首都医学科学创新中心-卢珊

研究人员

卢珊

lushan@cimrbj.ac.cn

研究员

肌萎缩侧索硬化症、额颞叶痴呆症、帕金森疾病、

基因与细胞治疗、RNA结合蛋白相分离

lushan@cimrbj.ac.cn

南开大学生物科学学士

北京生命科学研究所生物化学与分子生物学博士

工作经历

2026至今

首都医学科学创新中心分子与细胞治疗研究所研究员

2022-2026

Altos Lab Inc 资深研究员

2017-2022

加州大学圣地亚哥分校博士后

研究方向

卢珊实验室致力于神经退行性疾病研究，研究范畴涵盖肌萎缩侧索硬化（ALS）、额颞叶痴呆（FTD）与帕金森病（PD）。本实验室旨在阐明各类神经退行性疾病的发病机制，研发新型治疗方案，并筛选可用于疾病诊断的生物标志物。实验室主要围绕以下三大方向开展研究：

1. 解析RNA结合蛋白异常聚集诱发神经退行性病变的分子机制；

2. 开发基于基因治疗与细胞治疗的神经退行性疾病干预手段；

3. 发掘新型生物标志物，服务疾病早期诊断与精准医疗。

主要成果与贡献

1. 构建可重现肌萎缩侧索硬化、额颞叶痴呆患者体内TDP-43病理特征的细胞模型（Neuron, 2019; Science, 2021）

2. 阐明调控TDP-43病理性聚集物形成的分子机制，筛选得到调控TDP-43液液相分离及蛋白毒性的关键调控因子（Nature Cell Biology, 2022; Nature Cell Biology, 2025）

3. 建立高灵敏度蛋白质组学分析技术，用于挖掘治疗靶点与疾病特异性生物标志物（Nature Methods, 2015; Biophysics Reports, 2018; Journal of Proteome Research, 2024）

代表性文章 *：共同第一作者; #：共同通讯作者

Lu, S^#., Zhang S., Oung S., Zhang K., Yates, J.R., and Cleveland, D.W^#. TDP-43 skein-like inclusions are formed by BAG3- and HSP70-guided co-aggregation with actin-binding proteins. Nature Cell Biology, 2025, 27: 1925–1937. DOI: 10.1038/s41556-025-01789-5

Lu, S., Hu, J. Aladesuyi, B., Goginashvili, A. Vazquez-Sanchez, S., Diedrich, J., Gu, J., Blum, J., Oung, S., Yu, H., Ravits, J., Liu, C., Yates, J.R., and Cleveland, D.W. Heat shock chaperone HSPB1 regulation of cytoplasmic TDP-43 de-mixing and liquid-to-gel transition. Nature Cell Biology, 2022, 24: 1378-1393. DOI: 10.1038/s41556-022-00988-8

Lu, S., Ye, Q., Singh, D., …, Villa, E., Cleveland, D. W., & Corbett, K. D. The SARS-CoV-2 Nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein. Nature Communications, 2021, 12: 1-15. DOI: 10.1038/s41467-020-20768-y

Gasset-Rosa, F.*, Lu, S.*, Yu, H. Y.*, Chen, C.*, Melamed, Z., Guo, L., Shorter, J., Da Cruz, S., Cleveland, D. W. Cytoplasmic TDP-43 de-mixing independent of stress granules drives inhibition of nuclear import, loss of nuclear TDP-43, and cell death. Neuron, 2019, 102: 339-357. DOI: 10.1016/j.neuron.2019.02.038

Yu, H., Lu, S., Gasior, K., Singh, D., Vazquez-Sanchez, S., Tapia, O., ... & Cleveland, D. W. HSP70 chaperones RNA-free TDP-43 into anisotropic intranuclear liquid spherical shells. Science, 2020, 371: eabb4309. DOI: 10.1126/science.abb4309

Lu, S., Fan, S.-B., Yang, B., Li, Y.-X., Meng, J.-M., Wu, L., Li, P., Zhang, K., Zhang, M.-J., and Fu, Y. Mapping native disulfide bonds at a proteome scale. Nature Methods, 2015, 12: 329-331. DOI: 10.1038/nmeth.3283

Lu, S., Cao, Y., Fan, S.B., Chen, Z.L., Fang, R.Q., He, S.M. and Dong, M.Q. Mapping disulfide bonds from sub-micrograms of purified proteins or micrograms of complex protein mixtures. Biophysics Reports, 2018, 4: 68-81. DOI: 10.1007/s41048-018-0050-6

Ye, J.-B., He, X.-N., Wang, S.-J., Dong, M.-Q., Feng, W., Lu, S.^#, and Feng, F.-L.^# Test-time training for deep MS/MS spectrum prediction improves peptide identification. Journal of Proteome Research, 2024, 23: 550-559. DOI: 10.1021/acs.jproteome.3c00229

Zhu, X., Lu, J., Hu, X., Jin, T., Lu, S., & Feng, F. Hierarchical progressive learning for zero-shot peptide-HLA binding prediction and automated antigenic peptide design. Cell Reports, 2025, 44: 115763. DOI: 10.1016/j.celrep.2025.115763

Wu, J., Yan, Z., Li, Z., Qian, X., Lu, S., Dong, M., Zhou, Q., and Yan, N. Structure of the voltage-gated calcium channel Cav1. 1 at 3.6 Å resolution. Nature, 2016, 537: 191–196. DOI: 10.1038/nature19321