
沈张飞 研究员
微生物免疫与基因水平转移研究调控
邮箱:zhangfei_shen@shsmu.edu.cn
【个人简历】
沈张飞博士目前担任上海交通大学基础医学院生物化学与分子细胞课题组长、研究员。2009年9月至2014年6月,我在南京农业大学获得兽医学学士学位;随后于2014年9月至2020年3月在浙江大学获得动物科学博士学位,期间进行多项研究课题,获得多项学术荣誉。2018年10月至2020年1月,沈张飞以访学交流博士生身份在瑞士保罗谢勒研究所及哈佛大学医学院波士顿儿童医院开展研究,进一步深化了在生物化学、结构生物学及分子信号调控领域的研究,培养了较强的多学科交叉研究能力。2021年3月起,沈张飞博士在美国俄亥俄州立大学担任博士后研究员,主要运用生物物理与生物化学方法,阐明新型细菌免疫信号通路及水平基因转移的分子机制,核心研究方向包括抗噬菌体防御系统中的核酸识别。
沈张飞博士已发表科研论文30余篇,获批国家专利5项,以第一作者(含共同)发表论文10余篇,包括Nature、Cell、Molecular Cell、Nature Structural & Molecular Biology、Nature Communications、PNAS、eLife和Journal of Biological Chemistry等有影响力学术期刊,以及担任多家重要科学期刊的同行评审专家。此外,沈张飞博士还获得2024年美国生物化学与分子生物学学会(ASBMB)博士后研究奖,并在ASBMB会议上做口头报告。(https://www.x-mol.com/groups/shenlab)
【研究方向】
课题组将在微生物与免疫领域,聚焦外源核酸免疫应答与基因水平转移调控研究。课题组将解析微生物免疫系统如何识别并应答来自病毒、细菌等移动遗传元件的外源核酸入侵;以及关注病毒-宿主的免疫识别与分子互作,探究病毒入侵宿主的分子机制以及其他移动遗传元件进行基因水平转移的分子机制。课题组将整合结构生物学、生物化学、遗传学和微生物学研究方法,为开发新型抗病毒策略、抗菌工具、新型核酸编辑工具以及理解微生物免疫系统对外源核酸免疫识别的进化规律提供重要理论基础。
【科研项目】
国家海外高层次青年人才计划项目和上海市海外高层次青年人才计划项目。
【论文与专著】
1. Yang, X.Y.#, Shen, Z.#, Wang, C., Nakanishi, K., Fu, T.M., 2024. DNA defense module eliminates plasmid invasion by DNA-guided DNA targeting. Cell, 187(19):5253-5266. doi: 10.1016/j.cell.2024.07.028. PMID: 39173632.
2. Shen, Z.#, Yang, X.Y.#, Xia, S., Huang, W., Taylor, D.J., Nakanishi, K., Fu, T.M., 2023. Oligomerization-mediated activation of a short prokaryotic Argonaute. Nature, 621, 154-161. doi: 10.1038/s41586-023-06456-z. PMID: 37494956.
3. Shen, Z.#, Lin, Q.#, Yang, X.Y.#, Fosuah, E., Fu, T.M., 2023. Assembly-mediated activation of the SIR2-HerA supramolecular complex for anti-phage defense. Mol. Cell, 83, 1-14. doi: 10.1016/j.molcel.2023.11.007. PMID: 38096827.
4. Shen, Z., Assembly and Activation of the NLR Family in Innate Immune Regulation and Cell Death. Book: Cell Death Regulation in Pathology, IntechOpen, 14 May 2025. Crossref, doi:10.5772/intechopen.1010575.
5. Yang, X.Y.#, Shen, Z.#, Xie, J., Greenwald, J., Marathe, I., Lin, Q., Xie, W.J., Wysocki, V.H., Fu, T.M., 2024. Molecular basis of Gabija anti-phage supramolecular assemblies. Nat. Struct. Mol. Biol., 31(8):1243-1250. doi: 10.1038/s41594-024-01283-w. PMID: 38627580.
6. Li, Y.#, Shen, Z.#, Zhang, M.#, Yang, X.Y.#, Cleary, S.P., Xie, J., Marathe, I.A., Kostelic, M., Greenwald, J., Rish, A.D., Wysocki, V.H., Chen, C., Yu, Y., Chen, Q., Fu, T.M., 2024. PtuA and PtuB Assemble into an Inflammasome-like Oligomer for Anti-phage Defense. Nat. Struct. Mol. Biol., 31(3):413-423. doi: 10.1038/s41594-023-01172-8. PMID: 38177683.
7. Rish, A.D.#, Shen, Z.#, Chen, Z., Zhang, N., Zheng, Q., Fu, T.M., 2023. Molecular mechanisms of Holliday junction branch migration catalyzed by an asymmetric RuvB hexamer. Nat. Commun., 14(1), 1-10. doi: 10.1038/s41467-023-39250-6. PMID: 37322069.
