李丹 - 上海交通大学

个人简介

博士，上海交通大学特别研究员，课题组长，博士生导师学士 (1998-2002) 吉林大学博士 (2002-2008) 北京大学博士后(2008-2013) 加州大学洛杉矶分校(UCLA)/霍华德休斯医学院博士后

研究领域

李丹博士聚焦蛋白相分离和相变，开发基于冷冻电镜的电子衍射、螺旋纤维成像、in-cell核磁等前沿技术，研究蛋白分相正常生理功能的原子分子基础，及蛋白淀粉样相变导致神经退行性疾病的原子分子基础。蛋白相分离和相变、神经退行性疾病方向1: 综合运用多种生物物理、生物化学和细胞生物学手段，研究生理和病理条件下的蛋白质相分离和无膜细胞器的组装与调控。方向2: 研究神经退行性疾病，如阿尔兹海默症(AD)、帕金森症(PD)、渐冻人症(ALS)等，蛋白异常相变聚集的发生和致病机理。发展运用冷冻电镜电子衍射、螺旋纤维三维重构技术，解析蛋白淀粉样聚集纤维原子结构，阐释聚集体致病的分子机理, 开发相关疾病的治疗药物和临床诊断标记物。

近期论文

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Long H.F., Zhang S.N., Zeng S.Y., Tong Y.L., Liu J., Liu C.*, Li D.* Interaction of RAGE with α-synuclein fibrils mediates inflammatory response of microglia.Cell Rep, 2022 Sep 20;40(12):111401. Zhang S.N., Zhu Y., Lu J.X., Liu Z.Y., Lobato A.G., Zeng W., Liu J.Q., Zeng S.Y., Liu C., Liu J., He Z.H., Zhai R.G.*, Li D.* Specific binding of Hsp27 and phosphorylated Tau mitigates abnormal Tau aggregation-induced pathology. Elife. 2022 Sep 1;11:e79898 Tao Y.Q., Sun Y.P., Lv S.R., Xia W.C., Zhao K., Xu Q.H., Zhao Q.Y., He L., Wang Y., Liu C.*, Li D.* Heparin induces α-synuclein to form new fibril polymorphs with attenuated neuropathology. Nat Commun. 2022 Jul 22;13(1):4226. Zhao Q, Tao Y, Zhao K, Ma Y, Xu Q, Liu C, Zhang S, Li D. Structural Insights of Fe3+ Induced α-synuclein Fibrillation in Parkinson's Disease. J Mol Biol. 2022 Jun 8:167680. doi: 10.1016/j.jmb.2022.167680. Online ahead of print. Li D*, Liu C.* Conformational strains of pathogenic amyloid proteins in neurodegenerative diseases. Nat Rev Neurosci. 2022 May 30. doi: 10.1038/s41583-022-00603-7. Online ahead of print. Li Y, Lu S, Gu J, Xia W, Zhang S, Zhang S, Wang Y, Zhang C, Sun Y, Lei J, Liu C, Su Z*, Yang J*, Peng X*, Li D.* SARS-CoV-2 impairs the disassembly of stress granules and promotes ALS-associated amyloid aggregation. Protein & Cell. 2022 Aug;13(8):602-614. doi: 10.1007/s13238-022-00905-7. Epub 2022 Apr 6. Fan Y, Zhao Q, Xia W, Tao Y, Yu W, Chen M, Liu Y, Zhao J, Shen Y, Sun Y, Si C, Zhang S, Zhang Y, Li W, Liu C, Wang J*, Li D*. Generic amyloid fibrillation of TMEM106B in patient with Parkinson's disease dementia and normal elders. Cell Res. 2022 Jun;32(6):585-588. doi: 10.1038/s41422-022-00665-3. Epub 2022 Apr 27. Huang C, Lu J, Ma X, Qiang J, Wang C, Liu C, Fang Y, Zhang Y, Jiang L, Li D*, Zhang S.* The mouse nicotinamide mononucleotide adenylyltransferase chaperones diverse pathological amyloid client proteins. J Biol Chem. 2022 May;298(5):101912. doi: 10.1016/j.jbc.2022.101912. Epub 2022 Apr 7. Li Y, Gu J, Wang C, Hu J, Zhang S, Liu C, Zhang S, Fang Y, Li D. Hsp70 exhibits a liquid-liquid phase separation ability and chaperones condensed FUS against amyloid aggregation. iScience. 2022 May 5;25(6):104356. doi: 10.1016/j.isci.2022.104356. eCollection 2022 Jun 17. Li, Y., Gu, J., Liu, C.*, Li, D.* A high-throughput method for exploring the parameter space of protein liquid-liquid phase separation, Cell Reports Physical Science, Volume 3, Issue 3, 16 March 2022, 100764 D. Li* and C. Liu*, Spatiotemporal dynamic regulation of membraneless organelles by chaperone networks, Trends in Cell Biology, 2022 Jan;32(1):1-3 Dan Li* and Cong Liu*, Hierarchical chemical determination of amyloid polymorphs in neurodegenerative disease, Nature Chemical Biology, 2021 Mar;17(3):237-245doi: 10.1038/s41589-020-00708-z Yunpeng Sun#, Kun Zhao#, Wencheng Xia, Jinge Gu, Yeyang Ma, Xinrui Gui, Xia Zhang, Yanshan