李建華，現任香港理工大學應用生物與化學科技系教授。

Education and Academic Qualifications：

Bachelor of Science in Biochemistry, The Hong Kong University of Science and Technology

Master of Philosophy, The University of Hong Kong

Doctor of Philosophy, The University of Hong Kong

學術兼職：Academic and Professional Experience：

2010- Academic Editor, PLoS One

2011- Academic Editor, American Journal of Stem Cell Research

2011- Academic Editor, Journal of Liver: Disease & Transplantation

2017- Academic Editor, Medicine

2014- Active member, American Association for Cancer Research

2013- 國家自然科學基金委員會醫學科學部七處通訊評審專家

2020- Academic Editor, World Journal of Gastroenterology

Editorship:

Associate Editor, Clinical and Molecular Hepatology (CMH) (IF: 14) (2024 – now)

Editorial Board Member, Hepatoma Research (IF: 1.7) (2024-now)

Editorial Board Member, Scientific Reports (IF: 3.8) (2024-now)

Editorial Board Member, Journal of Clinical and Translational Hepatology (JCTH) (IF: 3.1) (2021-now)

Editorial Board Member, World Journal of Gastroenterology (IF: 4.3) (2020-now)

Topical Advisory Panel Members, Cancers (IF: 4.5)(2023-now)

Research Overview:

Our research focuses on characterization, niche interaction and therapeutic targeting of liver tumor-initiating cells and understanding the molecular aspects of cancer metastasis and drug resistance. 

Research work in our lab is generously funded by: 

Research Grants Council-

RGC General Research Fund –

RGC GRF 2024/25 (PI)

RGC GRF 2023/24 (PI)

RGC GRF 2022/23 (PI)

RGC GRF 2021/22 (PI)

RGC GRF 2020/21 (PI)

RGC GRF 2019/20 (PI)

RGC GRF 2018/19 (PI)

RGC GRF 2017/18 (PI)

RGC GRF 2015/16 (PI)

RGC GRF 2014/15 (PI)

RGC GRF 2013/14 (PI)

RGC GRF 2011/12 (PI)

RGC Collaborative Fund –

RGC TBRS 2024/25 (Co-PI)

RGC RIF 2022/23 (PI)

RGC RIF 2020/21 (Co-PI)

RGC RIF 2018/19 (Co-PI)

RGC CRF 2018/19 (Co-PI)

RGC TBRS 2016/17 (Co-PI)

RGC CRF 2009/10 (Co-I)

Food and Heath Bureau

HMRF 2017/18 (PI)

HMRF 2016/17 (PI)

HMRF 2015/16 (PI)

HMRF 2013/14 (PI)

National Natural Science Foundation of China (NSFC)

NSFC General Program 2020/21 (PI)

NSFC General Program 2018/19 (PI)

NSFC General Program 2016/17 (Co-I)

NSFC General Program 2012/13 (PI)

Innovation Technology Fund

ITF 2023/24 (PI)

ITF MRP 2021/22 (Co-I)

ITF 2020/21 (Co-I) x 2

ITF 2016/17 (Co-I)

ITF 2014/15 (Co-I)

ITF 2013/14 (PI)

Hong Kong Polytechnic University

ABCT Excellence Award 2023 (Research Output)

Faculty Award for Outstanding Researchers (2022) (PI)

Strategic Importance Project Fund (2020/2021) (Co-PI)

Strategic Importance Project Fund (2020/2021) (PI)

State Key Laboratory of Chemical Biology and Drug Discovery

Biopharma collaboration

 Arius Inc (2009)

 

 

Patents:

1、"Combination use of CD47 antibodies/inhibitors with sorafenib for treatment of liver cancer" (US patent US20170071918) (2017)

2、"The use of HCN inhibitors for treatment of cancers" (PCT/16/607,035)

Book Chapters

[3]Lee TK, Castilho A, Ma S, Ng IO. Epithelial-mesenchymal transition in cancer stem cells. In: Cancer Stem Cells (XY Guan, Ed.). Research Signpost 2010, ISBN: 978-81-7895-465-3.

[2]Lei MM, Lee TK^. Genetics: Gene expression (Encyclopedia of Gerontology and Population Aging, Springer Nature Switzerland AG 2019 D. Gu, M. E. Dupre (eds.). 

[1]Lee TK. Genetics: Gender (Encyclopedia of Gerontology and Population Aging, Springer Nature Switzerland AG 2020 D. Gu, M. E. Dupre (eds.). 

Representative Publications：

2024

[169]Teo JM, Chen Z, Chen W, Tan R, Cao Q, Chu Y, Ma D, Chen L, Yu H, Lam KH, Lee TK, Chakarov S, Becher B, Zhang N, Li Z, Ma S, Xue R, Ling GS. Tumor-associated neutrophils attenuate the immuno-sensitivity of hepatocellular carcinoma. J Exp Med 2024; accepted.

[168]Loh JJ*, Ng KY*, Huang IB, Deng M, Wang Y, Man KF, Lam KH, Lee TK, Tan JY, Cui Y, Yu H, Wong TL, Gao Y, Yun JP, Ma S^. DGKH-mediated phosphatidic acid oncometabolism as a driver of self-renewal and therapy resistance in hepatocellular carcinoma. Hepatology 2024; accepted.

[167]Leung RW, Lee TK^. Identification of KCTD17 as a RAS stabilizer in hepatocellular carcinoma. Clin Mol Hepatol 2024; in press

[166]Lei MM, Lee TK^. UBE2S: A novel driver of HIF-1alpha-induced metabolic reprogramming in hepatocellular carcinoma. Clin Mol Hepatol 2024; doi: 10.3350/cmh.2024.0568.

[165]Muliawan GK, Lee TK^. The roles of cancer stem cell-derived secretory factors in shaping the immunosuppressive tumor microenvironment in hepatocellular carcinoma. Front Immunol 2024; 15:1400112.

[164]Wing Ki Chau; Terence Kin Wah Lee^. Covalent conjugation of AZD8055 with unsaturated fatty acids for the development of mTOR nanoblockers: Increasing the therapeutic efficacy of hepatocellular carcinoma treatment. EBioMedicine. 2024;103:105113.DOI: 10.1016/j.ebiom.2024.105113

[163]Xie Y, Wu H, He Y, Liu L, Huang IB, Zhou L, Lin CY, Leung RW, Loh JJ, Lee TK, Ding J, Man K, Ma S^, Tong M^. Targeting AXL induces tumor-intrinsic immunogenic response in tyrosine kinase inhibitor-resistant liver cancer. Cell Death Dis 2024; 15(2):110.

2023

[162]Man KF#, Zhou L#, Yu HJ, Lam KH, Cheng W, Yu J, Lee TK, Yun JP, Guan XY, Liu M, Ma S^. SPINK1-induced tumor plasticity provides a therapeutic window for chemotherapy in hepatocellular carcinoma. Nature Communications. 2023;14(1):7863. #equal contribution.DOI: 10.1038/s41467-023-43670-9

[161]Lu Y, Chan YT, Wu J, Feng Z, Yuan H, Li Q, Xing T, Xu L, Zhang C, Tan HY, Lee TK, Feng Y, Wang N. CRISPR/Cas9 screens unravel miR-3689a-3p regulating sorafenib resistance in hepatocellular carcinoma via suppressing CCS/SOD1-dependent mitochondrial oxidative stress. Drug Resistance Updates.  2023; 71:101015,

[160]Leung CON, Yang Y, Leung RW, So KK, Guo HJ, Lei MM, Muliawan GK, Gao Y, Yu QQ, Yun JP, Ma S, Zhao Q^, Lee TK^. Broad-spectrum kinome profiling identifies CDK6 upregulation as a driver of lenvatinib resistance in hepatocellular carcinoma. Nature Communications. 2023;14(1):6699.

[159]Khan SA, Chan KY, Lee TK^. Global Trajectory and Future Prospects of Metronomic Chemotherapy Research: A Scientometric Analysis (2000-2022). Cancer Letters. 2023; :576:216401.

[158]Xiaozhe Zhang; Gao Shan; Na Li; Jingyi Chen; Changyang Ji; Xiaoxiao Li; Liwen Jiang; Terence Kin Wah Lee; Vincent W. Keng; Yanxiang Zhao. An autophagy-inducing stapled peptide induces mitochondria dysfunction and triggers autotic cell death in triple negative breast cancer. Cell Death Discovery. 2023; 9(1):303.  DOI: 10.1038/s41420-023-01600-0

[157]Xu Y#*, Yao Y#, Liang Y#, Zhang X, Mao XW, Tey SK, Wong SWK, Yeung CLS, Ng TM, Wong MYM, Che CM, Lee TK, Gao Y, Cui Y, Yam JWP*. Clathrin light chain A-enriched small extracellular vesicles remodel microvascular niche to induce hepatocellular carcinoma metastasis.  Journal of Extracellular Vesicles. 2023; 12(8):e12359.

[156]Cybulski JD, Leung KS, Leung CO, Baker DM, Lee TK^. Protocol to track the biosynthesis of cholesterol in cultured HCC cells using 13C compound-specific stable isotopic tracers. STAR Protocols 2023, 4(3):102506.

[155]Khan SA, Lee TK^. Identifying potential pharmacological targets and molecular pathways of Meliae cortex for COVID-19 therapy. Frontiers in Immunology. 2023;14:1128164.

[154]Yu H, Zhou L, Loong JH, Lam KH, Wong TL, Ng KY, Tong M, Ma VW, Wang Y, Zhang X, Lee TK, Yun JP, Yu J, Ma S. SERPINA12 promotes the tumorigenic capacity of hepatocellular carcinoma stem cells through hyperactivation of AKT/β-catenin signaling. Hepatology  2023;78(6):1711-1726.

[153]Ying F#, Chan MS#, Lee TK^. Cancer-associated fibroblasts in hepatocellular carcinoma and cholangiocarcinoma. Cellular and Molecular Gastroenterology and Hepatology. 2023;15(4):985-999.

