基本信息

洪伟  男  博导  中国科学院深圳先进技术研究院
电子邮件: wei.hong@siat.ac.cn
通信地址: 广东省深圳市南山区学苑大道1068号
邮政编码: 518055

研究领域

       蛋白质错误折叠或异常聚集与阿尔茨海默病、帕金森病等神经退行性疾病的发生密切相关,调节这些蛋白质在体内的平衡状态、抑制其异常聚集或中和其神经毒性是一种潜在的干预策略,深入理解这类蛋白质的异常聚集机制及其上下游信号通路在神经退行性病变中的作用,对于疾病发生机理的解析和新靶点的发现均具有重要意义。本课题组将基础研究与临床资源相结合,综合运用分子细胞生物学、蛋白质与多肽生物化学、诱导多能干细胞、神经电生理、动物行为学、病理学等技术方法,开展阿尔茨海默病等神经退行性疾病的分子机制、模型和诊疗策略研究。主要研究方向包括:

(1)疾病机制:解析自组装效应诱导Aβ二聚体生成的多肽生物学机制以及中枢免疫细胞介导的Aβ异常聚集机制,明确其在阿尔茨海默病中的作用;

(2)研究模型:利用患者脑源Aβ建立诱导性的阿尔茨海默病细胞、小鼠和非人灵长类动物模型,利用多种组学方法挖掘疾病早期的分子靶点;

(3)诊疗技术:开发靶向病理性Aβ的高亲和力纳米抗体和多肽药物,研究物理刺激与药物联用干预阿尔茨海默病的功能与机制,并开发新型的生物标志物检测技术。

招生招聘

招生专业
071006-神经生物学
071010-生物化学与分子生物学
071009-细胞生物学
招生方向
神经退行性疾病的分子病理学机制与诊疗策略
招聘信息
课题组长期招聘博士后,包括但不限于神经生物学、生物化学、分子细胞生物学、药学和医学等专业背景。

教育背景

2009-09--2014-06   武汉大学   博士
2005-09--2009-06   武汉大学   学士

工作经历


工作简历
2019-11~现在, 中国科学院深圳先进技术研究院, 副研究员
2014-11~2019-10,哈佛大学医学院, 博士后
社会兼职
2022-11-20-今,中国医促会认知障碍分会, 委员
2022-07-13-今,深圳市脑科学学会, 监事

奖励信息

2022 广东省**青年拔尖人才

2021 中国科学院**计划

2020 深圳市海外高层次人才

发表论文

  1. Lv Z, Chen L, Chen P, Peng H, Rong Y, Hong W, Zhou Q, Li N, Li B, Paolicelli RC, Zhan Y. Clearance of β-amyloid and synapses by the optogenetic depolarization of microglia is complement selective. Neuron 2024, 112:740-754

  2. Hong W, Liu W, Desousa AO, Young-Pearse T, Walsh DM. Methods for the isolation and analysis of Aβ from postmortem brain. Front Neurosci 2023, 17:1108715.

  3. Liu Q, Telezhkin V, Jiang W, Gu Y, Wang Y, Hong W, Tian W, Yarova P, Zhang G, Lee SM, Zhang P, Zhao M, Allen ND, Hirsch E, Penninger J, Song B. Electric field stimulation boosts neuronal differentiation of neural stem cells for spinal cord injury treatment via PI3K/Akt/GSK-3β/ β-catenin activation. Cell Biosci 2023, 13:4.

  4. Wang Z#, Jin M#, Hong W#, Liu W, Reczek D, Lagomarsino VN, Hu Y, Weeden T, Frosch MP, Young-Pearse TL, Pradier L, Selkoe D*, Walsh DM*. Learnings about Aβ from human brain recommend the use of a live-neuron bioassay for the discovery of next generation Alzheimer's disease immunotherapeutics. Acta Neuropathol Commun 2023, 11:39.

