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Professor MA, Stephanie Kwai Yee 馬桂宜

Professor MA, Stephanie Kwai Yee 馬桂宜

  • BSc, MSc (UBC); PhD (HKU)
  • Professor
  • Associate Director (Knowledge Exchange and Global), School of Biomedical Sciences
  • Assistant Dean (Innovation and Technology Transfer), HKUMed
  • Academic Lead, Imaging and Flow Cytometry / Bioreagent / Bioresearch Support Cores, Centre for PanorOmic Sciences, HKUMed
  • Associate Director, Knowledge Exchange Office, HKU
L1-47, Laboratory Block, 21 Sassoon Road, Hong Kong
+852 3917 9238 (office); 3917 9424 (Lab)
+852 2817 0857
  • Exploiting Stemness as a Cancer Cell Vulnerability

  • B.Sc., The University of British Columbia (1996-2000)
  • M.Sc., The University of British Columbia (2000-2003)
  • Ph.D., The University of Hong Kong (HKU) (2005-2007)
  • Postdoctoral Fellow, HKU (2007-2009)
  • Research Assistant Professor, HKU (2009-2012)
  • Assistant Professor, Department of Clinical Oncology, HKU (2012-2013)
  • Assistant Professor, School of Biomedical Sciences, HKU (2013-2018)
  • Associate Professor, School of Biomedical Sciences, HKU (2018-2023)
  • Professor, School of Biomedical Sciences, HKU (2023 onwards)
  • Founding Member, Vice-President and Co-Chair of Outreach Committee, The Hong Kong Young Academy of Sciences
  • Board Member, Hong Kong Science and Technology Parks Corporation
  • Principal Investigator, State Key Laboratory of Liver Research
  • Principal Investigator, MOE Key Laboratory of Tumor Molecular Biology
  • Principal Investigator, Laboratory for Synthetic Chemistry and Chemical Biology, Health@InnoHK
  • Principal Investigator, Centre for Translational Stem Cell Biology, Health@InnoHK
  • Senior Editor, Cancer Research
  • Editorial Board Member, Carcinogenesis
  • Editorial Board Member, Hepatology
  • Editorial Board Member, Differentiation

We are interested in understanding the general mechanism of tumorigenesis and developing strategies to prevent cancer through gaining new knowledge of the biological and molecular characteristics of cancer stem cells / tumor-initiating cells that are likely associated with the unfavorable outcome of this disease. Gastrointestinal tumor types particularly prevalent in Southeast Asia and Hong Kong, including hepatocellular carcinoma and gastric cancer, are currently used as model systems in our studies. Efforts are directed at conducting basic studies using a combination of molecular, cellular, OMICs, and disease modeling approaches, with an ultimate goal to translate the findings in the lab into better patient care in the clinic.

SMA lab

  • Ranked by Stanford University as a top 2% scientist (2022, 2023)
  • Ranked by ISI Essential Science Indicators as one of the top 1% most cited scholars in ‘Clinical Medicine’ and ‘All Fields” (2010-2018)
  • Published >100 articles