Fang, Bo Sun, Cong Liu*, Dan Li* The nuclear localization sequence mediates hnRNPA1 amyloid fibril formation revealed by cryoEM structure, Nature Communications, 2020, Dec 11;11(1):6349. doi: 10.1038/s41467-020-20227-8. Jinge Gu , Zhenying Liu , Shengnan Zhang , Yichen Li , Wencheng Xia , Chen Wang , Huaijiang Xiang , Zhijun Liu , Li Tan , Yanshan Fang , Cong Liu* , Dan Li*, Hsp40 proteins phase separate to chaperone the assembly and maintenance of membraneless organelles, PNAS, 2020, Dec 8;117(49):31123-31133 doi: 10.1073/pnas.2002437117. Zhao, K. , Li, Y., Liu, Z., Long, H., Zhao, C., Luo, F., Sun, Y., Tao, Y., Su, X.-D., Li, D.*, Li, X.*, Liu, C.*, Parkinson’s disease associated mutation E46K of α-synuclein triggers the formation of a distinct fibril structure. Nature Communications, 2020 May 26;11(1):2643. Lu J, Zhang S, Ma X, Jia C, Liu Z, Huang C, Liu C*, Li D.* Structural basis of the interplay between α-synuclein and Tau in regulating pathological amyloid aggregation. J. Biol. Chem. 2020 May 22;295(21):7470-7480. doi: 10.1074/jbc.RA119.012284. Ma X, Zhu Y, Lu J, Xie J, Li C, Shin WS, Qiang J, Liu J, Dou S, Xiao Y, Wang C, Jia C, Long H, Yang J, Fang Y, Jiang L, Zhang Y, Zhang S, Zhai RG*, Liu C*, Li D* Nicotinamide mononucleotide adenylyltransferase uses its NAD+ substrate-binding site to chaperone phosphorylated Tau. Elife. 2020 Apr 6;9. pii: e51859. doi: 10.7554/eLife.51859. Sun, Y., Hou, S., Zhao, K., Long, H., Liu, Z., Gao, J., Zhang, Y., Su, X. D., Li, D.*, Liu, C.*. Cryo-EM structure of full-length α-synuclein amyloid fibril with Parkinson’s disease familial A53T mutation, Cell Research, 2020 Apr;30(4):360-362. doi: 10.1038/s41422-020-0299-4. Liu, Z., Zhang S., Gu, J., Tong, Y., Li, Y., Gui, X., Long, H., Wang, C., Zhao, C., Lu, J., Lin, H., Li, Y., Liu, Z., Li, D.*, Liu, C.*, Hsp27 chaperones FUS phase separation under the modulation of stress-induced phosphorylation. Nature Structural and Molecular Biology. 2020 Apr;27(4):363-372. doi: 10.1038/s41594-020-0399-3. Wang, C., Tu, J., Zhang, S., Cai, B., Liu, Z., Hou, S., Zhong, Q., Hu, X., Liu, W., Li, G., Liu, Z., He, L., Diao, J., Zhu, Z. J., Li, D.*, Liu, C.*, Different regions of synaptic vesicle membrane regulate VAMP2 conformation for the SNARE assembly. Nature Communications. 2020 Mar 24;11(1):1531. doi: 10.1038/s41467-020-15270-4. Li, D.*, Liu, C.*, Structural Diversity of Amyloid Fibrils and Advances in Their Structure Determination. Biochemistry, 2020 Feb 11;59(5):639-646. doi: 10.1021/acs.biochem.9b01069. Gui, X., Luo, F., Li, YC, Zhou, H., Qin, Z., Liu, ZY, Gu, JG, Xie, MY, Zhao, K., Dai, B., Shin, WS, He, JH, He, L., Jiang, L., Zhao, ML, Sun, B., Li, XM, Liu, C.*, Li, D.* Structural basis for reversible amyloids of hnRNPA1 elucidates their role in stress granule assembly, Nature Communications, 2019 May 1;10(1):2006. Li, Y., Zhao, C., Luo, F., Liu, Z., Gui, X., Luo, Z., Zhang, X., Li, D.*, Liu, C.*, Li, X.* Amyloid fibril structure of alpha-synuclein determined by cryo-electron microscopy. Cell Research 2018 Sep;28(9):897-903. Li, D.*, Liu, C.* Better together: a hybrid amyloid signals necroptosis. Cell 2018 Volume 173, Issue 5, p1068–1070, 17 May. Luo, F., Gui, X., Zhou, H., Gu, J., Li, Y., Liu, X., Zhao, M., Li, D.*, Li, X.*, Liu, C.*. Atomic structures of FUS LC domain segments reveal bases for reversible amyloid fibril formation. Nature Struct. Mol. Biol. 2018 Apr;25(4):341-346