  5. Ahn EH, Lei K, Kang SS, Wang Z, Liu X, Hong W, Wang YT, Edgington-Mitchell LE, Jin L, Ye K. Mitochondrial dysfunction triggers the pathogenesis of Parkinson's disease in neuronal C/EBPβ transgenic mice. Molecular Psychiatry. 2021, 26:7838-7850.

  6. Corbett GT, Wang Z, Hong W, Colom-Cadena M, Rose J, Liao M, Asfaw A, Hall TC, Ding L, DeSousa A, Frosch MP, Collinge J, Harris DA, Perkinton MS, Spires-Jones TL, Young-Pearse TL, Billinton A, Walsh DM. PrP is a central player in toxicity mediated by soluble aggregates of neurodegeneration-causing proteins. Acta Neuropathologica. 2020, 139:503–526.

  7. Li S, Sunchen S, He D, Qin C, Zuo Z, Shen B, Cao Z, Hong W*, Miao L*. ImKTx96, a peptide blocker of the Kv1.2 ion channel from the venom of the scorpion Isometrus maculates. Peptides. 2020, 123:170172.

  8. Zott B, Simon MM, Hong W, Unger F, Chen-Engerer HJ, Frosch MP, Sakmann B, Walsh DM, Konnerth A. A vicious cycle of β amyloid-dependent neuronal hyperactivation. Science. 2019, 365:559-565.

  9. Brinkmalm G#Hong W#, Wang Z, Liu W, O'Malley TT, Sun X, Frosch MP, Selkoe DJ, Portelius E, Zetterberg H, Blennow K, Walsh DM. Identification of neurotoxic cross-linked amyloid-β dimers in the Alzheimer's brain. Brain. 2019, 142:1441-1457.

  10. Mengel D, Hong W, Corbett GT, Liu W, DeSousa A, Solforosi L, Fang C, Frosch MP, Collinge J, Harris DA, Walsh DM. PrP-grafted antibodies bind certain amyloid β-protein aggregates, but do not prevent toxicity. Brain Research. 2019, 1710:125-135.

  11. Hong W, Wang Z, Liu W, O'Malley TT, Jin M, Willem M, Haass C, Frosch MP, Walsh DM. Diffusible, highly bioactive oligomers represent a critical minority of soluble Aβ in Alzheimer's disease brain. Acta Neuropathologica. 2018, 136:19-40.

  12. Jin M#, O'Nuallain B#Hong W, Boyd J, Lagomarsino VN, O'Malley TT, Liu W, Vanderburg CR, Frosch MP, Young-Pearse T, Selkoe DJ*, Walsh DM*. An in vitro paradigm to assess potential anti-Aβ antibodies for Alzheimer's disease. Nature Communications. 2018, 9:2676.

  13. Zeng Z#, Zhang R#Hong W#, Cheng Y, Wang H, Lang Y, Ji Z, Wu Y, Li W, Xie Y*, Cao Z*. Histidine-rich Modification of a Scorpion-derived Peptide Improves Bioavailability and Inhibitory Activity against HSV-1. Theranostics. 2018, 8:199-211.

  14. Ondrejcak T, Klyubin I, Corbett GT, Fraser G, Hong W, Mably AJ, Gardener M, Hammersley J, Perkinton MS, Billinton A, Walsh DM, Rowan MJ. Cellular Prion Protein Mediates the Disruption of Hippocampal Synaptic Plasticity by Soluble Tau In Vivo. J Neurosci. 2018, 38:10595-10606.

  15. Wang Z, Jackson RJ, Hong W, Taylor WM, Corbett GT, Moreno A, Liu W, Li S, Frosch MP, Slutsky I, Young-Pearse TL, Spires-Jones TL, Walsh DM. Human Brain-Derived Aβ Oligomers Bind to Synapses and Disrupt Synaptic Activity in a Manner That Requires APP. J Neurosci. 2017, 37:11947-11966.

