基本信息

刘光慧  男  博导  中国科学院动物研究所
电子邮件: ghliu@ioz.ac.cn
通信地址: 北京市朝阳区大屯路甲3号​
邮政编码: 100101

研究领域

  1. 人类衰老的遗传和表观遗传信息解码
  结合非人灵长类动物模型、干细胞、基因编辑和多组学分析,研究人类衰老(如脑衰老)和老年病(如神经退行性疾病)的遗传和表观遗传学基础,探索延缓衰老和防治老年疾病的方法和手段,以期实现健康老龄化(healthy aging)的梦想。
  2. 基于干细胞的人类疾病研究和精准治疗
  利用患者诱导性多能干细胞(iPSC)和体外创建的疾病胚胎干细胞(ESC),结合细胞定向分化和移植技术,在功能基因组水平研究人类疾病的分子机理及新型靶标;发展基于干细胞技术的药物筛选和评价体系;研发针对特定疾病靶标的药物先导化合物;推动干细胞相关技术的临床转化。 
  3. 新型基因编辑和基因治疗技术的发展和应用
  以HDAdV,telHDAdV,TTALE和CRISPR/Cas9为基础,发展安全高效编辑人类基因组的新方法,开发基于干细胞去衰老及刺激组织原位再生的基因治疗新策略,为罕见疾病的基因修复、人类干细胞的遗传增强、以及衰老相关疾病的干预提供科学依据。

教育背景

2002-09--2007-07   中国科学院生物物理研究所   博士
1997-09--2002-07   北京大学   学士

工作经历

工作简历:

  2007-2012年分别在美国斯克利普斯研究所(The Scripps Research Institute)和索尔克生物学研究所(Salk Institute for Biological Studies)从事博士后(Research associate)研究;2012年加入中国科学院生物物理研究所,任研究员(PI);2016年获得国家杰出青年科学基金;2019年至今任中国科学院动物研究所研究员(PI)。


专利与奖励

奖励信息

    顾孝诚讲座奖(2019),药明康德生命化学研究奖(2019),中源协和生命医学创新突破奖(2019),中国青年科技奖特别奖(2018),谈家桢生命科学创新奖(2018),树兰医学青年奖(2017),首届老年医学杰出贡献奖(2017)。


出版信息

代表性论文

1.    Wang S, Zheng Y, Li J, Yu Y, Zhang W, Song M, Liu Z, Min Z, Hu H, Jing Y, He X, Sun L, Esteban C, Chan P, Qiao J, Zhou Q, Belmonte JC*, Jing Qu*, Tang F*, Liu GH*. Single-Cell Transcriptomic Atlas of Primate Ovarian Aging. Cell. 2020. 180(3):585-600 (Cover story)

2.    Ma S, Sun S, Geng L, Song M, Wang W, Ye Y, Ji Q, Zou Z, Wang S, He X, Li W, Rodriguez Esteban C, Long X, Guo G, Chan P, Zhou Q, Belmonte JC*, Zhang W*, Qu J*, Liu GH*. Caloric Restriction Reprograms the Single-Cell Transcriptional Landscape of Rattus Norvegicus Aging. Cell.2020. 180(5):984-1001.

3.    Little M, Liu GH, Shenoy K, Vunjak-Novakovic G, Radisic M. Engineering Tissues and Organs: The Road to the Clinic. Cell. 2020. 181(1):22-23. DOI: 10.1016/j.cell.2020.03.026 (Voices)

4.    He X, Memczak S, Qu J*, Belmonte JC*, Liu GH*. Single-cell “OMICS” in aging: a young growing field. Nat Metab. 2020. 2: 293–302

5.    Liu X, Belmonte JCI, Zhang W*, Liu GH*. A betagalactosidase kiss of death for senescent cells. Cell Res. 2020. DOI:10.1038/s41422-020-0325-6

