王鑫
福建省“闽江学者”特聘教授，国家杰青，国家优青，博士生导师
研究方向：认知障碍疾病的分子机制与治疗靶点
所在系部：神经科学研究所
办公电话：0592-2182261
邮 箱：wangx@xmu.edu.cn
课题组网页：http://wangxlab.xmu.edu.cn/
研究领域
本课题组致力于解析唐氏综合征和阿尔茨海默病这两类重要的认知障碍疾病的共患病机制和潜在药物靶点，近期在Cell, Nature Neuroscience, Nature Medicine, Journal of Clinical Investigation, Science Advances, National Science Review, Molecular Psychiatry, PLOS Biology等国际学术期刊上发表系列研究论文，系统解析了这类疾病的分子机制与治疗靶点。课题组利用基因修饰、电生理、药理学、多组学分析等相关技术，以临床样本和疾病动物模型为研究对象，深入阐明认知障碍疾病的分子机制，为临床诊断和靶向药物的开发提供模型和理论依据。主要方向包括：
1. 免疫调节异常参与认知障碍疾病的分子机制；
2. 蛋白转运和降解障碍导致认知障碍疾病的作用机制；
3. 能量代谢障碍参与认知障碍疾病的分子机制；
4. 认知障碍疾病药物靶点的研究和小分子药物的筛选。
学习经历
2009~2013 美国Sanford-Burnham医学研究所Biomedical Sciences专业 博士；
2005~2008 上海交通大学药学院药理学专业 硕士研究生；
2001~2005 重庆医科大学药学院药学专业 理学学士。
工作经历
2015~至今厦门大学医学院 教授；
2014~2015 美国Sanford-Burnham医学研究所 博士后；
2013~2014 美国加州大学圣地亚哥分校（UCSD）神经科学系、霍华德•休斯医学研究所（HHMI） 博士后；
2013~2013 美国Sanford-Burnham医学研究所 博士后；
2008~2009 美国Sanford-Burnham医学研究所 访问学者。
代表性成果
1. Gao Y, Hong Y, Huang L, Zheng S, Zhang H, Wang S, Yao Y, Zhao Y, Zhu L, Xu Q, Chai X, Zeng Y, Zeng Y, Zheng L, Zhou Y, Luo H, Zhang X, Zhang H, Zhou Y, Fu G, Sun H, Huang TY, Zheng Q, Xu H, Wang X*. β2-microglobulin functions as an endogenous NMDAR antagonist to impair synaptic function. Cell. 2023;186(5):1026-1038.
2. Zhao Y, Zheng Q, Hong Y, Gao Y, Hu J, Lang M, Zhang H, Zhou Y, Luo H, Zhang X, Sun H, Yan XX, Huang TY, Wang YJ, Xu H, Liu C, Wang X*. β2-microglobulin coaggregates with Aβ and contributes to amyloid pathology and cognitive deficits in Alzheimer’s disease model mice. Nat Neurosci. 2023. DOI: https://doi.org/10.1038/s41593-023-01352-1.
3. Zhang H#, Zheng Q#, Guo T#, Zhang S#, Zheng S, Wang R, Deng Q, Yang G, Zhang S, Tang L, Qi Q, Zhu L, Zhang X-F, Luo H, Zhang X, Sun H, Gao Y, Zhang H, Zhou Y, Han A, Zhang C-S, Xu H, Wang X*. Metabolic reprogramming in astrocytes results in neuronal dysfunction in intellectual disability. Mol Psychiatry. 2022. DOI: 10.1038/s41380-022-01521-x.
4. Zheng Q#, Song B#, Li G#, Cai F#, Wu M, Zhao Y, Jiang L, Guo T, Shen M, Hou H, Zhou Y, Zhao Y, Di A, Zhang L, Zeng F, Zhang X-F, Luo H, Zhang X, Zhang H, Zeng Z, Huang T, Dong C, Qing H, Zhang Y, Zhang Q, Wang X, Wu Y, Xu H*, Song W*, and Wang X*. USP25 inhibition ameliorates Alzheimer’s pathology through regulating APP processing and Aβ generation. J Clin Invest. 2022;132(5): e15217
5. Zhang H#, Hong Y#, Yang W, Wang R, Yao T, Wang J, Liu K, Yuan H, Xu C, Zhou Y, Li G, Zhang L, Luo H, Zhang X, Du D, Sun H, Zheng Q, Zhang Y-W, Zhao Y, Zhou Y, Xu H, Wang X*. SNX14 deficiency-induced defective axonal mitochondrial transport in Purkinje cells underlies cerebellar ataxia and can be reversed by valproate. Natl Sci Rev. 2021;8(7): nwab024.
