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Department of Basic Medical Sciences

RAO, Zihe

Resume


    • Professor & Head, Laboratory of Structural Biology, Tsinghua University  (1996–present)

    • President of Nankai University  (2006–2011)

    • Director-General of Institute of Biophysics, Chinese Academy of Sciences  (2003–2007)

    • Chairman of the Academic Board of Institute of Biophysics, Chinese Academy of Sciences  (2007– present)

    • Head of National Laboratory of Biomacromolecules  (2003–2007)

    • Postdoc Fellow  (1989-1991), Senior Research Scientist  (1992–1996), Laboratory of Molecular Biophysics, University of Oxford, UK

    • Research Assistant  (1977-1979), Research Associate  (1982–1985), Peking Insulin Structure Research Group, Institute of Biophysics, Chinese Academy of Sciences

    • Undergraduate Student  (1973-1977), Graduate Student  (1979-1982), From University of Science and Technology, Chinese Academy of Science




Research Fields & Emphasis

In 1996, Professor Rao returned to China to establish a structural biology laboratory in Tsinghua University, where his research focus was on understanding the molecular basis for the pathogenicity of infectious agents. His work provided unprecedented insights into the structure, replication and assembly of virus particles. His laboratory was the first to solve the structure of the SARS main-proteasePNAS 2003)as well as structures for Influenza virus (Nature 2008, 2009)Picornaviruses (Nature 2015), Flavivirus (Nature Microbiology 2016), Herpesvirus (Science 2018),and African Swine Fever Virus (Science 2019). He has also made major breakthroughs in understanding processes in energy transduction, metabolite transport, drug resistance and cell wall synthesis in Mycobacteria. His laboratories have provided much-needed structural data for the design and development of new anti-viral and anti-TB drugs. Amongst these, he has determined structures of several Mycobacterium tuberculosis drug targets including the CIII2-CIV2-SOD2 supercomplex (Science, 2018) and MmpL3 (Cell, 2019), most recently, he demonstrated the structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol (Science, 2020). In the recent global pandemic of COVID-19, he determined the structures of two key targets for antiviral development, Mainprotease and RNA-dependent RNA polymerase, reported the antiviral drug candidates targeting the main protease and a potent therapeutic antibody for neutralization of SARS-CoV-2, accelerating the global efforts against COVID-19 (Nature, 2020; Science (a), Science (b), Science (c)2020, Cell 2020, Cell (a) 2021, Cell (b)2021). To date, Rao has published 401 peer reviewed research papers, including 23 papers in ScienceNature and Cell, with more than 21,500 citations. His H-index is 72 and he also has 37 patents.



Academic Awards

Professor Rao was the Director-General of the Institute of Biophysics, Chinese Academy of Sciences, from 2003 to 2007. Under his leadership, the IBP has become one of the most respected institutes in life sciences in the world. Professor Rao served as President of Nankai University (2006–2011), a university ranked in the top 10 in China. In 2009, he was identified as one of the top 60 educators in the last 60 years in China. From 2006 to 2017, Professor Rao served as the Chairman of the Biophysics Society of China. From 2014 to 2017, served as the President of the International Union for Pure and Applied Biophysics (IUPAB). He is the founding President of the China Union of Life Science Societies, which brings together 22 life science societies across China. The Union has an ambitious mission to perform a leading role in promoting scientific research and worldwide collaborations. Professor Rao is also passionate about his charitable activities in promoting education and science, especially the Red Cross. In 2014, he became Chairman of the “Academician's Humanity Foundation”, a program under the Red Cross in China that supports medical education and the treatment of neglected diseases in China. He is also the Chairman of the C.C. Tan Life Sciences Award Committee (2009–date), the Chen Jiagen Life Sciences Award Committee (2016–date), and founder and Editor-in-Chief of Protein & Cell (2010), which has an Impact Factor of 10.164 in 2019.


