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)

1. 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.
2. 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 .
3. 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.
4. 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.
5. 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. 
6. 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.
7. Li ML, Shih SR, Tolbert BS, Brewer G. Enterovirus A71 Vaccines. Vaccines (Basel). 2021 Feb 27;9(3):199. doi: 10.3390/vaccines9030199.
8. 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.
9. 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.
10. 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.
11. 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
12. 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.
13. 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
14. 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
15. 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
16. 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
17. 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
18. 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
19. 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.
20. Gong YN, KM Lee, *Shin SR. Evolution and epidemiology of SARS-CoV-2 Virus. Methods Mol Biol. 2022.PMID: 35554897.
21. 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.
22. 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
23. 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
24. 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
25. 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
26. 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
27. 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
28. Han YJ, Lee KM, Wu GH, Gong YN, Dutta A, *Shih SR. Targeting influenza A virus by splicing inhibitor herboxidiene reveals the importance of subtype-specific signatures around splice sites. J Biomed Sci. 2023 Feb 3;30(1):10. doi: 10.1186/s12929-023-00897-4.PMID: 36737756 
29. Wu GH, Lee KM, Kao CY, *Shih SR. The internal ribosome entry site determines the neurotropic potential of enterovirus A71. Microbes Infect. 2023 Jan 25:105107. doi: 10.1016/j.micinf.2023.105107. Online ahead of print.PMID: 36708870
30.  Chen W, Chen YH, Liao YC, Huang XW, Lu TJ, *Shih SR. Effect of hot water extracts of Arthrospira maxima (spirulina) against respiratory syncytial virus. Phytomedicine. 2023 Feb;110:154611. doi: 10.1016/j.phymed.2022.154611. Epub 2022 Dec 17.PMID: 36580819.
31. Chuang CH, Huang CG, Huang CT, Chen YC, Kung YA, Chen CJ, Chuang TC, Liu CC, Huang PW, Yang SL, Gu PW, Shih SR, Chiu CH.Titers and breadth of neutralizing antibodies against SARS-CoV-2 variants after heterologous booster vaccination in health care workers primed with two doses of ChAdOx1 nCov-19: A single-blinded, randomized clinical trial.J Clin Virol. 2022 Dec;157:105328. doi: 10.1016/j.jcv.2022.105328. Epub 2022 Nov 12.PMID: 36399969 Free PMC article. Clinical Trial.
32. Lee CH, Huang PN, Mwale PF, Wang WC, Leu SJ, Tseng SN, Shih SR, Chiang LC, Mao YC, Tsai BY, Dlamini NB, Nguyen TC, Tsai CH, Yang YY The Bottlenecks of Preparing Virus Particles by Size Exclusion for Antibody Generation. Int J Mol Sci. 2022 Oct 26;23(21):12967. doi: 10.3390/ijms232112967.PMID: 36361757 Free PMC article.
33. Mackeown M, Kung YA, Davila-Calderon J ,Ford WP ,Luo L , Henry B , Li ML,Brewer G,  Shih SR  ,Tolbert BS . The 5'UTR of HCoV-OC43 adopts a topologically constrained structure to intrinsically repress translation. JOURNAL OF BIOLOGICAL CHEMISTR.APR 2023 ;299(4). DOI10.1016/j.jbc.2023.103028.
34. Shao PL, Tu HC, Gong YN, Shu HY, Kirby R, Hsu LY, Yeo HY, Kuo HY, Huang YC, Lin YF, Weng HY, Wu YL, Chen CC, Chen TW, Lee KM, Huang CG, Shih SR, Chen WJ, Wu CC, Yu CJ, Tsai SF. Emergence and Persistent Dominance of SARS-CoV-2 Omicron BA.2.3.7 Variant, Taiwan. Emerg Infect Dis. 2023 Apr;29(4):792-796. doi: 10.3201/eid2904.221497. Epub 2023 Mar 14. PMID: 36918378
35. Reinig S, *Shih SR. Non-neutralizing functions in anti-SARS-CoV-2 IgG antibodies. Biomed J.  2024 Feb;47(1):100666. doi: 10.1016/j.bj.2023.100666. Epub 2023 Sep 29.
36. Huang CG, Wu YC, Hsieh MJ, Lin YJ, Hsieh TH, Huang PW, Yang SL, Tsao KC, Shih SR, Lee LA. Impact of patient characteristics on innate immune responses and inflammasome activation in ex vivo human lung tissues infected with influenza A virus. Front Cell Infect Microbiol. 2023 Oct 13;13:1269329. doi: 10.3389/fcimb.2023.1269329. eCollection 2023. PMID: 37900310
37. Reinig S, Kuo C, Wu CC, Huang SY, Yu JS, Shih SR. Specific long-term changes in anti-SARS-CoV-2 IgG modifications and antibody functions in mRNA, adenovector, and protein subunit vaccines. J Med Virol. 2024 Jul;96(7):e29793. doi: 10.1002/jmv.29793. PMID: 39023111.
