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Shin-Ru Shih

Shin-Ru Shih

Highest Degree

Ph. D. in Virology Rutgers University

Areas of Specialty

Clinical Virology、Biotechnology、Molecular Biology、Biochemistry

Office Phone

5497

Lab phone

5497

Research website:

Research Center for Emerging Viral Infections

E-mail

srshih@mail.cgu.edu.tw

Lab & Research Interest

Research interests

Translational Research: from Basic Molecular Virology to Clinical Virology and Antiviral Research

 (Enterovirus 71 and Influenza Virus Researches)

Our team has been studying the emerging RNA viruses in many aspects, including identification of unknown viruses using novel biotechnology, pathogenesis study of those RNA viruses and antiviral developments. Our study of EV71 began in 1998, in which a large EV71 outbreak in Taiwan led to 78 mortalities. Our participation contributed significantly to the laboratory diagnosis of this virus in the outbreak. Our subsequent efforts focused on viral-host interactions, in which molecular targets for drug discovery were identified. Two series of compounds were also developed that inhibit EV71 replication, pyridyl imidazolidinones and pyrazolo[3,4-d]pyrimidines (targeting capsid protein VP1 and 3D polymerase, respectively). I was bestowed the National Medal for Outstanding Youth in 2004 for contributing to EV71 research in Taiwan. 

I received training in another RNA virus, influenza virus, and a Ph.D. in Molecular Virology at Rutgers University in the United States. Upon returning to Taiwan in 1996, I established the Molecular Virology Laboratory at Chang Gung University, having published more than 70 papers (nearly 50 over the past five years) on emerging RNA viruses, e.g., enteroviruses, SARS coronaviruses and influenza viruses. These papers have been cited at least 500 times over the past five years. Results of our study have also led to eight patents granted.

(I)    EV71 research

Our research efforts involving EV71 over the past decade have received international recognition. Previously, I served as the Executive Editor of Current Pharmaceutical Design, responsible for editing review articles on antiviral research. Following recognition of our anti-EV71 research by the Journal of Antimicrobial Chemotherapy, the journal invited me to contribute a “Leading Article”. In addition to the international recognition of our antiviral research in EV71, our basic virology and pathogenesis studies of EV71 have yielded increasingly fruitful results in recent years. More recently, I served as the host convener of a session on RNA viruses (Positive Strand RNA Viruses and Host Proteins Interactions) at the annual meeting of the American Society for Virology. Another notable index is our publishing of a series of papers in renowned international journals such as Nucleic Acids Research and PLoS Pathogens. The latest article in PLoS Pathogens describes a novel finding that EV71 protease 3C cleaves CstF-64 and inhibits cellular polyadenylation. The significance and novelty of our finding extend the scope of the research field of viral host interactions in picornaviruses. This explains why this article appeared in PLoS Pathogens, a prestigious journal with a high impact factor [impact factor = 9.125; 5/91 in the field of microbiology (the first four are review journals)].

(II)       Influenza virus research

Later on in 2004, with the emerging threat of avian influenza virus, our research group has devoted considerable efforts to influenza virus, including laboratory-based surveillance, viral-host interplay and antiviral development. I have conducted influenza virus research since my Ph.D. study, which allowed me to monitor the progress of this competitive research field. Over the past five years, we have published a series of articles in the Journal of Clinical Microbiology, Emerging Infectious Diseases, and Journal of Virology. The swine-origin influenza A H1N1 virus has spread rapidly worldwide recently. Based on our research capabilities cultivated in recent years, we have successfully established a rapid laboratory diagnostics procedure for this new N1N1 virus. We have also identified several molecular signatures that may serve as important virulence markers for the new H1N1 virus. The manuscript about this work has been accepted for publication by Emerging Infectious Diseases. The timely publication (several months after the new outbreak) of our research findings demonstrates our capability in actively researching emerging RNA viruses.

