Overview
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Principal Investigator: Dr. Vincent Lui
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Liver diseases affect all age groups from infants to old adults, constituting a major health burden and cause of human suffering. Patients often develop end-stage liver failure and require liver transplantation, but due to the scarcity of liver grafts, many of these patients die before liver transplantation. Furthermore, the number of liver disease patients is expected to soar due to our rapidly aging population. Better diagnosis and novel therapies for liver diseases are therefore urgently needed.
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Our research will advance diagnosis and development of novel therapies for two important liver diseases: Biliary Atresia (BA) and Alagille Syndrome (ALG). This will be achieved by a two-pronged approach using state-of-the-art liver organoid culture and single cell transcriptomics technologies. My work will provide insights into the patho-mechanisms, provide novel diagnostic markers and explore new therapeutic avenues to treat or ameliorate these two diseases.
We have successfully cultured liver stem cells (hepatoblasts) to organoids using less invasive Tru-cut needle biopsies from BA and normal control patients. Differentiation studies and transcriptomics analyses of hepatoblasts of healthy and patients of hepatobiliary diseases have revealed a partial shift from a bile duct cells to a liver cell transcriptional profile, and importantly abnormal expression of specific genes/pathways directly relevant to the disease initiation and progression, which shed important insights into the patho-mechanisms of BA diseases as well as provide targets for therapy development and patient management.
This 3D liver organoid culture is therefore very attractive for future translational applications for the study of liver diseases, representing a completely new research avenue for understanding organogenesis, for development of novel therapy screening methods and ultimately for patient management.
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