2024年10月04日 星期五
刘光慧
刘光慧
研究员( Professor Guanghui Liu)
        博士,中国科学院动物研究所研究员,衰老与再生研究组组长,膜生物学国家重点实验室副主任,中国科学院干细胞与再生医学创新研究院副院长,中国科学院干细胞与再生医学科学数据中心主任,国家自然科学基金委创新研究群体项目负责人,杰出青年基金项目获得者。
        2002年毕业于北京大学医学部,获理学学士学位;2007年于中国科学院生物物理研究所获得理学博士学位;2007-2012年先后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);2019年至今任中国科学院动物研究所研究员(PI)。
 
学术任职:
        国际健康与寿命研究学会(AHLR)创会理事,中国细胞生物学学会衰老细胞生物学分会创会会长,中国老年学和老年医学学会抗衰老分会主任委员,中国生物物理学会衰老生物学分会副理事长,中国老年医学学会基础与转化医学分会副会长,《Protein & Cell》副主编,《Stem Cell Research & Therapy》副主编,《Cell Reports》编委,《Aging Cell》编委,《Cell Proliferation》编委,《Cell Regeneration》编委,《Fundamental Research》编委。
 
获奖及荣誉:
        中国科学十大进展(2020),中国生命科学十大进展(2020),中国科学院杰出科技成就奖(2020),国务院政府特殊津贴(2020),Elsevier中国高被引学者(2020),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),中国生命科学十大进展(2018),树兰医学青年奖(2017),首届老年医学杰出贡献奖(2017)。
 
研究领域
         1. 人类衰老的遗传和表观遗传信息解码
结合灵长类动物模型、干细胞、基因编辑、全基因组范围筛选、单细胞测序及多组学分析,研究人类衰老和老年疾病的遗传和表观遗传学基础,探索延缓衰老(如脑衰老和心血管衰老)和防治老年疾病(如神经退行性疾病和动脉粥样硬化症)的方法和手段,以期实现健康老龄化(healthy aging)的目标。
        2. 基于干细胞技术的人类疾病机理研究和精准治疗
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、类器官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. 新型基因编辑手段和基因治疗技术的发展和应用
以HDAdV、telHDAdV、TTALE和CRISPR/Cas9为基础,发展安全高效地编辑人类基因组的新方法,开发以去衰老和促再生为目标的干细胞和基因治疗新策略,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。
 
