Transcription is the first and the most-regulated step of gene expression, by which RNA polymerase (RNAP) copies genetic information from DNA to RNA. It is fundamentally important to understand the structure, function, and regulation of the transcription machinery--RNAP. RNAPs are well conserved across bacterial species, but are less conserved between bacteria and human. Therefore, bacterial RNAPs are promising drug target for antibiotic discovery. Two categories of bacterial RNAP inhibitors (Rifamycins and Fidaxomicin) are currently in clinical use for the treatment of various infectious diseases.

Our lab focuses on the molecular mechanism of bacterial transcription and bacterial transcription regulation. We also develop new bactericidal antibiotics targeting bacterial RNA polymerase. We employ multiple approaches in Structure biology (X-ray crystallography and cryo-EM), Biochemistry, Enzymology, Microbiology and Bioinformatics. Our current projects includes:

1.     Molecular mechanism of bacterial transcription initiation

2.     Transcription regulation by alternative initiator “sigma” factors

3.     Molecular mechanism of transcription-coupled DNA repair

4.     Molecular mechanism of bacterial transcription termination

5.     Discovery and mechanism study of new RNAP regulatory proteins

6.     Discovery of new antibiotics targeting bacterial RNA polymerase

09/2000-07/2004      Fudan University, Shanghai, China         

                                  Bachelor in Life Sciences                                                                                                

09/2004-07/2009      Shanghai Institute of Materia Medica, CAS, Shanghai, China                         

                                  Ph.D. in drug design                                                                            

10/2009-07/2015      Postdoc in  Richard Ebright's lab, the Waksman Institute of Microbiology, Rutgers University

1. Xiaoxian Wu#, Chengzhi Yu#, Wenhui Mu, Zhanxi Gu, Yu Feng, Yu Zhang*, The structural mechanism for transcription activation by Caulobacter crescentus GcrA, Nucleic Acids Research 2023; doi: 10.1093/nar/gkad01

2. Linlin You, Expery O.Omollo, Chengzhi Yu, Rachel A Mooney, Jing Shi, Liqiang Shen, Xiaoxian Wu, Aijia Wen, Dingwei He, Yuan Zeng, Yu Feng*, Robert Landick*, Yu Zhang*, Nature 2023; 613(7945):783-789

3. Dingwei He#, Linlin You#, Xiaoxian Wu, Jing Shi, Aijia Wen, Zhi Yan, Wenhui Mu, Chengli Fang, Yu Feng*, Yu Zhang*. Pseudomonas aeruginosa SutA wedges RNAP lobe domain open to facilitate promoter DNA unwinding. Nature communications 2022, 13(1), 4204.

4. Binod K. Bharati#, Manjunath Gowder#, Fangfang Zheng, Khaled Alzoubi,Vladimir Svetlov, Venu Kamarthapu, Jacob W. Weaver, Vitaly Epshtein, Nikita Vasilyev, Liqiang Shen, Yu Zhang*, Evgeny Nudler*. Crucial role and mechanism of transcription-coupled DNA repair in bacteria. Nature 2022; 604, 152-159.

5. Yu Liu, Libing Yu, Chirangini Pukhrambam, Jared T. Winkelman, Emre Firlar, Jason T. Kaelber, Yu Zhang, Bryce E. Nickels, and Richard H. Ebright*. Structural and mechanistic basis of reiterative transcription initiation. Proceedings of the National Academy of Sciences 2022, 119, no. 5: e2115746119.

6. Chengli Fang, and Yu Zhang*. Bacterial MerR family transcription regulators: activationby distortion. Acta Biochimica et Biophysica Sinica 2022, 54 (1): 1-12.

7. Kun Huang#, Xiao-Xian Wu#, Cheng-Li Fang#, Zhou-Geng Xu#, Hong-Wei Zhang, Jian Gao, Chuan-Miao Zhou, Lin-Lin You, Zhan-Xi Gu, Wen-Hui Mu, Yu Feng*, Jia-Wei Wang*, Yu Zhang*. Pol IV and RDR2: A two-RNA-polymerase machine that produces double-stranded RNA. Science 2021;374(6575):1579-1586.

