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首頁 全所PI名錄
  • 惠利健
  • 研究員，研究組長，博士生導師
  • E-mail: huilab@@sibcb.ac.cn
  • 實驗室主頁: 
    個人簡介：

  • 　　2008- ： 研究員，中國科學院上海生命科學院上海生物化學和細胞研究所

    　　2004-2008：博士后，奧地利維也納Institute of Molecular Pathology (IMP)

    　　1998-2003：博士，中國科學院上海生命科學院上海細胞研究所

    　　1992-1997：學士，中國科學技術(shù)大學生物系

    社會任職：
  •  
    研究方向：
  • 肝臟疾病的分子病理機制
    研究工作：

  • 　　傳統(tǒng)上認為高等動物組織再生的細胞主要來源于干細胞分化。隨著體外細胞屬性轉(zhuǎn)變的發(fā)現(xiàn)，如去分化和轉(zhuǎn)分化，體內(nèi)基于細胞屬性轉(zhuǎn)變的再生也被在小鼠等模式生物中被鑒定，從而揭示了一個全新的高等動物組織再生模式。這一發(fā)現(xiàn)也提出了一系列重要科學問題。比如：細胞屬性轉(zhuǎn)變在組織再生中的貢獻如何?是否在進化上保守，并與人類疾病相關(guān)?其調(diào)控的細胞和分子機制是什么?屬性轉(zhuǎn)變是否也與腫瘤發(fā)生相關(guān)?以及對這些的了解是否可以促進對再生相關(guān)疾病的治療?

    　　我們實驗室以肝臟為研究體系，著力于研究組織損傷再生及其相關(guān)疾病發(fā)生的調(diào)控。特別關(guān)注肝臟再生和癌化過程中細胞屬性維持與轉(zhuǎn)變(包括轉(zhuǎn)分化、去分化等)的作用和分子機制，并希望能為終末期肝病和肝癌提供新的治療策略。

    　　1. 細胞屬性轉(zhuǎn)變

    　　我們前期工作揭示了高等動物細胞的跨胚層轉(zhuǎn)分化能力(Huang et al, Nature, 2011);此外合作發(fā)現(xiàn)肝臟損傷再生過程膽管細胞向肝細胞的轉(zhuǎn)分化(Deng et al, Cell Stem Cell, 2018);并鑒定了轉(zhuǎn)分化過程的染色體變化，提出了“染色體重塑檢查點”理論(Ji et al, Cell Research, 2017)。目前，我們計劃明確屬性轉(zhuǎn)變在組織再生中的作用，并且鑒定誘導細胞屬性轉(zhuǎn)變的信號以及細胞內(nèi)的響應(yīng)機制。希望這些工作能夠?qū)τ谠偕嚓P(guān)疾病，包括腫瘤發(fā)生，提供新的思路。

    　　2. 人類功能肝細胞的獲得及其應(yīng)用

    　　我們成功將人類非肝細胞直接轉(zhuǎn)分化為功能肝細胞(hiHep，Huang et al, Cell Stem Cell, 2014)，并依此構(gòu)建了新型生物人工肝裝置，成功救治肝衰竭大動物(Shi et al, Cell Research, 2016)，進入了臨床轉(zhuǎn)化，希望能為肝衰竭病人提供新的治療手段。近期，利用去分化的概念，我們實現(xiàn)了體外原代肝細胞的擴增(Zhang et al, Cell Stem Cell, 2018)。目前，我們計劃利用屬性轉(zhuǎn)變獲得的功能肝細胞，研究肝細胞替代治療在再生相關(guān)疾病中的應(yīng)用以及體外肝臟再生相關(guān)疾病的模擬。