8. Fosuah E. #, Shen, Z.#, Wang, C., Lin, Q., Fu, T.M., 2025. Assembly and activation of the death-inducing signaling complex. Proc. Natl. Acad. Sci. USA, in press.
9. Wang, C.#, Shen, Z.#, Yang, X.Y., Fu, T.M., 2024. Structures and functions of short Argonautes. RNA Biol., 21(1):883-889. doi: 10.1080/15476286.2024.2380948. PMID: 39219231.
10. Rish, A.D.#, Shen, Z.#, Fu, TM., 2022. It takes two to Tango: Two gates orchestrate the opening of human TRPM2. Cell Calcium, 101:102523. doi: 10.1016/j.ceca.2021.102523. Epub 2021 Dec 23. PMID: 34973600.
11. Wang, T.M.#, Cao, Z.#, Shen, Z.#, Yang, J.W., Chen, X., Yang, Z., Xu, K., Xiang, X.W., Yu, Q.H., Song, Y.M., Wang, W.W., Tian, Y.N., Sun, L.N., Zhang, L.B., Guo, S., Zhou, N.M.,2020. Existence and functions of hypothalamic kisspeptin neuropeptide signaling system in a non-chordate deuterostome species. eLife, 9: e53370. doi: 10.7554/eLife.53370. PMID: 32513385.
12. Shen, Z.#, Chen, Y.#, Hong, L.#, Cui, Z., Yang, H., He, X., Shi, Y., Shi, L., Han, F., Zhou, N.M., 2017. BNGR-A25L and -A27 are two functional G protein-coupled receptors for CAPA periviscerokinin neuropeptides in the silkworm, Bombyx mori. J. Biol. Chem., 292(40): 16554 - 16570. doi: 10.1074/jbc.M117.803445. PMID: 28842502.
13. Shen, Z., Jiang, X., Yan, L.L., Wang, W.W., Shi, Y., Shi, L.G., Liu, D.X., Zhou, N.M., 2018. Structural basis for the interaction of diapause hormone with its receptor in the silkworm, Bombyx mori. FASEB J., 32(3): 1338-1353. doi: 10.1096/fj.201700931R. PMID: 29101222.
14. Shen, Z., Yang, X.Y., Chen, Y., Shi, L.G., 2018. CAPA periviscerokinin-mediated activation of MAPK/ERK signaling through Gq-PLC-PKC-dependent cascade and reciprocal ERK activation- dependent internalized kinetics of Bom-CAPA-PVK receptor. Insect Biochem. Mol. Biol., 98: 1-15. doi: 10.1016/j.ibmb.2018.04.007. PMID: 29730398.
15. Shen, Z., Xie, H.Q., Shi, L.G., 2018. Current research status of embryo diapause regulated by diapause hormone and its receptors in the silkworm, Bombyx mori. Acta Entomologica Sinica, 61(11):1340-1349.
16. Zheng, W., Rawson, S., Shen, Z., Tamilselvan, E., Smith, H.E., Halford, J., Shen, C., Murthy, S.E., Ulbrich, M.H., Sotomayor, M., Fu, T.M., Holt, J.R., 2023. TMEM63 proteins function as monomeric high-threshold mechanosensitive ion channels. Neuron, 111(20): 3195-3210. doi: 10.1016/j.neuron.2023.07.006. PMID: 37543036.
17. Rish, A.D., Fosuah, E., Shen, Z., Marathe, I.A., Wysocki, V.H., Fu, T.M., 2025. Topological rearrangements activate the HerA-DUF anti-phage defense system. Mol. Cell, 85 (6), 1189-1201. doi: 10.1016/j.molcel.2025.02.001. PMID: 40010344.
18. Zheng, W., Rawson, S., Shen, Z., Tamilselvan, E., Smith, H.E., Halford, J., Shen, C., Murthy, S.E., Ulbrich, M.H., Sotomayor, M., Fu, T.M., Holt, J.R., 2023. TMEM63 proteins function as monomeric high-threshold mechanosensitive ion channels. Neuron, 111(20): 3195-3210. doi: 10.1016/j.neuron.2023.07.006. PMID: 37543036.
19. Wang, C., Rish, A.D., Armbruster, E.G., Xie, J., Loveland, A.B., Shen, Z., Gu, B., Korostelev, A.A., Pogliano, J., Fu, T.M., 2025. Disassembly activates Retron-Septu for antiphage defense. Science, 389(6762):eadv3344. doi: 10.1126/science.adv3344. PMID: 40504952.
20. Savidge, A., Zhang, H., Annasaheb, A.V., Kehling, A.C., Sim, G., Shen, Z., Fu, T,M., Nakanishi, K., 2025. Neurodevelopmental disorder-linked Argonaute mutations permit delayed RISC formation and unusual shortening of miRNAs by 3'→5' trimming. Proc. Natl. Acad. Sci. USA. 122(46):e2524644122. doi: 10.1073/pnas.2524644122. PMID: 41237208.