6.    Zhang W, Zhang S, Yan P, Ren J, Song M, Li J, Lei J, Pan H, Wang S, Ma X, Ma S, Li H,  Sun F, Wan H, Li W, Chan P, Zhou Q, Liu GH*, Tang F*, Qu J*. A Single-Cell Transcriptomic landscape of Primate Arterial Aging. Nat Commun. 2020. DOI: 10.1038/s41467-020-15997-0

7.    Li J, Zheng Y, Yan P, Song M, Wang S, Sun L, Liu Z, Ma S, Chan P, Zhou Q, Belmonte JC, Zhang W*, Liu GH*, Tang F*, Qu J,*. A Single-cell Transcriptomic Atlas of Primate Pancreatic Islet Aging. National Science Review. 2020. DOI: 10.1093/nsr/nwaa127

8.    Zhang W, Qu J, Liu GH*, Belmonte JC*. The Aging Epigenome and its Rejuvenation. Nat Rev Mol Cell Biol.2020. 21(3):137-150.

9.    Li H, Wu Z, Liu X, Zhang S, Ji Q, Jiang X, Liu Z, Wang S, Qu J, Zhang W, Song M*, Song E*, Liu GH*. ALKBH1 deficiency leads to loss of homeostasis in human diploid somatic cells. Protein Cell. 2020. DOI: 10.1007/s13238-020-00744-4

10.  Hu H, Ji Q, Song M, Ren J, Liu Z, Wang Z, Liu X, Yan K, Hu J, Wang S, Zhang W*, Liu GH*, Qu J*. ZKSCAN3 counteracts cellular senescence by stabilizing heterochromatin. Nucleic Acids Research. 2020. DOI: 10.1093/nar/gkaa425

11.  Bi S, Liu Z, Wu Z, Wang Z, Liu X, Wang S, Ren J, Zhang W*, Song M*, Liu GH*, Qu J*. SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer. Protein Cell. 2020. DOI: 10.1007/s13238-020-00728-4

12.  Wang F, Zhang W, Yang Q, Kang Y, Fan Y, Wei J, Liu Z, Dai S, Li H, Li Z, Xu L, Chu C, Qu J, Si C, Ji W*,Liu GH*, Long C*, Niu Y*. Generation of a Hutchinson-Gilford progeria syndrome monkey model by base editing. Protein Cell. 2020. In press

13.  Wang S, Min Z, Ji Q, Geng L, Su Y, Liu Z, Hu H, Wang L, Zhang W, Suzuiki K, Huang YZhang P, Tang T, Qu J*, Yu Y*, Liu GH*, Qiao J*. Rescue of Premature Aging Defects in Cockayne Syndrome Stem Cells by CRISPR/Cas9-mediated Gene Correction. Protein Cell. 2020. 11(1):1-22.

14.  Zhang J, Liu GH*, Qu J*, Song M*. Treating Osteoarthritis via Gene Therapy with Rejuvenation Factors. Gene Therapy. 2020. DOI: 10.1038/s41434-020-0149-5

15.  Martinez-Redondo P, Guillen-Guillen I, Davidsohn N, Wang C, Prieto J, Kurita M, Hatanaka F, Zhong C, Hernandez-Benitez R, Hishida T, Lezaki T, Sakamoto A, Nemeth AN, Hishida Y, Esteban CR, Shojima K, Huang L, Shokhirev M, Nuñez-Delicado E, Campistol JM, Guillen-Vicente I, Rodriguez-Iñigo E, Lopez-Alcorocho JM, Guillen-Vicente M, Church G, Reddy P, Guillen-Garcia P*, Liu GH*, Belmonte JCI*. αKLOTHO and sTGFβR2 treatment counteract the osteoarthritic phenotype developed in a rat model. Protein Cell. 2020. 11(3):219-226

16.  Yan P, Li Q, Wang L, Lu P, Suzuki K, Liu Z, Lei J, Li W, Ren R, He X, Wang S, Ding J, Chan P, Zhang W, Song M, Belmonte JC, Qu J#, Tang F#, Liu GH*. FOXO3-engineered human ESC-derived vascular cells promote vascular protection and regeneration. Cell Stem Cell. 2019. 24(3), 447-461

17.  Deng L, Ren R, Liu Z, Song M, Li J, Wu Z, Ren X, Fu L, Li W, Zhang W, Guillen P, Belmonte J, Chan P, Qu J#, Liu GH*. Stabilizing heterochromatin by DGCR8 alleviates senescence and osteoarthritis. Nat Commun. 2019. 10(1):3329.

