长聘教轨副教授
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。
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。
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。
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 structure and inhibitor design of human IAPP (amylin) fibrils.” Nature Structural & Molecular Biology, 27:653-659 (2020)
Cao, Q., Shin, W. S., Chan, H., Vuong, C. K., Dubois, B., Li, B., Murray, K. A., Sawaya, M. R., Feigon, J., Black, D. L., Eisenberg, D. S., and Jiang, L., “Inhibiting amyloid-β cytotoxicity through its interaction with the cell surface receptor LilrB2 by structure-based design.” Nature Chemistry, 10: 1213–1221 (2018)
Guenther, E. L*., Cao, Q*., Trinh, H., Lu, J., Sawaya, M. R., Cascio, D., Boyer, D. R., Rodriguez, J. A., Hughes, M. P., and Eisenberg, D. S., “Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.” Nature Structural & Molecular Biology, 25: 463-471 (2018)
Cao, Q., Anderson, D.H., Liang, W., Chou, J., and Saelices, L., “The inhibition of cellular toxicity of amyloid-beta by dissociated transthyretin.” The Journal of Biological Chemistry, 295, 14015-14024 (2020)
Wang, X.-J., Cao, Q., Zhang, Y., and Su, X.-D., “Activation and Regulation of Caspase-6 and Its Role in Neurodegenerative Diseases.” Annual Review of Pharmacology and Toxicology, 55: 553–572 (2015)
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