(III)     Others

Our team is widely recognized as a friendly collaborator in virus research worldwide. We have provided many timely materials (e.g., virus isolates, plasmids harboring viral genes, diagnostic reagents and antibodies) and protocols to many researchers, as well as provided the training programs of several special techniques in RNA virus research (e.g., reverse genetics, and plaque reduction assay) to other groups. Given the above contributions, I have been invited numerous times to several institutes for scientific talks, leading to the establishment of several international collaborations (e.g., Pasteur Institutes in Paris and in Shanghai, University of Hong Kong, and University of Medicine and Dentistry in New Jersey, United States.).

(IV) Summary:

Our laboratory over the past decade has actively researched on topics involving the EV71 outbreak, the SARS outbreak and several influenza endemics. I have published 30 first or corresponding author papers over the past five years. Those papers completed in Taiwan have been cited over 500 times over the past five years. These numbers reflect our contributions to emerging virus research. Our recently papers in the Journal of Virology, Journal of Infectious Diseases, Emerging Infectious Diseases, Nucleic Acids Research and PLoS Pathogens attest to our globally recognized contribution in the field of virus infection. Our efforts are underway to continue with translational research of emerging virus, i.e. from the basic virology to applied diagnostic virology and antiviral development. Hopefully, our efforts will provide valuable reagents, information and antivirals that are timely for a future outbreak of the RNA virus. As our long term study in the past has laid the foundation, our future efforts will build upon this knowledge to further elucidate the emerging RNA virus, as well as contribute to controlling and preventing viral infections.

Publication

  1. Liu YC, Kuo RL, Lin JY, Huang PN, Huang Y, Liu H, Arnold, JJ, Chen SJ, Wang, RY, Cameron CE and *Shih SR. Cytoplasmic viral RNA-dependent RNA polymerase disrupts the intracellular splicing machinery by entering nucleus and interfering with Prp8. PLoS Pathogens, 2014; 10(6):e1004199.
  2. Huang PN and *Shih SR. Update on enterovirus 71 infection. Current Opinion in Virology, 2014; 98-104. doi: 10.1016/j.coviro.2014.03.007..

  3. Kung YA, CT Hung, YC Liu and *Shih SR. Update on the development of enterovirus 71 vaccines. Expert Opinion On Biological Therapy, 2014; 14(10):1455-64.

  4. Weng KF, Hung CT, Hsieh PT, Li ML, Chen GW, Kung YA, Huang PN, Kuo RL, Chen LL, Lin JY, Wang RYL, Chen SJ, Tang P, Horng JT, Huang HI, Wang JR, Ojcius DM, Brewer G and *Shih SR. A Cytoplasmic RNA Virus Generates Functional Viral Small RNAs and Regulates Viral IRES Activity in Mammalian Cells. Nucleic Acids Research, 2014 Nov 10;42(20):12789-805.

  5. Balaji VA, Chen GW, Hsieh PT, Horng JT, Hsu JT, Hsieh HP, Chen TC, Weng KF and *Shih SR. BPR-3P0128 inhibits RNA-dependent RNA polymerase elongation and VPg uridylylation activities of enterovirus 71. Antiviral Research, 2014 Dec;112:18-25.

  6. Chen YH, Chang GK, Kuo SM, Huang SY, Hu IC, Lo YL,*Shih SRWell-tolerated Spirulina extract inhibits influenza virus replication and reduces virus-induced mortality. Sci Rep. 2016 Apr 12;6:24253. doi: 10.1038/srep24253.

  7. Chen MF, Weng KF, Huang SY, Liu YC , Tseng SN ,David M. Ojcius, *Shih SR . Pretreatment with a heat-killed probiotic modulates monocyte chemoattractant protein-1 and reduces the pathogenicity of influenza and enterovirus 71 infections. Mucosal Immunology. 016 Apr 13. doi: 10.1038/mi.2016.31. [Epub ahead of print]

  8.  Hung CT, Kung YA, Lai ML, Brewer G, Liu ST, *Shih SR. Additive promotion of viral internal ribosomal entry site-mediated translation by far upstream element-binding protein 1 and an enterovirus 71-induced cleavage product. PLoS Pathogens. 2016 Oct 25;12(10):e1005959. doi: 10.1371/ journal.ppat.1005959.

