“永新”青年学者、长聘教轨副教授
基于Aβ在阿尔兹海默症发病过程中可能扮演的重要角色，以及已报道的Aβ在神经细胞表面的天然受体LilrB2，开发阿尔兹海默症的早期诊疗药物。
基于已解析的纤维结构，通过设计可结合于纤维表面的小分子，以达到抑制蛋白纤维化的目的。设计出的抑制剂将在体外和细胞层面进行验证，这些抑制剂的成功设计将有助于相关疾病的药物研发。
通过使用冷冻电镜螺旋重构的方法解析与疾病相关的淀粉样纤维（一种蛋白质聚集形式）的近原子分辨率结构，从而探究其形成纤维的分子机理，以及研究这些蛋白的纤维化在相关疾病发病过程中所扮演的角色。
Cheng, Y., Kreutzberger, M., Han, J., Egelman, E#., and Cao, Q#. Molecular architecture of the assembly of Bacillus spore coat protein GerQ revealed by cryo-EM. Nat Commun 15, 8091 (2024).
Cheng, Y., Han, J., Song, M., Zhang S., Cao, Q#. Serine peptidase Vpr forms enzymatically active fibrils outside Bacillus bacteria revealed by cryo-EM. Nat Commun 14, 7503 (2023).
Jiang, Y. X*., Cao, Q*., Sawaya, M. R., Abskharon, R., Ge, P., DeTure, M., Dickson, D. W., Fu, J. Y., Loo, R. R. O., Loo, J. A., and Eisenberg, D. S., “Amyloid fibrils in disease FTLD-TDP are composed of TMEM106B not TDP-43” Nature, 605:304–309 (2022)
Cao, Q., Boyer, D. R., Sawaya, M. R., Abskharon, R., Saelices, L., Nguyen, B.A., Lu J., Murry, K.A., Kandeel, F., and Eisenberg, D.S., “Cryo-EM structures of hIAPP fibrils seeded by patient-extracted fibrils reveal new polymorphs and conserved fibril cores” Nature Structural & Molecular Biology, 28:724-730 (2021)
Cao, Q*., Boyer, D. R*., Sawaya, M. R., Ge, P., and Eisenberg, D.S., “Cryo-EM structures of four polymorphic TDP-43 amyloid cores.” Nature Structural & Molecular Biology, 26: 619-627 (2019)
Han, J., Song, M., Cheng, Y., Gong, W., Zhang, F#., and Cao, Q#., “Structure of human glycoprotein 2 reveals mechanisms underlying filament formation and adaption to proteolytic environment in the digestive tract” PLOS Biology (epub ahead of print)
Jiang, Y., Peña-Díaz, S#., Zhang, Z., Daugberg, A. O. H., Hemnández, M. L., Nielsen, J., Huang. Q., Qin, S., Dueholm, M. K. D., Dong, M., Pederen, J. S., Cao, Q#., Otzen, D#., and Wang, H#., “Natural design of a stabilized cross-β fold: Structure of the FuA FapC from Pseudomonas sp. UK4 reveals a critical role for stacking of imperfect repeats” Advanced Materials, 37, 250503 (2025)
Song, M., Han, J., and Cao, Q#., “Cryo-EM structure of amyloid fibrils formed by full-length human αA-crystallin with pathogenic mutation R116C” Communications Chemistry, 8, 233 (2025)
论文下载
支撑材料