18.  Fu L, Hu Y, Song M, Liu Z, Zhang W, Yu FX, Wu J, Wang S, Belmonte JC, Chan P, Qu J#, Tang F#,  Liu GH*. Upregulation of FOXD1 by YAP alleviates senescence and osteoarthritis. PLoS Biology. 2019. 17(4):e3000201

19.  Ren X, Hu B, Song M, Ding Z, Dang Y, Liu Z, Zhang W, Ji Q, Ren R, Ding J, Chan P, Jiang C, Ye K, Qu J#, Tang F#, Liu GH*. Maintenance of nucleolar homeostasis by CBX4 alleviates senescence and osteoarthritis. Cell Reports. 2019. 26(13):3643-3656.

20.  Ling C, Liu Z, Song M, Zhang W, Wang S, Liu X, Ma S, Sun S, Fu L, Chu Q, Belmonte JC, Wang Z, Qu J#, Yuan Y#, Liu GH*. Modeling CADASIL vascular pathologies with patient-derived induced pluripotent stem cells. Protein Cell. 2019. 10(4):249-271

21.  Cheng F, Wang S, Song M, Liu Z, Liu P, Chan P, Wang Y, Wang L, Zhang W*, Qu J*, Liu GH*. DJ-1 is dispensable for human stem cell homeostasis. Protein Cell. 2019. 10(11):846-853

22.  Geng L, Liu Z, Wang S, Sun S, Ma S, Liu X, Chan P, Sun L, Song M*, Zhang W*, Liu GH*, Qu J*. Low-dose quercetin positively regulates mouse healthspan. Protein Cell. 2019. 10(10):770-775.

23.  Song M, Belmonte JCI#, Liu GH*. Age-related cardiopathies gene editing. Aging (Albany NY). 2019. 11(5):1327-1328.

24.  Zhang X, Liu Z, Liu X, Wang S, Zhang Y, He X, Sun S, Ma S, Shyh-Chang N, Liu F, Wang Q, Wang X, Liu L, Zhang W*, Song M*, Liu GH*, Qu J*. Telomere-Dependent and Telomere-Independent Roles of RAP1 in Regulating Human Stem Cell Homeostasis. Protein Cell. 2019. 10(9):649-667.

25.  Geng L, Liu Z, Zhang W*, Li W, Wu Z, Wang W, Ren R, Su Y, Wang P, Ju Z, Chan P, Song M*, Qu J*, Liu GH*. Chemical Screen Identifies a Geroprotective Role of Quercetin in Premature Aging. Protein Cell. 2019. 10(6):417-435

26.  Hishida T, Vazquez-Ferrer E, Hishida-Nozaki Y, Sancho-Martinez I, Takahashi Y, Hatanaka F, Wu J, Ocampo A, Reddy P, Wu MZ, Gerken L, Shaw R, Esteban CR, Benner C, Nakagawa H, Garcia PG, Delicado EN, Castells A, Campistol JM, Liu GH*, Belmonte JC*. Mutations in foregut SOX2+ cells induce efficient proliferation via CXCR2 pathway. Protein Cell. 2019. 10(7):485-495.

27.  He X, Song M, Qu J, Guo Y, Cao H, Sun R*, Liu GH*, Shen Y*, Major Program Expert Group. Basic and Translational Aging Research in China: Present and Future. Protein Cell. 2019. 10(7):476-484.

