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。

2020

1. 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 In press.

2. 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 Apr 13. pii: jbc.RA119.012284. doi: 10.1074/jbc.RA119.012284. [Epub ahead of print]

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

2019

8. Jia, C., Ma, X., Liu, Z., Gu, J., Zhang, X., Li, D.#, Zhang, S.#, Different heat shock proteins bind α-synuclein with distinct mechanisms and synergistically prevent its amyloid aggregation. Frontiers in Neuroscience, 2019 November 1, volume 13, doi: 10.3389/fnins.2019.01124

9. 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.

10. Lu, J., Cao, Q., Wang, C., Zheng, J., Luo, F., Xie, J., Li, Y., Ma, X., He, L., Eisenberg, D., Nowick, J., Jiang, L.#, Li, D.#, Structure-Based Peptide Inhibitor Design of Amyloid-b Aggregation, Frontiers in Molecular Neuroscience, 2019 Mar 4;12:54.

2018

11. 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.

12. Li, D.#, Liu, C.#. Better together: a hybrid amyloid signals necroptosis. Cell 2018 Volume 173, Issue 5, p1068–1070, 17 May.

13. 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

#并列通讯作者

神经退行性疾病的诊断、治疗药物开发

(1) Jiang Bian*; Yi-qi Liu*; et al; Discovery of styrylaniline derivatives as novel alpha-synuclein aggregates ligands, European Journal of Medicinal Chemistry, 2021, 226(113887)

(2) Jiang Bian; Lihui Zhang; et al; Histone Deacetylase Inhibitors: Potent Anti-Leukemic Agents, Current Medicinal Chemistry, 2015.春季, 22(17): 2065-2074

(3) Yanfei Chen*; Jiang Bian*; et al; Design, Synthesis and Identification of N, N-Dibenzylcinnamamide(DBC) Derivatives as Novel Ligands for α-synuclein Fibrils by SPR Evaluation System, Bioorganic & Medicinal Chemistry, 2020, 28(7)(115358)

(4) Shenqing Zhang*; Hui Dong*; Jiang Bian*; Dan Li; Cong Liu; Targeting amyloid proteins for clinical diagnosis of neurodegenerative diseases, Fundamental Research, 2023(3): 505-519

(5) Chenyang Qiu*; Ruonan Wei*; Jiang Bian*; Xin Lin; Tengfei Bai; Jie He; Xiaomin Guo; YongChu; Novel 4-triazole phenyl amide (4-TPA) molecules: Potent promoters of α-synuclein fibril disassembly, European Journal of Medicinal Chemistry, 2024, 273(5)