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个人简介

张凯华,博士生导师,脑科学转化研究院青年研究员,附属中山医院双聘研究员。2016年毕业于中国科学院上海药物研究所获博士学位,师从赵强研究员和吴蓓丽研究员。同年8月进入美国加州大学旧金山分校开展博士后课题研究,受到美国院士Yifan Cheng和诺贝尔奖获得者David Julius的联合指导。2022年8月加入复旦大学,主要从事生物大分子结构与信号转导及神经炎症调控的研究。学术成果以第一作者(含共同)发表在Cell、Nature (2篇)、Nature Communications等国际学术期刊上,代表性研究工作被列为ESI高被引论文和F1000 prime推荐论文,现总引用数超2500次(Google Scholar)。主持国际Human Frontier Science Program(HFSP)长期计划项目、国家自然科学基金和上海市科委科研项目以及UCAS-BHP Billiton Scholarship项目等。入选上海市高层次人才计划,被推选参加第68届林道诺贝尔奖得主大会,获得“中国科学院院长特别奖”等荣誉称号。受邀担任Nature Structural & Molecular Biology、Cell Discovery和Communications biology等学术期刊审稿专家。

研究领域

炎症反应在机体发生病菌感染和组织损伤时发挥重要的防御作用,也与重大疾病密切相关,例如神经炎症几乎存在于所有神经退行性疾病中。课题组探究炎症相关信号通路的调控机制,包括离子通道和G蛋白偶联受体信号通路等方面,从分子水平追踪关键信号蛋白的动态性结构变化,并结合生物化学、神经生物学等手段阐明其与蛋白功能的关联,探究重要受体介导信号跨膜传输的作用机理,解析信号转导蛋白调控神经免疫系统通信和神经炎症的分子机制,并致力于特异性靶向药物设计。