28.  Zhang W, Wan H, Feng G, Qu J, Wang J, Jing Y, Ren R, Liu Z, Zhang L, Chen Z, Wang S, Zhao Y, Wang Z, Yuan Y, Zhou Q, Li W#, Liu GH*, Hu B#. SIRT6 deficiency results in developmental retardation in cynomolgus monkeys. Nature.2018. 560(7720):661-665.

29.  Zhang W, Song M, Qu J#,  Liu GH*. Epigenetic Modifications in Cardiovascular Aging and Diseases. Circ Res. 2018. 123(7):773-786.

30.  Geng L, Liu Z, Zhang W#, Li W, Wu Z, Wang W, Ren R, Su Y, Wang P, Ju Z, Chan P, Song M#, Qu J#, Liu GH*. Chemical Screen Identifies a Geroprotective Role of Quercetin in Premature Aging. Protein Cell. 2018. doi: 10.1007/s13238-018-0567-y.

31.  Wang S, Hu B, Ding Z, Dang Y, Wu J, Li D, Liu X, Xiao B, Zhang W, Ren R, Lei J, Hu H, Chen C, Chan P, Li D, Qu J#, Tang F#, Liu GH*. ATF6 safeguards organelle homeostasis and cellular aging in human mesenchymal stem cells. Cell Discovery. 2018. Jan 5;4:2.

32.  Wu Z, Zhang W, Song M, Wang W, Wei G, Li W, Lei J, Huang Y, Sang Y, Chan P, Chen C, Qu J#, Suzuki K#, Belmonte JC#,  Liu GH*. Differential stem cell aging kinetics in Hutchinson–Gilford progeria syndrome and Werner syndrome. Protein Cell. 2018. 9(4):333-350.

33.  Fang J, Yang J, Wu X, Zhang G, Li T, Zhang H, Wang CC,  Liu GH*, Wang L#. Metformin alleviates human cellular aging by upregulating the ER peroxidase GPx7. Aging Cell.2018.17(4):e12765.

34.  Ren R, Deng L, Xue Y, Suzuki K, Zhang W, Yu Y, Wu J, Sun L, Gong X, Luan H, Yang F, Ju Z, Ren X, Wang S, Tang H, Geng L, Zhang W, Li J, Qiao J, Xu T#, Qu J#, Liu GH*. Visualization of aging-associated chromatin alterations with an engineered TALE system. Cell Res. 2017. 27(4):483-504

35.  Yang J, Li J, Suzuki K, Liu X, Wu J, Zhang W, Ren R, Zhang W, Chan P, Belmonte JC, Qu J#, Tang F#,  Liu GH*. Genetic enhancement in cultured human adult stem cells conferred by a single nucleotide recoding. Cell Res. 2017. 27(9):1178-1181

36.  Ren R, Ocampo A,  Liu GH*, Belmonte JC#. Regulation of Stem Cell Aging by Metabolism and Epigenetics. Cell Metab. 2017. 26(3):460-474.

37.  Wang L, Yi F, Fu L, Yang J, Wang S, Wang Z, Suzuki K, Sun L, Xu X, Yu Y, Qiao J, Belmonte JC, Yang Z, Yuan Y#, Qu J#,  Liu GH*. CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs. Protein Cell. 2017. 8(5):365-378

38.  Kubben N, Zhang W, Wang L, Voss T, Yang J, Qu J,  Liu GH*, Misteli T#, Repression of the antioxidant NRF2 pathway in premature aging. Cell. 2016. 165(6):1361-74

39.  Pan H, Guan D, Liu X, Li J, Wang L, Wu J, Zhou J, Zhang W, Ren R, Zhang W, Li Y, Yang J, Hao Y, Yuan T, Yuan G, Wang H, Ju Z, Mao Z, Li J, Qu J#, Tang F#,  Liu GH*. SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2. Cell Res. 2016. 26(2):190-205.