  9. Kung YA, Hung CT, Chien KY, *Shih SR Control of the downregulating IRES trans-acting factor KSRP by ubiquitination. Nucleic Acids Res., 2017, 45:1, 271-287. (doi: 10.1093/nar/gkw1042.)

  10. Lee KM, Chen CG, *Shih SR. Viral internal ribosome entry site-dependent translation. Trends in Microbiology, 2017, 25:7, 546-561. (pii: S0966-842X(17)30022-7. doi: 10.1016/j.tim.2017.01.010.) 

  11.  Huang PN, Jheng JR, Arnold JJ, Wang JR, Cameron CE, *Shih SR. UGGT1 enhances enterovirus 71 pathogenicity by promoting viral RNA synthesis and viral replication. PLoS Pathogens. 2017 May 17;13(5):e1006375. doi: 10.1371/journal.ppat.1006375. eCollection 2017 May.PMID:28545059

  12. Kuo SM, Chen CJ, Chang SC, Liu TJ, Chen YS, Huang SY, *Shih SR. Inhibition of avian influenza A virus replication in human cells by host restriction factor TUFM is correlated with autophagy. mBio, in press, 2017. 

  13. Lee KM, Gong YN, Hsieh TH, Woodman A, Dekker NH, Cameron CE,*Shih SR. Discovery of enterovirus A-like nonstructural genomes in recent circulating viruses of the enterovirus A species. Emerging Microbes and Infections, 2018 Jun 21;7(1):111. doi: 10.1038/s41426-018-0107-0.

  14. Gong YN, RL Kuo, Chen GW, *Shih SR.  Centennial review of influenza in Taiwan, Biomedical Journal, 2018 Aug;41(4):234-241. doi: 10.1016/j.bj.2018.08.002. Epub 2018 Sep 10. Review.

  15. Yeung ML, Jia L, Yip CC, Chan JF, Teng JL, Chan KH, Cai JP, Zhang C, Zhang AJ, Wong WM, Kok KH, Lau SK, Woo PC, Lo JY, Jin DY, Shih SR, Yuen KY. Human tryptophanyl-tRNA synthetase is an IFN-γ-inducible entry factor for Enterovirus. J Clin Invest. 2018 Aug 28. pii: 99411. doi: 10.1172/JCI99411. [Epub ahead of print]

  16. Woodman A, Lee KM, Janissen R, Gong YN, Dekker N, Shih SR, Cameron CE. Predicting intraserotypic recombination in enterovirus 71. J Virol. 2019 Feb 5;93(4). pii: e02057-18. doi: 10.1128/JVI.02057-18. Print 2019 Feb 15.

  17. Kuo RL, Chen CJ, Wang RYL, Huang HI, Lin YH, Tam EH, Tu WJ, Wu SE, Shih SR. Role of enteroviral RNA-depedent RNA polymerase in regulation of MDA5-mdiated beta interferon activation. J Virol. 2019 May 1;93(10). pii: e00132-19. doi: 10.1128/JVI.00132-19. Print 2019 May 15.

  18. Gong YN, Tsao KC, Chen GW, Wu CJ, Chen YH, Liu YC, Yang SL, Huang YC, Shih SR. Population dynamics at neuraminidase position 151 of influenza A (H1N1)pdm09 virus in clinical specimens. J Gen Virol. 2019 May;100(5):752-759. doi: 10.1099/jgv.0.001258. Epub 2019 Apr 17.

  19. Huang SY, Huang CH, Chen CJ, Chen TW, Lin CY, Lin YT, Kuo, SM, Huang CG, Lee LA, Chen YH, Chen MF, Kuo RL and *Shih SR. Novel role of miR-1290 in host species specificity of influenza A virus. Mol Ther Nucleic Acids. 2019 May 15;17:10-23. doi: 10.1016/j.omtn.2019.04.028. [Epub ahead of print]