8. Hao Zhang, Nuo Cheng, Zhihui Li, Ling Bai, Chengli Fang, Yuwen Li, Weina Zhang, Xue Dong, Minghao Jiang, Yang Liang, Sujiang Zhang, Jianqing Mi, Jiang Zhu, Yu Zhang, Sai-Juan Chen, Yajie Zhao, Xiang-Qin Weng, Weiguo Hu*, Zhu Chen*, Jinyan Huang*, Guoyu Meng*. DNA crosslinking and recombination‐activating genes 1/2 (RAG1/2) are required for oncogenic splicing in acute lymphoblastic leukemia. Cancer Communications 2021. 41, no. 11: 1116-1136

9. Chengli Fang#, Steven J. Philips#, Xiaoxian Wu, Kui Chen, Jing Shi, Liqiang Shen, Juncao Xu, Yu Feng*, Thomas V. O’Halloran*, and Yu Zhang*. CueR activates transcription through a DNA distortion mechanism. Nature Chemical Biology 2021,17: 57-64.

10. Wenyue Dong, Xiaoqun Nie, Hong Zhu, Qingyun Liu, Kunxiong Shi, Linlin You, Yu Zhang, Hongyan Fan,Bo Yand, Chen Niu*, Liang-Dong Lyu*, Guo-Ping Zhao, Chen Yang*. Mycobacterial fatty acid catabolism is repressed by FdmR to sustain lipogenesis and virulence. Proceedings of the National Academy of Sciences 2021, no. 16: e2019305118

11. Kyle S. Skalenko, Lingting Li, Yuanchao Zhang, Irina O. Vvedenskaya, Jared T. Winkelman, Alexander L. Cope, Deanne M. Taylor, Premal Shaha, Richard H. Ebright, Justin B. Kinneyg, Yu Zhang, and Bryce E. Nickels*. Promoter-sequence determinants and structural basis of primer-dependent transcription initiation in Escherichia coli. Proceedings of the National Academy of Sciences 2021,118, no. 27: e2106388118

12. Chengli Fang#, Linyu Li#, Yihan Zhao, Xiaoxian Wu, Steven J. Philips, Linlin You, Mingkang Zhong, Xiaojin Shi, Thomas V. O'Halloran, Qunyi Li, Yu Zhang*. The bacterial multidrug resistance regulator BmrR distorts promoter DNA to activate transcription. Nature communications 2020, 11: 1-9.

13. Weifeng Huang, Yang Zhang, Liqiang Shen, Qian Fang, Qun Liu, Chenbo Gong, Chen Zhang, Yong Zhou, Cui Mao, Yongli Zhu, Jinghong Zhang, Hongping Chen, Yu Zhang, Yongjun Lin, Ralph Bock and Fei Zhou*. Accumulation of the RNA polymerase subunit RpoB depends on RNA editing by OsPPR16 and affects chloroplast development during early leaf development in rice." New Phytologist 2020, 228, no. 4: 1401-1416.

14. Lingting Li#, Vadim Molodstov#, Wei Lin, Richard Ebright*, Yu Zhang*. RNA extension drives a stepwise displacement of an initiation-factor structural module in initial transcription. PNAS 2020, 117(11): 5801-5809.

15. Ningning Zhuang#, Hao Zhang#, Lingting Li, Xiaoxian Wu, Chen Yang*, and Yu Zhang*. Crystal structures and biochemical analyses of the bacterial arginine dihydrolase ArgZ suggests a “bond rotation” catalytic mechanism. Journal of Biological Chemistry 2020, 295, 7: 2113-2124.

16. Fulin Wang#, Jing Shi#, Dingwei He#, Bei Tong, Chao Zhang, Aijia Wen, Yu Zhang*, Yu Feng*, and Wei Lin*. Structural basis for transcription inhibition by E. coli SspA. Nucleic acids research 2020, 48: 9931-9942.

17. JianPing Huang#, Chengli Fang#, Xiaoyan Ma#, Li Wang, Jing Yang, Jianying Luo, Yijun Yan, Yu Zhang*, Sheng-Xiong Huang*. Tropane alkaloids biosynthesis involves an unusual type III polyketide synthase and non-enzymatic condensation. Nature communications 2019, 10(1): 4036.

18. Juncao Xu#, Kaijie Cui#, Liqiang Shen, Jing Shi, Lingting Li, Linlin You, Chengli Fang, Guoping Zhao*, Yu Feng*, Bei Yang*, Yu Zhang*. Crl activates transcription by stabilizing active conformation of the master stress transcription initiation factor. eLife 2019, 8, e50928.

