李世华
教授
lishihualis@jnu.edu.cn
研究助理
李世华，暨南大学教授、博士生导师。1996-2019 年在美国Emory大学任教并晋升为正教授。2019年6月全职加盟暨南大学。李世华教授是亨廷顿舞蹈病（HD）领域的世界著名专家，自1993年来⼀直坚持用各种动物模型（小鼠, 猪, 猴) 对HD进行深⼊研究。李世华教授在建立及研究基因修饰小鼠模型的过程中发现小鼠模型不能表现选择性神经元死亡的典型病理变化，从而利用大动物疾病模型研究神经退行性疾病的病理机制。李世华教授参与并指导建立了世界首例转基因HD猴模型（2008年）、转基因HD猪模型（2010年）、HD基因敲入猪模型（2018年）及其它重要大动物疾病模型。近年来利用Crispr/Cas9 对HDKI猪模型开展了基因治疗。研究成果发表于Nature，Cell，Science，Nature Medicine，Nature Neuroscience，NatureGenetics，Nature Biomedical Engineering,Advance Science, Neuron等国际权威杂志。发表论文数近200 篇，累计引用达22000次, H Index 77.
2023
Zhu LH, Li SH, Li XJ,Yin P. Pathological insights from amyotrophic lateral sclerosis animal models: comparisons, limitations, and challenges. Transl Neurodegener. In press 2023 Tu Z, Yan S, Han BF, Li CJ, Liang WA, Lin YQ, Ding YY, Wei HY, Wang L, Xu H, Ye JM, Li B, Li SH, Li XJ. Tauopathy promotes spinal cord-dependent production of toxic amyloid-beta in transgenic monkeys. Signal Transduct Target Ther In press 2023
Li CJ, Lin YQ, Chen YZ, Song XC, Zheng X, Li JW, He J, Chen XS, Huang CH, Wang W, Wu JH, Wu JX, Gao JL, Tu ZC, Li X-J, Yan S, Li SH. A Specific Mini-intrabody Mediates Lysosome Degradation of Mutant Huntingtin. Adv Sci. In press, 2023
Liu, L., Tong, H., Sun, Y., Chen, X., Yang, T., Zhou, G., Li, X.-J. & Li, S. Huntingtin Interacting Proteins and Pathological Implications. International Journal of Molecular Sciences. 24 : 13060. DOI: 10.3390/ijms241713060.2023
Yan S, Zheng X, Lin YQ, Li CJ, Liu ZM, Li JW, Tu ZC, Zhao Y, Huang CH, Chen YZ, Li J, Song XC, Han BF, Wang W, Liang WE, Lai LX, Li XJ, LI SH. Cas9-mediated replacement of expanded CAG repeats in a pig model of Huntington’s disease. Nat Biomed Eng. 1-18 doi: 10.1038/s41551-023-01007-3. 2023
2022
Sun, Y., Tong, H., Yang, T., Liu, L., Li, X. J., & Li, S. Insights into White Matter Defect in Huntington's Disease. Cells, 11(21), 3381. https://doi.org/10.3390/cells11213381. 2022
Yang W, Guo X, Tu Z, Chen X, Han R, Liu Y, Yan S, Wang Q, Wang Z, Zhao X, Zhang Y, Xiong X, Yang H, Yin P, Wan H, Chen X, Guo J, Yan XX, Liao L, Li S, Li XJ. PINK1 kinase dysfunction triggers neurodegeneration in the primate brain without impacting mitochondrial homeostasis. Protein and Cell 13(1):26-46. 2022
Chen XX, Su YZ, Chen LQ, Che XS, Pan MT, Zhang YR, Wang Q, Yang WL, Yin P, He DJ, Guo XY, Yang S, Zhen Y, Yan S, Li XJ, LI SH. Differential expression and roles of Huntingtin and Huntingtin-associated protein 1 in the mouse and primate brains. Cell Mol Life Sci. 79(11):554. 2022
Han R, Liu YT, Li SH, Li XJ, Yang WL. PINK1/Parkin-mediated mitophagy: differences between in vitro and in vivo models. Autophagy. 3:1-10. 2022
Yang WL, Li S, Li XJ. AHI1: linking depression and impaired antiviral immune response. Cell Res. 32(10):869-870. 2022
Yin P, Li SH, Li XJ, Yang W. New pathogenic insights from large animal models of neurodegenerative diseases. Protein Cell. 13(10):707-720. 2022
