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STAFF

Dr WONG Chak Lui, Carmen|carmencl@pathology.hku.hk
PhD HK
Assistant Professor

Visit our lab webpage: www.carmenwong-lab.com

Research Interest

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.

Research Opportunities
Research projects and postgraduate positions are available. Please contact Dr. Carmen Wong for inquiries.

Education

Postdoctoral Training: The Johns Hopkins University, USA

Doctor of Philosophy: The University of Hong Kong, Hong Kong

Master of Science: Hong Kong University of Science and Technology, Hong Kong

Bachelor of Science: The University of British Columbia, Canada

Grants (As Principal Investigator)

Research Grant Council General Research Fund (RGC GRF) 2016

Research Grant Council General Research Fund (RGC GRF) 2015

Research Grant Council General Research Fund (RGC GRF) 2014

Research Grant Council General Research Fund (RGC GRF) 2013

Health and Medical Research Fund (HMRF) 2015

Health and Medical Research Fund (HMRF) 2015

Health and Medical Research Fund (HMRF) 2014

Health and Medical Research Fund (HMRF) 2013

Awards and Honors

Award of Young Researcher Career Development Scheme (YRCDS)
The State Key Laboratory for Liver Research, the University of Hong Kong, 2014

Presentation Award
3rd Annual Postdoc Symposium
The Johns Hopkins Postdoctoral Association, the Johns Hopkins University, 2011

Li Ka Shing Prize (for the best PhD thesis in Faculty of Dentistry, Engineering, Medicine, and Science)
Graduate School, the University of Hong Kong, 2008-2009

Dr. KP Stephen Chang Gold Medal (for the best PhD thesis in Faculty of Medicine)
Faculty of Medicine, the University of Hong Kong, 2008-2009

Hong Kong Young Scientist Award (Life Science)
Hong Kong Institution of Science, 2009

Croucher Foundation Fellowship (for overseas postdoctoral fellow training)
Croucher Foundation, 2009-2011

Best Presentation Award
The 13th Postgraduate Symposium
Faculty of Medicine, the University of Hong Kong, 2008

Young Investigator Award
Hong Kong Shanghai International Liver Congress, 2008

Young Investigator Award
The 14th Hong Kong International Cancer Congress, 2007

Research Personnel

Current:
David Kung-Chun Chiu, PhD student (2013-current)
Iris Ming-Jing Xu, PhD student (co-supervision) (2013-current)
Derek Lee, MPhil student (2015-current)
Yuen-Ki Chan, MPhil student (2016-current)
Aki Pui-Wah Tse, research assistant (2012-current)
Lynna Lan Li, research assistant (2016-current)
Janet Choi, research assistant (2016-current)

Alumni:
Robin Kit-Ho Lai, MPhil graduate (2013-2015)
Victor Yu-Chun Lee, MMedSc graduate (2013-2015)
Hui-Yu Koh, research assistant (2014-2015)

Achievements of Team Members

David Kung-Chun Chiu

Iris Ming-Jing Xu

Robin Kit-Ho Lai

Publications

Researcher Profile on HKU Scholars Hub

Research Articles:

