Dr. Carmen Wong is currently an Associate Professor and Principal Investigator in the Department of Pathology and State Key Laboratory of Liver Research at the University of Hong Kong. She is the program leader of the liver cancer program at Center of Oncology and Immunology at InnoHealth, Hong Kong.
She obtained her PhD degree in the University of Hong Kong and completed her post-doctoral training from the Nobel Laureate, Professor Gregg Semenza, in the Johns Hopkins University, studying the roles and molecular mechanisms of hypoxia (oxygen deprivation) in cancer metastasis.
Her research team currently focuses on the impact of hypoxia and other microenvironmental factors in the metabolic reprogramming and immune evasion in liver cancer. Over the years, her work has been published in PNAS, Gastroenterology, Journal of Hepatology, GUT, Hepatology, Nature Communications, Cell Reports, and the Journal of Clinical Investigation.
She is the recipient of the Croucher Innovation Award, Outstanding Young Researcher Award of HKU, National Natural Science Foundation of China Excellent Young Scientist Fund, Hong Kong Young Scientist Award, the Best PhD thesis Awards of HKU, Croucher Fellowship, University of British Columbia (Canada) Alumni Builder Award. She is an elected member of the Hong Kong Young Academy of Science. She is the co-editor-in-chief of Hepatology Communications (AASLD).
Hypoxia is an important characteristic of hepatocellular carcinoma (HCC), the most common form of primary liver cancer. Hypoxia stabilizes hypoxia-inducible factors (HIFs). HIFs, through their transcriptional activities, empower hypoxic HCC cells with a wide range of abilities to drive different steps of hepatocarcinogenesis including tumor initiation, metabolic adaptation, and immune evasion. HIFs activated the NOTCH signaling pathway to promote liver cancer stemness, macropinoctysis to scavenge extracellular proteins as the nutrient source, and the purinergic signaling to drive the accumulation of myeloid-derived suppressor cells (MDSCs) in HCC. To identify potential vulnerabilities of hypoxic HCC cells for therapeutic targeting, a genome-wide CRISPR-Cas9 library screening was performed in HCC cells under hypoxia and normoxia. The functional screening identified PTPMT1 in the cardiolipin synthesis pathway was crucial to the survival of hypoxic HCC cells. Cardiolipin is an important component of the inner mitochondrial membrane which anchors different complexes of the electron transport chain (ETC). Inhibition of PTPMT1 suppressed cardiolipin synthesis, thereby leading to the disintegration of the inner mitochondrial membrane and leakage of reactive oxygen species (ROS), and eventually inducing apoptosis in hypoxic HCC cells. We demonstrated that PTPMT1 inhibitor, alexidine, effectively suppressed HCC.