Yang W, Guo X, Tu Z, Chen X, Han R, Liu Y, Yan S, Wang Q, Wang Z, Zhao X, Zhang Y, Xiong X, Yang H, Yin P, Wan H, Chen X, Guo J, Yan XX, Liao L, Li SH, Li XJ. PINK1 kinase dysfunction triggers neurodegeneration in the primate brain without impacting mitochondrial homeostasis. Protein Cell. 13(1):26-46. doi: 10.1007/s13238-021-00888-x.2022
Yin P, Bai DZ, Deng FY, Zhang C, Jia QQ, Zhu LH, Chen LQ, Li B, Guo XY, Ye JM, Tan ZQ, Wang L, Li SH, Li，X-J. SQSTM1 mediated clearance of cytoplasmic mutant TARDBP/TDP-43 in the monkey brain. Autophagy. 18(8):1955-1968. doi: 10.1080/15548627.2021.2013653. 2022
2021
Yang WL, Chen XS, Li SH, Li XJ. Genetically modified large animal models for investigating neurodegenerative diseases. Cell & Bioscience (IF 6.07). Dec 21;11(1):218, 2021.
Yin P, Bai D, Zhu L, Deng F, Guo X, Li B, Chen L, Li SH, Li X-J. Cytoplasmic TDP-43 impairs the activity of the ubiquitin-proteasome system. Exp Neurol (IF 5.33). 4:113833. 2021
Jing L, Cheng S, Pan Y, Liu Q, Yang W, Li SH, Li XJ. Accumulation of endogenous mutant huntingtin in astrocytes exacerbates neuropathology of Huntington disease in mice. Mol Neurobiol.58(10):5112-5126. doi: 10.1007/s12035-021-02451-5. 2021
Bai D, Yin P, Zhang Y, Sun F, Chen L, Lin L, Yan S, Li SH, Li XJ. Lack of association of somatic CAG repeat expansion with striatal neurodegeneration in HD knock-in animal models. Hum Mol Genet. 30(16):1497-1508. doi: 10.1093/hmg/ddab129. 2021
Wang B, Xin N, Qian X, Zhai L, Miao Z, Yang Y, Li SH, Sun M, Xu X, Li XJ. Ahi1 regulates the nuclear translocation of glucocorticoid receptor to modulate stress response. Transl Psychiatry (IF 6.222). 11(1):188. 2021
2020
Liu Q, Cheng SY, Yang HM, Zhu LY, Pan YC, Jing L, Tang BS, Li SH, Li X-J. Loss of Hap1 selectively promotes striatal degeneration in Huntington disease mic. Proc Natl Acad Sci U S A. 117(33):20265-20273. 2020
Chen XX, Xin N, Pan YC, Zhu LY, Yin P, Liu Q, Yang WL, Xu XS, Li SH, Li XJ. Huntingtin-associated protein 1 in mouse hypothalamus stabilizes glucocorticoid receptor in stress response. Front Cell Neurosci. 14:125, 2020
Yang HM, Yang S, Jing L, Huang LX, Chen LX, Zhao XX, Yang WL, Pan YC, Yin P, Qin Z, Li SH, Li X-J. Truncation of mutant huntingtin in knock-in mice demonstrates exon1 huntingtin is a key pathogenic form. Nat Commun. 11(1):2582. 2020
Yin P, Liu Q, Pan Y, Yang W, Yang S, Wei W, Chen X, Hong Y, Bai D, Li XJ, Li SH. Phosphorylation of myelin regulatory factor by PRKG2 mediates demyelination in Huntington's disease. EMBO Rep. 9:e49783. doi: 10.15252. 2020
Liu Q, Huang S, Yin P, Yang S, Zhang J, Jing L, Cheng S, Tang B, Li XJ, Pan Y, Li SH. Cerebellum-enriched protein INPP5A contributes to selective neuropathology in mouse model of spinocerebellar ataxias type 17. Nat Commun. 11(1):1101. doi: 10.1038/, 2020