6. Zheng Q#, Li G#, Wang S, Zhou Y, Liu K, Gao Y, Zhou Y, Zheng L, Zhu L, Deng Q, Wu M, Di A, Zhang L, Zhao Y, Zhang H, Sun H, Dong C, Xu H, Wang X*. Trisomy 21-induced dysregulation of microglial homeostasis in Alzheimer’s brains is mediated by USP25. Sci Adv. 2021;7(1): eabe1340.
7. Zeng F#, Ma X#, Zhu L#, Xu Q, Zeng Y, Gao Y, Li G, Guo T, Zhang H, Tang X, Wang Z, Ye Z, Zheng L, Zhang H, Zheng Q, Li K, Lu J, Qi X, Luo H, Zhang X, Wang Z, Zhou Y, Yao Y, Ke R, Zhou Y, Liu Y, Sun H, Huang T, Shao Z, Xu H, and Wang X*. The deubiquitinase USP6 affects memory and synaptic plasticity through modulating NMDA receptor stability. PLoS Biol. 2019;17(12): e3000525.
8. Wang X, Zhao Y, Zhang X, Badie H, Zhou Y, Mu Y, Loo LS, Cai L, Thompson RC, Yang B, Chen Y, Johnson PF, Wu C, Bu G, Mobley WC, Zhang D, Gage FH, Ranscht B, Zhang YW, Lipton SA, Hong W, Xu H*. Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction via modulation of glutamate receptor recycling in Down's syndrome. Nat Med. 2013;19(4):473-80. (Cover story)
承担的重要课题
1. 国家自然科学基金杰出青年科学基金项目，82325018，2024-01至2028-12，主持。
2. 国家自然科学基金区域联合基金重点项目，U21A20358，2022-01至2025-12，主持。
3. 科技部重点研发计划课题，2021YFA1101401，2021-12至2026-06，主持。
4. 科技部科技创新2030—“脑科学与类脑研究”重大项目，2021ZD0202402，2021-12至2026-11，骨干。
5. 福建省自然科学基金重点项目，2021J02004，2021-11至2024-11，主持。
6. 广东省基础与应用基础研究基金区域联合基金重点项目，2021B1515120081，2021-10至2024-09，主持
7. 国家自然科学基金优秀青年基金项目，81822014，2019-1至2021-12，主持。
8. 国家自然科学基金面上项目，31871077，2019-1至2022-12，主持。
9. 福建省自然科学基金杰出青年基金项目，2017J06021，2017-4至2020-4，主持。
10. 国家自然科学基金面上项目，81571176，2016-1至2019-12，主持。
11. 厦门大学校长基金（中央高校基本科研业务费），2015至2017，主持。
获奖及荣誉
1. 厦门市科技进步一等奖，2018年；
2. 厦门市首批杰出青年人才，2018年；
3. 基金委优秀青年基金获得者，2018年；
4. 福建省引进高层次创新人才计划专家，2017年；
5. 福建省杰出青年基金获得者，2017年；
6. 闽江学者特聘教授，2016年；
7. 国家高层次青年人才，2016年；
8. 美国阿尔茨海默病协会青年学者奖（Young Scholar Award of Alzheimer's Association），2010年。
所有论文列表
1. Zhao Y, Zheng Q, Hong Y, Gao Y, Hu J, Lang M, Zhang H, Zhou Y, Luo H, Zhang X, Sun H, Yan XX, Huang TY, Wang YJ, Xu H, Liu C, Wang X*. β2-microglobulin coaggregates with Aβ and contributes to amyloid pathology and cognitive deficits in Alzheimer’s disease model mice. Nat Neurosci. 2023. DOI: https://doi.org/10.1038/s41593-023-01352-1.
