个人简介

杨伟莉，博士，研究员，获评国家教育部重点人才工程青年项目（2023）及广东省自然科学基金杰出青年项目（2022）。主要研究方向为重大神经退行性疾病（PD, AD等）的非人灵长类猴模型建立及分子病理机制研究。

2017年1月获中国科学院遗传与发育生物学研究所博士学位，师从国际著名神经退行性疾病研究专家李晓江教授。2017年初进入暨南大学继续在李晓江课题组从事博士后研究，并于同年至加州大学洛杉矶分校（UCLA）访问交流一年；2018-2019年至美国Emory大学人类遗传学系访问交流。2019年9月加入暨南大学粤港澳中枢神经再生研究院。

多年来主要利用最新基因打靶技术TALEN及CRISPR/Cas9建立重大神经退行性疾病猴模型，如参与创建出世界首例功能性敲除杜氏肌萎缩DMD基因猴模型，PINK1敲除、Parkin敲除的PD猴模型，自闭症猴模型及小脑症猴模型等，并对其病理机制进行了深入研究。尤其通过PINK1敲除猴模型发现帕金森病的重要致病基因—PINK1激酶对灵长类大脑神经细胞存活至关重要，而不影响小鼠神经细胞存活。深入研究发现，PINK1激酶仅在灵长类脑中特异表达而在小鼠脑中表达较少，且PINK1激酶对灵长类大脑神经细胞存活具有非线粒体功能的其它重要作用，提示同一致病基因在不同物种中的功能及表达具有明显区别。

近年来在Cell Research, Autophagy, Protein and Cell (2021, 2022), Molecular Neurodegeneration,Journal of Neuroscience,  Cell stem cell, Cell Discovery等杂志发表二十余篇具有国际影响力的文章。主持国家自然科学基金面上项目2项（2020, 2023），广东省自然科学基金杰出青年项目1项（2022），广东省自然科学基金面上项目1项（2021），广东省重点领域研发计划-脑科学与类脑研究项目课题骨干（2019），中央高校基本科研业务费青年基金项目（2020）。已获批5项发明专利授权，在神经退行性疾病的大动物模型制备及疾病机理研究上具有丰富经验。

论文列表

1.Han, R; Li, SH; Li, X; Yang, WL. PINK1/Parkin-mediated mitophagy: differences between in vitro and in vivo models. Autophagy, 2022, doi: 10.1080/15548627.2022.2139080. (Corresponding author)

2. 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 X-J*. PINK1 kinase dysfunction triggers neurodegeneration in the primate brain without impacting mitochondrial homeostasis. Protein Cell. 13(1):26-46, 2021. (#co-corresponding author)

3. Yang W*, Liu Y*, Tu Z, Xiao C, Yan S, Ma X, Guo X, Chen X, Yin P, Yang Z, Jiang T, Li, S, Qin C, Li X-J. CRISPR/Cas9-mediated PINK1 deletion leads to neurodegeneration in rhesus monkeys. Cell Res. 29(4):334-336, 2019. (co-first author)

4. Yin P, Li SH, Li X-J, Yang W*. New pathogenic insights from large animal models of neurodegenerative diseases. Protein Cell. doi: 10.1007/s13238-022-00912-8, 2022. (Corresponding author)

5.Yang W, Li S, Li X-J. A CRISPR monkey model unravels a unique function of PINK1 in primate brains. Mol Neurodegener. 14(1):17, 2019.

6. Chen, X; Wang, Q; Li, S; Li, XJ; Yang, WL. Mitochondrial-Dependent and Independent Functions of PINK1. Frontiers in Cell and Developmental Biology, 2022, 10:954536. (Corresponding author)  

7.Yang W^#, Chen X, Li S, Li X-J^#. Genetically modified large animal models for investigating neurodegenerative diseases. Cell Biosci. 11(1):218, 2021.  (#co-corresponding author)

8.Yang, WL#; Li, S; Li, XJ#. AHI1: linking depression and impaired antiviral immune response. Cell Research, 2022, 0:1-2. (#co-corresponding author)

9. Yang W*, Wang G*, Wang C*, Guo X, Yin P, Gao J, Tu Z, Wang Z, Wu J, Hu X, Li S, Li X-J. Mutant Alphα-Synuclein Causes Age-Dependent Neuropathology in Monkey Brain, J Neurosci. 35: 8345-58, 2015.  (co-first author)

10. Yang W, Tu Z, Sun Q, Li X-J. CRISPR/Cas9: Implications for Modeling and Therapy of Neurodegenerative Diseases, Front. Mol. Neurosci. 9:30, 2016.

11. Li B*, Zhao H*, Tu ZC*, Yang WL*（co-first author）, Han R, Wang L, Luo XP, Pan MT, Chen XS, Zhang JW, Xu HJ, Guo XY, Yan S, Yin, P, Zhao ZG, Liu JR, Luo YF, Li YF, Yang ZY, Zhang BG, Tan ZQ, Xu H, Jiang TZ, Jiang YH. Li SH, Zhang YQ, Li X-J. CHD8 mutations increase gliogenesis to enlarge brain size in the nonhuman primate Cell Discov 2023 In press.