Yang S, Yang H, Huang L, Chen L, Qin Z, Li SH, Li XJ. Lack of RAN-mediated toxicity in Huntington's disease knock-in mice. Proc Natl Acad Sci U S A.;117(8):4411-4417. 2020
2019
Zhu LY, Chen LQ, Yan LY Perkins BD, Li SH, Li BM, Xu HA, Li X-J. Mutant Ahi1 affects
retinal axon projection in zebrafish via toxic gain of function. Front Cell Neurosci. 21;13:81. doi: 10.3389/fncel.2019.00081. 2019
Yin P, Gao XY, Yang WL, Yan S, Yang S, Zhao T, Q Sun, Liu YB, Li SH, Li X-J. Caspase-4 mediates cytoplasmic accumulation of mutant TDP-43 in the non-human primate brain. Acta Neuropathol, 137(6):919-937. 2019
Yang W, Liu YB, Tu ZC, Xiao C, Yan S, Ma XS, Guo XY, Chen XS, Yin P, Yang ZY, Yang S, Jiang TZ, Li SH, Qin C, Li X-J. CRISPR/Cas9-mediated PINK1 deletion leads to neurodegeneration in rhesus monkeys. Cell Res, 29(4):334-336. 2019
Yang W, Li SH, Li X-J. A CRISPR monkey model reveals a unique function of PINK1 in primate brains. Mol Neurodegener. 14:17, 2019
2018
Yang S, Li SH, Li X-J. Shortening the half-life of Cas9 maintains its gene editing ability and reduces neuronal toxicity. Cell Rep, 25, 2653–2659, 2018
Yan S, Tu ZC, Liu ZM, Fan NN, Yang WL, Zhao Y, Ouyan Z, Lai CD, Yang HQ, Li L, Shi H, Xu GQ, Zhao H, Wei HJ, Pei Z, Li SH, Lai LX, Li X-J. A huntingtin knock-in pig model recapitulates features of selective neurodegeneration in Huntington’s disease. Cell 173(4):989-1002. 2018
Guo JF, Cui YT, Yang Y, Tang BS, Li YJ, Jin P, Li XJ, Yang S, Li SH. Piperine ameliorates SCA17 neuropathology via enhancing MANF expression and reducing ER stress. Mol Neurodegener. 30;13(1):4., 2018
2017
Li X-J, Tu ZC, Yang WL, Li SH. CRISPR: established editor of human embryos? Cell Stem Cell. 21(3):295-296. 2017
Zhao T, Hong Y, Yin P, Li SH, Li-XJ. Differential HspBP1 expression accounts for the greater vulnerability of neurons than astrocytes to misfolded proteins. Proc. Natl. Acad . Sci. USA 114(37):E7803-E7811. 2017
Yang S, Yang HM Chang RB Yang Y, Yin P, Yang WL, Huang SS Geartig, MA, Li SH, Li X-J. MANF regulates hypothalamic control of food intake and body weight. Nature Commun, Sep 18;8(1):579. 2017.
Yang S, Chang RB, Yang HM, Zhao T, Hong Y, Kong HE Sun XB Qin ZH, Jin P, Li SH, Li X-J. CRISP R/Cas9-mediated gene editing ameliorates neurotoxicity in mouse model of Huntington’s disease. J Clin Invest. 127(7):2719-2724. 2017
Xiang JX, Yang S Xin N, Gaertig MA, Reeves RH Li SH, Li X-J. DYRK1A regulates Hap1-Dcaf7/WDR68 binding with implication for delayed growth in Down syndrome. Proc. Natl. Acad . Sci. USA pii: 201614893. doi: 10.1073/pnas.1614893114.2017.
Tu ZC, Yang WL, Yan S, Yin A, Gao JQ, Liu XD, Zheng YH, Zheng JZ, Li ZJ, Yang S, LiSH, Guo XY, Li X-J. Promoting Cas9 degradation reduces mosaic mutations in non-human primate embryos. Sci Rep. 7:42081. 2017