19. Jing Shi#, Aijia Wen#, Minxing Zhao#, Linlin You, Yu Zhang, Yu Feng*, Structural basis of σ appropriation. Nucleic Acid Research 2019, 47(17):9423-9432.

20. Jing Shi, Xiang Gao, Tongguan Tian, Zhaoyang Yu, Bo Gao, Aijia Wen, Linlin You, Shenghai Chang, Xing Zhang, Yu Zhang, Yu Feng*, Structural basis of Q-dependent transcription antitermination, Nature Communications 2019, 10(1): 2925

21. Linlin You, Jing Shi, Liqiang Shen, Lingting Li, Chengli Fang, Chengzhi Yu, Wenbo Cheng, Yu Feng*, Yu Zhang*. Structural basis for transcription antitermination at bacterial intrinsic terminator. Nature communications 2019. 10(1) :3048

22. Chengli Fang#, Lingting Li#, Liqiang Shen, Jing Shi, Sheng Wang*, Yu Feng*, Yu Zhang*. Structures and mechanism of transcription initiation by bacterial ECF factors. Nucleic Acids Research 2019, 47(13):7094-7104

23. Lingting Li#, Chengli Fang#, Ningning Zhuang, Tiantian Wang, Yu Zhang*. Structural basis for transcription initiation by bacterial ECF σ factors. Nature Communications 2019. 10(1) :1153

24. Irina O. Vvedenskaya#, Jeremy G. Bird#, Yuanchao Zhang#, Yu Zhang, Xinfu Jiao, Ivan Barvík, Libor Krásny, Megerditch Kiledjian, Deanne M.Taylor, Richard H. Ebright*, Bryce E.Nickels*. CapZyme-Seq Comprehensively Defines Promoter-Sequence Determinants for RNA 5′ Capping with NAD+. Molecular Cell 2018. 70(3): 553-564

25. Xiaoxian Wu#, Diane L. Haakonsen#, Allen G. Sanderlin, Yue J, Liu, Liqiang Shen, Ningning Zhuang, Michael T. Laub*, Yu Zhang*. Structural insights into the unique mechanism of transcription activation by Caulobacter crescentus GcrA. Nucleic Acids Research 2018. 46 (6): 3245-3256.

26. Xiaobiao Han#, Liqiang Shen#, Qijun Wang, Xufeng Cen, Jin Wang, Meng Wu, Peng Li, Wei Zhao*, Yu Zhang*, and Guoping Zhao*. Cyclic AMP inhibits the activity and promotes the acetylation of acetyl-CoA synthetase through competitive binding to the ATP/AMP pocket. Journal of Biological Chemistry 2017 292: 1374-1384.

27. Sonia I. Maffioli#, Yu Zhang#, David Degen#, Thomas Carzaniga, Giancarlo Del Gatto, Stefania Serina, Paolo Monciardini, Carlo Mazzetti, Paola Guglierame, Gianpaolo Candiani, Alina Iulia Chiriac, Giuseppe Facchetti, Petra Kaltofen, Hans-Georg Sahl, Gianni Dehò, Stefano Donadio*, and Richard H. Ebright*. Antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase: pseudouridimycin. Cell 2017, 15;169(7):1240-1248.e23

28. Jeremy G. Bird#, Yu Zhang#, Yuan Tian, Natalya Panova, Ivan Barvík, Landon Greene, Min Liu, Brian Buckley, Libor Krásny, Jeehiun K. Lee, Craig D. Kaplan, Richard H. Ebright*, Bryce E. Nickels*. The mechanism of RNA 5' capping with NAD+, NADH, and desphospho-CoA. Nature 2016, 535(7612): 444-447.

