• Biology and pre-clinical research on cancer cell plasticity, with a focus on stemness and its link to drug resistance and immune evasion, using HCC as a model system

• 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)

Targeting the Roots of Cancer Through a Deeper Understanding of Cancer Stemness

Cancer is a complex biological system that can be examined through multiple conceptual frameworks. The “Hallmarks of Cancer,” initially published by Hanahan and Weinberg in 2000 and subsequently updated in 2011, serve as a foundational model for understanding the molecular and cellular features that characterize malignancy. Most recently, in 2022, Hanahan et al. introduced “Hallmarks of Cancer: New Dimensions”, which emphasizes additional emerging hallmarks and enabling characteristics, notably those encompassed under the concept of ‘unlocking phenotypic plasticity.’

Compared to the extensive differentiation processes during organogenesis—where cells undergo significant developmental specialization—normal somatic cells are generally restricted in their capacity to differentiate, maintaining tissue organization and function. In contrast, cancer cells often acquire molecular and phenotypic alterations that confer increased plasticity, enabling them to adopt diverse cell states along a phenotypic continuum. This phenotypic plasticity facilitates non-genetic, dynamic cell state transitions that contribute to tumor heterogeneity and promote mechanisms of therapy resistance. Tumors frequently contain less differentiated, stem-like cell populations that exhibit resistance to conventional treatments and are associated with tumor relapse and metastasis.

Our research focuses on elucidating how a de-differentiated, stemness-like cellular state in cancer contributes to therapeutic resistance and disease recurrence. We utilize model systems of tumor types prevalent in Southeast Asia and Hong Kong, like hepatocellular carcinoma. Our approach integrates molecular, cellular, OMICs, and disease modeling methodologies in both basic and preclinical studies. The ultimate aim is to translate these scientific insights into improved clinical strategies for patient management and therapy.

On-going research funding as PC, PI or Co-PI

• RGC General Research Fund (PI)
• RGC Research Impact Fund (PC and Co-PI)
• RGC Collaborative Research Fund (Co-PI)
• RGC Collaborative Research Equipment Fund (PC)
• RGC Theme-Based Research Scheme (PC)
• RGC Research Fellow Scheme (PI)
• NSFC General Program (PI)
• ITF Innovation and Technology Support Programme (PI)
• ITF Mainland-HK Joint Funding Scheme (PI)
• Laboratory for Synthetic Chemistry and Chemical Biology (LSCCB), InnoHK (PI)
• Centre for Translational Stem Cell Biology (CTSCB), InnoHK (PI)

^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.
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.
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. (Awarded the 2011 Faculty Outstanding Research Output Prize, HKUMed)
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.
5. 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/microRNA-1246 signaling axis drives Wnt/β-catenin activation in liver cancer stem cells. Hepatology 2016; 64:2062-76.
6. 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.
7. 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.
8. 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; 25:690-701. #equal contribution
9. 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.
10. 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.
11. 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.
12. 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.
13. 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; 37:109976.
14. 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.
15. 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
16. Lee TK, Guan XY, Ma S^. Cancer stem cells in hepatocellular carcinoma: from origin to clinical implications. Nat Rev Gastroenterol Hepatol 2022; 19:26-44.
17. 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; 71:1656-68. #equal contribution (Awarded the 2022 Faculty Outstanding Research Output Prize, HKUMed)
18. Yu HJ, 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.
19. 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
20. Loh JJ, Ma S^. Hallmarks of cancer stemness. Cell Stem Cell 2024; 31:617-39.
21. 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 2025; 82:308-25.
22. Ng KY#, Koo TY#, Huang IB, Lee TK, Fong TL, Gao Y, Wong TL, Gao Y, Yun JP, Guan XY, Liu M, Chung CY^, Ma S^. AGPAT4 targeted covalent inhibitor potentiates targeted therapy to overcome cancer cell plasticity in hepatocellular carcinoma mouse models. Sci Transl Med 2025; 17:eadn9472. #equal contribution