38. Chiang HJ, Peng HH, Weng KF, Hsiung KC, Liang CY, Kuo SL, David M Ojcius ,  Young DE,  *Shih SR. Mineralo-organic particles inhibit influenza A virus infection by targeting viral hemagglutinin activity. Nanomedicine (Lond) 2024;19(28):2375-2390.doi: 10.1080/17435889.2024.2403326. Epub 2024 Sep 25.
39. Huang CG,  Hsieh MJ,  Wu YC,  Huang PW,  Lin YJ  , Tsao KC,  Shih SR,  Lee LA. Influence of Donor-Specific Characteristics on Cytokine Responses in H3N2  Influenza A Virus Infection: New Insights from an Ex Vivo Model. Int J Mol Sci2024 Oct 11;25(20):10941. doi: 10.3390/ijms252010941.
40. Hsiung KC, Chiang HJ, Sebastian Reinig,*Shih SR. "Vaccine Strategies Against RNA Viruses: Current Advances and Future Directions" Vaccines  Volume12 Issue12 DOI10.3390/vaccines12121345 .2024 Dec.
41. Huang  PN , Hsia, SH, Huang, KYA , Chen CJ , Wang  ET ,Shih SR , Lin TY. Reflecting on the 1998 enterovirus outbreak: A 25-year retrospective and learned lessons. BIOMEDICAL JOURNAL. Feb 2025. Volume 48 Issue1 DOI10.1016/j.bj.2024.100715.
42. Cheng CY ,Su YS ,Chen CL ,Chang MG ,Huang SW, Huang PN ,Shih SR, Hsu YS , Chiu CH. Safety, tolerability, and efficacy of intranasally-administered detoxified LTh(αK) in mild-to-moderate COVID-19 patients: A randomized, double-blinded, placebo-controlled phase 2 study. HUMAN VACCINES & IMMUNOTHERAPEUTICS. Volume20 Issue1 DOI10.1080/21645515.2024.2432105.2024 Dec.
43. Gong YN ,  Kuo NY ,  Yeh TS,  Shih SR ,  Chen GW. Genomic Surveillance of SARS-CoV-2 in Taiwan: A Perspective on Evolutionary Data Interpretation and Sequencing Issues. Biomed J .2025-8 26:100820. doi: 10.1016/j.bj.2024.100820. 
44. Kung YA , Chuang CH, Chen YC , Yang HP , Li HC , Chen CL , Rajendra Prasad Janapatla , Chen CJ, Shih SR , Chiu CH. Worldwide SARS-CoV-2 Omicron variant infection: Emerging sub-variants and future vaccination perspectives. J Formos Med Assoc . 124(7), pp.592-599 Jul 2025.
45. Lee KM , Wu CC, Fan YT , Chiang  HJ , Lien PY ,Wang JP,Huang  YC; Shih  SR . Subversion of phosphorylated SR proteins by enterovirus A71 in IRES-dependent translation revealed by RNA-interactome analysis. PLOS PATHOGENS. JUN 2025 .Volume21 Issue6 DOI10.1371/journal.ppat.1013242.
46. Li WC, Chang CY, Liu YP , Chen  LH ,Gong YN , Lin YJ , Chen GW, *Shih SR . Intensive reassortment and frequent intercontinental transmission revealed by long-term genetic analysis of H10 avian influenza viruses in Taiwan. EMERGING MICROBES & INFECTIONS. Aug 31 2025 Volume14Issue1DOI10.1080/22221751.2025.2556794.
47. Shi TH , Kuo C,Lin YT, Liu YC, Huang CG, *Shih SR. Moringin as a Lead Compound for Anti-Enteroviruses and Coronaviruses Broad-Spectrum Inhibition of Viral Proteases: Comparative Evaluation With Glucomoringin and Antiviral Agents. JOURNAL OF MEDICAL VIROLOGY. NOV 5 2025. Volume97Issue11DOI10.1002/jmv.70665.
48. Reinig S , Kuo C , Huang, SY Hsiung, KC , Chen PK , Ito  E, Lee IK, Tsai CY , Lin SM, *Shih SR. COVID-19 vaccination induces cross-reactive dengue virus antibodies with altered isotype profiles and in vitro antibody-dependent enhancement. FRONTIERS IN IMMUNOLOGY. DEC 17 2025.Volume16 DOI10.3389/fimmu.2025.1683070. 
49. Jian TY, Huang SY , Chang CY,Huang  CH , Kiew LV , Lin YL,Lin  YT ,Liu YC, Chen, YC ,Huang YX , Chou HS,Yap  SF ,  Chen AY ,Liang YC, Kung  YA , Wang PY, Huang PN , Huang CG, Chang CC , *Shih SR. HLA-C-derived peptide MH-1 as an early-stage intervention against SARS-CoV-2 infection. MOLECULAR MEDICINE.FEB 16 2026.Volume32Issue1.DOI10.1186/s10020-026-01434-3.