#Corresponding authors
*Contributed equally

  1. Chiu DK, Xu IM, Lai RK, Tse AP, Wei LL, Koh H, Li LL, Lee D, Lo RC, Wong CM, Ng IO#, Wong CC#. Hypoxia induces myeloid-derived suppressor cell recruitment to hepatocellular carcinoma through chemokine (C-C motif) Ligand 26. In Press. Hepatology.
  2. Lai RK, Chiu DK, Tse AP, Xu IM, Law DC, Lee D, Wei LL, Wong CM, Ng IO#, Wong CC#. NDUFA4L2 fine-tunes oxidative stress to promote hepatocellular carcinoma. 2016 Jun; 22(12):3105-17. Clinical Cancer Research.
  3. Xu IM, Lai RK, Lin SH, Tse AP, Chiu DK, Wong CM, Cai Z, Wong CC#, Ng IO#. Transketolase counteracts oxidative stress to drive cancer development. Proceedings of National Academy of Sciences.  2016 Feb;113(6):E725-34.
  4. Wong CM, Lai W, Law CT, Ho DW, Tsang FH, Au SL, Sze KM, Lee JM, Wong CC, Ng IO. Up-regulation of histone methyltransferase SETDB1 by multiple mechanisms in hepatocellular carcinoma promotes cancer metastasis. Hepatology. In Press.
  5. Wong CM, Wei L, Au SL, Fan DN, Zhou Y, Tsang FH, Law CT, Lee JM, He X, Shi J, Wong CC, Ng IO. MiR-200b/200c/429 subfmaily negatively regulates Rho/ROCK signaling pathway to suppress hepatocellular carcinoma metastasis. Oncotarget. 2015 May 30;6(15):13658-70.
  6. Leung CO, Wong CC, Fan DN, Kai AK, Tung EK, Xu IM, Ng IO, Lo RC. PIM1 regulates glycolysis and promotes tumor progression in hepatocellular carcinoma. Oncotarget. 2015 May; 6 (13): 10880-92.
  7. Tsang FH, Au SL, Wei L, Fan DN, Lee JM, Wong CC, Ng IO, Wong CM. Long non-coding RNA HOTTIP is frequently up-regulated in hepatocellular carcinoma and is targeted by tumor suppressive miR-125b. Liver International. 2015 May; 35 (5):1597-606.
  8. Wong CC#*, Au SL*, Tse AP, Xu IM, Lai RK, Wei LL, Fan DN, Tsang FH, Wong CM, Ng IO#. Switching of pyruvate kinase isoform L to M2 promotes metabolic reprogramming in hepatocarcinogenesis. PLoS ONE. 2014 Dec 26;9(12):e115036.
  9. Wong CC#, Tse PW, Huang Y, Zhu Y, Chiu DK, Lai RK, Au SL, Kai AK, Lee JM, Wei LL, Tsang FH, Lo RC, Shi J, Zheng Y, Wong CM, Ng IO#. Lysyl Oxidase-Like 2 is critical to tumor microenvironment and metastatic niche formation in hepatocellular carcinoma. Hepatology. 2014 Nov;60(5):1645-58.
  10. Au SL, Wong CC, Lee JM, Wong CM, Ng IO. EZH2-mediated H3K27me3 involves in epigenetic repression of Deleted in liver cancer 1 in human cancers. PLoS ONE. 2013 Jun 27;8(6):e68226.
  11. Gilkes DM, Chaturvedi P, Bajpai S, Wong CC, Wei H, Pitcairn S, Hubbi ME, Wirtz D, Semenza GL. Collagen prolyl hydroxylases are essential for breast cancer metastasis. Cancer Research. 2013 Jun 1;73(11):3285-96.
  12. Gilkes DM, Bajpai S, Wong CC, Chaturvedi P, Hubbi ME, Wirtz D, Semenza GL. Procollagen lysyl hydroxylase 2 is essential for hypoxia-induced breast cancer metastasis. Molecular Cancer Research. 2013 May;11(5):456-66.
  13. Hubbi ME, Kshitiz, Gilkes DM, Rey S, Wong CC, Luo W, Kim D, Dang CV, Levchenko A, Semenza GL. A non-transcriptional role of HIF-1α as a direct inhibitor of DNA replication. Science Signaling. 2013 Feb 12;6(262):ra10.
  14. Fan DN, Tsang FH, Au SL, Wong CC, Wei LL, Lee JM, He X, Ng IO, Wong CM. SUV39H1 overexpression promotes HCC progression and is negatively regulated by microRNA-125b. Hepatology. 2013 Feb;57(2):637-47.
  15. Chaturvedi P, Gilkes DM, Wong CC, Kschitiz, Zhang H, Wei H, Takano N, Schito L, Levchenko A, Semenza GL. Hypoxia-inducible factors promote metastasis by mediating bidirectional signaling between breast cancer cells and mesenchymal stem cells. Journal of Clinical Investigation. 2013 Jan 2;123(1):189-205.
  16. Schito L, Rey S, Tafani M, Zhang H, Wong CC, Russo A, Russo MA, Semenza GL. HIF-1-dependent PDGF-B expression promotes lymphatic metastasis of hypoxic breast cancer cells. Proceedings of National Academy of Sciences. 2012 Oct 2;109(40):E2707-16.
