曹骎

长聘教轨副教授

  • 电话:+86-021
  • 邮箱: caoqin@sjtu.edu.cn(招聘结构生物学、分子生物学方向博士后)
  • 地址:上海交通大学转化医学大楼E322
  • 课题组长,博士生导师。致力于使用冷冻电镜技术解析淀粉样纤维的分子结构,并基于结构设计抑制剂。代表性著作包括Nature (2022), Nat. Chem. (2018)、Nat. Struct. & Mol. Bio. (2018, 2019, 2020, 2021)等。

学术经历

  • 2019年9月-2021年4月:加州大学洛杉矶分校,助理研究员
  • 2013年9月-2019年9月:加州大学洛杉矶分校,博士后
  • 2008年9月-2013年7月:北京大学,生命科学院,生物化学与分子生物学,博士
  • 2004年9月-2008年7月:上海交通大学,生命科学与技术学院,生物工程系,学士

研究方向

基于冷冻电镜的淀粉样纤维结构解析

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。

基于结构的纤维化抑制剂设计

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与其天然受体相互作用的阿尔兹海默症诊疗药物研发

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。

代表论著

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    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)

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    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)

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    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)

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    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)

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    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)

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    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)

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    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)

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    Lu, J., Cao, Q., Hughes, M.P., Sawaya, M.R., Boyer, D.R., Cascio, D., and Eisenberg., D.S., “The cryo-EM structure of the fibril-forming low-complexity domain of hnRNPA2 reveals distinct differences from pathogenic amyloid and shows how mutation converts it to the pathogenic form.” Nature Communication, 11:4090 (2020)

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    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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    Cao, Q., Wang, X.-J., Li, L.-F., and Su, X.-D., “The regulatory mechanism of the caspase 6 pro-domain revealed by crystal structure and biochemical assays.” Acta Crystallographica Section D Biological Crystallography, 70: 58–67 (2014)