代表论著:
1.Wang W, Zheng Y, Sun S, Li W, Song M, Ji Q, Wu Z, Liu Z, Fan Y, Liu F, Li J, Esteban CR,Wang S, Zhou Q, Belmonte JCI, Zhang W*, Qu J*, Tang F*, Liu GH*. A Genome-wide CRISPR-Based Screen Identifies KAT7 as a Senescence Driver. Science Translational Medicine. 2021.13, Jan 6;13(575):eabd2655.
2.Zou Z, Long X, Zhao Q, Zheng Y, Song M, Ma S, Wang S, He Y, Esteban CR, Huang J, Yu N, Chan P, Belmonte JCI, Zhang W*, Qu J*, Liu GH*. A single-cell transcriptomic atlas of human skin aging. Developmental Cell. 2021. 56(3):383-397(Cover story)
3.Liang C, Liu Z, Song M, Li W, Wu Z, Wang Z, Wang Q, Wang S, Yan K, Sun L, Hishida T, Cai Y, Izpisua Belmonte JC, Guillen P, Chan P, Zhou Q, Zhang W*, Qu J*, Liu GH*. Stabilization of Heterochromatin by CLOCK Promotes Stem Cell Rejuvenation and Cartilage Regeneration. Cell Research. 2021. 31(2):187-205.
4.Zhang H, Li J, Ren J, Sun S, Ma S, Zhang W, Yu Y, Cai Y, Yan K, Li W, Hu B, Chan P, Zhao GG, Belmonte JC, Zhou Q, Qu J*, Wang S*, Liu GH*. Single-nucleus transcriptomic landscape of primate hippocampal aging. Protein Cell. 2021. DOI: 10.1007/s13238-021-00852-9
5.Li H, Wei X, Zhou L, Zhang W, Wang C, Guo Y, Li D, Chen J, Liu T, Zhang Y, Ma S, Wang C, Tan F, Xu J, Liu Y, Yuan Y, Chen L, Wang Q, Qu J, Shen Y, Liu S, Fan G, Liu L, Liu X, Hou Y, Liu GH*, Gu Y*, Xu X*. Dynamic cell transition and immune response landscapes of axolotl limb regeneration revealed by single-cell analysis. Protein Cell.  2021. 12(1):57-66.
6.Aging Atlas Consortium, Zhang W*, Jing Qu*, Bao Y*, Liu GH*. Aging Atlas: a multi-omics database for aging biology. Nucleic Acids Research. 2021. 8;49(D1):D825-D830.
7.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)
8.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 theSingle-Cell Transcriptional Landscape of Rattus Norvegicus Aging. Cell. 2020. 180(5):984-1001.
9.Ma S, Sun S, Li J, Fan Y, Qu J, Sun L, Wang S, Zhang Y, Yang S, Liu Z, Wu Z, Zhang S, Wang Q, Zheng A, Duo S, Yu Y, Belmonte JCI, Chan P, Zhou Q, Song M*, Zhang W*, Liu GH*. Single-Cell Transcriptomic Atlas of Primate Cardiopulmonary Aging. Cell Research. 2020. 10;1-18.
10.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. 11(9):688-695.
11.Yan P, Liu Z, Song M, Wu Z, Xu W, Li K, Ji Q, Wang S, Liu X, Yan K, Esteban CR, Ci W, Izpisua Belmonte JC, Xie W, Ren J, Zhang W*, Sun Q*, Qu J*, Liu GH*. Genome-wide R-loop landscapes during cell differentiation and reprogramming. Cell Reports. 2020. 32(1):107870
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 baseediting. Protein Cell. 2020. 11(11):809-824. (Cover story)
13.Zheng Y, Liu X, Le W, Xie L, Li H, Wen W, Wang S, Ma S, Huang Z, Ye J, Shi W, Ye Y, Liu Z, Song M, Zhang W, Belmonte JCI, Xiao C, Qu J*, Wang H*, Liu GH*, Su W*. A human circulating immune cell landscape in aging and COVID-19. Protein Cell. 2020. 192:111357.
14.Wang S, Min Z, Ji Q, Geng L, Su Y, Liu Z, Hu H, Wang L, Zhang W, Suzuiki K, Huang Y,Zhang 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. 
15.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. (cover story)
16.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. Nature Communications. 2019.10(1):3329.
17.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.
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.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.
20.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. 
21.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.
22.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.
23.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. 
24.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. 
25.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. (cover story)
26.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 Research.2017. 27(4):483-504.(cover story)
27.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 Research.2017. 27(9):1178-1181.
28.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 PatientiPSCs. Protein Cell.2017. 8(5):365-378. (cover story)
29.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):1361-1374.
30.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 Research.2016. 26(2):190-205. 
31.Suzuki K, Tsunekawa Y, Hernandez-Benitez R, Wu J, Zhu J, Kim EJ, Hatanaka F, Yamamoto M, Araoka T, Li Z, Kurita M, Hishida T, Li M, Aizawa E, Guo S, Chen S, Goebl A, Soligalla RD, Qu J, Jiang T, Fu X, Jafari M, Esteban CR, Berggren WT, Lajara J, Nuñez-Delicado E, Guillen P, Campistol JM, Matsuzaki F, Liu GH, Magistretti P, Zhang K, Callaway EM, Zhang K, Belmonte JC. In Vivo Genome Editing via CRISPR/Cas9 Mediated Homology-Independent Targeted Integration.Nature. 2016. 540(7631):144-149.
32.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 withPatients-Derived iPSCs. Protein Cell.2016.7(3):210-221.
33.Wang H, Diao D, Shi Z, Zhu X, Gao Y, Gao S, Liu X, Wu Y, Rudolph KL, Liu GH, Li T, Ju Z. SIRT6 Controls Hematopoietic Stem Cell Homeostasis through Epigenetic Regulation of Wnt Signaling.Cell Stem Cell.2016. 7;18(4):495-507.
34.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):478-488. (cover story)
35.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):1160-1163.
36.Reddy P, Ocampo A, Suzuki K, Luo J, Bacman SR, Williams SL, Sugawara A, Okamura D, Tsunekawa Y, Wu J, Lam D, Xiong X, Montserrat N, Esteban CR, Liu GH, Sancho-Martinez I, Manau D, Civico S, Cardellach F, Del Mar O'Callaghan M, Campistol J, Zhao H, Campistol JM, Moraes CT, Izpisua Belmonte JC. Selective Elimination of Mitochondrial Mutations in the Germline by Genome Editing. Cell. 2015; 161(3):459-469.
37.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 aGlioblastoma Stem Cell-Like Phenotype. Nature Communications.2015. 6:10068. 
 
综述或评述:
1.The Aging Epigenome and its Rejuvenation. Nature Review Molecular Cell Biology.2020. 21(3):137-150. 
2.Engineering Tissues and Organs: The Road to the Clinic. Cell.2020. 181(1):22-23. DOI: 10.1016/j.cell.2020.03.026. (Voices)
3.Single-Cell “OMICS” in Aging: AYoung Growing Field. Nature Metabolism.2020. 2: 293-302.
4.A Beta-Galactosidase Kiss of Death for Senescent Cells. Cell Research.2020. 30(7):556-557.
5.Treating Osteoarthritis via Gene Therapy with Rejuvenation Factors. Gene Therapy.2020. 27(7-8):309-311. 
6.Protein Quality Control of Cell Stemness.Cell Regeneration.2020. 12;9(1):22.
7.Age-Related Cardiopathies Gene Editing. Aging. 2019. 11(5):1327-1328. 
8.Epigenetic Modifications in Cardiovascular Aging and Diseases. Circulation Research. 2018. 123(7):773-786. 
9.Regulation of Stem Cell Aging by Metabolism and Epigenetic Factors. Cell Metabolism.2017. 26(3):460-474.