2022

[152]Yan T, Huang C, Lei J, Guo Q, Su G, Wu T, Jin X, Peng C, Cheng J, Zhang L, Liu Z, Lee TK, Ying F, Liangpunsakul S, Li Y, Lu Y. Development and Validation of a nomogram for forecasting survival of alcohol related hepatocellular carcinoma patients. Front Oncol 2022;12:976445.

[151]Rainbow Wing Hei Leung; Terence Kin Wah Lee^. Wnt/β-Catenin Signaling as a Driver of Stemness and Metabolic Reprogramming in Hepatocellular Carcinoma. Cancers 2022; 14(21):5468.DOI: 10.3390/cancers14215468

[150]Lei MM#, Leung CON#, Lau EY#, Leung RW, Ma VW, Tong M, Lu YY, Huang CY, Zhu QH, Ng IO, Ma S, Lee TK^. SCYL3, as a novel binding partner and regulator of ROCK2, promotes hepatocellular carcinoma progression.  JHEP Reports. 2022:5(1):100604.

[149]Wun CK#, Mok HK#, Chen T#, Wu TS, Taniya K, Nakagawa K, Day S, Tang CC, Huang Z, Su H, Yu WY^, Lee TK^, Lo TWB^. Atomically dispersed 3d metal bimetallic dual-atom catalysts and classification of the structural descriptors. Chem Catalysis 2022; 2(9):2346-2363.

[148]Wong MT, Wong TL, Zhou L, Man K, Purcell J, Lee TK, Yun JP, Ma S. Protein tyrosine kinase 7 (PTK7) promotes metastasis in hepatocellular carcinoma under SOX9 regulation and TGF-β signaling. Cellular and Molecular Gastroenterology and Hepatology.  2022;15(1):13-37.

[147]Stephanie Ma; Terence Lee; Fan Ying; Terence Kin Wah Lee^.  A special issue of Essays in Biochemistry on cancer stem cells. Essays in Biochemistry; 2022;66(4):287-289. DOI: 10.1042/EBC20220049

[146]Khan SA, Lee TK^. Investigations of Nitazoxanide Molecular Targets and Pathways for the Treatment of Hepatocellular Carcinoma Using Network Pharmacology and Molecular Docking. Frontiers in Pharmacology. 2022; 13:968148.

[145]Khan SA, Lee TK^. Network Pharmacology and Molecular Docking-Based Investigations of Kochiae Fructus’s Active Phytomolecules, Molecular Targets, and Pathways in Treating COVID-19. Frontiers in Microbiology. 2022; 13:972576.

[144]Mok EH#, Leung CO#, Zhou L, Lei MM, Leung HW, Tong M, Wong TL, Lau EY, Ng IO, Ding J, Yun JP, Yu J, Zhu HL, Lin CH, Lindholm D, Leung KS, Cybulski JD, Baker DM, Ma S, Lee TK^. Caspase 3-induced SREBP2 activation drives drug resistance through the promotion of cholesterol biosynthesis in hepatocellular carcinoma.Cancer Research. 2022; 82(17):3102-3115.

[143]Stephanie Ma; Terence Lee; Chin Ngok Chu; Terence Kin Wah Lee^. Targeting protein kinases in cancer stem cells. Essays in Biochemistry; 2022;66(4):399-412.DOI: 10.1042/EBC20220002

[142]Shakeel Ahmad Khan; Terence Kin Wah Lee^. Network Pharmacology Based Study on Active Phytochemicals and Molecular Mechanism of Cnidium monnieri in treating Hepatocellular Carcinoma. International Journal of Molecular Sciences; 2022; 23,5400.DOI: 10.3390/ijms23105400

[141]Catherine Yujia Gu; Terence Kin Wah Lee^. CircTUBD1: A Novel Circular RNA Molecule as a Therapeutic Target in Radiation-induced Liver Fibrosis. Journal of Clinical and Translational Hepatology; 2022; 10(4):571–573.DOI: 10.14218/JCTH.2022.00132

[140]Gu CY, Lee TK^. Preclinical mouse models of hepatocellular carcinoma: An overview and update. Experimental Cell Research. 2022;412(2):113042.

[139]Shen J, Yang C, Zhang MS, Chin WC, Chan FF, Law CT, Wang GC, Cheng CL, Chen M, Wan RT, Wu M, Kuang Z, Sharma R, Lee TK, Ng IO Wong CC#, Wong CM#. Histone chaperone FACT complex coordinates with HIF to mediate expeditious transcription program to adapt to poorly oxygenated cancers.  Cell Reports.  2022;38(5):110304.

[138]Tey SK#, Wong SW#, Chan JY, Mao XW, Ng TH, Yeung CL, Leung Z, Fung HL, Tang AH, Wong DK, Mak LY, Yuen MF, Sin CF, Ng IO, Ma S, Lee TK, Cao PH, Zhong K, Gao Y, Yun JP, Yam JW. Patient pIgR-enriched extracellular vesicles drive cancer stemness, tumorigenesis and metastasis in hepatocellular carcinoma.  Journal of Hepatology. 2022, 76(4):883-95.

[137]Lee TK, Guan XY, Ma S. Cancer stem cells in hepatocellular carcinoma: a review from origin to clinical implications.Nature Reviews Gastroenterology and Hepatology. 2021;19(1):26-44.

2021

[136]JJ, Li TW, Zhou L, Wong TL, Liu X, Ma VW, Lo CM, Man K, Lee TK, Ning W, Tong M^, Ma S^. FSTL1 secreted by Activated Fibroblasts Promotes Hepatocellular Carcinoma Metastasis and Stemness. Cancer Research. 2021; 81(22):5692-5705. 

[135]Mok KC, Tsoi H, Man EPS, Leung MH, Chau KM, Wong LS, Chan WL, Chan SY, Luk MY, Chan JYW, Leung JKM, Chan YHY, Batalha S, Lau V, Siu DCW, Lee TK, Gong C, Khoo US. Repurposing hyperpolarization-activated cyclic nucleotide-gated channels as a novel therapy for breast cancer. Clin Transl Med, 2021;11(11):e578. 

[134]Leung RW#, Ho NP#, Leung CO#, LEE TK^. UBE2T: A new molecular regulator of cancer stemness in hepatocellular carcinoma. Oncotarget 2021;12: 1727–1728.

[133]Tong M, Wong TL, Zhao H, Zhang Y, Xie YN, Li CH, Zhou L, Che N, Yun JP, Man K, Lee TK, Cai Z, Ma S. Loss of tyrosine catabolic enzyme 4-hydroxyphenylpyruvate dioxygenase HPD promotes glutamine anaplerosis through mTOR signaling in liver cancer. Cell Reports. 2021; 36(8):109617.

[132]Katherine Po Sin Chung; Rainbow Wing Hei Leung; Terence Kin Wah Lee^. Hampering Stromal Cells in the Tumor Microenvironment as a Therapeutic Strategy to Destem Cancer Stem Cells. Cancers 2021; 13(13):3191. DOI: 10.3390/cancers13133191

[131]Lei MM, Lee TK^. Cancer Stem Cells: Emerging Key Players in Immune Evasion of Cancers. Frontiers in Cell and Developmental Biology. 2021; 9:692940. 

[130]Leung HW#, Leung CO#, Lau EY, Chung KPS, Mok EH, Lei MM, Leung RW, Tong M, Keng VW, Ma C, Zhao Q, Ng IO, Ma S, Lee TK^. EPHB2 activates β-catenin to enhance cancer stem cell properties and drive sorafenib resistance in hepatocellular carcinoma. Cancer Res 2021; 81(12):3229-3240.

[129]Loong JH, Wong TL, Tong M, Sharma R, Zhou L, Ng KY, Yu HJ, Li CH, Man K, Lo CM, Guan XY, Lee TK, Yun JP, Ma S. Glucose deprivation induced aberrant FUT1-mediated fucosylation drives cancer stemness in hepatocellular carcinoma. Journal of Clinical Investigation. 2021; 131(11):e143377.

[128]Martina Mang Leng Lei; Terence Kin Wah Lee^. Orchestrating the Crosstalk Between Liver Cancer Cells and Neutrophils Through the Cardiotrophin‐Like Cytokine Factor 1–Mediated Chemokine (C‐X‐C motif) Ligand 6/TGF‐β Axis. Hepatology 2021;73(5):1631-1633.DOI: 10.1002/hep.31768

[127]Ng KY, Shea QT, Wong TL, Luk ST, Tong M, Lo CM, Man K, Yun JP, Guan XY, Lee TK, Zheng YP, Ma S. Chemotherapy enriched THBS2-deficient cancer stem cells drive hepatocarcinogenesis through matrix softness induced histone H3 modifications.Advanced Science 2021; 8(5):2002483.

[126]Chan LK, Ho DW, Kam CS, Chiu EY, Lo IL, Yau DT, Cheung ET, Tang CN, Tang VW, Lee TK, Wong CC, Chok KS, Chan AC, Cheung TT, Wong CM, Ng IO. RSK2-inactivating mutations potentiate MAPK signaling and support cholesterol metabolism in hepatocellular carcinoma. Journal of Hepatology. 2021, 74(2):360-371

[125]Huang YH#, Zhang CZ#, Huang QS#, Yeong J, Wang F, Yang X, He YF, Zhang XL, Zhang H, Chen SL, Zheng YL, Deng R, Lin CS, Yang MM, Li Y, Jiang C, Lee TK, Ma S, Zeng MS, Yun JP. Clinicopathologic features, tumor immune microenvironment and genomic landscape of EBV-associated intrahepatic cholangiocarcinoma. J Hepatol 2021;74(4):838-849.

