Dr LEE Kin Wah, Terence | tkwlee@hkucc.hku.hk
Assistant Professor
Bsc HK; MPhil HK; PhD HK
Research Interest
Molecular Pathogenesis and Therapeutic Targeting of Hepatocellular Carcinoma (HCC)
Research Description
My research interest focuses on translational cancer research, of which includes (1) molecular pathogenesis and therapeutic targeting of liver cancer metastasis and; (2) identification, characterization and therapeutic targeting of liver tumor-initiating cells (T-ICs) / cancer stem cells (CSCs).
(1) Molecular pathogenesis and therapeutic targeting of liver cancer metastasis:
Liver cancer (hepatocellular carcinoma, HCC) is the fifth most common malignancy worldwide and is the second leading cause of cancer fatalities in Southeast Asia and locally in Hong Kong. Because of the high incidence and severe casualty rate, HCC is recognized as a major public health concern. The high mortality rate has been attributed to late presentation as well as frequent tumor recurrence and metastasis after surgical resection. Metastasis is a complicated process involving accumulation of multiple genetic alterations of both oncogenes and tumor-suppressor genes. To date, the molecular mechanism of HCC metastasis remains unclear, which greatly impedes the effort in developing effective therapies against this deadly disease. In the past 10 years, I have primarily focused my research to delineate the molecular mechanism of HCC metastasis by cDNA microarray approach. Currently, we are employing peptide microarray approach not only to understand the molecular events involved in HCC metastasis but also their therapeutic implications.
(2)Identification, characterization and therapeutic targeting of liver T-ICs / CSCs:
In the past several years, accumulating evidence has lent support to the concept of a “stem cell model of carcinogenesis”, which suggests that tumors are organized in a hierarchy of heterogeneous cell populations and that the capability to sustain tumor formation and growth exclusively resides in a rare fraction of cells called T-ICs or CSCs. This recent discovery of the role of stem cells in cancer has altered the landscape of cancer research. In this regard, my research studies are also on identification of liver T-IC markers and their related signaling pathways. In addition, we are also investigating therapeutic strategy against liver T-ICs by targeting their self-renewal pathways.Research Grants
- General research Fund (GRF) (2011) (PI) (HKD650,000)
- Collaborative Research Fund (2009) (Co-I)
“Molecular pathology of liver cancer - a multidisciplinary study” (HKD $8,100,000) - Seed Funding for Basic Research (2009) (PI)
“The significance of nucleophosmin phosphorylation (Threonine234) in HCC metastasis” - Seed Funding for Basic Research (2008) (PI)
“The novel role of a splice variant of carboxypeptidase E (CPE-deltaN) in HCC metastasis” - Donation from Arius Inc., Toronto (2004) (PI)
“The study of HCC cancer biology” (HKD $249,100)
Awards and Honors
- Hong Kong Young Scientist Award (Life Sciences), Hong Kong Institution of Science (2006)
- Young Investigator Award, Hong Kong-Shanghai International Liver Congress (2006)
- Li Ka Shing Prize for the Best M.Phil. Thesis, The University of Hong Kong (1999-2001)
- Young Investigator Award, The 11th Asian Pacific Congress of Gastroenterology / 8th Asian Pacific Congress Digestive Endoscopy, Hong Kong (2000)
- Young Investigator Award, The 6th Hong Kong International Cancer Congress, Hong Kong (1999)
Recent Publication lists (recent 3 years)
Click here for detail publication list on PubMed
Lee TK, Castilho A, Cheung VC, Tang KH, Ma S, Ng IO. CD24+ liver tumor-initiating cells drive self-renewal and tumor initiation through Stat3-mediated nanog regulation. Cell Stem Cell 2011; 9:50-63
Luk Su*, Lee TK* Lee DT, Chiu YT, Ma S, Ng IO, Wong YC, Wong YC, Chan FL, Ling MT. Chemopreventive effect of PSP through targeting of prostate cancer stem-like population. PLoS One 2011; 6:e19804 (*contributed equally)
Lee TK*, Murthy S*, Cawley NX, Dhanvantari S, Hewitt SM, Lou H, Lau S, Ma S, Huynh T, Wesley RA, Ng IO, Pacak K, Poon RT, Loh YP. Carboxypeptidase E spice isoform is a novel tumor inducer and biomarker for predicting future metastasis in human cancers. J Clin Invest 2011; 121:880-92. (*contributed equally)
Ma S, Tang KH, Chan YP, Lee TK, Kwan PS, Castilho A, Ng IO, Man K, Lo CM, Wong N, To KF, Zheng BJ, Lai PB, Chan KW, Guan XY. miR-130b promotes CD133+ liver tumor-initiating cell growth and self-renewal via tumor protein 53-induced nuclear protein 1. Cell Stem Cell 2010; 7:694-707.
Lee TK, Castilho A, Cheung VC, Tang KH, Ma S, Ng IO. Lupeol targets liver tumor-initiating cells through phosphatase and tensin homolog modulation. Hepatology 2010; 53:160-70.