40.  Fu L, XX, Ren R, Wu J, Zhang W, Yang J, Ren X, Wang S, Zhao Y, Sun L, Yu Y, Wang Z, Yang Z, Yuan Y, Qiao J, Belmonte JC#, Qu J#,  Liu GH*. Modeling Xeroderma Pigmentosum associated neurological pathologies with patients-derived iPSCs. Protein Cell. 2016.7(3):210-21.

41.  Li Y, Zhang W, Chang L, Han Y, Sun L, Guo X, Tang H, Liu Z, Deng H, Ye Y, Ren R, Wang Y, Li J, Qiao J, Qu J#, Zhang W#,  Liu GH*. Vitamin C alleviates aging defects in a stem cell model for Werner syndrome. Protein Cell.2016. 7(7):478-88.

42.  Zhang W, Li J, Suzuki K, Qu J, Wang P, Zhou J, Liu X, Ren R, Xu X, Ocampo A, Yuan T, Yang J, Li Y, Shi L, Guan D, Pan H, Duan S, Ding Z, Li M, Yi F, Bai R, Wang Y, Chen C, Yang F, Li X, Wang Z, Aizawa E, Goebl A, Soligalla RD, Reddy P, Esteban CR, Tang F#,  Liu GH*, Belmonte JC#. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging. Science. 2015; 348(6239):1160-3.

43.  Duan S, Yuan G, Liu X, Ren R, Li J, Zhang W, Wu J, Xu X, Fu L, Li Y, Yang J, Zhang W, Bai R, Yi F, Suzuki K, Gao H, Esteban CR, Zhang C, Belmonte JC, Chen Z, Wang X, Jiang T, Qu J#, Tang F#,  Liu GH*. PTEN deficiency reprograms human neural stem cells towards a glioblastoma stem cell-like phenotype. Nat Commun.2015. 6:10068.

44.  Suzuki K, Yu C, Qu J, Li M, Yao X, Yuan T, Goebl A, Tang S, Ren R, Aizawa E, Zhang F, Xu X, Soligalla R, Chen F, Kim J, Kim NY, Liao HK, Benner C, Esteban CR, Jin Y, Liu GH*, Li Y#, Belmonte JC#. Targeted gene correction in human disease-specific induced pluripotent stem cells minimally impacts whole-genome mutational load. Cell Stem Cell. 2014; 15, 31–36. 

45.   Liu GH*, Suzuki K, Li M, Qu J, Montserrat N, Tarantino C, Gu Y, Yi F, Xu X, Zhang W, Ruiz S, Plongthongkum N, Zhang K, Masuda S, Nivet E, Tsunekawa Y, Soligalla R, Goebl A, Aizawa E, Kim N, Kim J, Dubova I, Li Y, Ren R, Benner C, del Sol A, Bueren J, Trujillo J, Surralles J, Esteban C, Izpisua Belmonte JC#. Modeling Fanconi Anemia pathogenesis and therapeutics using integration-free patient iPSCs. Nat Commun. 2014. 7;5:4330. 

46.  Yang J, Cai N, Yi F,  Liu GH*, Qu J#, Belmonte JC#. Gating pluripotency via nuclear pores. Trends Mol Med. 2014. 20(1):1-7.

47.  Wu K, Ren R, Su W, Wen Bo, Zhang Yuying, Yi Fei, Qiao X, Yuan T, Wang J, Liu L, Belmonte JC#,  Liu GH*, Chen C#. A novel suppressive effect of alcohol dehydrogenase 5 in neuronal differentiation. J Biol Chem. 2014. 289(29):20193-9.

48.  Xu XL#, Yang JP, Fu LN, Ren RT, Yi F, Suzuki K, Liu K, Ding ZC, Qu J, Zhang WQ, Li Y, Yuan TT, Yuan GH, Sui LN, Guan D, Duan SL, Pan HZ, Wang P, Zhu XP, Montserrat N, Li M, Bai RJ, Liu L, Izpisua Belmonte JC,  Liu GH*. Direct reprogramming of porcine fibroblasts to neural progenitor cells. Protein Cell. 2014. 5(1):4-7.