• Listed by Clarivate as a top 1% most-cited scholar in her field (2010–2018), by Stanford University as a top 2% scientist worldwide (2022-2024), and by Research.com as a top scientist, with a national ranking of 65 in molecular biology (2025)
• 2007 Li Ka Shing Prize for the Best PhD Thesis, HKU
• 2008 Young Scientist Award in Life Sciences, Hong Kong Institution of Science
• 2012-13 Outstanding Young Researcher Award, HKU
• 2014 Croucher Innovation Award
• 2014 Scientific Research Outstanding Achievement Award (Second-class Award in Science and Technology Section), Higher Education Institution of China
• 2017 University of British Columbia Alumni Builder Award (Canada)
• 2018 Ton Duc Thang University Scientific Prize – Rising Star Award (Vietnam)
• 2021 RGC Research Fellow Scheme
• 2023 Croucher Senior Research Fellowship
• 2022-23 Outstanding Researcher Award, HKU

• Ma S, Tong M, Guan XY. Use of annexin A3 as a diagnostic and prognostic biomarker and therapeutic target for treating hepatocellular carcinoma. US Patent No: 9,487,831 B2. Patent granted 8 Nov 2016.
• Ma S, Tong M, Guan XY. Use of annexin A3 as a diagnostic and prognostic biomarker and therapeutic target for treating hepatocellular carcinoma. Divisional Patent. US Patent No: 10,000,558. Patent granted 19 Jun 2018.
• Wong AS, Ma S, Xu F, Tong M. Compositions and methods of using NMDAR inhibitors and kinase inhibitors to treat liver cancer. US Patent No: US 2023/0355596 A1. Patent granted 9 Nov 2023.
• Ma S, Chung CYS, Ng KY, Koo TY. Compositions of AGPAT4 inhibitors and methods of using thereof to treat cancer. US Non-Provisional Patent Application No: 19/189,569. Filed 25 Apr 2025.

• Principal Investigator, Laboratory for Synthetic Chemistry and Chemical Biology (LSCCB), InnoHK
• Principal Investigator, Centre for Translational Stem Cell Biology (CTSCB), InnoHK
• Founding Member and current Vice-President and Chair of the Policy Advisory Committee, Hong Kong Young Academy of Sciences
• Member, Future Forum Young Scientist Innovation Alliance (China)
• Member of the Board of Directors, Hong Kong Science and Technology Park (HKSTP)
• Member of the Board of Directors, International Society of Differentiation
• Member of the Advisory Board, Hong Kong Life Sciences Society (HKLSS)

Senior Editor of Cancer Research and an Editorial Board Member of Hepatology, Carcinogenesis and Differentiation.

• Dr. Kai Yu NG, Johnson – Senior Research Officer
• Dr. Tin Lok WONG, Eric – Senior Research Officer
• Dr. Gladys POON – Research Assistant Professor
• Dr. Ianto Bosheng HUANG – Postdoctoral Fellow
• Dr. Huajian YU – Postdoctoral Fellow
• Dr. Ka Hei LAM, Sheree – Postdoctoral Fellow
• Dr. Shiu Yeung LAM, Lance – Postdoctoral Fellow
• Dr. Ut Kei LOU, Venus – Postdoctoral Fellow
• Yinjia HUANG, Angel – HKU Presidential PhD student (2022-2026)
• Jingyi YUAN – PhD student (2022-2026)
• Yee Lok TSOI, Elok – RGC HKPFS PhD student (2023-2027)
• Yalu CUI – PhD student (2023-2027)
• Yuxin HU – RGC HKPFS PhD student (2024-2027)
• Yanshu KONG, Angela – RGC HKPFS PhD student (2024-2028)
• Changmo PARK – RGC HKPFS PhD student (2024-2028)
• Lamia CHOWDHURY – PhD student (2025-2028)
• Rafter WU – PhD student (2025-2029)
• Juyu CHEN – Technical Officer
• Henry CHOI Chi Hin – BBMS FYP student (2025-2026)