[124]Che N#, Ng KY#, Wong TL, Tong M, Kau PW, Chan LH, Lee TK, Huen MS, Yun JP, Ma S. PRMT6 deficiency induces autophagy in hostile microenvironments of hepatocellular carcinoma tumors by regulating BAG5-associated HSC70 stability. Cancer Lett 2021; 501:247-262 #equal contribution

[123]Ho NP#, Leung CO#, Wong TL, Lau EY, Lei MM, Mok EH, Leung HW, Tong M, Ng IO, Yun JP, Ma S, Lee TK^. The interplay of UBE2T and Mule in regulating Wnt/β-catenin activation to promote hepatocellular carcinoma progression. Cell Death Dis 2021;12(2):148.

2020

[122]Mao XW#, Tey SK#, Yeung CLS, Kwong EML, Fung YME, Chung CYS, Mak LY, Wong DKH, Yuen MF, Ho JCM, Pang H, Wong MP, Leung CON, Lee TK, Ma V, Cho WCS, Cao PH, Xu X, Gao Y, Yam JWP. Nidogen 1-enriched extracellular vesicles facilitate extrahepatic metastasis of liver cancer by activating pulmonary fibroblasts to secrete tumor necrosis factor receptor 1. Adv Sci 2020; 7(21): 2002157.

[121]Mok EH, Lee TK^. The Pivotal Role of the Dysregulation of Cholesterol Homeostasis in Cancer: Implications for Therapeutic Targets. Cancers 2020;12(6):1410. DOI: 10.3390/cancers12061410.

[120]Mok EH, Leung CON, Lee TK^. MAP9/ERCC3 signaling cascade: A new insight on understanding the chromosomal instability in hepatocellular carcinoma. EBioMed 2020;54:102709. doi: 10.1016/j.ebiom.2020.102709

[119]Ming‐Sum Leung; Kristy Kwan‐Shuen Chan; Wen‐Juan Dai; Cheuk‐Yan Wong; Kwan‐Yung Au; Pik‐Ying Wong; Carmen Chak‐Lui Wong; Terence Kin‐Wah Lee; Irene Oi‐Lin Ng; Weiyuan John Kao et al. Anti-tumor effects of PIM kinase inhibition on progression and chemoresistance of hepatocellular carcinoma. The Journal of Pathology. 2020;252(1):65-76.DOI: 10.1002/path.5492

[118]Leung CO#, Tong M#, Chung KP, Zhou L, Che N, Tang KH, Ding J, Lau EY, Ng IO, Ma S^, Lee TK^. Overriding adaptive resistance of sorafenib through combination therapy with SHP2 blockade in hepatocellular carcinoma. Hepatology 2020; 72(1):155-168. #equal contribution

[117]Leung HW#, Lau EY#, Leung CO, Lei MM, Mok EH, Ma V, Cho WC, Ng IO, Yun JP, Cai SH, Yu HJ, Ma S, Lee TK^. NRF2/SHH signaling cascade promotes tumor-initiating cell lineage and drug resistance in hepatocellular carcinoma. Cancer Lett 2020; 476:48-56.

[116]Luk ST, Ng KY, Zhou L, Tong M, Wong TL, Yu HJ, Lo CM, Man K, Guan XY, Lee TK, Ma S. Deficiency in embryonic stem cell marker REX1 activates MKK6-dependent p38 MAPK signaling to drive hepatocarcinogenesis. Hepatology 2020; 72(1):183-97.

[115]Wong TL, Ng KY, Tan KV, Chan LH, Zhou L, Che N, Hoo RL, Lee TK, Richard S, Lo CM, Man K, Khong PL, Ma S. CRAF Methylation by PRMT6 Regulates Aerobic Glycolysis–Driven Hepatocarcinogenesis via ERK‐Dependent PKM2 Nuclear Relocalization and Activation. Hepatology 2020; 71(4):1279-1296.DOI: 10.1002/hep.30923 

[114]Ching, R. H. H., Sze, K. M. F., Lau, E. Y. T., Chiu, Y. T., Lee, J. M. F., Ng, I. O. L. & Lee, T. K. W. (Corresponding Author), .C-terminal truncated hepatitis B virus X protein regulates tumourigenicity, self-renewal, and chemoresistance via STAT3/Nanog signalling pathway: abridged secondary publication.1 Jun 2020, In: Hong Kong medical journal = Xianggang yi xue za zhi. 26, 3, p. 22-25.

[113]Steve T. Luk; Kai‐Yu Ng; Lei Zhou; Man Tong; Tin‐Lok Wong; Huajian Yu; Chung‐Mau Lo; Kwan Man; Xin‐Yuan Guan; Terence K. Lee et al..Deficiency in Embryonic Stem Cell Marker Reduced Expression 1 Activates Mitogen‐Activated Protein Kinase Kinase 6–Dependent p38 Mitogen‐Activated Protein Kinase Signaling to Drive Hepatocarcinogenesis.Hepatology.2020-07 DOI: 10.1002/hep.31020 

2019 

[112]Gurung S, Chung KP, Lee TK^. Emerging role of fatty acid binding proteins in cancer pathogenesis. Histol Histopathol 2019; 34 (1):1-12. 

[111]Luk, S. T., Ng, K. Y., Zhou, L., Tong, M., Wong, T. L., Yu, H., Lo, C. M., Man, K., Guan, X. Y., Lee, T. K. & Ma, S., .Deficiency in Embryonic Stem Cell Marker Reduced Expression 1 Activates Mitogen-Activated Protein Kinase Kinase 6–Dependent p38 Mitogen-Activated Protein Kinase Signaling to Drive Hepatocarcinogenesis.1 Jan 2019, (Accepted/In press) In: Hepatology. 

[110]Leung, H. W. & Lee, K. W., .EPH receptor B2 augments cancer stemness and drug resistance via a Wnt positive signaling loop in hepatocellular carcinoma.10 Dec 2019.  

[109]Leung, H. W., Lee, K. W. & Lau, E. Y. T., .NRF2/SHH signaling cascade promotes tumor-initiating cell lineage and drug resistance in hepatocellular carcinoma.Jul 2019, Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA.  

[108]Mok, H. K., Leung, H. W., Lau, E. Y. T. & Lee, K. W., Nuclear factor (erythroid-derived 2)-like 2 promotes tumor-initiating cell lineage and drug resistance in hepatocellular carcinoma.10 Dec 2019. 

[107]Leung, C. O. N., Tong, M., Chung, K. P. S., Zhou, L., Che, N., Tang, K. H., Ding, J., Lau, E. Y. T., Ng, I. O. L., Ma, S. & Lee, T. K. W., .Overriding Adaptive Resistance to Sorafenib Through Combination Therapy With Src Homology 2 Domain–Containing Phosphatase 2 Blockade in Hepatocellular Carcinoma.1 Jan 2019, (Accepted/In press) In: Hepatology. 

[106]Lee, T. K., Murthy, S. R. K., Cawley, N. X., Dhanvantari, S., Hewitt, S. M., Lou, H., Lau, T., Ma, S., Huynh, T., Wesley, R. A., Ng, I. O., Pacak, K., Poon, R. T. & Loh, Y. P.,.Retraction: An N-terminal truncated carboxypeptidase e splice isoform induces tumor growth and is a biomarker for predicting future metastasis in human cancers (Journal of Clinical Investigation (2011) 121:3 (880–892) DOI: 10.1172/JCI40433). 2019, In: Journal of Clinical Investigation. 129, 4, p. 1804  

[105]Ho, P. Y. & Lee, K. W., UBE2T: A molecular regulator for cancer stemness in hepatocellular carcinoma.10 Dec 2019. 

[104]Ho DW, Tsui YM, Sze KM, Chan LK, Cheung TT, Lee E, Sham PC, Tsui SK, Lee TK, Ng IO. Single-cell transcriptomics reveals the landscape of intra-tumoral heterogeneity and stemness-related subpopulations in liver cancer. Cancer Lett 2019; 459:176-85.

2018

[103]Chan LH#, Zhou L#, Ng KY#, Wong TL#, Lee TK, Sharma R, Loong JH, Ching YP, Yuan YF, Xie D, Lo CM, Man K, Artegiani B, Clevers H, Yan HH, Leung SY, Richard S, Guan XY, Huen MS, Ma S. PRMT6 regulates RAS/RAF binding and MEK/ERK-mediated cancer stemness activities in hepatocellular carcinoma through CRAF methylation. Cell Rep 2018; 25(3):690-701. #equal contribution

[102]Tong M, Che N, Zhou L, Luk ST, Kau PW, Chai S, Ngan ES, Lo CM, Man K, Ding J, Lee TK, Ma S. Efficacy of annexin A3 blockade in sensitizing hepatocellular carcinoma to sorafenib and regorafenib. J Hepatol 2018; 69(4):826-839.

[101]Cheng BY#, Lau EY#, Leung DH#, Ho NP, Cheng LK, Lin CH, Lo RC, Ma S, Ng IO, Lee TK^. IRAK1 augments cancer stemness and drug resistance via the AP-1/AKR1B10 signaling cascade in hepatocellular carcinoma. Cancer Research. 2018; 78(9):2332-2342. DOI: 10.1158/0008-5472.CAN-17-2445

[100]Lo RC, Leung CO, Chan KK, Ho DW, Wong CM, Lee TK, Ng IO. Cripto-1 contributes to stemness in hepatocellular carcinoma by stabilizing Dishevelled-3 and activating Wnt/β-catenin pathway. Cell Death and Differentiation. 2018; 25(8):1426-1441.DOI: 10.1038/s41418-018-0059-x

[99]Gong C, Man EP, Tsoi H, Lee TK, Lee P, Ma ST, Wong LS, Luk MY, Rakha EA, Green AR, Ellis IO, Cheung KL, Khoo US. BQ323636.1, a novel splice variant to NCOR2, as a predictor for tamoxifen resistant breast cancer. Clin Cancer Res 2018; 24(15):3681-3691.

