chen and I am a rising senior at the University of Pennsylvania. I am majoring in biochemistry and minoring in healthcare management & neuroscience. During my junior year, I had the opportunity to begin work in the Wells lab, but it was really through the STEER program this summer that I was able to really get involved in my research project.
What is your summer research project?
(Background: Biliary atresia is a rare gastrointestinal disease in babies where bile flow from the liver to the gallbladder is obstructed. In babies with BA, the extrahepatic bile ducts get damaged in utero and then are obstructed/fibrosed. This prevents the proper flow of bile, so bile builds up in the liver and damages it. This causes liver fibrosis, which eventually leads to liver cirrhosis and liver failure. There are currently no treatments or cure for BA besides a liver transplant, which makes BA the leading indication for pediatric liver transplant. As such, we are interested in studying this disease to hopefully shed more light on prevention and treatment options. Although the cause of BA is still unknown, research seems to point to environmental insults as the primary cause. The Wells lab has already isolated biliatresone, an isoflavonoid from the Dysphania plant, as a biliary toxin. However, this compound is only found in one plant in the outbacks of Australia, so we are trying to see if more common/human accessible compounds, similar to biliatresone, also cause bile duct damage in vitro and in vivo. This is what my project focuses on.)
My project is to investigate the effects of 12 electrophilic compounds, all structurally or functionally similar to biliatresone, and their impacts on cholangiocytes. We have started dosage studies for 4 compounds (COS, DEL, PTL, IAL) to identify the ideal dosage for each compound such that it causes cell damage, but not necessarily cell death. To do this, we treated 2D cell cultures with a range of dosages for each compound and stained with CK19 and phalloidin to evaluate toxicity. Once the ideal dosages have been identified, the goal is to study these 12 compounds in both in vitro and in vivo models.
The original 12 compounds of interest included a class of compounds called microcystins, which is produced by blue-green algae. Knowing this, we have also been working on designing an epidemiological study to investigate if there is any spatial correlation between proximity to water sources (like lakes, rivers, and oceans) and the prevalence of BA cases.
What are the implications of your research?
There are a lot of unknowns with the disease biliary atresia. We don’t know the cause and we don’t know the cure. Therapeutic options for babies with BA are also very limited, with the most significant of these options being the Kasai procedure. This helps to drain bile from the liver to the small intestines directly and bypasses the obstructed ducts. But even with this surgery, about 50% of babies with BA have to undergo liver transplant before the age of 2 and the remaining kids will need a liver transplant at some point later in life. As such, we are hoping that by exploring the toxin model for BA we can gain a better understanding of the pathophysiology of this disease, which can help lead to better prevention and treatment options. We are also hoping that the epidemiology studies will reveal significant correlations so that we can better recognize and address BA at a population level.
What new skills have you gained through your research?
It was such an honor to be a part of this program. I learned so much from my PI, other lab members, collaborators, and everyone involved in the STEER program. In order to complete my summer project, I had to first learn about the pathophysiology of biliary atresia. In my investigation of the 12 compounds of interest, I not only learned a lot about each compound but also became familiar with using the SciFinder database. Because the program was remote, I was unable to perform wet lab work, but I did learn how to use ImageJ to analyze images that Gauri shared with me. By being involved in the planning phases for the epidemiology studies, I also learned a lot about study design, such as thinking about different databases and control groups. Finally, this program taught me so much about environmental health research and about engaging with communities– I am looking forward to learning more and doing more in the fight for environmental justice.