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施信如 講座教授

 

施 信 如 (Shin-Ru Shih)
施信如

學歷

美國紐澤西羅格斯大學分子生物及生物化學博士

任課科目

臨床病毒學(實驗及實習) 、分子生物學、細胞生物學

研究專長

Clinical Virology、Biotechnology、Molecular Biology、Biochemistry

辦公室分機

5497

實驗室分機

3725

個人網頁

分子病毒實驗室

E-mail

srshih@mail.cgu.edu.tw

研究方向及研究室特色(Lab & Research Interest)

 

我們實驗室主要致力於新興病毒的研究，尤其是流感病毒及腸病毒71型這兩個容易有變異的RNA病毒。研究的方向包括(1)新型(突變株)病毒的檢驗(2)病毒與宿主互動的研究(3)抗病毒藥物的研發。

在新型病毒的檢驗方面，我們以特別的細胞株(例如某種基因缺陷或大量表達的細胞株)來培養病毒，加上各種不同的分子檢驗方式偵測鑑定新型病毒。而在病毒與宿主互動的研究方面，我們致力於宿主蛋白質如何調控病毒基因的複製及病毒蛋白質如何干擾宿主細胞基因的表達與調控，藉由病毒與宿主互動的研究，讓我們了解流感病毒跨越宿主的機制，也讓我們了解腸病毒71型的分子致病機轉。而病毒與宿主互動的研究，也讓我們從中發掘重要的分子標的，進一步研發抗病毒藥物。

 

論文與著作(Publication)

 五年內論文：

1.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

2. 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. 

3. 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.

4.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.

5. 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]

6.  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.

7. 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.

8. 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;100(5):752-759. doi: 10.1099/jgv.0.001258. Epub 2019 Apr 17.

9. 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 15;17:10-23. doi: 10.1016/j.omtn.2019.04.028. [Epub ahead of print]

10. 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

11. 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 9;14(9):e0221048. doi: 10.1371/journal.pone.0221048.

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

13. 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 ;64:152904. doi: 10.1016/j.phymed.2019.152904. Epub 2019 Apr 4.

14. 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. pii: S1046-2023(19)30192-6. doi: 10.1016/j.ymeth.2019.08.011. [Epub ahead of print] Review.

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

16. 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 

17. 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

18. 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.

19. Huang KA, Huang PN, Huang YC, Yang SL, Tsao KC, Chiu CH, Shih SR, Lin TY. Emergence of genotype C1 Enterovirus A71 and its link with antigenic variation of virus in Taiwan. PLoS Pathog. 2020 Sep 16;16(9):e1008857. doi: 10.1371/journal.ppat.1008857. eCollection 2020 Sep.

20. 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.

21. Wang HC, Hung HC, Huang PN, Kung YA, Tseng SN, Wang YM, Shih SR, Tsu-An Hsu J. Engineering a novel IgG-like bispecific antibody against enterovirus A71. Biochem Biophys Rep. 2020 Dec 5;24:100860. doi: 10.1016/j.bbrep.2020.100860. eCollection 2020 Dec.

22. Wang HC, Huang PN, Hung HC, Tseng SN, Chang CC, Tsai YR, Wang YM, Shih SR, Hsu JT. Effect of a Neuropilin-1-Derived Virus Receptor Trap on  Enterovirus A71 Infection In Vitro. Antimicrob Agents Chemother. 2020 Dec 16;65(1):e00695-20. doi: 10.1128/AAC.00695-20. Print 2020 Dec 16.

23. Li ML, Chen BS, Shih SR. Editorial: Viral Encephalitis. Front Microbiol. 11:599257. doi: 10.3389/fmicb.2020.599257. eCollection 2020.

24. 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.

25. 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 .

26. Liu YC, Mok BW, Wang P, Kuo RL, Chen H, *Shih SR. Cellular 5’-3’ mRNA exoribonuclease XRN1 inhibits interferon beta activation and facilitates influenza A virus replication. mBio. 2021 Aug 31;12(4):e0094521. doi: 10.1128/mBio.00945-21. Epub 2021 Jul 27.

27. Janissen R, Woodman A, Shengjuler D, Vallet T, Lee KM, Kuijpers L, Moustafa IM, Fitzgerald F, Huang PN, Perkins AL, Harki DA, Arnold JJ, Solano B, Shih SR, Vignuzzi M, Cameron CE, Dekker NH. Induced intra- and intermolecular template switching as a therapeutic mechanism against RNA viruses Mol Cell. 2021 Nov4;81(21): 4467-4480.e7.doi:10.1016/ j.molcel. 2021.10.003. Epub 2021 Oct 22.PMID: 34687604.