Key Words


COVID-19, SARS-CoV, Influenza virus, Hand-foot-mouth disease, herpes virus, human immunodeficiency virus, hepatitis A virus, Tubercle Bacillus, X-Ray diffraction crystallography, Cryo-EM, Biophysics



Selected Publications

(1) Co-transcriptional capping machineries in SARS-CoV-2 RTC: Coupling of N7-methyltransferase and 3'-5' exoribonuclease with polymerase reveals mechanisms for capping and proofreading. Yan L, Yang Y, Li M, Zhang Y, Zheng L, Ge J, Huang Y, Liu Z, Wang T, Gao S, Zhang R, Huang Y, Guddat LW, Gao Y*, Rao Z*, Lou Z*. Cell. 2021 May 24; doi.org/10.1016/j.cell.2021.05.033

(2) Cryo-EM Structure of an Extended SARS-CoV-2 Replication and Transcription Complex Reveals an Intermediate State in Cap Synthesis. Yan L, Ge J, Zheng L, Zhang Y, Gao Y, Wang T, Huang Y, Yang Y, Gao S, Li M, Liu Z, Wang H, Li Y, Chen Y, Guddat LW, Wang Q, Rao Z*, Lou Z*. Cell. 2021 Jan 7;184(1):184-193

(3) Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody. Lv Z, Deng YQ, Ye Q, Cao L, Sun CY, Fan C, Huang W, Sun S, Sun Y, Zhu L, Chen Q, Wang N, Nie J, Cui Z, Zhu D, Shaw N, Li XF, Li Q, Xie L, Wang Y*, Rao Z*, Qin CF*, Wang X*. Science. 2020 Jul 23. DOI: 10.1126/science.abc5881

(4) Structures of fungal and plant acetohydroxyacid synthases. Lonhienne T, Low YS, Garcia MD, Croll T, Gao Y, Wang Q, Brillault L, Williams CM, Fraser JA, McGeary RP, West NP, Landsberg MJ, Rao Z, Schenk G, Guddat LW*. Nature. 2020 Jul 8.  doi: 10.1038/s41586-020-2514-3.

(5) Structural Basis for RNA Replication by the SARS-CoV-2 Polymerase. Wang Q, Wu J, Wang H, Gao Y, Liu Q, Mu A, Ji W, Yan L, Zhu Y, Zhu C, Fang X, Yang X, Huang Y, Gao H, Liu F, Ge J, Sun Q, Yang X, Xu W, Liu Z, Yang H, Lou Z, Jiang B, Guddat LW, Gong P, Rao Z. Cell. 2020 May 22:S0092-8674(20)30629-2.

(6) Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol. Zhang L, Zhao Y, Gao Y, Wu L, Gao R, Zhang Q, Wang Y, Wu C, Wu F, Gurcha SS, Veerapen N, Batt SM, Zhao W, Qin L, Yang X, Wang M, Zhu Y, Zhang B, Bi L, Zhang X, Yang H, Guddat LW, Xu W, Wang Q, Li J, Besra GS, Rao Z. Science. 2020 Jun 12;368(6496):1211-1219.

(7) Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Dai W, Zhang B, Su H, Li J, Zhao Y, Xie X, Jin Z, Liu F, Li C, Li Y, Bai F, Wang H, Cheng X, Cen X, Hu S, Yang X, Wang J, Liu X, Xiao G, Jiang H, Rao Z, Zhang LK, Xu Y, Yang H, Liu H. Science. 2020 Apr 22:eabb4489.

(8) Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Gao Y, Yan L, Huang Y, Liu F, Zhao Y, Cao L, Wang T, Sun Q, Ming Z, Zhang L, Ge J, Zheng L, Zhang Y, Wang H, Zhu Y, Zhu C, Hu T, Hua T, Zhang B, Yang X, Li J, Yang H, Liu Z, Xu W, Guddat LW, Wang Q, Lou Z, Rao Z. Science. 2020 May 15;368(6492):779-782.

(9) Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y, Zhang B, Li X, Zhang L, Peng C, Duan Y, Yu J, Wang L, Yang K, Liu F, Jiang R, Yang X, You T, Liu X, Yang X, Bai F, Liu H, Liu X, Guddat LW, Xu W, Xiao G, Qin C, Shi Z, Jiang H, Rao Z, Yang H. Nature. 2020 Jun;582(7811):289-293.

(10) Host-mediated ubiquitination of a mycobacterial protein suppresses immunity. Wang L, Wu J, Li J, Yang H, Tang T, Liang H, Zuo M, Wang J, Liu H, Liu F, Chen J, Liu Z, Wang Y, Peng C, Wu X, Zheng R, Huang X, Ran Y, Rao Z, Ge B. Nature. 2020 Jan;577(7792):682-688. doi: 10.1038/s41586-019-1915-7.

(11) Structural basis for enzymatic photocatalysis in chlorophyll biosynthesis. Zhang S, Heyes DJ, Feng L, Sun W, Johannissen LO, Liu H, Levy CW, Li X, Yang J, Yu X, Lin M, Hardman SJO, Hoeven R, Sakuma M, Hay S, Leys D, Rao Z, Zhou A, Cheng Q, Scrutton NS. Nature. 2019 Oct;574(7780):722-725. doi: 10.1038/s41586-019-1685-2. Epub 2019 Oct 23.

(12) Architecture of African swine fever virus and implications for viral assembly. Wang N, Zhao D, Wang J, Zhang Y, Wang M, Gao Y, Li F, Wang J, Bu Z, Rao Z, Wang X. Science. 2019 Nov 1;366(6465):640-644. doi: 10.1126/Science.aaz1439. Epub 2019 Oct 17.

(13) Crystal Structures of Membrane Transporter MmpL3, an Anti-TB Drug Target. Zhang B, Li J*, Yang X, Wu L, Zhang J, Yang Y, Zhao Y, Zhang L, Yang X, Yang X, Cheng X, Liu Z, Jiang B, Jiang H, Guddat LW, Yang H*, Rao Z*. Cell. 2019 Jan 24;176(3):636-648.e13

(14) An electron transfer path connects subunits of a mycobacterial respiratory supercomplex. Gong H, Li J, Xu A, Tang Y, Ji W, Gao R, Wang S, Yu L, Tian C, Li J, Yen HY, Man Lam S, Shui G, Yang X, Sun Y, Li X, Jia M, Yang C, Jiang B, Lou Z, Robinson CV, Wong LL, Guddat LW, Sun F*, Wang Q*, Rao Z*. Science. 2018 Oct 25. pii: eaat8923. doi: 10.1126/science.aat8923

(15) Crystal structure of a membrane-bound O-acyltransferase. Ma D, Wang Z, Merrikh CN, Lang KS, Lu P, Li X, Merrikh H, Rao Z, Xu W*. Nature. 2018 Oct;562(7726):286-290

(16) Yuan S, Wang J, Zhu D, Wang N, Gao Q, Chen W, Tang H, Wang J, Zhang X, Liu H*, Rao Z* and Wang X*. Cryo-EM structure of a Herpesvirus capsid at 3.1 Å. Science. 2018 Apr 6;360(6384). pii: eaao7283. doi: 10.1126/science.aao7283.

(17) Yao R, Ming Z, Yan L, Li S, Wang F, Ma S, Yu C, Yang M, Chen L, Chen L, Li Y, Yan C, Miao D, Sun Z, Yan J, Sun Y, Wang L, Chu J, Fan S, He W, Deng H, Nan F, Li J, Rao Z*, Lou Z*, Xie D*. DWARF14 is a non-canonical hormone receptor for strigolactone. Nature. 2016 Aug 25;536(7617):469-73.

(18) Wang X, Ren J, Gao Q, Hu Z, Sun Y, Li X, Rowlands DJ, Yin W, Wang J*, Stuart DI*, Rao Z* & Fry EE*. The structure of hepatitis A virus and the origins of picornaviruses. Nature. 2015 Jan 1;517(7532):85-8.

(19) Yuan P, Bartlam M, Lou Z, Chen S, Zhou J, He X, Lv Z, Ge R, Li X, Deng T, Fodor E, Rao Z* & Liu Y*. Crystal structure of an avian influenza polymerase PA(N) reveals an endonuclease active site. Nature. 2009;458(7240):909-13

(20) He X, Zhou J, Bartlam M, Zhang R, Ma J, Lou Z, Li X, Li J, Joachimiak A., Zeng Z, Ge R, Rao Z* & Liu YF*. Crystal structure of the polymerase PA(C)-PB1(N) complex from an avian influenza H5N1 virus Nature. 2008;454(7208):1123-6.

(21) Sun F, Huo X, Zhai YJ, Wang AJ, Xu JX, Su D, Bartlam M & Rao Z*. Crystal Structure of Mitochondrial Respiratory Membrane Protein Complex Ⅱ. Cell. 2005;121:1043-1057

(22) Rao Z, Belyaev A, Fry E, Jones I, Roy P & Stuart D. Crystal Structure of SIV Matrix Antigen and its Implications for Virus Assembly. Nature. 1995;378(6558):743-747

(23) Rao Z, Handford P, Mayhew M, Knott V, Brownlee G & Stuart D. The Structure of a Calcium Binding Epidermal Growth Factor-like Domain - its Role in Protein-Protein Interactions. Cell. 1995;82(1):131-141


Contacts

Email: raozh at mail.tsinghua.edu.cn

Phone: +86-10-62771493