[98]Gurung, S. & Lee, K. W., .Adipocyte-derived FABP4 regulates of cancer stemness and drug resistance in hepatocellular carcinoma.14 Jun 2018.Research output: Unpublished conference presentation (presented paper, abstract, poster) › Poster › Academic research › peer-review

[97]Gurung, S., Chung, K. P. S. & Lee, T. K. W., .Emerging role of fatty acid binding proteins in cancer pathogenesis.1 Jan 2018, In: Histology and Histopathology. 34, 1, p. 1-12 12 p.Research output: Journal article publication › Review article › Academic research › peer-review 

[96]Leung, H. W. & Lee, K. W., EPH receptor B2 augments cancer stemness and drug resistance via a Wnt positive signaling loop in hepatocellular carcinoma.14 Aug 2018.Research output: Unpublished conference presentation (presented paper, abstract, poster) › Poster › Academic research › peer-review 

[95]Cheng, B. Y. L., Lau, E. Y. T., Leung, H. W., Ng, I. O. & Lee, K. W., .IRAK1 augments cancer stemness and drug resistance via the AP-1/AKR1B10 signaling cascade in hepatocellular carcinoma.14 Apr 2018..Research output: Unpublished conference presentation (presented paper, abstract, poster) › Poster › Academic research › peer-review

[93]Leung, H. W. & Lee, K. W., Nuclear factor (erythroid-derived 2)-like 2 promotes tumor-initiating cell lineage and drug resistance in hepatocellular carcinoma.14 Apr 2018.Research output: Unpublished conference presentation (presented paper, abstract, poster) › Poster › Academic research › peer-review

[93]Gurung, S. & Lee, K. W., The pivotal role of adipocytes on regulation of cancer stemness and drug resistance in hepatocellular carcinoma.14 Apr 2018.Research output: Unpublished conference presentation (presented paper, abstract, poster) › Poster › Academic research › peer-review

[92]Ho, P. Y. & Lee, K. W., .UBE2T: a molecular regulator for cancer stemness and drug resistance in hepatocellular carcinoma.14 Apr 2018.Research output: Unpublished conference presentation (presented paper, abstract, poster) › Poster › Academic research › peer-review

[91]Ho, P. Y. & Lee, K. W., .UBE2T: A molecular regulator for cancer stemness in hepatocellular carcinoma.14 Jun 2018.Research output: Unpublished conference presentation (presented paper, abstract, poster) › Poster › Academic research › peer-review

2017

[90]Lau, E. Y. T., Ho, N. P. Y. & Lee, K. W., .Cancer stem cells and their microenvironment: Biology and therapeutic implications.26 Feb 2017, In: Stem Cells International. 2017, 3714190..Research output: Journal article publication › Review article › Academic research › peer-review

[89]Ho, P. Y. & Lee, K. W., .Interleukin-1 Receptor Kinase 1 augments cancer stemness and drug resistance via AP-1/AKR1B10 signaling cascade in hepatocellular carcinoma.29 Sept 2017.Research output: Unpublished conference presentation (presented paper, abstract, poster) › Poster › Academic research › peer-review

[88]Ma, M. K. F., Ng, I. O. & Lee, K. W., Stearoyl-CoA Desaturase (SCD1) regulates liver tumor initiating cells through modulating ER stress.1 Apr 2017.Research output: Unpublished conference presentation (presented paper, abstract, poster) › Poster › Academic research › peer-review

[87]Zhang, B.; Zhang, Y.; Zou, X.; Chan, A.W.H.; Zhang, R.; Lee, T.K.-W.; Liu, H.; Lau, E.Y.-T.; Ho, N.P.-Y.; Lai, P.B.S. et al.The CCCTC-binding factor (CTCF)–forkhead box protein M1 axis regulates tumour growth and metastasis in hepatocellular carcinoma.Journal of Pathology.2017,243(4):418-430.DOI: 10.1002/path.4976. 

[86]Lau CC#, Ng KY#, Wong TL, Tong M, Lee TK, Ming XY, Law S, Lee NP, Cheung AL, Qin YR, Chan KW, Ning W, Guan XY, Ma S. FSTL1 promotes metastasis and chemoresistance in esophageal squamous cell carcinoma through NFκB-BMP signaling crosstalk. Cancer Res 2017; 77(21): 5886-5899. #equal contribution.DOI: 10.1158/0008-5472.CAN-17-1411

[85]Li XF, Chen C, Xiang DM, Qu L, Sun W, Lu XY, Zhou TF, Chen SZ, Ning BF, Cheng Z, Xia MY, Shen WF, Yang W, Wen W, Lee TK, Cong WM, Wang HY, Ding J. Chronic inflammation-elicited liver progenitor cell conversion to liver cancer stem cell with clinical significance. Hepatology 2017; 66(6): 1934-1951.DOI: 10.1002/hep.29372

[84]Ng KY, Chan LH, Chai S, Tong M, Guan XY, Lee NP, Yuan YF, Xie D, Lee TK, Dusetti NJ, Carrier A, Ma S. TP53INP1 down-regulation activates a p73-dependent DUSP10/ERK signaling pathway to promote metastasis of hepatocellular carcinoma. Cancer Research 2017; 77(17): 4602-4612.DOI: 10.1158/0008-5472.CAN-16-3456

[83]Ma MK, Lau EY, Leung DH, Lo J, Ho NP, Cheng LK, Ma S, Lin CH, Copland JA, Lo RC, Ng IO, Lee TK^. Stearoyl-CoA desaturase regulates sorafenib resistance via modulation of ER stress induced differentiation. J Hepatol 2017; 67(5): 979-990.DOI: 10.1016/j.jhep.2017.06.015

[82]Wu CX, Xu A, Zhang CC, Olson P, Chen L, Lee TK, Cheung TT, Lo CM, Wang XQ. Notch inhibitor PF-03084014 inhibits hepatocellular carcinoma growth and metastasis via suppression of cancer stemness due to reduced activation of Notch1-Stat3. Molecular Cancer Therapeutics. 2017; 16(8): 1531-1543.DOI: 10.1158/1535-7163.MCT-17-0001

[81]Tsui YM, Sze KM, Tung EK, Lee TK, Ng IO. Dishevelled-3 phosphorylation is governed by HIPK2/PPIcα/ITCH axis and the non-phosphorylated form promotes cancer stemness via LGR5 in hepatocellular carcinoma. Oncotarget 2017; 8(24): 39430-39442.DOI: 10.18632/oncotarget.17049

[80]Cui CP, Wong CC, Kai AK, Ho DW, Lau EY, Tsui YM, Chan LK, Cheung TT, Chok KS, Chan AC, Lo RC, Lee JM, Lee TK, Ng IO. SENP1 promotes hypoxia-induced cancer stemness by HIF-1α deSUMOylation and SENP1/HIF-1α positive feedback loop. Gut 2017; 66(12): 2149-2159.DOI: 10.1136/gutjnl-2016-313264

[79]Lau EY, Ho NP, Lee TK^. Cancer stem cells and their microenvironment: biology and therapeutic implications. Stem Cell Int 2017; 2017: 3714190.DOI: 10.1155/2017/3714190

[78]Xiang DM, Wang X, Liu H, Cheng Z, Han T, Li XF, Sun W, Yang W, Chen C, Xia MY, Yang YC, Liu N, Yin SY, Jin GZ, Lee TK, Dong LW, Hu HP, Wang HY, Ding J. Shp2 promotes liver cancer stem cell expansion by augmenting β-catenin signaling and predicts chemotherapeutic response of patients. Hepatology 2017; 65(5): 1566-1580.DOI: 10.1002/hep.28919

[77]Ching RH#, Sze MF#, Lau EY#, Chiu EY, Lee JM, Ng IO, Lee TK^. C-terminal truncated hepatitis B virus X protein regulates tumorigenicity, self-renewal and drug resistance via STAT3/Nanog signaling pathway. Oncotarget 2017;8(14): 23507-23516.DOI: 10.18632/oncotarget.15183

2016

[76]Cheng, B. Y. L., Lee, K. W. & Ng, I. O. L., .Inhibition of TLR/IRAK pathway in hepatocellular carcinoma augmented therapeutic responses,16 Apr 2016.,Research output: Unpublished conference presentation (presented paper, abstract, poster) › Poster › Academic research › peer-review

[75]Ma, M. K. F. & Lee, K. W., Targeting liver-tumor initiating cells via hampering the lipogenesis pathways through Stearoyl - CoA desaturase,16 Apr 2016.,Research output: Unpublished conference presentation (presented paper, abstract, poster) › Poster › Academic research › peer-review

[74]Ho PY, Lee TK^. Targeting immune checkpoint proteins as novel strategy for treatment of hepatocellular carcinoma. Liver: Dis & Transplant 2016;5:2.