28. Hsieh SM, Liu MC, Chen YH, Lee WS, Hwang SJ, Cheng SH, Ko WC, Hwang KP, Wang NC, Lee YL, Lin YL, Shih SR, Huang CG, Liao CC, Liang JJ, Chang CS, Chen C, Lien CE, Tai IC, Lin TY. Safety and immunogenicity of CpG 1018 and aluminium hydroxide-adjuvanted SARS-CoV-2 S-2P protein vaccine MVC-COV1901: interim results of a large-scale, double-blind, randomised, placebo-controlled phase 2 trial in Taiwan. Lancet Respir Med. 2021 Dec;9(12):1396-1406. doi: 10.1016/S2213-2600(21)00402-1. Epub 2021 Oct 13.PMID: 34655522.

29. Chen YC, Kung YA, Janapatla RP, Hsu MH, Lien R, Chen JC, Shih SR, Chiu CH. Neutralization antibody titers against SARS-CoV-2 in an infant born to a mother with COVID-19. Pediatr Neonatol. 2021 Nov;62(6):661-663. doi: 10.1016/j.pedneo.2021.07.007. Epub 2021 Sep 10.

30. Li ML, Shih SR, Tolbert BS, Brewer G. Enterovirus A71 Vaccines. Vaccines (Basel). 2021 Feb 27;9(3):199. doi: 10.3390/vaccines9030199.

31. Kuo RL, Chen YT, Li HA, Wu CC, Chiang HC, Lin JY, Huang HI, Shih SR, Chin-Ming Tan B. Molecular determinants and heterogeneity underlying host response to EV-A71 infection at single-cell resolution. RNA Biol. 2021 May;18(5):796-808. doi: 10.1080/15476286.2021.1872976. Epub 2021 Feb 23.

32. 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.

33. Mwale PF, Lee CH, Huang PN, Tseng SN, Shih SR, Huang HY, Leu SJ, Huang YJ, Chiang LC, Mao YC, Wang WC, Yang YY. In Vitro Characterization of Neutralizing Hen Antibodies to Coxsackievirus A16 . Int J Mol Sci. 2021 Apr 16;22(8):4146. doi: 10.3390/ijms22084146.

34. Lee KM, Wu CC, Wu SE, Lin YH, Wang LT, Chang CR, Huang PN, Shih SR, Kuo RL. The RNA-dependent RNA polymerase of enterovirus A71 associates with ribosomal proteins and positively regulates protein translation. RNA Biol.17(4):608-622. doi: 10.1080/15476286.2020.1722448. Epub 2020 Feb 6. PMID: 32009553

35.Huang CG, Dutta A, Huang CT, Chang PY, Hsiao MJ, Hsieh YC, Lin SM, Shih SR, Tsao KC, Yang CT. Relative COVID-19 Viral Persistence and Antibody Kinetics. Pathogens. 2021 Jun 13;10(6):752. doi: 10.3390/pathogens10060752.

36. Hsieh SM, Liu WD, Huang YS, Lin YJ, Hsieh EF, Lian WC, Chen C, Janssen R, Shih SR, Huang CG, Tai IC, Chang SC. Safety and immunogenicity of a Recombinant Stabilized Prefusion SARS-CoV-2 Spike Protein Vaccine (MVC-COV1901) Adjuvanted with CpG 1018 and Aluminum Hydroxide in healthy adults: A Phase 1, dose-escalation study. EClinicalMedicine. 100989. doi: 10.1016/j.eclinm.2021.100989. Online ahead of print. PMID: 34222848

37. Lin JY, Weng KF, Chang CK, Gong YN, Huang GJ, Lee HL, Chen YC, Huang CC, Lu JY, Huang PN, Chiang HJ, Chen CM, *Shih SR. Enterovirus A71 Induces Neurological Diseases and Dynamic Variants in Oral Infection of Human SCARB2-Transgenic Weaned Mice. J Virol. 2022. JVI0089721. doi: 10.1128/JVI.00897-21. Online ahead of print. PMID: 34379497

38. Kung YA, Chiang HJ, Li ML, Gong YN, Chiu HP, Hung CT, Huang PN, Huang SY, Wang PY, Hsu TA, Brewer G, *Shih SR. Acyl-Coenzyme A Synthetase Long-Chain Family Member 4 Is Involved in Viral Replication Organelle Formation and Facilitates Virus Replication via Ferroptosis.  mBio. 2022. e0271721. doi: 10.1128/mbio.02717-21. Online ahead of print. PMID: 35038927

39. Chen CY, Liu KT, Shih SR, Ye JJ, Chen YT, Pan HC, Hsu HJ, Sun CY, Lee CC, Wu CY, Lai CC, Wu IW. Neutralization Assessments Reveal High Cardiothoracic Ratio and Old Age as Independent Predictors of Low Neutralizing Antibody Titers in Hemodialysis Patients Receiving a Single Dose of COVID-19 Vaccine. J Pers Med. 12(1):68. doi: 10.3390/jpm12010068. PMID: 35055386.

