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Shin-Ru Shih

Shin-Ru Shih

shu\in-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. 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.)

  2. Huang KY, Chen MF, Huang YC, Shih SR, Chiu CH, Lin JJ, Wang JR, Tsao KC, Lin TY. Epitope-associated and specificity-focused features of EV71-neutralizing antibody repertoires from plasmablasts of infected children. Nat Commun. 2017 Oct 2;8(1):762. doi: 10.1038/s41467-017-00736-9.

  3. Chen CJ, Wu GH, Kuo RL, *Shih SR. Role of the intestinal microbiota in the immunomodulation of influenza virus infection. Microbes Infect. 2017 Dec;19(12):570-579. doi: 10.1016/j.micinf.2017.09.002.

  4. Chang CK, Chen CJ, Wu CC Chen SW, Shih SR, Kuo RL. Cellular hnRNP A2/B1 interacts with the NP of influenza A virus and impacts viral replication. PLoS One. 2017 Nov 16;12(11):e0188214. doi: 10.1371/journal.pone.0188214.

  5. 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.) 

  6. 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 17;13(5):e1006375. doi: 10.1371/journal.ppat.1006375.

  7. 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. 2017 Jun 13;8(3). pii: e00481-17. doi: 10.1128/mBio.00481-17.

  8. Huang CG, Lee LA, Fang TJ, Li HY, Liao CT, Kang CJ, Yen TC, Tsao KC, Chen TC, Shih SR. Human papillomavirus infection is not associated with laryngeal squamous cell carcinoma in Taiwan. J Microbiol Immunol Infect. 2018 Feb 21. pii: S1684-1182(18)30047-1. doi: 10.1016/j.jmii.2018.02.002

  9. Huang CG, Lee LA, Wu YC, Hsiao MJ, Horng JT, Kuo RL, Huang CH, Lin YC, Tsao KC, Chen MC, Chen TC, Shih SR. A pilot study on primary cultures of human respiratory tract epithelial cells to predict patients' responses to H7N9 infection. Oncotarget. 2018 Feb 20;9(18):14492-14508. doi: 10.18632/oncotarget.24537. 

  10. 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.

  11. 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.

  12. 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]

  13. 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.

  14. 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.

  15. 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.

  16. 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]

  17. Lin RW, Chen GW, Sung HH, Lin RJ, Yen LC, Tseng YL, Chang YK, Lien SP, Shih SR, Liao CL. Naturally occurring mutations in PB1 affect influenza A virus replication fidelity, virulence and adaptability. J Biomed Sci. 2019 Jul 31;26(1):55. doi: 10.1186/s12929-019-0547-4

  18. Li ML, Lin JY, Chen BS, Weng KF, Shih SR, Calderon JD, Tolbert BS, Brewer G. EV71 3C protease induces apoptosis by cleavage of hnRNP A1 to promote apaf-1 translation. PLoS One. 2019 Sep 9;14(9):e0221048. doi: 10.1371/journal.pone.0221048.

  19. Lin JY, Kung YA, *Shih SR. Antivirals and vaccines for enterovirus A71. J Biomed Sci. 2019 Sep 3;26(1):65. doi: 10.1186/s12929-019-0560-7. Review.

  20. Huang CT, Hung CY, Hseih YC, Chang CS, Velu AB, He YC, Huang YL, Chen TA, Chen TC, Lin CY, Lin YC, Shih SR, Dutta A.Effect of aloin on viral neuraminidase and hemagglutinin-specific T cell immunity in acute influenza. Phytomedicine. 2019 Nov;64:152904. doi: 10.1016/j.phymed.2019.152904. Epub 2019 Apr 4.

  21. Lee KM, Gong YN, *Shih SR. Methods for detection and study of virus-derived small RNAs produced from the intramolecular base-pairing region of the picornavirus genome. Methods. 2019 Sep 5. pii: S1046-2023(19)30192-6. doi: 10.1016/j.ymeth.2019.08.011. [Epub ahead of print] Review.

  22. Liu YC , Kuo RL, *Shih SR. COVID-19: The first documented coronavirus pandemic in history. Biomedical Journal.2020 April. https://doi.org/10.1016/j.bj.2020.04.007.