    承擔科研項目情況：
    代表論著：
    1. Wang Y, Zheng Q, Sun Z, Wang C, Cen J, Zhang X, Jin Y, Wu B, Yan T, Wang Z, Gu Q, Lv X, Nan J, Wu Z, Sun W, Pan G, Zhang L*, Hui L*, Cai X*. Reversal of liver failure using a bioartificial liver device implanted with clinical-grade human-induced hepatocytes. Cell Stem Cell. 2023 Apr 11:S1934-5909(23)00084-X. 
    2. Li L, Cui L, Lin P, Liu Z, Bao S, Ma X, Nan H, Zhu W, Cen J, Mao Y, Ma X, Jiang L, Nie Y, Ginhoux F, Li Y*, Li H*, Hui L*. Kupffer-cell-derived IL-6 is repurposed for hepatocyte dedifferentiation via activating progenitor genes from injury-specific enhancers. Cell Stem Cell. 2023 Mar 2; 30(3):283-299.
    3. Wang C, Zhang L, Sun Z, Yuan X, Wu B, Cen J, Cui L, Zhang K, Li C, Wu J, Shu Y, Sun W, Wang J, Hui L*. Dedifferentiation-associated inflammatory factors of long-term expanded human hepatocytes exacerbate their elimination by macrophages during liver engraftment. Hepatology. 2022 Dec; 76(6):1690-1705. 
    4. Ma X, Cao X, Zhu L, Li Y, Wang X, Wu B, Wei G*, Hui L*. Pre-existing chromatin accessibility of switchable repressive compartment delineates cell plasticity. Natl Sci Rev. 2021 Dec 31; 9(6):nwab230. 
    5. Zhang L, Ge JY, Zheng YW, Sun Z, Wang C, Peng Z, Wu B, Fang M, Furuya K, Ma X, Shao Y, Ohkohchi N, Oda T, Fan J, Pan G, Li D*, Hui L*. Survival-Assured Liver Injury Preconditioning (SALIC) Enables Robust Expansion of Human Hepatocytes in Fah-/- Rag2-/- IL2rg-/- Rats. Adv Sci (Weinh). 2021 Oct; 8(19):e2101188.
    6. Sun L, Wang Y, Cen J, Ma X, Cui L, Qiu Z, Zhang Z, Li H, Yang R, Wang C, Chen X, Wang L, Ye Y, Zhang H, Pan G, Kang J, Ji Y*, Zheng Y *, Zheng S*, and Hui L*. Modeling liver cancer initiation with organoids derived from directly reprogrammed human hepatocytes. Nature Cell Biology, 2019 Aug; 21(8):1015-1026. (*: Co-corresponding authors)
    7. Qiu Z, Li H, Zhang Z, Zhu Z, He S, Wang X, Wang P, Qin J, Zhuang L, Wang W, Xie F, Gu Y, Zou K, Li C, Li C, Wang C, Cen J, Chen X, Shu Y, Zhang Z, Sun L, Min L, Fu Y, Huang X, Lv H, Zhou H, Ji Y, Zhang Z, Meng Z, Shi X,* Zhang H,* Li Y,* and Hui L,* A Pharmacogenomic Landscape in Human Liver Cancers. Cancer Cell, 2019 Aug 12; 36(2):179-193.e11. (*: Co-corresponding authors)
    8. Li W, Yang L, He Q, Hu C, Zhu L, Ma X, Ma X, Bao S, Li L, Chen Y, Deng X, Zhang X, Cen J, Zhang L, Wang Z, Xie W, Li H*, Li Y*, and Hui L*. A Homeostatic Arid1a-Dependent Permissive Chromatin State Licenses Hepatocyte Responsiveness to Liver-Injury-Associated YAP Signaling. Cell Stem Cell. 2019 Jul 3; 25(1):54-68. (*: Co-corresponding authors)
    9. 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)
    10. 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)
    11. 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.
    12. 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.
    13. 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.
    14. 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.
    15. 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)
    16. 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.
    17. 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..
    18. 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.
    19. 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.
    20. 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.
    21. 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.
    22. 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.
    23. 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.
    24. 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.
    25. 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)
    26. 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.
    27. 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.

    綜述及評論

    1. He Q, Cui L, Yuan X, Wang M, Hui L. Cell identity conversion in liver regeneration after injury. Curr Opin Genet Dev. 2022 Aug; 75:101921.
    2. Sun L, Hui L. Progress in human liver organoids. J Mol Cell Biol. 2020 Aug 1; 12(8):607-617.
    3. Li W, Li L, Hui L. Cell Plasticity in Liver Regeneration. Trends Cell Biol. 2020 Apr; 30(4):329-338.
    4. Huang P, Sun L, Zhang L, Hui L. Conversion of Fibroblasts to Hepatocytes In Vitro. Methods Mol Biol. 2019; 1905:93-101.
    5. Zhang L, Hui L. Bioengineering: Bile ducts regenerated. Nature. 2017 Jul 12; 547(7662):171-172.
    6. 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.
    7. Li D, Li W, Hui L. Hybrid hepatocyte: A newly identified player for regeneration in hepatic injuries. Hepatology. 2016 Dec; 64(6):2244-2246.
    8. 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.
    9. 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.
    10. Min L, He B, Hui L. Mitogen-activated protein kinases in hepatocellular carcinoma development. Semin Cancer Biol. 2011 Feb; 21(1):10-20.
    11. Huang P, Han J, Hui L. MAPK signaling in inflammation-associated cancer development. Protein Cell. 2010 Mar; 1(3):218-26.
    獲獎及榮譽：
    研究組成員：

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