2. Gao Y, Hong Y, Huang L, Zheng S, Zhang H, Wang S, Yao Y, Zhao Y, Zhu L, Xu Q, Chai X, Zeng Y, Zeng Y, Zheng L, Zhou Y, Luo H, Zhang X, Zhang H, Zhou Y, Fu G, Sun H, Huang TY, Zheng Q, Xu H, Wang X*. β2-microglobulin functions as an endogenous NMDAR antagonist to impair synaptic function. Cell. 2023. PMID: 36868208
3. Zhang H#, Zheng Q#, Guo T#, Zhang S#, Zheng S, Wang R, Deng Q, Yang G, Zhang S, Tang L, Qi Q, Zhu L, Zhang X-F, Luo H, Zhang X, Sun H, Gao Y, Zhang H, Zhou Y, Han A, Zhang C-S, Xu H, Wang X*. Metabolic reprogramming in astrocytes results in neuronal dysfunction in intellectual disability. Mol Psychiatry. 2022. PMID: 35338313
4. Zheng Q#, Song B#, Li G#, Cai F#, Wu M, Zhao Y, Jiang L, Guo T, Shen M, Hou H, Zhou Y, Zhao Y, Di A, Zhang L, Zeng F, Zhang X-F, Luo H, Zhang X, Zhang H, Zeng Z, Huang T, Dong C, Qing H, Zhang Y, Zhang Q, Wang X, Wu Y, Xu H*, Song W*, and Wang X*. USP25 inhibition ameliorates Alzheimer’s pathology through regulating APP processing and Aβ generation. J Clin Invest. 2022;132(5): e15217. PMID: 35229730
5. Tang XY, Xu L, Wang J, Hong Y, Wang Y, Zhu Q, Wang D, Zhang XY, Liu CY, Fang KH, Han X, Wang S, Wang X, Xu M, Bhattacharyya A, Guo X*, Lin M*, Liu Y*. DSCAM/PAK1 pathway suppression reverses neurogenesis deficits in iPSC-derived cerebral organoids from patients with Down syndrome. J Clin Invest. 2021;131(12): e135763. PMID: 33945512
6. Zhang H#, Hong Y#, Yang W, Wang R, Yao T, Wang J, Liu K, Yuan H, Xu C, Zhou Y, Li G, Zhang L, Luo H, Zhang X, Du D, Sun H, Zheng Q, Zhang Y-W, Zhao Y, Zhou Y, Xu H, Wang X*. SNX14 deficiency-induced defective axonal mitochondrial transport in Purkinje cells underlies cerebellar ataxia and can be reversed by valproate. Natl Sci Rev. 2021;8(7): nwab024. PMID: 34691693
7. Zheng Q#, Li G#, Wang S, Zhou Y, Liu K, Gao Y, Zhou Y, Zheng L, Zhu L, Deng Q, Wu M, Di A, Zhang L, Zhao Y, Zhang H, Sun H, Dong C, Xu H, Wang X*. Trisomy 21-induced dysregulation of microglial homeostasis in Alzheimer’s brains is mediated by USP25. Sci Adv. 2021;7(1): eabe1340. PMID: 33523861
8. Huo Y#, Gao Y#, Zheng Q, Zhao D, Guo T, Zhang S, Zeng Y, Cheng Y, Gu H, Zhang L, Zhu B, Luo H, Zhang X, Zhou Y, Zhang YW, Sun H, Xu H, Wang X*. Overexpression of Human SNX27 Enhances Learning and Memory Through Modulating Synaptic Plasticity in Mice. Front Cell Dev Biol. 2020;8:595357. PMID: 33330482
9. Lin C#, Jiang M#, Liu L#, Chen X, Zhao Y, Chen L, Hong Y, Wang X, Hong C, Yao X, Ke R*. Imaging of individual transcripts by amplification-based single-molecule fluorescence in situ hybridization. N Biotechnol. 2021;61:116-123. PMID: 33301924
10. Zhao D, Zhou Y, Huo Y, Meng J, Xiao X, Han L, Zhang X, Luo H, Can D, Sun H, Huang TY, Wang X, Zhang J, Liu FR, Xu H, Zhang YW*. RPS23RG1 modulates tau phosphorylation and axon outgrowth through regulating p35 proteasomal degradation. Cell Death Differ. 2021;28(1):337-348. PMID: 32908202