[73]Chai S, Ng KY, Tong M, Lau EY, Lee TK, Chan KW, Yuan YF, Cheung TT, Cheung ST, Wang XQ, Wong N, Lo CM, Man K, Guan XY, Ma S. Octamer4/microR-1246 signaling axis drives Wnt/β-catenin activation in liver cancer stem cells. Hepatology 2016; 64(6): 2062-2076.DOI: 10.1002/hep.28821

[72]Ma W, Sze KM, Chan LK, Lee JM, Wei LL, Wong CM, Lee TK,Wong CC, Ng IO. RhoE/ROCK2 regulates chemoresistance through NF-kappaB/IL-6/STAT3 signaling in hepatocellular carcinoma. Oncotarget 2016; 7(27): 41445-41459.DOI: 10.18632/oncotarget.9441

[71]Leung CO, Mak WN, Kai AK, Chan KS, Lee TK, Ng IO, Lo RC. Sox9 confer stemness properties in hepatocellular carcioma through Frizzled-7 mediated Wnt/beta-catenin signaling. Oncotarget 2016; 7(20): 29371-29386.DOI: 10.18632/oncotarget.8835

[70]Lau EY, Lo J, Cheng BY, Ma MK, Lee MF, Ng KY, Chai S, Lin N, Tsang SY, Ma S, Ng IO, Lee TK^. Cancer-Associated Fibroblasts Regulate Tumor-Initiating Cell Plasticity in Hepatocellular Carcinoma through c-Met/FRA1/HEY1 Signaling. Cell Rep 2016; 15(6): 1175-1189.DOI: 10.1016/j.celrep.2016.04.019

[69]Lau EY, Lee TK^. What are the options for hepatocellular carcinoma patients who progress under sorafenib? Hepatic Oncology 2016; 3(2): 105–108.DOI: 10.2217/hep-2016-0003

[68]Tang KD, Liu J, Jovanovic L, An J, Hill MM, Vela I, Lee TK, Ma S, Nelson C, Russell PJ, Clements JA, Ling MT. Adipocytes promote prostate cancer stem cell self-renewal through amplification of the cholecystokinin autocrine loop. Oncotarget 2016; 7(4): 4939-4948.DOI: 10.18632/oncotarget.6643

[67]Tang KD, Holzapfel BM, Liu J, Lee TK, Ma S, Jovanovic L, An J, Russell PJ, Clements JA, Hutmacher DW, Ling MT. Tie-2 regulates the stemness and metastatic properties of prostate cancer cells. Oncotarget 2016; 7(3): 2572-2584.DOI: 10.18632/oncotarget.3950

[66]Lau EY#, Lo J#, So FT, Lu P, Chan VS, Cheung VC, Ching RH,  Cheng BJ, Ma MK, Ng IO, Lee TK^. Anti-CD47 antibody suppresses tumor growth and augments the effect of chemotherapy treatment in hepatocellular carcinoma. Liver International. 2016; 36(5): 737-745. #equal contribution.DOI: 10.1111/liv.12963

2015

[65]Ching RH, Lau EY, Ling PM, Lee JM, Ma MK, Cheng BJ, Lo RC, Ng IO, Lee TK^. Phosphorylation of Nucleophosmin at Threonine 234/237 is associated with HCC metastasis. Oncotarget 2015; 6(41): 43483-43495.DOI: 10.18632/oncotarget.5820

[64]Lo J, Lau EY, Ching RH, Cheng BY, Ma MK, Ng IO, Lee TK^. Nuclear factor kappa B-mediated CD47 up-regulation promotes sorafenib resistance and its blockade synergizes the effect of sorafenib in hepatocellular carcinoma in mice. Hepatology 2015;62(2): 534-545.DOI: 10.1002/hep.27859

[63]Tong M, Fung TM, Luk ST, Ng KY, Lee TK, Lin CH, Yam JW, Chan KW, Ng F, Zheng BJ, Yuan YF, Xie D, Lo CM, Man K, Guan XY, Ma S. ANXA3/JNK signaling promotes self-renewal and tumor growth, and its blockade provides a therapeutic target for hepatocellular carcinoma. Stem Cell Reports 2015;5(1): 45-59.DOI: 10.1016/j.stemcr.2015.05.013

2014

[62]Ma KF, Ng IO, Lee TK^. Roles of stearoyl-CoA desaturase-1 in hepatocellular carcinoma. J Liver: Dis & Transplant 2014; 3: 2.

[61]Liu J#, Lau EY#, Chen J, Yong J, Tang KD, Lo J, Ng IO, Lee TK^, Ling MT. Polysaccharopeptide enhanced the anti-cancer effect of gamma-tocotrienol through activation of AMPK. BMC Complementary and Alternative Medicine. 2014; 14: 303. #equal contribution.DOI: 10.1186/1472-6882-14-303

[60]Lee TK^, Cheung VC, Lu P, Lau EY, Ma S, Tang KH, Tong M, Lo J, Ng IO. Blockade of CD47-mediated cathepsin S/protease-activated receptor 2 signaling provides a therapeutic target for hepatocellular carcinoma. Hepatology 2014; 60(1): 179-191.DOI: 10.1002/hep.27070

[59]Chai S, Tong M, Ng KY, Kwan PS, Chan YP, Fung TM, Lee TK, Wong N, Xie D, Yuan YF, Guan XY, Ma S. Regulatory role of miR-142-3p on the functional hepatic cancer stem cell marker CD133. Oncotarget 2014 5(14): 5725-5735.DOI: 10.18632/oncotarget.2167

2012

[58]Lee TK, Cheung VC, Ng IO. Liver tumor initiating cells as therapeutic target for hepatocellular carcinoma. Cancer Lett 2013; 338(1): 101-109.DOI: 10.1016/j.canlet.2012.05.001

[57]Lo J, Ng IO, Lee TK^. CD47 – a potential therapeutic target for hepatocellular carcinoma. J Liver: Dis & Transplant 2013; 2: 2.

[56]Lau EY, Ng IO, Lee TK^. Cancer associated fibroblasts and hepatocellular carcinoma. J Liver: Dis & Transplant 2012; 1:2.

[55]Tang KH, Ma S, Lee TK, Chan YP, Kwan PS, Tong CM, Ng IO, Man K, To KF, Lai PB, Lo CM, Guan XY, Chan KW. CD133⁺ liver tumor-initiating cells promote tumor angiogenesis, growth, and self-renewal through neurotensin/interleukin-8/CXCL1 signaling. Hepatology 2012; 55(3): 807-20.DOI: 10.1002/hep.24739

[54]Tse EY, Ko FC, Tung EK, Chan LK, Lee TK, Ngan ES, Man K, Wong AS, Ng IO, Yam JW. Caveolin-1 overexpression is associated with hepatocellular carcinoma tumorigenesis and metastasis. J Pathol 2012; 226(4): 645-653.DOI: 10.1002/path.3957

2011

[53]Luk SU, Lee TK, Liu J, Lee DT, Chiu YT, Ma S, Ng IO, Wong YC, Chan FL, Ling MT. Chemopreventive effect of PSP through targeting of prostate cancer stem cell-like population. PLoS One 2011; 6(5): e19804.DOI: 10.1371/journal.pone.0019804

[52]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(1): 50-63.DOI: 10.1016/j.stem.2011.06.005

[51]Ma S, Chan YP, Kwan PS, Lee TK, Yan M, Tang KH, Ling MT, Vielkind JR, 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 Research. 2011; 71(2): 583-592. DOI: 10.1158/0008-5472.CAN-10-2587

[50]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 2011; 53(1): 160-70.DOI: 10.1002/hep.24000

[49]Lee, T.K.; Murthy, S.R.K.; Cawley, N.X.; Dhanvantari, S.; Hewitt, S.M.; Lou, H.; Lau, T.; Ma, S.; Huynh, T.; Wesley, R.A. et al.An N-terminal truncated carboxypeptidase E splice isoform induces tumor growth and is a biomarker for predicting future metastasis in human cancers.Journal of Clinical Investigation.2011,121(3):880-892.DOI: 10.1172/JCI40433.

[48]Luk, S.U.; Yap, W.N.; Chiu, Y.-T.; Lee, D.T.W.; Ma, S.; Lee, T.K.W.; Vasireddy, R.S.; Wong, Y.-C.; Ching, Y.P.; Nelson, C. et al..Gamma-tocotrienol as an effective agent in targeting prostate cancer stem cell-like population.International Journal of Cancer.2011 128(9):2182-2191.DOI: 10.1002/ijc.25546.

2010

[47]Ma, S.; Tang, K.H.; Chan, Y.P.; Lee, T.K.; Kwan, P.S.; Castilho, A.; Ng, I.; Man, K.; Wong, N.; To, K.-F. et al..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(6):694-707.DOI: 10.1016/j.stem.2010.11.010. 

[46]Ng, K.T.P.; Lee, T.K.W.; Cheng, Q.; Wo, J.Y.H.; Sun, C.K.W.; Guo, D.-Y.; Lim, Z.X.; Lo, C.-M.; Poon, R.T.P.; Fan, S.-T. et al.Suppression of tumorigenesis and metastasis of hepatocellular carcinoma by shRNA interference targeting on homeoprotein Six1.International Journal of Cancer.2010,127(4):859-872.DOI: 10.1002/ijc.25105. 

2009

[45]Lee, T.K.W.; Castilho, A.; Ma, S.; Ng, I.O.L..Liver cancer stem cells: Implications for a new therapeutic target.Liver International.2009 ,29(7):955-965.DOI: 10.1111/j.1478-3231.2009.02040.x. 

[44]Liu, L.X.; Lee, N.P.; Chan, V.W.; Xue, W.; Zender, L.; Zhang, C.; Mao, M.; Dai, H.; Wang, X.L.; Xu, M.Z. Lee, T.K.W.et al..Targeting cadherin-17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma.Hepatology.2009,50(5):1453-1463 .DOI: 10.1002/hep.23143.

2008

[43]Ma, S.; Kwok, W.C.; Lee, T.K.-W.; Kwan, H.T.; Wo, J.Y.-H.; Zheng, B.-J.; Guan, X.-Y..Aldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populations.Molecular Cancer Research.2008,6(7):1146-1153.DOI: 10.1158/1541-7786.MCR-08-0035.

[42]Ma, S.; Lee, T.K.; Zheng, B.-J.; Chan, K.W.; Guan, X.-Y..CD133⁺HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway.Oncogene.2008,27(12):1749-1758.DOI: 10.1038/sj.onc.1210811.

[41]Ling, M.-T.; Chiu, Y.-T.; Lee, T.K.W.; Leung, S.C.L.; Fung, M.K.L.; Wang, X.; Wong, K.F.; Wong, Y.-C..Id-1 Induces Proteasome-dependent Degradation of the HBX Protein.Journal of Molecular Biology.2008, 382(1):34-43.DOI: 10.1016/j.jmb.2007.06.020.