21. Zheng, W.#, Shen, C.#, Wang, L.#, Rawson, S.#, Xie, W.J., Nist-Lund, C., Wu, J., Shen, Z., Xia, S., Holt, J.R., Wu, H., Fu, T.M., 2022. pH regulates potassium conductance and drives a constitutive proton current in human TMEM175. Sci. Adv., 8(12): eabm1568. doi: 10.1126/sciadv.abm1568. PMID: 35333573.
22. Cao, Z.#, Yan, L.#, Shen, Z., Chen, Y., Shi, Y., He, X., Zhou, N., 2020. A novel splice variant of Gq-coupled Bombyx CAPA-PVK receptor 1 functions as a specific Gi/o-linked receptor for CAPA-PK. BBA-Mol. Cell Res., 1867(8):118718. doi: 10.1016/j.bbamcr.2020.118718. PMID: 32289337.
23. Gu, L.#, Wang, L.#, Chen, H.#, Hong, J.#, Shen, Z., Dhall, A., Lao, T., Liu, C., Wang, Z., Xu, Y., Tang, H.W., Chakraborty, D., Chen, J., Liu, Z., Rogulja, D., Perrimon, N., Wu, H., Shi, Y., 2020. CG14906 (mettl4) methylates U2 snRNA m6A in Drosophila. Cell Discov., 6(1):1-4. doi: 10.1038/s41421-020-0178-7. PMID: 32637152.
24. Tang, H.W., Weng, J.H., Lee, W.X., Hu, Y., Gu, L., Cho, S., Lee, G., Binari, R., Li, C., Cheng, M.E., Kim, A.R., Xu, J., Shen, Z., Xu, C., Asara, J.M., Blenis, J., Perrimon, N., 2021. mTORC1-chaperonin CCT signaling regulates m6A RNA methylation to suppress autophagy. Proc. Natl. Acad. Sci. USA, 118(10): e2021945118. doi: 10.1073/pnas.2021945118. PMID: 33649236.
25. Chen, H.#, Gu, L.#, Orellana, EA., Wang, Y., Guo, J., Liu, Q., Wang, L., Shen, Z., Wu, H., Gregory, R.I., Xing, Y., Shi, Y., 2020. METTL4 is an snRNA m6Am methyltransferase that regulates RNA splicing. Cell Res., 30(6): 544-547. doi: 10.1038/s41422-019-0270-4. PMID: 31913360.
26. Xie, H., Li, X., Yang, W., Yu, L., Jiang, X., Chen, Y., Shen, Z., Li, C., Gu, M., Shi, L., 2020. N6-(2-Hydroxyethyl)-adenosine suppresses proliferation and induces apoptosis in human gastric carcinoma through mediating mitochondrial dysfunction and cell cycle arrest. Int. J. Mol. Sci., 21(16): 5815. doi: 10.3390/ijms21165815. PMID: 32823628.
27. Wang, S.L.#, Wang, W.W.#, Ma, Q., Shen, Z., Zhang, M.Q., Zhou, N.M., Zhang, C.X., 2019. Elevenin signaling modulates body color through the tyrosine-mediated cuticle melanism pathway. FASEB J., 33(9):9731-9741. doi: 10.1096/fj.201802786RR. PMID: 31162939.
28. Xie, H., Li, X., Chen, Y., Lang, M., Shen, Z., Shi, L., 2019. Ethanolic extract of cordyceps cicadae exerts antitumor effect on human gastric cancer SGC-7901 cells by inducing apoptosis, cell cycle arrest and endoplasmic reticulum stress. J. Ethnopharmacol., 20(231): 230-240. doi: 10.1016/j.jep.2018.11.028. PMID: 30468850.
29. Yang, J., Shen, Z., Jiang, X., Yang, H., Huang, H., Jin, L., Chen, Y., Shi, L., Zhou, N., 2016. Agonist-activated Bombyx corazonin receptor is internalized via an arrestin-dependent and clathrin-independent pathway. Biochemistry, 55(28): 3874-3887. doi: 10.1021/acs.biochem.6b00250. PMID: 27348044.
30. Jiang, X., Yang, J., Shen, Z., Chen, Y., Shi, L., Zhou, N., 2016. Agonist-mediated activation of Bombyx mori diapause hormone receptor signals to extracellular signal-regulated kinases 1 and 2 through Gq-PLC-PKC-dependent cascade. Insect Biochem. Mol. Biol., 75: 78-88. doi: 10.1016/j.ibmb.2016.06.005. PMID: 27318251.
31. Ye, Y.X., Pan, P.L., Xu, J.Y., Shen, Z., Kang, D., Lu, J.B., Hu, Q.L., Huang, H.J., Lou, Y.H., Zhou, N.M., Zhang, C.X., 2017. Forkhead box transcription factor L2 activates Fcp3C to regulate insect chorion formation. Open Biology, 7(6): 170061. doi: 10.1098/rsob.170061. PMID: 28615473.