11. Rong Z, Cheng B, Zhong L, Ye X, Li X, Jia L, Li Y, Shue F, Wang N, Cheng Y, Huang X, Liu CC, Fryer JD, Wang X, Zhang YW, Zheng H*. Activation of FAK/Rac1/Cdc42-GTPase signaling ameliorates impaired microglial migration response to Aβ 42 in triggering receptor expressed on myeloid cells 2 loss-of-function murine models. FASEB J. 2020;34(8):10984-10997. PMID: 32613609
12. Lin C, Jiang M, Duan S, Qiu J, Hong Y, Wang X, Chen X, Ke R*. Visualization of individual microRNA molecules in fixed cells and tissues using target-primed padlock probe assay. Biochem Biophys Res Commun. 2020;526(3):607-611. PMID: 32247612
13. Zeng F#, Ma X#, Zhu L#, Xu Q, Zeng Y, Gao Y, Li G, Guo T, Zhang H, Tang X, Wang Z, Ye Z, Zheng L, Zhang H, Zheng Q, Li K, Lu J, Qi X, Luo H, Zhang X, Wang Z, Zhou Y, Yao Y, Ke R, Zhou Y, Liu Y, Sun H, Huang T, Shao Z, Xu H, and Wang X*. The deubiquitinase USP6 affects memory and synaptic plasticity through modulating NMDA receptor stability. PLoS Biol. 2019;17(12): e3000525. PMID: 31841517
14. Zhang H#, Zhu L#, Wang F#, Wang R, Hong Y, Chen Y, Zhu B, Gao Y, Luo H, Zhang X, Sun H, Zhou Y*, Yao Y*, Wang X*. Novel KCNJ10 Compound Heterozygous Mutations Causing EAST/SeSAME-Like Syndrome Compromise Potassium Channel Function. Front Genet. 2019;10:912. PMID: 31781151
15. Lin KM#, Su G#, Wang F, Zhang X, Wang Y, Ren J, Wang X*, Yao Y*, Zhou Y*. A de novo SCN8A heterozygous mutation in a child with epileptic encephalopathy: a case report. BMC Pediatr. 2019;19(1):400. PMID: 31672125
16. Zeng Y, Wang N, Guo T, Zheng Q, Wang S, Wu S, Li X, Wu J, Chen Z, Xu H, Wang X*, Lin B*. Snx27 Deletion Promotes Recovery From Spinal Cord Injury by Neuroprotection and Reduces Macrophage/Microglia Proliferation. Front Neurol. 2018;9:1059. PMID: 30619032
17. Zhao D, Meng J, Zhao Y, Huo Y, Liu Y, Zheng N, Zhang M, Gao Y, Chen Z, Sun H, Wang X, Jing C, Zhang T, Zhang X, Luo H, Wang X, Zhang J, Liu FR, Li Y, Bu G, Wen L, Huang TY, Xu H, Zhang YW. RPS23RG1 Is Required for Synaptic Integrity and Rescues Alzheimer's Disease-Associated Cognitive Deficits. Biol Psychiatry. 2018. pii: S0006-3223(18)31782-7. PMID: 30292394
18. Zhang H, Huang T, Hong Y, Yang W, Zhang X, Luo H, Xu H, Wang X*. The Retromer Complex and Sorting Nexins in Neurodegenerative Diseases. Front Aging Neurosci. 2018;10:79. PMID: 29632483
19. Zhao Y, Li X, Huang T, Jiang LL, Tan Z, Zhang M, Cheng IH, Wang X, Bu G, Zhang YW, Wang Q, Xu H. Intracellular trafficking of TREM2 is regulated by presenilin 1. Exp Mol Med. 2017;49(12):e405. PMID: 29611543
20. Zheng H, Jia L, Liu CC, Rong Z, Zhong L, Yang L, Chen XF, Fryer JD, Wang X, Zhang YW, Xu H, Bu G*. TREM2 Promotes Microglial Survival by Activating Wnt/β-catenin Pathway. J Neurosci. 2017;37(7):1772-1784. PMID: 28077724