49.  Xu X, Duan S, Yi F, Ocampo A,  Liu GH*, Belmonte JC#. Mitochondrial regulation in pluripotent stemcells. Cell Metab. 2013. 18:325-32.

50.  Pan H, Cai N, Li M,  Liu GH*, Belmonte JC#. Autophagic control of cell stemness. EMBO Mol. Med.2013 5(3):327-31.

51.  Zhang WQ, Qu J, Suzuki K,  Liu GH*, Belmonte JC#. Concealing cellular defects in pluripotent stem cells. Trends Cell Biol. 2013. 23(12):587-92.

52.  Guan D, Zhang W, Zhang W#,  Liu GH*, Belmonte JC#. Switching cell fate, ncRNAs coming to play. Cell Death Dis. 2013.17;4:e464.

53.  Sui L,  Liu GH*, Belmonte JC#. hESC-derived pancreatic progenitors. Cell Res. 2013. 23(5):592-4.

54.  Zhang K, Yi F,  Liu GH*, Belmonte JC#. New march towards the regeneration of sensation and cognition: hear more, see more and learn more. J Mol Cell Biol. 2013; 5(2):151-3.

55.  Liu W, Li M, Qu J, Yi F#,  Liu GH*.Reevaluation of the safety of induced pluripotent stem cells: a call from somatic mosaicism. Protein Cell. 2013; 4(2):83-5.

56.  Liu GH*, Qu J, Suzuki K, Nivet E, Li M, Montserrat N, Yi F, Xu X, Ruiz S, Zhang W, Ren B, Wagner U, Kim A, Li Y, Goebl A, Kim J, Soligalla R, Dubova I, Thompson J, Yates J III, Esteban C, Sancho-Martinez I, Belmonte JC#. Progressive degeneration of human neural stem cells caused by pathogenic LRRK2. Nature. 2012; 491(7425):603-7. 

57.  Li M*, Liu GH*, Belmonte JC. Navigating the epigenetic landscape of pluripotent stem cells. Nat Rev Mol Cell Biol. 2012; 13(8):524-35. (*equal contribution)

58.  Liu GH*, Ding Z, Izpisua Belmonte JC#. iPSC technology to study human aging and aging-related disorders. Curr Opin Cell Biol. 2012; 24(6):765-74.

59.  Liu GH*, Li M, Qu J, Belmonte JC#. Gating neural development and aging via nuclear pores. Cell Res. 2012; 22(8):1212-4.

60.  Wang P, Zhang W, Yang J, Qu J#,  Liu GH*. Higher-order genomic organization in pluripotent stem cells. Protein Cell. 2012; 3(7):483-6.

61.  Liu GH*, Suzuki K*, Qu J*, Sancho-Martinez I, Yi F, Li M, Kumar S, Nivet E, Kim J, Soligalla RD, Dubova I, Goebl A, Plongthongkum N, Fung HL, Zhang K, LoringJ,Laurent L, and Belmonte JC. Targeted gene correction of laminopathy-associated LMNA mutations in patient-specific iPSCs. Cell Stem Cell. 2011; 8(6):688-94. (*equal contribution)

62.  Pan H, Zhang W, Zhang W#,  Liu GH*.Find and Replace: editing human genome in pluripotent stem cells. Protein Cell. 2011; 2(12):950-6. 

63.  Liu GH, Barkho BZ, Ruiz S, Diep D, Qu J, Yang SL, Panopoulos AD, Suzuki K, Kurian L, Walsh C, Thompson J, Boue S, Fung HL, Sancho-Martinez I, Zhang K, III JY, Belmonte JC#. Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature. 2011; 14;472: 221-5


 

Book chapter

 Liu GH*, Yang J, Ding Z, Ocampo A, Qu J, Suzuki K, Izpisua Belmonte JC#. Chapter: iPSC disease modeling of laminopathies. Human iPS Cells in Disease Modeling (Springer). 2016. pp 53-67