神经退行性疾病中的蛋白质异常聚集传播机制和干预策略

洪伟，博士，副研究员，博士生导师，入选中国科学院百人计划，广东省珠江青年拔尖人才，深圳市海外高层次人才。实验室主要利用人源诱导多能干细胞、跨物种动物模型和临床样本，研究阿尔茨海默病等神经退行性疾病的蛋白质异常聚集和传播机制，开发靶向性的抗体药物和递送策略。已发表SCI论文33篇，其中第一或通讯作者（含并列）15篇，包括Acta neuropathologica、Brain、Alzheimer's Research & Therapy、Biomaterials等，被引用2800余次，H指数21。主持国家自然科学基金、中国科学院和省市级项目9项。

学习经历

2009-09至2014-06，武汉大学，生命科学学院，微生物学，博士

2005-09至2009-06，武汉大学，生命科学学院，生命科学与技术基地班，本科

工作经历

2019-11至今，中国科学院深圳先进技术研究院，脑认知与脑疾病研究所，副研究员

2014-11至2019-10，哈佛大学医学院，博士后

国际影响力

国际大会报告：

(1) 2017-11，Diffusible Alzheimer’s disease brain-derived Aβ disrupts synaptic plasticity; The 47th Annual Meeting of the Society for Neuroscience, Washington DC, USA. Oral presentation

(2) 2018-11，Identification of neurotoxic cross-linked Aβ heterodimers in Alzheimer's disease brain; The 48th Annual Meeting of the Society for Neuroscience, San Diego, CA, USA. Oral presentation

所获荣誉

2022 广东省重点人才计划

2021 中国科学院重点人才计划

2020 深圳市海外高层次人才

科研成果

主持项目：

(1) 国家自然科学基金面上项目，32471010，Aβ慢性自组装诱导神经毒性二聚体生成的机制及其在阿尔茨海默病中的作用研究，2025-01至2028-12，51万元，在研，主持

(2) 国家自然科学基金青年项目，32100800，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，2022-01至2024-12，30万元，结题，主持

(3) 深圳市基础研究重点项目，JCYJ20220818100802005，阿尔茨海默病早期分子靶标及其新作用机制研究，2023-02至2026-02，200万元，在研，主持

(4) 中国科学院青年人才项目，阿尔茨海默病分子机制与诊疗策略，2022-01至2024-12，400万元，结题，主持

(5) 广东省自然科学基金面上项目，2021A1515010861，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，2021-01至2023-12，10万元，结题，主持

(6) 深圳市基础研究重点项目，JCYJ20200109115631248，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，2020-11至2023-11，250万元，结题，主持

(7) 深圳市国际合作研究项目，GJHZ20200731095205016，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，2021-06至2023-06，50万元，结题，主持

1. Chen P^#, Li J^#, Telezhkin V^#, Gu Y, Tao M, Guo L, Song S, Dong R, Luo X, Wang Y, Liu Q, Tian W, Meng W^*, Hong W^*, Song B^*. Pulsed electromagnetic stimulation promotes neuronal maturation by up-regulating cholesterol biosynthesis. Stem Cell Research & Therapy 2025, 16:406.

2. Song S^#, Liu Q^#, Huang X, Chen P, Tao M, Pei X, Wang H, Han Y, Chen J, Hong W^*, Zhang Z^*. Long-term electroacupuncture and repetitive transcranial magnetic stimulation differentially slow the progression of Alzheimer's disease in AppNL-G-F mice. Alzheimer's Research & Therapy 2025, 17:140

3. Song S^#, Liu Q^#, Chen R, Chen P, Tao M, Li S, Guo L, Zhu X, Liu Y, Liu L, Sasaguri H, Saito T, Saido TC, Walsh DM, Zhang Z^*, Hong W^*. Experimental evidence that readily diffusible forms of Aβ from Alzheimer's disease brain have seeding activity. Acta Neuropathologica Communications 2025, 13:112.

4. Liu Q, Song S, Liu L^*, Hong W^*. In vivo seeding of amyloid-β protein and implications in modeling Alzheimer’s disease pathology. Biomolecules 2025, 15: 571.

5. He Z#, Zhang W^#, Chen P, Li S, Tao M, Yue F, Hong W^*, Feng S^*, Jing N^*. Amyloid-beta oligomers drive amyloid deposit and cascaded tau pathology of Alzheimer's disease in aged brains of non-human primates. Journal of Genetics and Genomics 2025. Online ahead of print.

6. Li S^#, Liu Y^#, Luo X, Hong W. Systematic Evaluation of Extracellular Coating Matrix on the Differentiation of Human-Induced Pluripotent Stem Cells to Cortical Neurons. International Journal of Molecular Sciences 2025, 26:230.

7. 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.

8. 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 Neuropathologica Communications 2023, 11:39.

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. 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.

11. 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.

12. 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.

13. 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.

14. 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.