  17. Ma W, Wong CC, Tung EK, Wong CM, Ng IO. RhoE is frequently downregulated in HCC and suppresses HCC invasion through antagonizing the Rho/ROCK/MYPT pathway. Hepatology. 2013 Jan;57(1):152-61.
  18. Wong CC, Zhang H, Gilkes DM, Chen J, Wei H, Chaturvedi P, Hubbi M, Semenza GL. Inhibitors of Hypoxia-Inducible Factor 1 block breast cancer metastatic niche formation and lung metastasis. Journal of Molecular Medicine. 2012 Jul;90(7):803-15.
  19. Au SL, Wong CC, Lee JM, Fan DN, Ng IO, Wong CM. Enhancer of zeste homolog 2 (EZH2) epigenetically silences multiple tumor suppressor miRNAs to promote liver cancer metastasis. Hepatology. 2012 Aug;56(2):622-31.
  20. Wong CM*, Wong CC*, Lee JM, Fan DN, Au SL, Ng IO. Sequential alterations of miRNA expression in hepatocellular carcinoma development and venous metastasis. Hepatology. 2012 May;55(5):1453-61.
  21. Zhang H, Wong CC, Wei H, Gilkes DG, Korangath P, Chaturvedi P, Schito L, Chen J, Krishnamachary, Winnard Jr P, Raman V, Zhen L, Mitzner W, Sukumar S, Semenza GL. HIF-1 dependent expression of angiopoietin-like 4 and LICAM mediates vascular metastasis of hypoxic breast cancer cells to the lungs. Oncogene. 2012 Apr 5;31(14):1757-70.
  22. Wong CC, Gilkes DG, Zhang H, Chen J, Wei H, Chaturvedi P, Fraley SI, Wong CM, Khoo US, Ng IO, Wirtz D, Semenza GL. HIF-1 is a master regulator of breast cancer metastatic niche formation. Proceedings of National Academy of Sciences. 2011 Sep 27;108(39):16369-74.
  23. Gao P, Wong CC, Lee JM, Tung EK, Wong CM, Ng IO. Deregulation of microRNA expression occurs early and accumulates in early stages of HBV-associated multistep hepatocarcinogenesis. Journal of Hepatology. 2011 Jun; 54 (6): 1177-84.
  24. Wong CM, Wong CC, Ng YL, Au SL, Ko FC, Ng IO. Transcriptional repressive H3K9 and H3K27 methylations contribute to DNMT1-mediated DNA methylation recovery. PLoS ONE.  2011 Feb 8;6(2):e16702.
  25. Wong CC*, Wong CM*, Tung EK, Au SL, Lee JM, Man K, Ng IO.  MiR-139 suppresses metastasis and progression of hepatocellular carcinoma through regulation of Rho-kinase 2 (ROCK2). Gastroenterology. 2011 Jan;140(1):322-31. (Top 2% of published articles in biology and medicine, Faculty of 1000)
  26. Wong CC, Wong CM, Tung EK, Man K, Ng IO.  Rho-kinase 2 (ROCK2) is frequently over-expressed in hepatocellular carcinoma and involved in tumor invasion.  Hepatology.  2009 May; 29 (5) 1583-94. 
  27. Wong CC, Wong CM, Ko FC, Chan LK, Ching YP, Yam JW, Ng IODeleted in liver cancer 1 (DLC1) negatively regulates Rho/ROCK/MLC pathway in hepatocellular carcinoma.  PLoS ONE.  2008 July 23; 3(7): e2779.
  28. Lung HL, Lo CC, Wong CC, Cheung AK, Cheong KF, Wong N, Kwong FM, Chan KC, Law EW, Tsao SW, Chua D, Sham JS, Cheng Y, Stanbridge EJ, Robertson GP, Lung ML. Identification of tumor suppressive activity by irradiation microcell-mediated chromosome transfer and involvement of alpha B-crystallin in nasopharyngeal carcinoma. International Journal of Cancer. 2008 Mar; 122 (6): 1288-96.
  29. Wong CM, Ng YL, Lee JM, Wong CC, Cheung OF, Chan CY, Tung EK, Ching YP, Ng IO. Tissue factor pathway inhibitor-2 as a frequently silenced tumor suppressor gene in hepatocellular carcinoma. Hepatology. 2007 May; 45 (5): 1129-38.  

Review Articles and Commentary:

  1. Wong CC, Kai AK, Ng IO. The impact of hypoxia in hepatocellular carcinoma metastasis. Frontiers of Medicine. 2014 Mar;8(1):33-41.
  2. Wong CC, Wong CM, Au SL, Ng IO. Rho GTPases and rho effectors in hepatocellular carcinoma Metastasis: ROCK N’ Rho Move it. Liver International. 2010 May;30(5):642-56.
  3. Wong CC, Ng IO. Gene expression profiles in different stages of hepatocarcinogenesis. Journal of Gastroenterology and Hepatology. 2008 Jan; 23 (1): 1-3.