1. 研究领域
课题组借助全基因组CRISPR筛选平台、病毒反向遗传操作系统、细胞生化免疫、动物模型等来解析病毒与宿主的相互作用关系，探究病毒的入胞与复制、细胞组织嗜性与跨物种传播、免疫与致病机制，发掘靶向宿主的抗病毒与免疫靶点以及疫苗开发等。
（1）新发突发病毒如冠状病毒、黄病毒、甲病毒、布尼亚病毒等的入胞机制与宿主嗜性
（2）病毒的感染免疫与致病机制
（3）靶向宿主因子的抗病毒与免疫策略（host-directed therapeutics）
（4）重要动物与人类新发病毒的诊断与疫苗开发
2. 近年来科研成果（论文、专利、获奖等）
主要学术贡献:
（1）证实轮状病毒和宿主编码与鼠冠状病毒ns2类似的能拮抗宿主免疫反应的磷酸二酯酶 (Zhang et al., PNAS 2013)
（2）鉴定发现了宿主信号肽酶能有效切割黄病毒的多聚蛋白并促进复制与包装(Zhang et al., Nature 2016)
（3）鉴定发现了致关节炎类甲病毒的入胞受体(Zhang et al., Nature 2018)
荣誉与获奖:
2018年国家海外青年人才项目入选者
2018年美国STAT Wunderkinds Award获得者
发表论文:
1. Zhu YK#, Feng F#, Hu GW#, Wang YY#, Yu Y, Zhu YY, Xu W, Cai X, Sun ZP, Han WD, Ye R, Qu D, Chen HJ, Huang XX, Ding Q, Xie YH, Cai QL*, Yuan ZH*, Zhang R*. 2021. A genome-wide CRISPR screen identifies host factors that regulate the SARS-CoV-2 entry. Nature Communications. 12(1):961.doi: 10.1038/s41467-021-21213-4.
2. Zhao M#, Yu Y#, Sun LM#, Xing JQ, Li TT, Zhu YK, Wang M, Xue W, Tian Xia1, Cai H, Han QY, Yin XY, Li WH, Li AL, Cui JW, Yuan ZH, Zhang R, Zhou T*, Zhang XM*, Li T*. 2021. GCG inhibits SARS-CoV-2 replication by disrupting the liquid phase condensation of its nucleocapsid protein. Nature Communications. in press
3. Liu Y#, Hu GW#, Wang YY#, Ren WL#, Zhao XM, Ji FS, Zhu YK, Feng F, Gong ML, Ju XH, Li CH, Hong JX, Zhu YF, Cai X, Guo JY, Xie M, Dong L, Zhu ZH, Xu X, Na J, Wu JP, Xun Lan1, Xie YH, Wang XQ, Yuan ZH*, Zhang R*, Ding Q*. 2021. Functional and Genetic Analysis of Viral Receptor ACE2 Orthologs Reveals a Broad Potential Host Range of SARS-CoV-2. Proc Natl Acad Sci U S A. in press
4. Ren WL#, Zhu YK#, Wang YY#, Shi HY, Yu Y, Hu GW, Feng F, Zhao XM, Lan J, Wu JP, Kenney DJ, Douam F, Tong YM, Zhong J, Xie YH, Wang XQ, Yuan ZH, Zhou DM, Zhang R*, Ding Q*. 2021. Comparative analysis reveals the genetic determinants of ACE2 required by SARS-CoV-2 for cell entry. PLoS Pathog. In press
5. Zhao B#*, Ni C#, Gao R#, Wang YY, Yang L, Wei JS, Lv T, Liang JQ, Zhang QS, Xu W, Xie YH, Wang XY, Yuan ZH, Liang JB*, Zhang R*, Lin XH*. 2020. Recapitulation of SARS-CoV-2 infection and cholangiocyte damage with human liver ductal organoids. Protein & Cell. 11(10):771-775.doi: 10.1007/s13238-020-00718-6.
6. Kim AS#, Zimmerman O#, Fox JM, Nelson CA, Basore K, Zhang R, Durnell L, Desai C, Bullock C, Deem SL, Oppenheimer J, Shapiro B, Wang T, Cherry S, Coyne CB, Handley SA, Landis MJ*, Fremont DH*, Diamond MS*. 2020. An Evolutionary Insertion in the Mxra8 Receptor-Binding Site Confers Resistance to Alphavirus Infection and Pathogenesis. Cell Host & Microbe. 27, 428-440 e429 (2020).