12. Tu Z*, Yang W*（co-first author）, Yan S*, Yin A, Gao J, Liu X, Zheng Y, Zheng J, Li Z, Yang S, Li, SH, Guo X and Li X-J. Promoting Cas9 degradation reduces mosaic mutations in non-human primate embryos. Sci Rep. 7: 42081, 2017.

13. Chen Y*, Zheng Y*, Kang Y*, Yang W*(co-first author) , Niu Y, Guo X, Tu Z, Si C, Wang H, Xing R, Pu X, Yang SH, Li S, Ji W, Li X-J. Functional disruption of the dystrophin gene in Rhesus Monkey Using CRISPR/Cas9. Hum. Mol. Genet. 24, 3764-74, 2015.

14. Yang W, Zhang Y, Yang J, Tan L, Yang K. Potential anti-osteoporosis effect of biodegradable magnesium implanted in STZ-induced diabetic rats. J Biomed Mater Res A.  99, 386-94, 2011.

15. Tu Z, Yang W, Yan S, Guo X, Li X-J. CRISPR/Cas9: a powerful genetic engineering tool for establishing large animal models of neurodegenerative diseases. Mol Neurodegener. 10:35, 2015.

16. Li X-J, Tu Z, Yang W, Li S. CRISPR: Established Editor of Human Embryos? Cell Stem Cell.  21(3):295-296, 2017.

17. Yin P, Guo X, Yang W, Yan S, Yang S, Zhao T,  Sun Q, Liu Y, Li S, Li X-J. Caspase-4 mediates cytoplasmic accumulation of TDP-43 in the primate brains. Acta Neuropathol. 137(6):919-937, 2019.

18. Yin P, Liu Q, Pan Y, Yang W, Yang S, Wei W, Chen X, Hong Y, Bai D, Li X-J, Li S. Phosphorylation of myelin regulatory factor by PRKG2 mediates demyelination in Huntington's disease. EMBO Reports. 21: e49783, 2020.

19. Yan S, Tu Z, Liu Z, Fan N, Yang H, Yang S, Yang W, Zhao Y, Ouyang Z, Lai C,Yang H, Li L, Liu Q, Shi H, Xu G, Zhao H, Wei H, Pei Z, Li S, Lai L, Li X-J. A Huntingtin Knockin Pig Model Recapitulates Features of Selective Neurodegeneration in Huntington's Disease. Cell. 173(4):989-1002, 2018.

20. Jing L, Cheng S, Pan Y, Liu Q, Yang W, Li S, Li X-J. Accumulation of Endogenous Mutant Huntingtin in Astrocytes Exacerbates Neuropathology of Huntington Disease in Mice. Mol Neurobiol. 2021.

21. Yang S, Yang HM, Chang RB Yang Y, Yin P, Yang W, Huang SS Geartig, MA, Li SH, Li X-J. MANF regulates hypothalamic control of food intake and body weight. Nature Commun. 18;8(1):579, 2017.

22. Zhao H, Tu ZC, Xu HJ, Yan S, Yan HH, Zheng YH, Yang W, Zheng JH, Li ZJ, Tian R, Lu YM Gao XY, Jiang YH, Li X-J. Zhang YQ. Altered neurogenesis and disrupted expression of synaptic proteins in SHANK3 deficient non-human primate prefrontal cortex. Cell Res. 27(10):1293-1297. 2017.

23. Niu Y, Guo X, Chen Y, Wang C, Gao J, Yang W, Kang Y, Si W, Wang H, Yang SH, Li S, Ji W, Li X-J. Early Parkinson's disease symptoms in α-synuclein transgenic monkeys. Hum. Mol. Genet.  24, 2308-17, 2015.

24. Chen X, Sun Y, Chen L, Chen XS, Pan M, Zhang Y, Wang Q, Yang W, Yin P, He D, Guo X, Yang S, Zeng Y, Yan S, Li XJ, Li S. Differential expression and roles of Huntingtin and Huntingtin-associated protein 1 in the mouse and primate brains. Cell Mol Life Sci. 2022 Oct 17;79(11):554. doi: 10.1007/s00018-022-04577-8. PMID: 36251080.

25. Chen X, Xin N, Pan Y, Zhu L, Yin P, Liu Q, Yang W, Xu X, Li S, Li XJ. Huntingtin-Associated Protein 1 in Mouse Hypothalamus Stabilizes Glucocorticoid Receptor in Stress Response. Front Cell Neurosci. 2020 Jun 4;14:125. doi: 10.3389/fncel.2020.00125. PMID: 32581713; PMCID: PMC7289054.

联系方式：weiliyang12@jnu.edu.cn. 暨南大学粤港澳中枢神经再生研究院315室，欢迎感兴趣的研究生及本科生加入！