人才队伍

情况简介
院士风采
杰出青年
全所PI名录
 
 
地址:上海市岳阳路320号
邮编:200031
电话:86-21-54920000
传真:86-21-54921011
邮箱:sibcb@sibcb.ac.cn

全所PI名录 >

 
惠利健
研究员,研究组长,博士生导师
E-mail: huilab@@sibcb.ac.cn


个人简介

        2008- :        研究员,中国科学院上海生命科学院上海生物化学和细胞研究所
        2004-2008:博士后,奥地利维也纳Institute of Molecular Pathology (IMP)
        1998-2003:博士,中国科学院上海生命科学院上海细胞研究所
        1992-1997:学士,中国科学技术大学生物系


研究方向

肝脏疾病的分子病理机制


研究工作

        传统上认为高等动物组织再生的细胞主要来源于干细胞分化。随着体外细胞属性转变的发现,如去分化和转分化,体内基于细胞属性转变的再生也被在小鼠等模式生物中被鉴定,从而揭示了一个全新的高等动物组织再生模式。这一发现也提出了一系列重要科学问题。比如:细胞属性转变在组织再生中的贡献如何?是否在进化上保守,并与人类疾病相关?其调控的细胞和分子机制是什么?属性转变是否也与肿瘤发生相关?以及对这些的了解是否可以促进对再生相关疾病的治疗?
 
        我们实验室以肝脏为研究体系,着力于研究组织损伤再生及其相关疾病发生的调控。特别关注肝脏再生和癌化过程中细胞属性维持与转变(包括转分化、去分化等)的作用和分子机制,并希望能为终末期肝病和肝癌提供新的治疗策略。
   
        1. 细胞属性转变
        我们前期工作揭示了高等动物细胞的跨胚层转分化能力(Huang et al, Nature, 2011);此外合作发现肝脏损伤再生过程胆管细胞向肝细胞的转分化(Deng et al, Cell Stem Cell, 2018);并鉴定了转分化过程的染色体变化,提出了“染色体重塑检查点”理论(Ji et al, Cell Research, 2017)。目前,我们计划明确属性转变在组织再生中的作用,并且鉴定诱导细胞属性转变的信号以及细胞内的响应机制。希望这些工作能够对于再生相关疾病,包括肿瘤发生,提供新的思路。
 
        2. 人类功能肝细胞的获得及其应用
        我们成功将人类非肝细胞直接转分化为功能肝细胞(hiHep,Huang et al, Cell Stem Cell, 2014),并依此构建了新型生物人工肝装置,成功救治肝衰竭大动物(Shi et al, Cell Research, 2016),进入了临床转化,希望能为肝衰竭病人提供新的治疗手段。近期,利用去分化的概念,我们实现了体外原代肝细胞的扩增(Zhang et al, Cell Stem Cell, 2018)。目前,我们计划利用属性转变获得的功能肝细胞,研究肝细胞替代治疗在再生相关疾病中的应用以及体外肝脏再生相关疾病的模拟。


代表性论文

  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.

综述及评论

  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.

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