^corresponding author

  1. 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. [Citations: >1060]
  2. 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. [Citations: >800] (F1000 Rating: 8 Must Read; Mishra L: 2008.
  3. Ma S^, Tang KH, Chan YP, Lee TK, Kwan PS, Castilho A, Ng IO, Man K, Wong N, To KF, Zheng BJ, Lai PB, Lo CM, 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. [Citations: >375]
    (Awarded the 2011 Outstanding Research Output Award, Faculty of Medicine, HKU)
  4. 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; 55:807-20. [Citations: >205]
  5. Ma S, Bao JY, Kwan PS, Chan YP, Tong M, Fu L, Zhang N, Tong AH, Qin YR, Tsao SW, Chan KW, Lok S^, Guan XY^. Identification of PTK6, via RNA sequencing analysis, as a suppressor of esophageal squamous cell carcinoma. Gastroenterology 2012; 143:675-86.
  6. 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; 5:45-59.
  7. 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^. Oct4/miR-1246 signaling axis drives Wnt/β-catenin activation in liver cancer stem cells. Hepatology 2016; 64:2062-76.
  8. 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 Res 2017; 77:4602-12.
  9. 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; 69:826-39.
  10. 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^. Protein arginine methyltransferase PRMT6 regulates RAS/RAF binding and MEK/ERK-mediated cancer stemness activities in hepatocellular carcinoma through CRAF methylation. Cell Rep 2018; 25:690-701. #equal contribution
  11. 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; 71:1279-96.
  12. 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 to sorafenib through combination therapy with SHP2 blockade in hepatocellular carcinoma. Hepatology 2020: 72:155-68. #equal contribution
  13. 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; 72:183-97.
  14. 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; 501:247-62 #equal contribution
  15. 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. Adv Sci 2021; 8:2002483.
  16. 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. J Clin Invest 2021; 131:143377.
  17. 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 Rep 2021; 36:109617.
  18. Loh 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 Res 2021; 81:5692-705.
  19. Xu F#, Tong M#, Tong CS, Chan BK, Chu HY, Wong TL, Fong JH, Cheung MS, Mak KH, Pardeshi L, Huang YH, Wong KH, Choi GC, Ma S^, Wong AS^. A combinatorial CRISPR-Cas9 screen identifies ifenprodil as an adjunct to sorafenib for liver cancer treatment. Cancer Res 2021; 81:6219-32. #equal contribution
  20. Lee TK, Guan XY, Ma S^. Cancer stem cells in hepatocellular carcinoma: a review from origin to clinical implications. Nat Rev Gastroenterol Hepatol 2022; 19:26-44
  21. Zhou L#, Yu KH#, Wong TL#, Zhang Z, Chan CH, Loong JH, Che N, Yu HJ, Tan KV, Tong M, Ngan ES, Ho JW^, Ma S^. Lineage tracing and single-cell analysis reveal proliferative Prom1+ tumor-propagating cells and their dynamic cellular transition during liver cancer progression. Gut 2022; 711658-68. #equal contribution
    ​(Awarded the 2022 Outstanding Research Output Award, Faculty of Medicine, HKU)
  22. Man KF, Ma S^. Mechanisms of resistance to tyrosine kinase inhibitors in liver cancer stem cells and potential therapeutic approaches. Essays Biochem 2022; 66:371-86.
  23. Lam KH, Ma S^. Noncellular components in the liver cancer stem cell niche: biology and potential clinical implications. Hepatology 2023; 78:991-1005.
  24. 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. Cell Mol Gastroenterol Hepatol 2023: 15:13-37.
  25. 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; 78:1711-26.
  26. Wong TL#, Loh JJ#, Lu SX#, Yan H, Siu HC, Ren X, Chan D, Kam M, Zhou L, Tong M, Copland J, Chen L, Yun JP, Leung SY, Ma S^. ADAR1-mediated RNA editing of SCD1 drives drug resistance and self-renewal in gastric cancer. Nat Commun 2023; 14:2861. #equal contribution
  27. Gao Y, Tong M, Wong TL, Ng KY, Xie YN, Wang Z, Yu HJ, Loh JJ, Li M^, Ma S^. Long noncoding RNA URB1-antisense RNA 1 (AS1) suppresses sorafenib-induced ferroptosis in hepatocellular carcinoma by driving ferritin phase separation. ACS Nano 2023; 17:22240-58.
  28. 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. Nat Commun 2023; 14:7863. #equal contribution
  29. 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; 15:110.
  30. Loh JJ, Ma S^. Hallmarks of cancer stemness. Cell Stem Cell 2024; in press.
  1. RGC GRF 2020/21 (PI)
  2. ITC Health@InnoHK – Laboratory for Synthetic Chemistry and Chemical Biology (Co-PI)
  3. ITC Health@InnoHK – Centre for Translational Stem Cell Biology (Co-PI)
  4. NSFC General Program 2020 (PI)
  5. RGC RIF 2020/21 (PC)
  6. ITF ITSP Seed Project 2020 (PI)
  7. HMRF 2020 (PI)
  8. RGC GRF 2021/22 (PI)
  9. RGC Research Fellow Scheme 2021/22
  10. RGC RIF 2022/23 (Co-PI)
  11. Croucher Senior Research Fellowship 2023
  12. RGC GRF 2023/24 (PI)
  13. NSFC General Program 2023 (PI)
  14. RGC Collaborative Research Equipment Grant 2023/24 (PC)
  • Outstanding Young Scientist Travel Award, National Institute of Health, USA (2001)
  • Li Ka Shing Prize (for the best Ph.D. thesis in the Faculties of Dentistry, Engineering, Medicine and Science), Graduate School, HKU (2006/2007)
  • International Society for Stem Cell Research (ISSCR) Travel Award, USA (2007)
  • Hong Kong Young Scientist Award (Life Sciences), Hong Kong Institution of Science (2008)
  • State Key Laboratory of Liver Research – Young Researcher Career Development Scheme (YRCDS), HKU (2011)
  • Faculty Outstanding Research Output Award, Faculty of Medicine, HKU (2011) – in the capacity of first and corresponding author
  • Faculty Outstanding Research Output Award, Faculty of Medicine, HKU (2012) – in the capacity of co-author
  • Outstanding Young Researcher Award, HKU (2012/2013)
  • Croucher Innovation Award, The Croucher Foundation (2014)
  • Higher Education Institution of China - Scientific Research Outstanding Achievement Awards (Second-class Award in Science and Technology Section) (2014)
  • University of British Columbia (UBC) Alumni Builder Award (2017/18)
  • Ton Duc Thang University Scientific Prize – Rising Star Award, Vietnam (2018)
  • RGC Research Fellow (2021/22)
  • Croucher Senior Research Fellowship, The Croucher Foundation (2023)
  • Outstanding Researcher Award, HKU (2022/23)

  • Dr. Kai Yu NG, Johnson (Senior Research Officer)
  • Dr. Tin Lok WONG, Eric (Research Assistant Professor)
  • Dr. Ianto Bosheng HUANG (Postdoctoral Fellow)
  • Dr. Jia Jian LOH (Postdoctoral Fellow)
  • Dr. Huajian YU (Postdoctoral Fellow)
  • Ka Hei LAM, Sheree (PhD student, 2021-2024)
  • Huanwen WU (PhD student, 2021-2024)
  • Ut Kei LOU, Venus (PhD student 2021-2025)
  • Yinjia HUANG, Angel (HKU Presidential PhD student, 2022-2026)
  • Jingyi YUAN (PhD student, 2022-2026)
  • Sukbum KIM, Matt (MPhil student, 2022-2024)
  • Jia Yan TAN (Co-supervised MPhil student, 2022-2024)
  • Cheuk Chun HO, Joseph (Part-time MPhil student, 2022-2025)
  • Yee Lok TSOI, Elok (HKPF PhD student, 2023-2027)
  • Yalu CUI (PhD student, 2023-2027)
  • Ruochen MA (PhD student, 2023-2026)
  • Yanshu KONG, Angela (Research Assistant)
  • Chun Yuen WONG, Don (Research Assistant)
  • Juyu CHEN (Technical Officer)

Last updated: April 30, 2024