21. Zheng Q, Huang T, Zhang L, Zhou Y, Luo H, Xu H, Wang X*. Dysregulation of Ubiquitin-Proteasome System in Neurodegenerative Diseases. Front Aging Neurosci. 2016;8:303. PMID: 28018215
22. Wang X*, Zhou Y, Wang J, Tseng IC, Huang T, Zhao Y, Zheng Q, Gao Y, Luo H, Zhang X, Bu G, Hong W, Xu H*. SNX27 Deletion Causes Hydrocephalus by Impairing Ependymal Cell Differentiation and Ciliogenesis. J Neurosci. 2016;36(50):12586-12597. PMID: 27974614
23. Huang TY, Zhao Y, Li X, Wang X, Tseng IC, Thompson R, Tu S, Willnow TE, Zhang YW, Xu H*. SNX27 and SORLA Interact to Reduce Amyloidogenic Subcellular Distribution and Processing of Amyloid Precursor Protein. J Neurosci. 2016;36(30):7996-8011. PMID: 27466343
24. Zhang X, Hu J, Zhong L, Wang N, Yang L, Liu CC, Li H, Wang X, Zhou Y, Zhang Y, Xu H, Bu G*, Zhuang J*. Quercetin stabilizes apolipoprotein E and reduces brain Aβ levels in amyloid model mice. Neuropharmacology. 2016;108:179-192. PMID: 27114256
25. Zhao Y, Tseng IC, Heyser CJ, Rockenstein E, Mante M, Adame A, Zheng Q, Huang T, Wang X, Arslan PE, Chakrabarty P, Wu C, Bu G, Mobley WC, Zhang YW, St George-Hyslop P, Masliah E, Fraser P, Xu H*. Appoptosin-Mediated Caspase Cleavage of Tau Contributes to Progressive Supranuclear Palsy Pathogenesis. Neuron. 2015;87(5):963-75. PMID: 26335643
26. Aquizu N, Cantagrel V, Zaki M, Al-Gazali L, Wang X, et al. Biallelic mutations in SNX14 lead to a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction. Nat Genet. 2015;47(5):528-34. PMID: 25848753
27. Wang X, Huang T, Zhao Y, Thompson RC, Bu G, Zhang YW, Hong W, Xu H*. Sorting nexin 27 regulates Aβ production through modulating γ-secretase activity. Cell Rep. 2014;9(3):1023-33. PMID: 25437557
28. Wang X, Huang T, Bu G, Xu H*. Dysregulation of protein trafficking in neurodegeneration. Mol Neurodegener. 2014;9(1):31. PMID: 25152012
29. Wang X, Zhao Y, Zhang X, Badie H, Zhou Y, Mu Y, Loo LS, Cai L, Thompson RC, Yang B, Chen Y, Johnson PF, Wu C, Bu G, Mobley WC, Zhang D, Gage FH, Ranscht B, Zhang YW, Lipton SA, Hong W, Xu H*. Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction via modulation of glutamate receptor recycling in Down's syndrome. Nat Med. 2013;19(4):473-80. PMID: 23524343
30. Zhao Y, Wang Y, Yang J, Wang X, Zhao Y, Zhang X, Zhang YW*. Sorting nexin 12 interacts with BACE1 and regulates BACE1-mediated APP processing. Mol Neurodegener. 2012; 7(30). PMID: 22709416
31. Liu Y, Zhang YW, Wang X, Zhang H, You X, Liao FF, Xu H*. Intracellular trafficking of Presenilin 1 is regulated by β-amyloid precursor protein and phospholipase D1. J Biol Chem. 2009; 284(18):12145-52. PMID: 19276086
32. Nie H, Li Z, Lukas RJ, Shen Y, Song L, Wang X, Yin M*. Construction of SH-EP1-alpha4beta2-hAPP695 cell line and effects of nicotinic agonists on beta-amyloid in the cells. Cell Mol Neurobiol. 2008;28(1):103-12. PMID: 17912626