  23. Huang CG, Lee KM, Hsiao MJ, Yang SL, Huang PN, Gong YN, Hsieh TH, Huang PW, Lin YJ, Liu YC, Tsao KC, *Shih SR. Culture-based virus isolation to evaluate potential infectivity of clinical specimens tested for COVID-19. Journal of Clinical Microbiology, 2020 Jul 23;58(8):e01068-20. doi: 10.1128/JCM.01068-20. Print 2020 Jul 23.PMID: 32518072 

  24. Zhou D, Duyvesteyn HME, Chen CP, Huang CG, Chen TH, Shih SR, Lin YC, Cheng CY, Cheng SH, Huang YC, Lin TY, Ma C, Huo J, Carrique L, Malinauskas T, Ruza RR, Shah PNM, Tan TK, Rijal P, Donat RF, Godwin K, Buttigieg KR, Tree JA, Radecke J, Paterson NG, Supasa P, Mongkolsapaya J, Screaton GR, Carroll MW, Gilbert-Jaramillo J, Knight ML, James W, Owens RJ, Naismith JH, Townsend AR, Fry EE, Zhao Y, Ren J, Stuart DI, Huang KA. Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient.Nat Struct Mol Biol. 2020 Jul 31. doi: 10.1038/s41594-020-0480-y. Online ahead of print.PMID: 32737466

  25. Gong YN, KC Tsao, Hsiao MJ, Huang CG, Huang PN, Huang PW, Lee KM, Liu YC, Yang SL, RL Kuo, Chen KF, Liu YC Huang SY, Huang HI, Liu MT, Yang JR, Chiu CH, Yang CT, Chen GW, *Shih SR. SARS-CoV-2 genomic surveillance in Taiwan revealed novel ORF-8 deletion mutant and clade associated with infections in Middle East. Emerging Microbes and Infections, 2020 Dec;9(1):1457-1466. doi: 10.1080/22221751.2020.1782271.

  26. Hung HC, Ke YY, Huang SY, Huang PN, Kung YA, Chang TY, Yen KJ, Peng TT, Chang SE, Huang CT, Tsai, YR, Wu SH, Lee SJ, Lin JH, Liu BS, Sung WC, *Shih SR, Chen CT, J, Hsu. Discovery of M protease inhibitors encoded by SARS-CoV-2. Antimicrob Agents Chemother. 2020 Aug 20;64(9):e00872-20. doi: 10.1128/AAC.00872-20. Print 2020 Aug 20.

  27. Huang KA, Tan TK, Chen TH, Huang CG, Harvey R, Hussain S, Chen CP, Harding A, Gilbert-Jaramillo J, Liu X, Knight M, Schimanski L, Shih SR, Lin YC, Cheng CY, Cheng SH, Huang YC, Lin TY, Jan JT, Ma C, James W, Daniels RS, McCauley JW, Rijal P, Townsend AR. Breadth and function of antibodies to acute SARS-CoV-2 infection in humans. PLoS Pathog. 2021 Feb 26;17(2):e1009352. doi: 10.1371/journal.ppat.1009352. Online ahead of print.

  28. Huang SY, Kung YA, Huang PN, Chang SY, Gong YN, Han YJ, Chiang HJ, Liu KT, Lee KM, Chang CY, Chang CC, Huang CG, *Shih SR. Stability of SARS-CoV-2 Spike G614 Variant Surpasses that of the D614 Variant after Cold Storage. mSphere. 2021 Mar 31;6(2):e00104-21. doi: 10.1128/mSphere.00104-21.

  29. Kiew LV, Chang CY, Huang SY, Wang PW, Heh CH, Liu CT, Cheng CH, Lu YX, Chen YC, Huang YX, Chang SY, Tsai HY, Jung YA, Huang PN, Hsu MH, Leo BF, Foo YY, Su CH, Hsu KC, Huang PH, Ng CJ, Kamarulzaman A, Yuan CJ, Shieh DB, *Shih SR, Chung LY, Chang CC. Development of flexible electrochemical impedance spectroscopy-based biosensing platform for rapid screening of SARS-CoV-2 inhibitors. Biosensor and Bioelectronics, 2021 Apr 3;183:113213. doi: 10.1016/j.bios.2021.113213. Online ahead of print.PMID: 33857754 .