2007

[40]Ma, S.; Guan, X.-Y.; Lee, T.K.; Chan, K.W..Clinicopathological significance of missing in metastasis B expression in hepatocellular carcinoma.Human Pathology.2007,38(8):1201-1206.DOI: 10.1016/j.humpath.2007.01.004.

[39]Lee, T.K.; Poon, R.T.P.; Man, K.; Guan, X.-Y.; Ma, S.; Liu, X.B.; Myers, J.N.; Yuen, A.P.W..Fascin over-expression is associated with aggressiveness of oral squamous cell carcinoma.Cancer Letters.2007,254(2):308-315.DOI: 10.1016/j.canlet.2007.03.017.

[38]Ma, S.; Chan, K.; Hu, L.; Lee, T.K.; Wo, J.Y.; Ng, I.O.; Zheng, B.; Guan, X..Identification and Characterization of Tumorigenic Liver Cancer Stem/Progenitor Cells.Gastroenterology.2007, 132(7):2542-2556.DOI: 10.1053/j.gastro.2007.04.025.

[37]Zhang, X.; Ling, M.-T.; Wang, Q.; Lau, C.-K.; Leung, S.C.L.; Lee, T.K.; Cheung, A.L.M.; Wong, Y.-C.; 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.Journal of Biological Chemistry.2007,282(46): 33284-33294.DOI: 10.1074/jbc.M705089200. 

[36]Man, K.; Ng, K.T.; Lo, C.M.; Ho, J.W.; Sun, B.S.; Sun, C.K.; Lee, T.K.; Poon, R.T.P.; Fan, S.T..Ischemia-reperfusion of small liver remnant promotes liver tumor growth and metastases - Activation of cell invasion and migration pathways.Liver Transplantation.2007, 13(12):1669-1677.DOI: 10.1002/lt.21193.  

[35]Lee, T.K.; Poon, R.T.P.; Wo, J.Y.; Ma, S.; Guan, X.-Y.; Myers, J.N.; Altevogt, P.; Yuen, A.P.W..Lupeol suppresses cisplatin-induced nuclear factor-κB activation in head and neck squamous cell carcinoma and inhibits local invasion and nodal metastasis in an orthotopic nude mouse model.Cancer Research.2007, 67(18):8800-8809.DOI: 10.1158/0008-5472.CAN-07-0801. 

[34]Ng, K.T.; Man, K.; Ho, J.W.; Sun, C.K.; Lee, T.K.; Zhao, Y.; Lo, C.M.; Poon, R.T.; Fan, S.T..Marked suppression of tumor growth by FTY720 in a rat liver tumor model: The significance of down-regulation of cell survival Akt pathway.International Journal of Oncology.2007,30(2):375-380

[33]Pang, R.; Lee, T.K.W.; Poon, R.T.P.; Fan, S.T.; Wong, K.B.; Kwong, Y.; Tse, E..Pin1 Interacts With a Specific Serine-Proline Motif of Hepatitis B Virus X-Protein to Enhance Hepatocarcinogenesis.Gastroenterology.2007,132(3):1088-1103.DOI: 10.1053/j.gastro.2006.12.030. 

[32]Sun, C.K.; Ng, K.T.; Sun, B.S.; Ho, J.W.Y.; Lee, T.K.; Ng, I.; Poon, R.T.P.; Lo, C.M.; Liu, C.L.; Man, K. et al..The significance of proline-rich tyrosine kinase2 (Pyk2) on hepatocellular carcinoma progression and recurrence.British Journal of Cancer.2007,97(1):50-57.DOI: 10.1038/sj.bjc.6603827.

2006

[31]Xu, X.; Man, K.; Zheng, S.S.; Liang, T.B.; Lee, T.K.; Ng, K.T.; Fan, S.T.; Lo, C.M..Attenuation of acute phase shear stress by somatostatin improves small-for-size liver graft survival.Liver Transplantation.2006,12(4):621-627.DOI: 10.1002/lt.20630.

[30]Ng, K.T.; Man, K.; Sun, C.K.; Lee, T.K.; Poon, R.T.; Lo, C.-M.; Fan, S.-T..Clinicopathological significance of homeoprotein Six1 in hepatocellular carcinoma.British Journal of Cancer.2006, 95(8):1050-1055.DOI: 10.1038/sj.bjc.6603399.

[29]Man, K.; Zhao, Y.; Xu, A.; Lo, C.M.; Lam, K.S.L.; Ng, K.T.; Ho, J.W.Y.; Sun, C.K.; Lee, T.K.; Li, X.L. et al..Fat-derived hormone adiponectin combined with FTY720 significantly improves small-for-size fatty liver graft survival.American Journal of Transplantation.2006,6 (3):467-476 .DOI: 10.1111/j.1600-6143.2005.01201.x.

[28]Zhou, C.; Ling, M.-T.; Kin-Wah Lee, T.; Man, K.; Wang, X.; Wong, Y.-C..FTY720, a fungus metabolite, inhibits invasion ability of androgen-independent prostate cancer cells through inactivation of RhoA-GTPase.Cancer Letters.2006,233(1):36-47.DOI: 10.1016/j.canlet.2005.02.039.

[27]Pang, R.W.; Lee, T.K.; Man, K.; Poon, R.T.; Fan, S.-T.; Kwong, Y.-L.; Tse, E..PIN1 expression contributes to hepatic carcinogenesis.Journal of Pathology.2006,210(1):19-25.DOI: 10.1002/path.2024.

[26]Lee, T.K.; Poon, R.T.P.; Yuen, A.P.; Man, K.; Zhen, F.Y.; Xin, Y.G.; Sheung, T.F..Rac activation is associated with hepatocellular carcinoma metastasis by up-regulation of vascular endothelial growth factor expression.Clinical Cancer Research.2006 ,12(17):5082-5089.DOI: 10.1158/1078-0432.CCR-05-2794.

[25]Man, K.; Su, M.; Ng, K.T.; Lo, C.M.; Zhao, Y.; Ho, J.W.; Sun, C.K.; Lee, T.K.; Fan, S.T..Rapamycin attenuates liver graft injury in cirrhotic recipient - The significance of down-regulation of Rho-ROCK-VEGF pthway.American Journal of Transplantation.2006, 6(4):697-704.DOI: 10.1111/j.1600-6143.2005.01231.x.

[24]Lee, K. W., Poon, R. T. P., Yuen, A. P., Ling, M. T., Wang, X. H., Wong, Y. C., Guan, X. Y., Man, K., Tang, Z. Y. & Fan, S. T.,.Regulation of angiogenesis by Id-1 through hypoxia-inducible factor-1α-mediated vascular endothelial growth factor up-regulation in hepatocellular carcinoma.Clinical Cancer Research.2006,12(23):6910-6919.DOI: 10.1158/1078-0432.CCR-06-0489.  

[23]Lee, T.K.; Man, K.; Poon, R.T.P.; Lo, C.M.; Yuen, A.P.; Ng, I.O.; Ng, K.T.; Leonard, W.; Fan, S.T..Signal transducers and activators of transcription 5b activation enhances hepatocellular carcinoma aggressiveness through induction of epithelial-mesenchymal transition.Cancer Research.2006 ,66(20):9948-9956.DOI: 10.1158/0008-5472.CAN-06-1092. 

[22]Lee, T.K.; Poon, R.T.P.; Yuen, A.P.; Ling, M.T.; Kwok, W.K.; Wang, X.H.; Wong, Y.C.; Guan, X.; Man, K.; Chau, K.L. et al..Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition.Clinical Cancer Research.2006,12(18): 5369-5376.DOI: 10.1158/1078-0432.CCR-05-2722. 

2005

[21]Ho, J.W.Y.; Man, K.; Sun, C.K.; Lee, T.K.; Poon, R.T.P.; Fan, S.T..Effects of a novel immunomodulating agent, FTY720, on tumor growth and angiogenesis in hepatocellular carcinoma.Molecular Cancer Therapeutics.2005,4(9): 1430-1438.DOI: 10.1158/1535-7163.MCT-05-0021. 

[20]Man, K.; Ng, K.T.; Lee, T.K.; Lo, C.M.; Sun, C.K.; Li, X.L.; Zhao, Y.; Ho, J.W.; Fan, S.T..FTY720 attenuates hepatic ischemia-reperfusion injury in normal and cirrhotic livers.American Journal of Transplantation.2005,5(1): 40-49.DOI: 10.1111/j.1600-6143.2004.00642.x.EID: 2-s2.0-11844305973

[19]Lee, T.K.; Man, K.; Ho, J.W.; Wang, X.H.; Poon, R.T.P.; Xu, Y.; Ng, K.T.; Chu, A.C.; Sun, C.K.; Ng, I.O. et al.FTY720: A promising agent for treatment of metastatic hepatocellular carcinoma.Clinical Cancer Research.2005,11(23): 8458-8466.DOI: 10.1158/1078-0432.CCR-05-0447. 

[18]Lee, T.K.; Man, K.; Ho, J.W.; Wang, X.H.; Poon, R.T.; Sun, C.K.; Ng, K.T.; Ng, I.O.; Xu, R.; Fan, S.T. Significance of the Rac signaling pathway in HCC cell motility: Implications for a new therapeutic target.Carcinogenesis.2005,26(3):681-687.DOI: 10.1093/carcin/bgi002. 

2004

[17]Zhao, Y.; Man, K.; Lo, C.M.; Ng, K.T.; Li, X.L.; Sun, C.K.; Lee, T.K.; Dai, X.W.; Fan, S.T..Attenuation of small-for-size liver graft injury by FTY720: Significance of cell survival Akt signaling pathway.American Journal of Transplantation.2004,4(9):1399-1407. DOI: 10.1111/j.1600-6143.2004.00527.x. 

[16]Lee, T.K.-W.; Man, K.; Poon, R.T.-P.; Lo, C.-M.; Ng, I.O.-L.; Fan, S.-T..Disruption of p53-p21/WAF1 cell cycle pathway contributes to progression and worse clinical outcome of hepatocellular carcinoma.Oncology Reports.2004 ,12(1): 25-31. 

