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Members of CAS, CAE
National Outstanding Young Scientists Award
Principal Investigators
Address: 320 Yue Yang Road, Shanghai 200031, P.R. China
Tel: 86-21-54920000
Fax: 86-21-54921011
Email: sibcb@sibs.ac.cn
Website: www.sibcb.ac.cn
Principal Investigators
HUI Lijian
Ph.D., Professor
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China.
Email: huilab@@sibcb.ac.cn

Research Areas
liver cancer, cirrhosis, cellular signaling, the MAPK pathway, targeted therapy

Research Interests

To understand the mechanistic regulation underlying tumorigenesis of normal cells is a long-term interest of my scientific research. Recently, taken hepatocytes as the experimental system, my lab has initiated studies on cell lineage conversion, specifically focusing on induction of functional hepatocyte-like cells from cells of non-hepatic origin. Striving to understand these two seemingly different phenomena, we slowly find ourselves in querying the essential scientific question: How is cell identity maintained through preventing the conversion of terminally differentiated cells to other cell types, including transdifferentiation to different lineages and transformation to tumor cells? We wish that with the efforts to address this question we would eventually contribute to the development of novel therapies for liver diseases and cancers.
1.        The mechanism of tumorigenic transformation of hepatocytess
Epidemiological studies of human liver cancers indicate that genetic and epigenetic alterations are accumulated in a multi-stage manner. Advances in understanding molecular aberrations in malignant liver cancers have led to the development of efficient targeted therapies. On the other hand, preventive therapeutic approaches have been proposed to intervene at the initial phase of liver tumorigenesis (Nature Cell Biology, 2012). The critical step for developing effective preventive therapies is to identify targetable molecules and pathways responsible for liver cancer initiation.
2.        Generating hepatocyte-like cells via transdifferentiation
We have previously shown that mouse fibroblasts are directly converted into induced hepatocyte-like (iHep) cells by Foxa3, Gata4 and Hnf1a expression and p19Arf inactivation (Nature, 2011). We are now working on converting non-hepatic human cells into hepatocytes by defined transcription factors, which could be used for generation of potential sources of hepatocytes for disease modeling, transplantation, and tissue engineering independent of donor organs.
3.        Cell identity maintenance C linking the tumorigenesis and lineage conversion
During the generation of iHep cells, we observed an extensive cell death, senescence and proliferation arrest in wild-type fibroblasts upon overexpression of the 3 hepatic transcription factors. Cell fate conversion is a dramatic process that is extremely rare in nature. It is conceivable that cells with defined identity should be preserved to maintain the physiological function of a given tissue. It is interesting that the p19Arf/p53 pathway is found to suppress both tumorigenesis and cell fate conversion. We speculate that the p19Arf/p53 pathway may be employed by normal cells as a common mechanism to maintain the cell identity.

