Professor WONG Chak Lui, Carmen

Tumor microenvironment formation Cancer metabolism Roles of hypoxia in cancer development Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. It is the fifth most common cancer in the world and the second leading cause of cancer deaths. High mortality rate in HCC is mainly due to late symptom presentation and lack of curative therapy. Therefore, knowledge on the molecular biology of HCC is warranted for the development of better diagnostic platforms and therapeutic regimens. Our research focuses on two emerging and fundamental aspects in HCC: (1) Tumor microenvironment in HCC: Solid tumors, in addition to malignant cells, are made up of other non-malignant cell types (stromal cells). Solid tumors are embedded in a remodeled extracellular matrix (ECM). Solid tumors are constantly experiencing inflammation and temporal changes of oxygen tension. These cellular and non-cellular components provide a unique tumor microenvironment conferring malignant cells oncogenic and metastatic properties. Our research focuses on the molecular mechanisms involved in the formation of tumor microenvironment of HCC. Currently, we are investigating the clinical implications, regulations, and roles of hypoxia (oxygen deprivation) in ECM modification in HCC. We are also investigating the roles of hypoxia in stromal cell-cancer cell interaction. (2) Metabolic reprogramming in HCC: The major difference between cancer cell and normal cell is that cancer cell growth is uncontrollable. Unlike normal differentiated cells which utilize mitochondrial oxidative phosphorylation to produce energy, cancer cells metabolize glucose by aerobic glycolysis, a phenomeon called the “Warburg Effect”. Although aerobic glycolysis is an energy-inefficient process, it advantages cancer cells to divert glucose intermediates for anabolic reactions and anti-oxidant production. Liver has many unique metabolic functions including gluconeogenesis, glycogen synthesis and storage, and blood glucose homeostasis. However, how the metabolic machineries are reprogrammed during the formation of HCC is largely unknown. Our group is investigating the signaling pathways that rewire the metabolic programs in HCC. We are also identifying novel functions of metabolic enzymes in HCC. We are also studying the therapeutic potential of drugs that target the metabolic machinery of HCC.