[15]Man, K.; Lee, T.K.; Liang, T.B.; Lo, C.M.; Fung, P.C.-W.; Tsui, S.H.; Li, X.L.; Ng, K.T.; Fan, S.T..FK 409 ameliorates small-for-size liver graft injury by attenuation of portal hypertension and down-regulation of Egr-1 pathway.Annals of Surgery.2004.240(1):159-168.DOI: 10.1097/01.sla.0000129673.13552.c0.

[14]Lee, T.K.; Man, K.; Ho, J.W.; Sun, C.K.; Ng, K.T.; Wang, X.H.; Wong, Y.C.; Ng, I.O.; Xu, R.; Fan, S.T.FTY720 induces apoptosis of human hepatoma cell lines through cell lines through P13-K-mediated Akt dephosphorylation.Carcinogenesis.2004, 25(12):2397-2405.DOI: 10.1093/carcin/bgh250.

[13]Li, X.L.; Man, K.; Ng, K.T.; Lee, T.K.; Lo, C.M.; Fan, S.T..Insulin UW solution exacerbates hepatic ischemia/reperfusion injury by energy depletion through the IRS-2/SREBP-1c pathway.Liver Transplantation.2004,10(9):1173-1182.DOI: 10.1002/lt.20240. 

[12]Pang, R.; Yuen, J.; Yuen, M.F.; Lai, C.L.; Lee, T.K.W.; Man, K.; Poon, R.T.P.; Fan, S.T.; Wong, C.M.; Ng, I.O.L. et al.PIN1 overexpression and β-catenin gene mutations are distinct oncogenic events in human hepatocellular carcinoma.Oncogene.2004,23(23): 4182-4186.DOI: 10.1038/sj.onc.1207493. 

2003

[11]Liang, T.-B.; Man, K.; Lee, T.K.-W.; Tsui, S.H.-T.; Lo, C.-M.; Xu, X.; Zheng, S.-S.; Fan, S.-T.; Wong, J..Distinct intragraft response pattern in relation to graft size in liver transplantation.Transplantation.2003, 75(5): 673-678 .DOI: 10.1097/01.TP.0000048490.24429.89.

[10]Man, K.; Lo, C.-M.; Liu, C.-L.; Zhang, Z.-W.; Lee, T.K.-W.; Ng, I.O.-L.; Fan, S.-T.; Wong, J..Effects of the intermittent Pringle manoeuvre on hepatic gene expression and ultrastructure in a randomized clinical study.British Journal of Surgery.2003 90( 2):183-189.DOI: 10.1002/bjs.4027.EID: 2-s2.0-0037326916

[9]Man, K.; Fan, S.-T.; Lo, C.-M.; Liu, C.-L.; Fung, P.C.-W.; Liang, T.-B.; Lee, T.K.-H.; Tsui, S.H.-T.; Ng, I.O.-L.; Zhang, Z.-W. et al..Graft Injury in Relation to Graft Size in Right Lobe Live Donor Liver Transplantation: A Study of Hepatic Sinusoidal Injury in Correlation with Portal Hemodynamics and Intragraft Gene Expression.Annals of Surgery.2003, 237( 2):256-264.DOI: 10.1097/00000658-200302000-00015.EID: 2-s2.0-0037316049

[8]Li, X.-L.; Man, K.; Liu, Y.-F.; Lee, T.K.-W.; Tsui, S.H.-T.; Lau, C.-K.; Lo, C.-M.; Fan, S.-T..Insulin in University of Wisconsin solution exacerbates the ischemic injury and decreases the graft survival rate in rat liver transplantation.Transplantation.2003,76(1): 44-49.DOI: 10.1097/01.TP.0000067242.14209.0D.EID: 2-s2.0-0037962323

[7]Man, K.; Lo, C.-M.; Lee, T.K.-W.; Li, X.-L.; Ng, I.O.-L.; Fan, S.-T..Intragraft gene expression profiles by cDNA microarray in small-for-size liver grafts.Liver Transplantation.2003,9(4): 425-432.DOI: 10.1053/jlts.2003.50066.EID: 2-s2.0-0037387674

[6]Lee, T.K.-W.; Man, K.; Ling, M.-T.; Wang, X.-H.; Wong, Y.-C.; Lo, C.-M.; Poon, R.T.-P.; Ng, I.O.-L.; Fan, S.-T..Over-expression of Id-1 induces cell proliferation in hepatocellular carcinoma through inactivation of p16INK4a/RB pathway.Carcinogenesis.2003, 24(11):1729-1736.DOI: 10.1093/carcin/bgg145.EID: 2-s2.0-0242559090

2002

[5]Ling, M. T., Wang, X., Ouyang, X. S., Lee, K. W., Fan, T. Y., Xu, K., Tsao, S. W. & Wong, Y. C.,  Activation of MAPK signaling pathway is essential for Id-1 induced serum independent prostate cancer cell growth.Oncogene.2002，21(55):8498-8505 .DOI: 10.1038/sj.onc.1206007. 

[4]Lee, T.; Lau, T.; Ng, I.  .Doxorubicin-induced apoptosis and chemosensitivity in hepatoma cell lines.Cancer Chemotherapy and Pharmacology.2002,49(1):78-86. DOI: 10.1007/s00280-001-0376-4.

[3]Qin, L.F.; Lee, T.K.W; Ng, I.O.L.Gene expression profiling by cDNA array in human hepatoma cell line in response to cisplatin treatment.Life Sciences.2002,70(14):1677-1690.DOI: 10.1016/S0024-3205(01)01554-5.EID: 2-s2.0-0037154778 

2001

[2]Lee, T.K.-W.; Han, J.-S.; Fan, S.-T.; Liang, Z.-D.; Tian, P.-K.; Gu, J.-R.; Ng, I.O.-L..Gene delivery using a receptor-mediated gene transfer system targeted to hepatocellular carcinoma cells.International Journal of Cancer.2001，93(3): 393-400 .DOI: 10.1002/ijc.1340.EID: 2-s2.0-0035426950

2000

[1]Ng, I.O.-L.; Liang, Z.-D.; Cao, L.; Lee, T.K.-W..DLC-1 is deleted in primary hepatocellular carcinoma and exerts inhibitory effects on the proliferation of hepatoma cell lines with deleted DLC-1.Cancer Research.2000，60(23)： 6581-6584 

  

1、Eunice Yuen Ting Lau (Postdoctoral Fellow, 2016-2017)

2、Abstract award – Cancer Stem cell Conference, Cleveland, Ohio, USA (2016)

 3、2023 Top 2% Scientists Worldwide by Stanford University.Lee, K. W. (Recipient), 2023 

4、ABCT Excellence Award 2023 (Research Output)。Lee, K. W. (Recipient), Dec 2023

5、Faculty Awards for Outstanding Achievement，Lee, K. W. (Recipient), Jun 2022

6、PolyU Faculty Awards for Outstanding Achievement 2022，Lee, K. W. (Recipient), 2022

7、Reaching Out Award under the HKSAR Government Scholarship Fund。Chung, P. S. (Recipient) & Lee, K. W. (Supervisor), Jun 2020

8、The Best Poster Oral Award。GURUNG, S. (Recipient) & Lee, K. W. (Recipient), Jun 2018

9、Travel Award, The 76th Annual Meeting of the Japanese Cancer Association。Ho, P. Y. (Recipient) & Lee, K. W. (Supervisor), Sept 2017

10、Travel Award, The Liver Week 2017, The Korean Association for the Study of the Liver (KASL)。Ho, P. Y. (Recipient) & Lee, K. W. (Supervisor), Jun 2017

11、Travel Award, The Liver Week 2018, The Korean Association for the Study of the Liver (KASL), Annual meeting of The Korean Association for the study of Liver。Ho, P. Y. (Recipient) & Lee, K. W. (Supervisor), Jun 2018

12、Travel Awards。GURUNG, S. (Recipient), HO, P. Y. (Recipient) & Lee, K. W. (Recipient), Jun 2018 

1、Chemistry for a Sustainable Future: Innovation and Challenges

Wong, W. Y. (Chair), Chai, Y. (Co-chair), Yung, K. F. (Co-chair), Lee, K. W. (Member of organizing committee) & Wong, M. K. (Member of organizing committee)

10 Nov 2023 → 11 Nov 2023

Activity: Participating in or organising an event › Organizer / committee member

2、Journal of Clinical and Translational Hepatology (Journal)

Lee, K. W. (Editor)

26 Apr 2021

Activity: Publication peer-review and editorial work › Editorial work for journals

3、Overriding adaptive resistance to sorafenib via combination therapy with SHP2 blockade in hepatocellular carcinoma

Lee, K. W. (Invited speaker)

5 Apr 2019

Activity: Talk or presentation › Invited talk

4、Overriding adaptive resistance to sorafenib via combination therapy with SHP2 blockade in hepatocellular carcinoma

Lee, K. W. (Invited speaker)

Dec 2019

Activity: Talk or presentation › Oral presentation

5、GRC General Research Fund (GRF). Information Session on Application for Research Grants for academic staff, Hong Kong Polytechnic University

Lee, K. W. (Invited speaker)

2019

Activity: Talk or presentation › Invited talk

6、Hong Kong Society for Cell Biology (External organisation)

Lee, K. W. (Council member)

17 Sept 2019 → …

Activity: Office holder / membership of professional bodies › Office holder / member of committee

7、IRAK1 augments cancer stemness and drug resistance via the AP-1/AKR1B10 signaling cascade in hepatocellular carcinoma

Lee, K. W. (Invited speaker)

4 Dec 2018

Activity: Talk or presentation › Oral presentation

8、Interleukin-1 Receptor Kinase 1 augments cancer stemness and drug resistance via AP-1/AKR1B10 signaling cascade in Hepatocellular Carcinoma