近期论文

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Zhang, K., Julius, D., and Cheng, Y. 2021. Structural snapshots of TRPV1 reveal mechanism of polymodal functionality, Cell, 184: 5138-5150 e12. Zhang, K., Wu, H., Hoppe, N., Manglik, A., and Cheng, Y. 2022. Fusion protein strategies for cryo-EM study of G protein-coupled receptors, Nat Commun, 13: 4366. Zhang, K.*, Zhang, J.*, Gao, Z.G., Zhang, D., Zhu, L., Han, G.W., Moss, S.M., Paoletta, S., Kiselev, E., Lu, W., Fenalti, G., Zhang, W., Muller, C.E., Yang, H., Jiang, H., Cherezov, V., Katritch, V., Jacobson, K.A., Stevens, R.C., Wu, B., and Zhao, Q. 2014. Structure of the human P2Y12 receptor in complex with an antithrombotic drug, Nature, 509: 115-8. (*, co-first author) Zhang, J.*, Zhang, K.*, Gao, Z.G., Paoletta, S., Zhang, D., Han, G.W., Li, T., Ma, L., Zhang, W., Muller, C.E., Yang, H., Jiang, H., Cherezov, V., Katritch, V., Jacobson, K.A., Stevens, R.C., Wu, B., and Zhao, Q. 2014. Agonist-bound structure of the human P2Y12 receptor, Nature, 509: 119-22. (*, co-first author) Zhang, K., Julius, D., and Cheng, Y. 2022. A step-by-step protocol for capturing conformational snapshots of ligand gated ion channels by single-particle cryo-EM, STAR Protoc, 3: 101732. Zhou, X.X., Bracken, C.J., Zhang, K., Zhou, J., Mou, Y., Wang, L., Cheng, Y., Leung, K.K., and Wells, J.A. 2020. Targeting Phosphotyrosine in Native Proteins with Conditional, Bispecific Antibody Traps, J Am Chem Soc, 142: 17703-17713. Schoof, M., Faust, B., Saunders, R.A., Sangwan, S., Rezelj, V., Hoppe, N., Boone, M., Billesbolle, C.B., Puchades, C., Azumaya, C.M., Kratochvil, H.T., Zimanyi, M., Deshpande, I., Liang, J., Dickinson, S., Nguyen, H.C., Chio, C.M., Merz, G.E., Thompson, M.C., Diwanji, D., Schaefer, K., Anand, A.A., Dobzinski, N., Zha, B.S., Simoneau, C.R., Leon, K., White, K.M., Chio, U.S., Gupta, M., Jin, M., Li, F., Liu, Y., Zhang, K., Bulkley, D., Sun, M., Smith, A.M., Rizo, A.N., Moss, F., Brilot, A.F., Pourmal, S., Trenker, R., Pospiech, T., Gupta, S., Barsi-Rhyne, B., Belyy, V., Barile-Hill, A.W., Nock, S., Liu, Y., Krogan, N.J., Ralston, C.Y., Swaney, D.L., Garcia-Sastre, A., Ott, M., Vignuzzi, M., Consortium, Q.S.B., Walter, P., and Manglik, A. 2020. An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike, Science, 370: 1473-1479. Faust, B., Billesbolle, C.B., Suomivuori, C.M., Singh, I., Zhang, K., Hoppe, N., Pinto, A.F.M., Diedrich, J.K., Muftuoglu, Y., Szkudlinski, M.W., Saghatelian, A., Dror, R.O., Cheng, Y., and Manglik, A. 2022. Autoantibody mimicry of hormone action at the thyrotropin receptor, Nature, 609: 846-853. Zhang, D., Gao, Z.G., Zhang, K., Kiselev, E., Crane, S., Wang, J., Paoletta, S., Yi, C., Ma, L., Zhang, W., Han, G.W., Liu, H., Cherezov, V., Katritch, V., Jiang, H., Stevens, R.C., Jacobson, K.A., Zhao, Q., and Wu, B. 2015. Two disparate ligand-binding sites in the human P2Y1 receptor, Nature, 520: 317-21. Gordon, D.E., Hiatt, J., Bouhaddou, M., Rezelj, V.V., Ulferts, S., Braberg, H., Jureka, A.S., Obernier, K., Guo, J.Z., Batra, J., Kaake, R.M., Weckstein, A.R., Owens, T.W., Gupta, M., Pourmal, S., Titus, E.W., Cakir, M., Soucheray, M., McGregor, M., Cakir, Z., Jang, G., O’Meara, M.J., Tummino, T.A., Zhang, Z., Foussard, H., Rojc, A., Zhou, Y., Kuchenov, D., Huttenhain, R., Xu, J., Eckhardt, M., Swaney, D.L., Fabius, J.M., Ummadi, M., Tutuncuoglu, B., Rathore, U., Modak, M., Haas, P., Haas, K.M., Naing, Z.Z.C., Pulido, E.H., Shi, Y., Barrio-Hernandez, I., Memon, D., Petsalaki, E., Dunham, A., Marrero, M.C., Burke, D., Koh, C., Vallet, T., Silvas, J.A., Azumaya, C.M., Billesbolle, C., Brilot, A.F., Campbell, M.G., Diallo, A., Dickinson, M.S., Diwanji, D., Herrera, N., Hoppe, N., Kratochvil, H.T., Liu, Y., Merz, G.E., Moritz, M., Nguyen, H.C., Nowotny, C., Puchades, C., Rizo, A.N., Schulze-Gahmen, U., Smith, A.M., Sun, M., Young, I.D., Zhao, J., Asarnow, D., Biel, J., Bowen, A., Braxton, J.R., Chen, J., Chio, C.M., Chio, U.S., Deshpande, I., Doan, L., Faust, B., Flores, S., Jin, M., Kim, K., Lam, V.L., Li, F., Li, J., Li, Y.L., Li, Y., Liu, X., Lo, M., Lopez, K.E., Melo, A.A., Moss, F.R., 3rd, Nguyen, P., Paulino, J., Pawar, K.I., Peters, J.K., Pospiech, T.H., Jr., Safari, M., Sangwan, S., Schaefer, K., Thomas, P.V., Thwin, A.C., Trenker, R., Tse, E., Tsui, T.K.M., Wang, F., Whitis, N., Yu, Z., Zhang, K., Zhang, Y., Zhou, F., Saltzberg, D., Consortium, Q.S.B., Hodder, A.J., Shun-Shion, A.S., Williams, D.M., White, K.M., Rosales, R., Kehrer, T., Miorin, L., Moreno, E., Patel, A.H., Rihn, S., Khalid, M.M., Vallejo-Gracia, A., Fozouni, P., Simoneau, C.R., Roth, T.L., Wu, D., Karim, M.A., Ghoussaini, M., Dunham, I., Berardi, F., Weigang, S., Chazal, M., Park, J., Logue, J., McGrath, M., Weston, S., Haupt, R., Hastie, C.J., Elliott, M., Brown, F., Burness, K.A., Reid, E., Dorward, M., Johnson, C., Wilkinson, S.G., Geyer, A., Giesel, D.M., Baillie, C., Raggett, S., Leech, H., Toth, R., Goodman, N., Keough, K.C., Lind, A.L., Zoonomia, C., Klesh, R.J., Hemphill, K.R., Carlson-Stevermer, J., Oki, J., Holden, K., Maures, T., Pollard, K.S., Sali, A., Agard, D.A., Cheng, Y., Fraser, J.S., Frost, A., Jura, N., Kortemme, T., Manglik, A., Southworth, D.R., Stroud, R.M., Alessi, D.R., Davies, P., Frieman, M.B., Ideker, T., Abate, C., Jouvenet, N., Kochs, G., Shoichet, B., Ott, M., Palmarini, M., Shokat, K.M., Garcia-Sastre, A., Rassen, J.A., Grosse, R., Rosenberg, O.S., Verba, K.A., Basler, C.F., Vignuzzi, M., Peden, A.A., Beltrao, P. and Krogan, N.J. 2020. Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms, Science, 370.

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