40. Liu KT, Gong YN, Huang CG, Huang PN, Yu KY, Lee HC, Lee SC, Chiang HJ, Kung YA, Lin YT, Hsiao MJ, Huang PW, Huang SY, Wu HT, Wu CC, Kuo RL, Chen KF, Hung CT, Oguntuyo KY, Stevens CS, Kowdle S, Chiu HP, Lee B, Chen GW, *Shih SR. Quantifying Neutralizing Antibodies in Patients with COVID-19 by a Two-Variable Generalized Additive Model. mSphere.e0088321. doi: 10.1128/msphere.00883-21. Online ahead of print. PMID: 35107336

41. Kung YA, Lee KM, Chiang HJ, Huang SY , Wu CJ, *Shih SR. Molecular Virology of SARS-CoV-2 and Related Coronaviruses. Microbiology and Molecular Reviews. 2022 Mar 28:e0002621. doi: 10.1128/mmbr.00026-21. Online ahead of print.PMID: 35343760

42. Nguyen TT, Chiu CH, Lin CY, Chiu NC, Chen PY, Le TTV, Le DN, Duong AH, Nguyen VL, Huynh TN, Truong HK, Phan TL, Nguyen TTT, Shih SR, Huang CG, Weng YJ, Hsieh EF, Chang S, Chen C, Tai IC, Huang LM. Efficacy, safety, and immunogenicity of an inactivated, adjuvanted enterovirus 71 vaccine in infants and children: a multiregion, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet. 2022 Apr 12:S0140-6736(22)00313-0. doi: 10.1016/S0140-6736(22)00313-0. Epub ahead of print. PMID: 35427481.

43. Gong YN, KM Lee, *Shin SR. Evolution and epidemiology of SARS-CoV-2 Virus. Methods Mol Biol. 2022.PMID: 35554897.

44. Hsieh SM, Chang SC, Cheng HY, Shih SR, Lien CE Durability and Immunogenicity of Neutralizing Antibodies Response Against Omicron Variants After Three Doses of Subunit SARS-CoV-2 Vaccine MVC-COV1901: An Extension to an Open-Label, Dose-Escalation Phase 1 Study. Infect Dis Ther. 2022.PMID: 35579840.

45. Chen CP, Huang KA, Shih SR, Lin YC, Cheng CY, Huang YC, Lin TY, Cheng SH. Anti-Spike Antibody Response to Natural Infection with SARS-CoV-2 and Its Activity against Emerging Variants. Microbiol Spectr. 2022 Aug 31;10(4):e0074322. doi: 10.1128/spectrum.00743-22. Epub 2022 Jun 15.PMID: 35703556

46. Chiu YF, Huang YW, Chen CY, Chen YC, Gong YN, Kuo RL, Huang CG, Shih SR. Visualizing Influenza A Virus vRNA Replication. Front Microbiol. 2022 Jun 6;13:812711. doi: 10. 3389/ fmicb.2022.812711. eCollection 2022. PMID: 35733972

47. Chen CY, Liu KT, Shih SR, Ye JJ, Chen YT, Hsu CK, Pan HC, Hsu HJ, Sun CY, Lee CC, Wu CY, Lai CC, Wu IW. Adequacy of Hemodialysis Serves as an Independent Predictor of Humoral Response to ChAdOx1 Prime-Boost Vaccination in Hemodialysis Patients. Viruses. 2022 May 26;14(6):1149. doi: 10.3390/v14061149.PMID: 35746621

48. Wang PJ, Pang YH, Huang SY, Fang JT, Chang SY, Shih SR, Huang TW, Chen YJ, Sun CK. Microwave resonant absorption of SARS-CoV-2 viruses. Sci Rep. 2022 Jul 22;12(1):12596. doi: 10.1038/s41598-022-16845-5.PMID: 35869163

49. Kung YA, Huang SY, Huang CG, Liu KT, Huang PN, Yu KY, Yang SL, Chen CP, Cheng CY, Lee IK, Lin SM, Chang HP, Lin YT, Liu YC, Chen GW, *Shih SR. Factors influencing neutralizing antibody titers elicited by coronavirus disease 2019 vaccines. Microbes Infect. 2022 Sep 9:105044. doi: 10.1016/j.micinf.2022.105044. Online ahead of print.PMID: 36096357

50. Chen CJ, Yang LY, Chang WY, Huang YC, Chiu CH, Shih SR, Huang CG, Huang KA. A randomized controlled trial of heterologous ChAdOx1 nCoV-19 and recombinant subunit vaccine MVC-COV1901 against COVID-19. Nat Commun. 2022 Sep 17;13(1):5466. doi: 10.1038/s41467-022-33146-7.PMID: 36115850

 

 

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