Ho, P. Y. (Invited speaker) & Lee, K. W. (Other)

14 Jun 2017

Activity: Talk or presentation › Oral presentation

9、Stearoyl-CoA Desaturase regulates sorafenib resistance via modulation of ER stress induced differentiation

Lee, K. W. (Invited speaker)

Aug 2017

Activity: Talk or presentation › Invited talk

10、Destemming” liver cancer stem cells as novel strategy against liver cancer

Lee, K. W. (Invited speaker)

16 Nov 2017

Activity: Talk or presentation › Invited talk

11、Targeting Liver-tumor Initiating Cells via Hampering Stearoyl-CoA Desaturase (SCD1) Mediated ER Stress

Lee, K. W. (Invited speaker)

20 Sept 2016 → 23 Sept 2016

Activity: Talk or presentation › Oral presentation

12、Targeting Liver-tumor Initiating Cells via Hampering Stearoyl-CoA Desaturase (SCD1) Mediated ER Stress

Lee, K. W. (Invited speaker)

12 Dec 2016 → 13 Dec 2016

Activity: Talk or presentation › Invited talk

13、Cancer-Associated Fibroblasts Regulate Tumor-Initiating Cell Plasticity in Hepatocellular Carcinoma through c-Met/FRA1/HEY1 Signaling

Lau, E. Y. T. (Invited speaker) & Lee, K. W. (Invited speaker)

20 Sept 2016 → 23 Sept 2016

Activity: Talk or presentation › Oral presentation

 

 

 潛心免疫治療 劍指肝細胞癌

——記香港理工大學應用生物與化學科技系李建華教授

如果說，有一種病能讓人聞之膽寒、談之色變，那么毫無疑問就是“癌癥”了。所謂“癌癥”，也就是惡性腫瘤，作為病中之王，是威脅現代人類生命的主要“殺手”之一。根據最新統計數據顯示，中國新診斷癌癥482萬例，占全球病例的24.1%;癌癥死亡病例257萬例，占全球病例26.5%。我國已經成為名副其實的“癌癥大國”，在這其中，癌癥發病率和死亡率排名前列的就有“肝細胞癌”。

在發病形勢如此嚴峻的形勢下，探索研究有效的癌癥治療方法，成為眾多醫學科研人員矢志努力的目標。香港理工大學應用生物與化學科技系李建華教授，就是其中一員，多年來，他一直將肝細胞癌作為研究對象，聚焦于癌癥干細胞、治療抗藥性、腸道微生物群和癌癥免疫學的研究，取得了一系列成果，為癌癥免疫療法的新進展做出了重要貢獻，在臨床應用和治療上為廣大患者減輕痛苦，守護生命健康，造福人類社會。

立志攻克肝癌 探索耐藥機制

古人云“不為良相，當為良醫”，在古人眼中，若不能做一位治理國家的宰相，那就去當一名救死扶傷的醫生，正所謂“良相治國，良醫治人”。李建華自小就有著遠大的抱負和夢想，他在大學期間立下了治病救人兼濟天下的壯志。隨著學習的深入，他對于醫學的認知逐漸發生了微妙的變化。

1997年，在讀博期間，李建華在導師的指導下開啟了肝細胞癌分子機制的相關研究，此后，他開啟了一扇新的科研大門。在研究中，他發現肝細胞癌發病率實在是太高了，肝細胞癌以起病隱匿、發展迅速、病勢兇險的特點成為全球發病和致死率極高的癌癥。李建華表示，肝細胞癌之所以如此可怕，是因為其難以發現，即便是在中晚期，腫瘤大小也不會那么明顯，而一旦發現癥狀，其病變的程度已經難以挽回了，即使創造條件治療，也是效果差、復發率高，這一點才是最致命的。

為此，李建華內心燃起一股斗志，他毅然選擇了肝細胞癌作為研究對象，矢志攻克這種癌癥。2007年，索拉非尼藥物獲得美國食品藥品監督管理局(FDA)批準，作為第一款肝細胞癌全身性治療藥物，其有效改善了晚期患者的生存率。但是時間一長，癌細胞對此產生了耐藥性，最終又陷入泥潭之中，全球醫學科研人員開始深入研究肝癌細胞對索拉非尼耐藥機制。此時已經成為肝細胞癌研究領域知名專家的李建華，也帶領團隊投入其中，經過多年研究，他證明了對索拉非尼耐藥后，癌干細胞(CSC)的干細胞特性會增強，靶向介導肝癌干細胞特性的信號通路可能是逆轉抗藥性的一種重要策略。

2016年，李建華加入香港理工大學，并組建了研究團隊聚焦于研究對抗肝細胞癌獲得耐藥性，并逐步取得了進展。2021年，李建華帶領團隊通過建立索拉非尼耐藥的肝細胞癌患者的源性腫瘤異種移植模型(PDTXs)，發現EPHB2激酶在獲得性耐藥機制的形成中起到極其關鍵的作用。一開始，經過測序及定量分析，李建華團隊發現肝臟腫瘤干細胞標志物在源性腫瘤異種移植模型中顯著上調，且肝癌組織中EPHB2的表達明顯高于正常及肝纖維化組織，這提示了EPHB2的致癌性。

為了進一步研究EPHB2在肝癌中的促腫瘤作用，李建華和團隊在免疫活性小鼠中進行了內源EPHB2的敲除，并發現此后腫瘤結節的大小和數量顯著減少，而且小鼠的存活時間更長。接著，他們又通過探尋上下游效應因子及一系列體內外實驗，最終確定了一個EPHB2/β-catenin/TCF1的正反饋環，以調節肝癌的腫瘤干性和對索拉非尼的耐藥性。最后，李建華團隊通過肝癌小鼠模型，成功證明EPHB2通過TCF1/EPHB2/β-catenin正反饋環來調節腫瘤的干性和耐藥性，從而使靶向EPHB2與其他靶點聯合治療，成為肝癌靶向治療的全新可能。

正如人類探索宇宙的奧秘從不停歇一般，李建華和團隊對于肝細胞癌的全新治療探索和研究也步履不息，他們致力于開發肝癌細胞的靶向藥物，最終目標是實現擊破腫瘤細胞。這一次，他們取得了巨大的階段性突破。

創新免疫療法 守護人類健康

當前普遍認為，每個人的體內實際上都存在潛在的癌細胞，這些細胞是正常細胞在特定條件下發生突變的結果。癌細胞轉化為惡性腫瘤，甚至導致患者死亡，往往與免疫系統的功能失調密切相關。目前，癌癥的主要治療方法包括外科切除、放射治療和化學治療，特別是靶向藥物的應用在局部治療方面取得了一定進展，同時治療相關副作用也有所減輕。然而，這些方法仍無法從根本上解決癌癥的復發、轉移和擴散問題。換言之，人類尚未實現對癌癥的完全治愈。因此，針對免疫系統的免疫療法逐漸成為一種新興的抗癌治療策略，正在受到越來越多的關注。

近來，李建華又在癌癥免疫療法上取得了新進展，他發表了《一種基于肽嵌合抗原受體巨噬細胞靶向癌干細胞的全新療法》，該文章探討了抑制腫瘤干細胞(CSCs)特性療法的可能性。李建華指出，腫瘤干細胞在生成新腫瘤方面的增強能力表明，這些細胞可能在逃避免疫監視方面具備一定優勢。因此，他們的研究團隊鑒定了若干假定的肝臟腫瘤干細胞標記物，包括CD24和CD47。通過實驗觀察，發現這些標記物確實具有誘導巨噬細胞，從而逃避吞噬作用的獨特特性。

基于此項發現，李建華團隊進一步提出了“使用巨噬細胞靶向治療方法可能實現對肝臟腫瘤干細胞的弱點靶向”的相關假設。據介紹，盡管CAR-T細胞療法在治療血液惡性腫瘤方面取得過喜人成績，但其在實體瘤中的應用卻非常具有挑戰性，因為T細胞不具備強穿透性且無法在腫瘤微環境中存活。腫瘤微環境(TME)為癌癥的發生和發展提供著重要的生態位，腫瘤相關巨噬細胞(TAMs)是腫瘤微環境的重要組成部分�？梢哉f，它是許多實體瘤的腫瘤微環境中最豐富的先天免疫細胞，可調節腫瘤細胞增殖、抗原呈遞及免疫逃逸和治療抵抗等各種腫瘤行為，在腫瘤進展中扮演著關鍵性角色。而且這些功能特性使CAR-巨噬細胞(CAR-Ms)正在成為一種針對實體癌的全新免疫療法，以克服CAR-T療法的不足。

李建華介紹說，“傳統上CAR-M療法指的是通過病毒感染將編輯過的特定CAR基因轉移到巨噬細胞中，但此方法成本高昂、涉及程序繁瑣，并且在長期的安全性上保障不足。為了克服這些缺點，我們采用了一種替代方法獲取CAR-巨噬細胞，以減少其不確定性，縮短生產時間，且性能可逆。如果后續實驗一切順利的話，我們或許會實現通過質譜分析鑒定選擇性結合肝臟腫瘤干細胞受體表面的肽，來建立起肝臟腫瘤干細胞特異性的pCARMs庫;同時，基于細胞模型的功能表征優化pCAR-Ms，并在相應的動物模型中評估其療效。”總而言之，李建華團隊已經設計好了一種系統方法，他們致力于將pCAR-Ms策略推向肝細胞癌治療，這些研究成果一旦落地應用，在不遠的未來，或在臨床上將真正實現攻克癌癥疾病，為患者締造福祉。

由于多年來在肝細胞癌治療研究領域中的優秀成果和突出貢獻，李建華于2023年入選斯坦福大學全球前2%的頂尖科學家榜單。這一榮譽實至名歸，反映了李建華在肝細胞癌研究方面的深入探索與不懈努力，為人類的生命健康做出了重要貢獻。