7. Zhang R, Earnest JT, Kim AS, Winkler ES, Desai P, Adams L, Hu GW, Bullock C, Gold B, Cherry S, Diamond MS. 2019. Expression of the Mxra8 receptor promotes alphavirus infection and pathogenesis in mice and Drosophila. Cell Reports. 28(10):2647-2658
8. Basore K, Kim AS, Nelson CA, Zhang R, Smith BK, Uranga C, Vang L, Cheng M, Gross ML, Smith J, Diamond MS*, Fremont DH*. 2019. Cryo-EM structure of Chikungunya virus in complex with the Mxra8 receptor. Cell. pii: S0092-8674 (19)30392-7
9. Zhang R, Kim AS, Fox JM, Nair S, Basore K, Klimstra WB, Rimkunas R, Fong RH, Lin H, Poddar S, Crowe JE, Doranz BJ, Fremont DH, Diamond MS. 2018. Mxra8 is an entry receptor for multiple arthritogenicalphaviruses. Nature. 557(7706):570-574
10. Johnson B#, VanBlargan LA#, Xu W#, White JP, Shan C, Shi PY, Zhang R, Adhikari J, Gross ML, Leung DW, Diamond MS*, Amarasinghe GK*. 2018. Human IFIT3 Modulates IFIT1 RNA Binding Specificity and Protein Stability. Immunity. 48(3):487-499
11. Drappier M, Jha BK, Stone S, Elliott R, Zhang R, Vertommen D, Weiss SR, Silverman RH, Michiels T. 2018. A novel mechanism of RNase L inhibition: Theiler's virus L* protein prevents 2-5A from binding to RNase L. PLoS Pathog. 14(4):e1006989
12. Goldstein SA#, Thornbrough JM#, Zhang R#, Jha BK, Li Y, Elliott R, Quiroz-Figueroa K, Chen A, Silverman RH and Weiss SR*. 2017. Lineage A Betacoronavirus NS2 proteins and homologous Torovirus Berne pp1a-carboxyterminal domain are phosphodiesterases that antagonize activation of RNase L. J Virol. 91(5). pii: e02201-16
13. Richard AS, Shim BS, Schmitt K, Zhang R, Kwon YC, Otsuka Y, Diamond MS, Choe H. 2017. AXL-dependent infection of fetal endothelial cells distinguishes Zika virus from other pathogenic flaviviruses. Proc Natl Acad Sci U S A. 114(8):2024-2029
14. Zhu Z, Gorman MJ, McKenzie LD, Chai JN, Hubert CG, Prager BC, Fernandez E, Richner JM, Zhang R, Shan C, Tycksen E, Wang X, Shi PY, Diamond MS*, Rich JN*, Chheda MG*. 2017. Zika virus has oncolytic activity against glioblastoma stem cells. J Exp Med. 214(10):2843-2857
15. Zhang R, Miner JJ, Gorman MJ, Rausch K, Ramage H, White JP, Zuiani A, Zhang P, Fernandez E, Zhang Q, Dowd KA, Pierson TC, Cherry S, Diamond MS. 2016. A CRISPR screen defines a signal peptide processing pathway required by flaviviruses. Nature. 535(7610):164-168
16. Zhang R#, Li Y#, Cowley TJ, Steinbrenner AD, Phillips JM, Yount BL, Baric RS, Weiss SR. 2015. The nsp1, nsp13, and M proteins contribute to the hepatotropism of murine coronavirus JHM.WU. J Virol. 89:3598-3609
17. Gusho E#, Zhang R#, Jha BK#, Thornbrough JM, Dong B, Gaughan C, Elliott R, Weiss SR*, Silverman RH*. 2014. Murine AKAP7 has a 2',5'-phosphodiesterase domain that can complement an inactive murine coronavirus ns2 gene. MBio. 5(4):e01312-14. doi: 10.1128/mBio.01312-14.
18. Zhang R#, Jha BK#, Ogden KM, Dong B, Zhao L, Elliott R, Patton JT, Silverman RH*, Weiss SR*. 2013. Homologous 2',5'-phosphodiesterases from disparate RNA viruses antagonize antiviral innate immunity. Proc Natl Acad Sci U S A. 110:13114-13119
19. Zhang R, Chen C, Sun Z, Tan F, Zhuang J, Tian D, Tong G, Yuan S. 2012. Disulfide linkages mediating nucleocapsid protein dimerization are not required for porcine arterivirus infectivity. J Virol. 86:4670-4681
(Note, #co-first author,*co-corresponding author；last updated 03/2021)
申请专利:
Methods of inhibiting viral replication comprising the singlal peptidase complex. US Patent 2017/0101642 A1
Composition and Methods for Inhibition of Alphavirus Infection. US Patent PCT/US2019/012435
3. 在研科研项目
国家海外青年人才引进项目、复旦大学人才启动项目、国自然面上项目、国自然新冠专项、科技部重点研发计划等支持。