Selected Publications

  1. Zhang K, Zhang L, Liu W, Ma X, Cen J, Sun Z, Wang C, Feng S, Zhang Z, Yue L, Sun L, Zhu Z, Chen X, Feng A, Wu J, Jiang Z, Li P, Cheng X, Gao D, Peng L*, Hui L*. In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity. Cell Stem Cell. 2018 Dec 6; 23(6):806-819.  (*: Co-corresponding authors)
  2. Deng X, Zhang X, Li W, Feng RX, Li L, Yi GR, Zhang XN, Yin C, Yu HY, Zhang JP, Lu B, Hui L*, Xie WF*. Chronic Liver Injury Induces Conversion of Biliary Epithelial Cells into Hepatocytes. Cell Stem Cell. 2018 Jul 5; 23(1):114-122. (*: Co-corresponding authors)
  3. Hu C, Li W, Tian F, Jiang K, Liu X, Cen J, He Q, Qiu Z, Kienast Y, Wang Z, Zhang H, Ji Y, Hu J, Hui L. Arid1a regulates response to anti-angiogenic therapy in advanced hepatocellular carcinoma. J Hepatol. 2018 Mar; 68(3):465-475.
  4. Gao Y, Zhang X, Zhang L, Cen J, Ni X, Liao X, Yang C, Li Y, Chen X, Zhang Z, Shu Y, Cheng X, Hay DC, Lai D, Pan G, Wei G, Hui L. Distinct Gene Expression and Epigenetic Signatures in Hepatocyte-like Cells Produced by Different Strategies from the Same Donor. Stem Cell Reports. 2017 Dec 12; 9(6):1813-1824.
  5. Ji S, Zhu L, Gao Y, Zhang X, Yan Y, Cen J, Li R, Zeng R, Liao L, Hou C, Gao Y, Gao S, Wei G, Hui L. Baf60b-mediated ATM-p53 activation blocks cell identity conversion by sensing chromatin opening. Cell Res. 2017, May; 27(5):642-656.
  6. Yue L, Li L, Li D, Yang Z, Han S, Chen M, Lan S, Xu X, Hui L. High-throughput screening for Survivin and Borealin interaction inhibitors in hepatocellular carcinoma. Biochem Biophys Res Commun. 2017,484:642-7.
  7. Ni X, Gao Y, Wu Z, Ma L, Chen C, Wang L, Lin Y, Hui L*, Pan G*. Functional human induced hepatocytes (hiHeps) with bile acid synthesis and transport capacities: A novel in vitro cholestatic model. Sci Rep. 2016 Dec 9; 6:38694. (*: Co-corresponding authors)
  8. Li L, Li D, Tian F, Cen J, Chen X, Ji Y, Hui L. Hepatic Loss of Borealin Impairs Postnatal Liver Development, Regeneration, and Hepatocarcinogenesis. J Biol Chem. 2016; 291(40): 21137-21147.
  9. Zhang L, Shao Y, Li L, Tian F, Cen J, Chen X, Hu D, Zhou Y, Xie W, Zheng Y, Ji Y, Liu M, Li D, Hui L. Efficient liver repopulation of transplanted hepatocyte prevents cirrhosis in a rat model of hereditary tyrosinemia type I. Sci Rep. 2016 Aug 11;6:31460..
  10. Qiu Z, Zou K, Zhuang L, Qin J, Li H, Li C, Zhang Z, Chen X, Cen J, Meng Z, Zhang H, Li Y, Hui L. Hepatocellular carcinoma cell lines retain the genomic and transcriptomic landscapes of primary human cancers. Sci Rep. 2016 Jun 7; 6:27411.
  11. Li D, Fu J, Du M, Zhang H, Li L, Cen J, Li W, Chen X, Lin Y, Conway EM, Pikarsky E, Wang H, Pan G, Ji Y, Wang HY, Hui L. Hepatocellular carcinoma repression by TNFα-mediated synergistic lethal effect of mitosis defect-induced senescence and cell death sensitization. Hepatology. 2016 64(4):1105-1120.
  12. Shi XL, Gao Y, Yan Y, Ma H, Sun L, Huang P, Ni X, Zhang L, Zhao X, Ren H, Hu D, Zhou Y, Tian F, Ji Y, Cheng X, Pan G, Ding YT, Hui L. Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes. Cell Res. 2016 Feb; 26(2):206-16.
  13. Zhang H, Zheng H, Mu W, He Z, Yang B, Ji Y, Hui L. DUSP16 ablation arrests the cell cycle and induces cellular senescence. FEBS J. 2015 Dec; 282(23):4580-94.
  14. Mu W, Hu C, Zhang H, Qu Z, Cen J, Qiu Z, Li C, Ren H, Li Y, He X, Shi X, Hui L. miR-27b synergizes with anticancer drugs via p53 activation and CYP1B1 suppression. Cell Res. 2015 Apr; 25(4):477-95.
  15. Huang P, Zhang L, Gao Y, He Z, Yao D, Wu Z, Cen J, Chen X, Liu C, Hu Y, Lai D, Hu Z, Chen L, Zhang Y, Cheng X, Ma X, Pan G, Wang X, Hui L. Direct reprogramming of human fibroblasts to functional and expandable hepatocytes. Cell Stem Cell. 2014 Mar 6; 14(3):370-84.
  16. Li D, Cen J, Chen X, Conway EM, Ji Y, Hui L. Hepatic loss of survivin impairs postnatal liver development and promotes expansion of hepatic progenitor cells in mice. Hepatology. 2013 Dec; 58(6):2109-21.
  17. Min L, Ji Y, Bakiri L, Qiu Z, Cen J, Chen X, Chen L, Scheuch H, Zheng H, Qin L, Zatloukal K, Hui L*, Wagner EF*. Liver cancer initiation is controlled by AP-1 through SIRT6-dependent inhibition of survivin. Nat Cell Biol. 2012 Nov; 14(11):1203-11. (*: Co-corresponding authors)
  18. Schultze SM, Mairhofer A, Li D, Cen J, Beug H, Wagner EF, Hui L. p38α controls erythroblast enucleation and Rb signaling in stress erythropoiesis. Cell Res. 2012 Mar; 22(3):539-50.
  19. Huang P, He Z, Ji S, Sun H, Xiang D, Liu C, Hu Y, Wang X, Hui L. Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature. 2011 May 11; 475(7356):386-9.


  1. Zhang L, Hui L. Bioengineering: Bile ducts regenerated. Nature. 2017 Jul 12; 547(7662):171-172.
  2. Rebouissou S, Zucman-Rossi J, Moreau R, Qiu Z, Hui L. Note of caution: Contaminations of hepatocellular cell lines. J Hepatol. 2017 Nov; 67(5):896-897.
  3. Li D, Li W, Hui L. Hybrid hepatocyte: A newly identified player for regeneration in hepatic injuries. Hepatology. 2016 Dec; 64(6):2244-2246.
  4. Ji S, Zhang L, Hui L. Cell fate conversion: direct induction of hepatocyte-like cells from fibroblasts. J Cell Biochem. 2013 Feb; 114(2):256-65.
  5. Mu W, Hui L. Establishing a cancer cell in the inflammatory tissue: an epigenetic circuit. Acta Biochim Biophys Sin. 2012 Apr; 44(4):279-80.
  6. Min L, He B, Hui L. Mitogen-activated protein kinases in hepatocellular carcinoma development. Semin Cancer Biol. 2011 Feb; 21(1):10-20.
  7. Huang P, Han J, Hui L. MAPK signaling in inflammation-associated cancer development. Protein Cell. 2010 Mar; 1(3):218-26.

Education Background & Academic Experience
From 2008: Principle Investigator. Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Shanghai, China.
2003-2008: Postdoctoral Fellow. Institute of Molecular Pathology (IMP), Vienna, Austria.
1998-2003: PhD. Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Shanghai, China.
1992-1997: BS. University of Science and Technology of China (USTC), Hefei, China.

Research Team


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