29. Jared T Winkelman#, Irina O Vvedenskaya#, Yuanchao Zhang#, Yu Zhang#, Jeremy G Bird, Deanne M Taylor, Richard L Gourse, Richard H Ebright*, Bryce E Nickels*. Multiplexed protein-DNA cross-linking: Scrunching in transcription start site selection. Science 2016, 351(6277):1090-1093

30. Yu Zhang#, David Degen#, Mary X Ho#, Elena Sineva, Katherine Y Ebright, Yon W Ebright, Vladimir Mekler, Hanif Vahedian-Movahed, Yu Feng, Ruiheng Yin, Steve Tuske, Herbert Irschik, Rolf Jansen, Sonia Maffioli, Stefano Donadio, Eddy Arnold, Richard H Ebright*. GE23077 binds to the RNA polymerase “I” and “I+1” sites and prevents the binding of initiating nucleotides. Elife 2014, 3, e02450

31. Yu Zhang, Yu Feng, Sujoy Chatterjee, Steve Tuske, Mary X Ho, Eddy Arnold, Richard H Ebright*. Structural basis of transcription initiation. Science 2012, 338 (6110), 1076-1080

32. Yu Zhang#, Haitao Zhang#, Xin-gang Yao#, Hong Shen, Jing Chen, Chenjing Li, Lili Chen, Mingyue Zheng, Jiming Ye, Lihong Hu*, Xu Shen*, Hualiang Jiang*. (+)-Rutamarin as a dual inducer of both GLUT4 translocation and expression efficiently ameliorates glucose homeostasis in insulin-resistant mice. PLOS ONE 2012, 7 (2), e31811

33. Yu Zhang#, Yan Li#, Yue-wei Guo*, Hua-liang Jiang, Xu Shen*. A sesquiterpene quinone, dysidine, from the sponge Dysidea villosa, activates the insulin pathway through inhibition of PTPases. Acta Pharmacol Sin. 2009, 30 (3), 333-345

34. Qiong Liu#, Yu Zhang#, Zhonghui Lin, Hong Shen, Lili Chen, Lihong Hu*, Hualiang Jiang*, Xu Shen*. Danshen extract 15,16-dihydrotanshinone I functions as a potential modulator against metabolic syndrome through multi-target pathways. J Steroid Biochem Mol Biol. 2010, 120 (4), 155-163.

35. Deju Ye#, Yu Zhang#, Mingfang Zheng, Xu Zhang, Xiaomin Luo, Xu Shen*, Hualiang Jiang*, Hong Liu*. Novel thiophene derivatives as PTP1B inhibitors with selectivity and cellular activity. Bioorg Med Chem 2010, 18 (5), 1773-1782

36. Tiancen Hu#, Yu Zhang#, Lianwei Li, Shuai Chen, Jing Chen, Jianping Ding, Hualiang Jiang*, Xu Shen*. Two adjacent mutations on the dimer interface of SARS coronavirus 3C-like protease cause different conformational changes in crystal structure. Virology 2009, 388 (2), 324-334

1. ​Ebright R, Feng Y, and Zhang Y.  Bipartite inhibitors of bacterial RNA polymerase: Sal-target inhibitor/nucleoside-analog-inhibitor conjugates. US 2014/0162940 A1.

2. Ebright R, Degen D, Zhang Y, and Ebright Y.  Bipartite inhibitors of bacterial RNA polymerase. US 2014/0206602 A1.

2016 Speaker at the17^th symposium of Shanghai Structure Biology, Shanghai, China;

2017 Speaker at FASEB meeting, Mechanism and regulation of prokaryotic transcription, VT, USA;

2017 Speaker at the 20^th symposium of Shanghai Structure Biology, Shanghai, China;

2017 Speaker at the Annual meeting of the society of microbiology, Zhenzhou, China;

2018 Organizer of the 11^th Sino-German Frontiers of Science Symposium 2018, Shanghai, China;

已指导学生

李玲婷  博士研究生  071005-微生物学  

申立强  博士研究生  071005-微生物学  

武霄仙  博士研究生  071005-微生物学  

方城力  博士研究生  071005-微生物学  

尤琳琳  博士研究生  071005-微生物学  

李国强  博士研究生  071005-微生物学  

何定伟  博士研究生  071005-微生物学  

曾媛  博士研究生  071005-微生物学  

章洪伟  博士研究生  071005-微生物学  

现指导学生

董尚志  博士研究生  071005-微生物学  

俞承志  博士研究生  071005-微生物学  

黄坤  博士研究生  071005-微生物学  

谷战西  博士研究生  071005-微生物学  

徐炜莹  硕士研究生  071005-微生物学  

张宇翔  博士研究生  071005-微生物学  

石国龙  硕士研究生  071005-微生物学  

孙淑怡  硕士研究生  071005-微生物学