Liver Cancer Lab

Liver cancer has become the second leading cause of cancer mortality worldwide and is associated with poor prognosis. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, constituting more than 85% of hepatic malignancies. Currently, there are limited therapeutic options. Innovative research on the pathogenesis of this lethal disease at the molecular and cellular levels is needed to improve its diagnosis and develop novel treatment strategies.

HCC originates from the transformation of normal hepatocytes, the major cell type for liver functions, through a series of genetic alterations. Emerging evidence suggests that hepatocytes are heterogeneous in both metabolic function and regenerative capability.

Our research intends to determine which subgroup(s) of hepatocytes give rise to HCC and which molecular events play a key role in driving the initiation and progression of HCC. To tackle these fundamental questions, our team develop and employ state-of-the-art mouse models and cutting-edge molecular technologies. We also develop PDXs (patient-derived xenograft) and PDO (patient-derived organoids) as pre-clinical models to facilitate the translation of our research and collaborate with local and international clinician scientists to explore the potential of novel biomarkers and therapeutic targets identified from our studies for the diagnosis, prognosis and treatment of liver cancer.

Due to a lack of suitable genetic mouse models, the roles of distinct subsets of hepatocytes in liver homeostasis, regeneration and tumourigenesis remain largely unclear.

My laboratory has developed multiple unique genetic mouse models to address these important questions.

We recently reported an unexpected self-maintaining mode during liver homeostasis and regeneration, and identified Lgr5+ hepatocytes as the major cells of origin in a liver cancer model. We have also identified novel biomarkers and therapeutic targets for liver cancer. Our research will continue to yield novel insights into cellular and molecular origins in the primary liver cancer.