Waisbourd-Zinman O.: Unravelling the pathogenesis of biliary atresia
Interviewed today in the ESPGHAN podcast series is Dr Orit Waisbourd-Zinman, of Israel, who as a fellow in hepatology at the Children’s Hospital of Philadelphia was offered the chance to take part in studies of how “biliatresone”, a compound isolated from Australian plants (Dysphania sp.), might disrupt formation of extrahepatic biliary structures, as was postulated when sheep during drought ate unusual fodder, including Dysphania, and bore lambs that had biliary atresia. Extrahepatic cholangiocytes of mice and zebrafish given biliatresone had abnormal primary cilia (a glance of interest toward “syndromic” biliary atresia, with abnormalities of situs generally associated with ciliopathy, is in order here) ; the biliary-atresia phenotype could be ameliorated by administration of glutathione. Dr Waisbourd-Zinman has now returned to Israel, at the Schneider Children’s Medical Center, where she continues to investigate what the goddess Serendipity so generously cast into her lap. She addresses for us her working hypotheses regarding biliary-atresia pathogenesis and aetiology, tells us what her laboratory studies concern (what models, what techniques), and forecasts for us what paths biliary-atresia research may take. Literature : Waisbourd-Zinman O et al. The toxin biliatresone causes mouse extrahepatic cholangiocyte damage and fibrosis through decreased glutathione and SOX17. Hepatology 2016 Sep 64(3):880-893. doi: 10.1002/hep.28599. Epub 2016 May 20. PMID: 27081925. PMCID: PMC4992464 Fried S et al. Extrahepatic cholangiocyte obstruction is mediated by decreased glutathione Wnt and Notch signaling pathways in a toxic model of biliary atresia. Sci Rep 2020 May 5 10(1):7599. doi: 10.1038/s41598-020-645035. PMID: 32371929. PMCID: PMC7200694. Fried S et al. Wnt and Hippo signaling pathways and microtubules: Insights into biliary atresia mechanisms using a toxic model of the disease. Pediatr Res, in press; 2024. Dr Waisbourd-Zinman´s favourite song: Don't let the sun go down on me - Elton John https://open.spotify.com/track/11FcfHd3SOmmrWJPGe7Y30?si=96ee50d24ce243f3 ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo