ZHANG KePh.D.
- Academic title：Principal Investigator
- Discipline：Regulation of Viral and Host Gene Expression
- Departments：Viral Infection and RNA Metabolism
- Phone：86-21-54923061
- E-mail：kzhang6@siii.cas.cn
- Mailing Address：Life Science Research Building, 320 Yueyang Road, Xuhui District, Shanghai 200031, P.R. China
Academic Experience
2021.11-present, Principal investigator, Shanghai Institute of Immunity and Infection, CAS
2019.04-2021.10, Research Associate, University of Texas Southwestern Medical Center
2013.03-2019.03, Postdoctoral fellow, University of Texas Southwestern Medical Center
Education
2005-2012, Ph.D., Institute of Microbiology, CAS
2001-2005, BS, Beijing Forestry University
Our lab has been working on investigating the molecular mechanisms of viral-host interactions. Our main focus is on the RNA metabolism during RNA viruses (such as influenza A and vesicular stomatitis viruses) infection, aiming to developing novel antiviral strategies. Gene expression in eukaryotic cells is controlled by multiple mechanisms, including transcription and mRNA processing in the nucleus, messenger RNA (mRNA) export from nucleus to the cytoplasm, and translation in the cytoplasm. During infection, viruses suppress host gene expression pathways using different strategies. One the other hand, viruses favor their own replication by using host gene expression system. We will the determine the molecular mechanism that how viruses inhibit the host mRNA nuclear export pathway, promote the degradation of host mRNA. We will also investigate the new mechanism that how viruses promote their replication by using host transcription, mRNA splicing, and mRNA nuclear export machineries. These areas of research will lead to new insights into host-viruses interaction and will provide a platform for exploring novel therapeutics targets for developing antiviral drugs. By using the combination of Molecular virology, Cell biology, Biochemistry and Animal models approaches, the overarching goals of our research are to:
(1) Investigate the regulation of host RNA metabolism during viral infection
(2) Determine the molecular mechanism of viral RNA metabolism regulation
(3) Identify novel chemical compounds to intervene viral RNA metabolism
Selected Publications (*First author, #Corresponding author)
1. Zhang K, Miorin L, Makio T, Dehghan I, Gao S, Xie Y, Zhong H, Esparza M, Kehrer T, Kumar A, Hobman TC, Ptak C, Gao B, Minna JD, Chen Z, García-Sastre A, Ren Y, Wozniak RW, Fontoura BMA. (2020) Nsp1 Protein of SARS-CoV-2 Disrupts the mRNA Export Machinery to Inhibit Host Gene Expression. Science Advances. 7(6):eabe7386. doi: 10.1126/sciadv.abe7386.
2. Miorin L, Kehrer T, Sanchez-Aparicio MT, Zhang K, Cohen P, Patel RS, Cupic A, Makio T, Mei M, Moreno E, Danziger O, White KM, Rathnasinghe R, Uccellini M, Gao S, Aydillo T, Mena I, Yin X, Martin-Sancho L, Krogan NJ, Chanda SK, Schotsaert M, Wozniak RW, Ren Y, Rosenberg BR, Fontoura BMA, García-Sastre A. (2020) SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling. PNAS. 117(45):28344-28354. doi: 10.1073/pnas.2016650117
3. Zhang K*, Xie Y*, Mu？oz-Moreno R, Wang J, Zhang L, Esparza M, García-Sastre A, Fontoura BMA, Ren Y. (2019) Structural Basis for Influenza Virus NS1 Protein Block of mRNA Nuclear Export. Nature Microbiology. 4(10):1671-1679. doi: 10.1038/s41564-019-0482-x (* Co-first author).
4. Zhang K, Shang G, Padavannil A, Wang J, Sakthivel R, Chen X, Kim M, Thompson MG, García-Sastre A, Lynch KW, Chen ZJ, Chook YM, Fontoura BMA. (2018) Structural–functional interactions of NS1-BP protein with the splicing and mRNA export machineries for viral and host gene expression. PNAS. 115(52):E12218-E12227. doi: 10.1073/pnas.1818012115.
5. Mor A, White A, Zhang K, Thompson M, Esparza M, Mu？oz-Moreno R, Koide K, Lynch KW, García-Sastre A, Fontoura BMA. (2016) Influenza virus mRNA trafficking through host nuclear speckles. Nature Microbiology. 1(7):16069. doi: 10.1038/nmicrobiol.2016.69.
6. Zhang K*, Wang Z*, Fan G, Wang J, Gao S, Li Y, Sun L, Yin C, Liu W. (2015) Two polar residues within C- terminal domain of M1 are critical for the formation of influenza A Virions. Cellular Microbiology 17(11): 1583-93. doi: 10.1111/cmi.12457 (* Co-first author).
7. Yarbrough ML, Zhang K, Sakthivel R, Forst CV, Posner BA, Barber GN, White MA, Fontoura BMA. (2014) Primate-specific miR-576-3p sets host defense signalling threshold. Nature Communications 5: 4963. doi: 10.1038/ncomms5963.
8. Zhang K, Wang Z, Liu X, Yin C, Basit Z, Xia B, Liu W. (2012) Dissection of Influenza A Virus M1 Protein: pH-Dependent Oligomerization of N-Terminal Domain and Dimerization of C-Terminal Domain. PLoS ONE 7(5): e37786. doi: 10.1371/journal.pone.0037786.
Principal Investigator: ZHANG Ke
Assistant: FANG Xia
Address: Life Science Research Building 320 Yueyang Road, Xuhui District, 200031
Tel：86-21-5492 3020Fax：86-21-5492 3044Email：kefachu@siii.cas.cn