  16. Zeng Z#, Han S#Hong W, Lang Y, Li F, Liu Y, Li Z, Wu Y, Li W, Zhang X*, Cao Z*. A Tat-conjugated Peptide Nucleic Acid Tat-PNA-DR Inhibits Hepatitis B Virus Replication In Vitro and In Vivo by Targeting LTR Direct Repeats of HBV RNA. Mol Ther Nucleic Acids. 2016, 5:e295.

  17. Zeng Z, Zhang Q, Hong W, Xie Y, Liu Y, Li W, Wu Y, Cao Z. A Scorpion Defensin BmKDfsin4 Inhibits Hepatitis B Virus Replication in Vitro. Toxins (Basel). 2016, 8.

  18. Hong W#, Lang Y#, Li T, Zeng Z, Song Y, Wu Y, Li W, Cao Z. A p7 Ion Channel-derived Peptide Inhibits Hepatitis C Virus Infection in Vitro. J Biol Chem. 2015, 290:23254-63.

  19. Han SS, Li ZY, Zhu JY, Han K, Zeng ZY, Hong W, Li WX, Jia HZ, Liu Y, Zhuo RX, Zhang XZ. Dual-pH Sensitive Charge-Reversal Polypeptide Micelles for Tumor-Triggered Targeting Uptake and Nuclear Drug Delivery. Small. 2015, 11:2543-54.

  20. Hong W, Li T, Song Y, Zhang R, Zeng Z, Han S, Zhang X, Wu Y, Li W, Cao Z. Inhibitory activity and mechanism of two scorpion venom peptides against herpes simplex virus type 1. Antiviral Research. 2014, 102:1-10.

  21. Song Y, Gong K, Yan H, Hong W, Wang L, Wu Y, Li W*, Li W*, Cao Z*. Sj7170, a unique dual-function peptide with a specific alpha-chymotrypsin inhibitory activity and a potent tumor-activating effect from scorpion venom. J Biol Chem. 2014, 289:11667-80.

  22. Hong W, Zhang R, Di Z, He Y, Zhao Z, Hu J, Wu Y, Li W, Cao Z. Design of histidine-rich peptides with enhanced bioavailability and inhibitory activity against hepatitis C virus. Biomaterials. 2013, 34:3511-22.

  23. Cao Z#, Yu Y#, Wu Y#, Hao P#, Di Z#, He Y#, Chen Z, Yang W, Shen Z, He X, Sheng J, Xu X, Pan B, Feng J, Yang X, Hong W, Zhao W, Li Z, Huang K, Li T, Kong Y, Liu H, Jiang D, Zhang B, Hu J, Hu Y, Wang B, Dai J, Yuan B, Feng Y, Huang W, Xing X, Zhao G, Li X*, Li Y*, Li W*. The genome of Mesobuthus martensii reveals a unique adaptation model of arthropods. Nature Communications. 2013, 4:2602.

  24. He Y#, Zhao R#, Di Z, Li Z, Xu X, Hong W, Wu Y, Zhao H, Li W, Cao Z. Molecular diversity of Chaerilidae venom peptides reveals the dynamic evolution of scorpion venom components from Buthidae to non-Buthidae. J Proteomics. 2013, 89:1-14.

  25. Zhao Z, Hong W, Zeng Z, Wu Y, Hu K, Tian X, Li W*, Cao Z*. Mucroporin-M1 inhibits hepatitis B virus replication by activating the mitogen-activated protein kinase (MAPK) pathway and down-regulating HNF4alpha in vitro and in vivo. J Biol Chem. 2012, 287:30181-90.

  26. Li Q#, Zhao Z#, Zhou D, Chen Y, Hong W, Cao L, Yang J, Zhang Y, Shi W, Cao Z, Wu Y, Yan H*, Li W*. Virucidal activity of a scorpion venom peptide variant mucroporin-M1 against measles, SARS-CoV and influenza H5N1 viruses. Peptides. 2011, 32:1518-25.

  27. Yan R#, Zhao Z#, He Y, Wu L, Cai D, Hong W, Wu Y, Cao Z*, Zheng C*, Li W*. A new natural alpha-helical peptide from the venom of the scorpion Heterometrus petersii kills HCV. Peptides. 2011, 32:11-9. 