Ma S, Chan YP, Kwan PS, Lee TK, Yan M, Tang KH, Ling MT, Vielkind J, Guan XY, Chan KW. microRNA-616 induces androgen-independent growth of prostate cancer cells by suppressing expression of tissue factor pathway inhibitor TFPI-2. Cancer Res2011; 71:583-92.
Luk Su, Yap WN, Chiu YT, Lee DT, Ma S, Lee TK, Vasireddy RS, Wong YC, Ching YP, Nelson C, Yap YL, Ling MT. Gamma-tocotrienol as an effective agent in targeting prostate stem cell-like population. Int J Cancer 2010; 128:2182-91
Ng KT, Lee TK, Cheng Q, Wo JY, Sun CK, Guo DY, Lim ZX, Lo CM, Poon RT, Fan ST, Man K. Suppression of tumorigenesis and metastasis of hepatocellular carcinoma by shRNA interference targeting on homeoprotein Six1. Int J Cancer 2010; 127: 859-72.
Lee TK*, Castilho A*, Ma S, Ng IO. Liver cancer stem cells: Implications for a new therapeutic target. Liver Int2009; 29: 955-65. (* co-first authors)
Lee TK*, Castilho A*, Ma S, Ng IO. Epithelial-mesenchymal transition in cancer stem cells. In: Cancer Stem Cells (Ed. XY Guan). Research Signpost 2010, ISBN: 978-81-7895-465-3. (* co-first authors)
Liu LX, Lee NP, Chan VW, Xue W, Zender L. Zhang C, Mao M, Dai H, Wang XL, Xu MZ, Lee TK, Ng IO, Chen Y, Kung HF, Lowe SW, Poon RT, Wang JH, Luk JM. Targeting caderin-17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma. Hepatology 2009; 50: 1453-63.
Ma S, Lee TK, Zheng BJ, Chan KW, Guan XY. CD133+ HCC cancer stem cells promote chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene 2008; 27: 1749-58.
Ma S, Chan KW, Lee TK, Tang KH, Wo JY, Zheng BJ, Guan XY. Aldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populations. Mol Cancer Res 2008; 6: 1146-53
Ling MT, Chiu YT, Lee TK, Leung SC, Fung MK, Wang X, Wong KF, Wong YC. Id-1 induces proteasome-dependent degradation of the HBX protein. J Mol Biol 2008; 382: 34-43.
Ma S, Chan KW, Hu L, Lee TK, Wo JY, Ng IO, Zheng BJ, Guan XY. Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology 2007; 132: 2542-56.
Ma S, Guan XY, Lee TK, Chan KW. Clinicopathological significance of missing in metastasis B expression in hepatocellular carcinoma. Hum Pathol 2007; 38: 1201-6.
Lee TK, Poon RT, Wo JY, Ma S, Guan XY, Myers JN, Yuen AP. Lupeol suppresses cisplatin-induced nuclear factor-kappaB activation in head and neck squamous cell carcinoma and inhibits local invasion and nodal metastasis in an orthotopic nude mouse model. Cancer Res 2007; 67; 8800-9.
Lee TK, Poon RT, Man K, Guan XY, Ma S, Liu XB, Myers JN, Yuen AP. Fascin over-expression is associated with aggressiveness of oral squamous cell carcinoma. Cancer Lett2007; 253: 308-15.
Zhang X, Ling MT, Wang Q, Lau CK, Leung SC, Lee TK, Cheung AL, Wong YC, Wang X. Identification of a novel inhibitor of differentiation-1 (ID-1) binding partner, caveolin-1, and its role in epithelial-mesenchymal transition and resistance to apoptosis in prostate cancer cells. J Biol Chem 2007; 282: 33284-94.
Man K, Ng KT, Lo CM, Ho JW, Sun BS, Sun CK, Lee TK, Poon RT, Fan ST. Ischemia-reperfusion of small liver remnant promotes liver tumor growth and metastases-activation of cell invasion and migration pathways. Liver Transpl 2007; 12: 1669-77.
Sun CK, Ng KT, Sun BS, Ho JW, Lee TK, Ng IO, Poon RT, Lo CM, Liu CL, Man K, Fan ST. The significance of proline-rich tyrosine kianse2 (Pyk2) on hepatocellular progression and recurrence. Br J Cancer 2007; 97: 50-7.
Pang R, Lee TK, Poon RT, Fan ST, Wong KB, Kwong YL, Tse E. Pin1 interacts with a specific serine-proline motif of hepatitis B virus X-protein to enhance hepatocarcinogenesis. Gastroenterology 2007; 132: 1088-103.
Ng KT, Man K, Ho JW, Sun CK, Lee TK, Zhao Y, Lo CM, Poon RT, Fan ST. Marked suppression of tumor growth by FTY720 in a rat liver tumor model: the significance of down-regulation of cell survival Akt pathway. Int J Oncol 2007; 30: 375-80.