科研活动


科研项目
( 1 ) 非人灵长类动物模型分析, 负责人, 企业委托, 2020-05--2020-12
( 2 ) 基于人源神经毒性Aβ二聚体的阿尔茨海默症诊疗策略研究, 负责人, 地方任务, 2021-01--2023-12
( 3 ) 基2020N382 基于人源诱导性多能干细胞的阿尔茨海默症机制和修复策略研究, 负责人, 地方任务, 2020-11--2023-11
( 4 ) 光敏修饰抗肿瘤药物联合纳米载体在胶质母细胞瘤治疗中的应用, 负责人, 地方任务, 2021-06--2023-06
( 5 ) 阿尔茨海默病分子机制与诊疗策略, 负责人, 中国科学院计划, 2022-01--2024-12
( 6 ) 靶向神经毒性Aβ二聚体的构象特异性抗体干预阿尔茨海默病的功能与机制研究, 负责人, 国家任务, 2022-01--2024-12
( 7 ) 基20220289 阿尔茨海默病早期分子靶标及其新作用机制研究, 负责人, 地方任务, 2023-02--2026-02
( 8 ) 帕金森病新型靶向多肽药物研发, 参与, 地方任务, 2022-10--2027-09
( 9 ) 深圳市神经系统疾病免疫机制与干预重点实验室, 参与, 地方任务, 2023-03--2025-03
参与会议
(1)Identification of neurotoxic cross-linked Aβ heterodimers in Alzheimer's disease brain   第48届神经科学学会年会(SFN)   2018-11-07
(2)Diffusible Alzheimer’s disease brain-derived Aβ disrupts synaptic plasticity   第47届神经科学学会年会(SFN)   2017-11-15

专利申请

  1. 罗显钖,洪伟,陶敏;一种表达人源Tau 的神经元及其制备方法和应用;2024-03-27,中国,申请号:202410360296.1

  2. 罗显钖,洪伟,李思瑶,陈瑞香,郭丽萍;一种携带钙离子报告基因的神经元及其制备方法和应用;2024-02-20,中国,申请号:202410188197.X

  3. 祝茜茜,洪伟,郭丽萍,刘琰,刘倩敏;一种靶向β-淀粉样蛋白的纳米抗体及其用途;2023-12-29,中国,申请号:202311866452.3

  4. 陈平,洪伟,陶敏,陈瑞香,郭丽萍;一种Aβ 单体的制备及质量控制方法;2023-12-20,中国;申请号:202311762568.2

  5. 洪伟,陈平,陶敏,陈瑞香,刘琰 ; 一种神经毒性β-淀粉样蛋白二聚体及其制备方法与应用,2022-11-11,中国,申请号:202211410313.5

  6. 陈平,洪伟,陈爽;一种快速构建sandwich ELISA的方法,2021-12-28,中国,申请号:202111632558.8

  7. 陈爽,洪伟,陈平,罗显钖;一种β-淀粉样蛋白聚合物的制备方法及其产品和应用,2021-12-13,中国,申请号:202111520894.3

  8. 陈平,洪伟,陈爽,祝茜茜;一种利用亲和层析介质富集抗体的方法及其应用,2021-12-10,中国,申请号:202111509636.5

  9. 洪伟,陈爽,陈平,祝茜茜;一种纳米抗体及其制备方法和应用,2021-12-10,中国,申请号:202111509637.X

  10. 洪伟,陈爽,陈平;一种脑组织可溶性β-淀粉样蛋白样品的制备方法及其应用,2020-12-17,中国,申请号:202011496460.X.

  11. 陈爽,洪伟,陈平;一种工程化神经细胞及其制备方法和应用,2020-12-17,中国,申请号:202011496075.5

指导学生

现指导学生

罗显钖  硕士研究生  086000-生物与医药  

刘琰  硕士研究生  086000-生物与医药