新興病毒分子醫學國際碩士學位學程

研究方向及研究室特色(Lab & Research Interest)

1.      本實驗室致力於利用動物模式來深入研究病毒在宿主體內進行複製的相關機制。具體而言，我們已經成功建立了多種動物感染模式，包括腸病毒、流感病毒以及新冠病毒的動物模型。這些模型為我們提供了一個強有力的工具，以便在接近自然的生物環境中觀察和分析病毒的複製過程及其與宿主之間的相互作用。在這些動物感染模式的基礎上，我們進行了廣泛的研究，以揭示病毒在宿主體內的動態行為和複製策略。這些研究不僅加深了我們對病毒生物學的理解，還為抗病毒藥物和疫苗的開發提供了重要的理論支持和實驗數據。通過這些模型，我們能夠模擬和分析不同藥物和疫苗在體內的作用效果，評估其安全性和有效性，從而加快其研發進程和臨床應用。

2.      本實驗室已成功建立了一套利用抗生素處理改變腸道菌相與糞菌移植的方法，這些方法用以研究和確認腸道菌叢對於腸道RNA病毒感染的關係。我們的研究首先通過抗生素處理來改變小鼠或其他實驗動物的腸道菌相，隨後進行糞菌移植，這種技術能夠精確地調控腸道微生物群的組成，為進一步研究提供了穩定且可控的模型。在此基礎上，我們將利用功能性多重體學分析平台（Functional Multi-Omics Analysis Platform），這一先進的技術能夠對bacterial microbiome（細菌微生物群）、virome（病毒群）與宿主之間的關係進行全面而深入的分析。多重體學分析涵蓋了基因組學、轉錄組學、蛋白質組學、代謝組學等多個領域，能夠系統性地揭示腸道菌叢對於腸道RNA病毒感染的影響機制。通過這些技術手段，我們期望更加詳細地了解病毒感染的致病機制與宿主的防禦作用。例如，我們可以觀察到在不同菌相組成下，腸道RNA病毒感染的程度及其引起的免疫反應，從而找出特定的腸道細菌或其代謝產物對抗病毒感染的潛力。這些研究不僅有助於闡明腸道菌叢在病毒感染過程中的具體作用，還能為篩選和測試具有抗RNA病毒感染潛力的腸道細菌及其活性成分提供理論支持。

3.      負責維運BSL-3高防護實驗室，我們致力於建立並執行嚴格的生物安全操作規範，確保實驗室內所有研究活動在最高安全標準下進行。BSL-3實驗室專門處理可能對人類健康造成重大威脅的傳染性病原體，因此，我們的工作重點在於防止病原體意外釋放並保護實驗人員的安全。我們制定了全面的生物安全手冊，涵蓋從病原體操作到廢棄物處理的每一個環節，並定期進行安全審查和演練，確保所有操作都符合國際標準和法規要求。在這個高防護環境中，我們不僅進行前沿的科研工作，還負責訓練高防護實驗室的人才。這些人才包括研究人員、技術員和管理人員，他們接受嚴格的生物安全和操作規範培訓，熟悉各種應急處理流程，以應對任何潛在的安全威脅。我們的培訓計劃包括理論學習和實踐操作，確保學員能夠在真實環境中應用所學知識，為未來的科研和防疫工作奠定堅實的基礎。此外，我們積極參與多項產學合作計畫，與國內外廠商緊密合作，協助他們開發和測試各類防疫產品，如新型抗病毒藥物、疫苗和診斷試劑等。這些合作不僅促進了科研成果的轉化，還為防疫工作提供了實質性的支持。我們利用BSL-3實驗室的先進設施和技術優勢，為企業提供高效可靠的研發服務，推動防疫產品的快速上市和應用。通過這些努力，我們不僅提升了自身的科研能力，還在防疫和公共健康領域發揮了重要作用。我們的工作促進了產學研三方的緊密合作，實現了科技成果的高效轉化和應用，為社會帶來了實質性的健康和經濟效益。總之，我們的BSL-3高防護實驗室不僅是科研創新的平台，還是防疫人才培養和產業發展的重要支柱。

論文與著作(Publication)

1.      Chen TC, Liu SC, Huang PN, Chang HY, Chern JH, Shih SR. Antiviral activity of pyridyl imidazolidinones against enterovirus 71 variants. J Biomed Sci. 2008 May;15(3):291-300. doi: 10.1007/s11373-007-9228-5. Epub 2008 Jan 15. PubMed PMID: 18196474.

2.      Lin JY, Li ML, Huang PN, Chien KY, Horng JT, Shih SR. Heterogeneous nuclear ribonuclear protein K interacts with the enterovirus 71 5' untranslated region and participates in virus replication. J Gen Virol. 2008 Oct;89(Pt 10):2540-2549. doi: 10.1099/vir.0.2008/003673-0. PubMed PMID: 18796723.

3.      Chen TC, Weng KF, Chang SC, Lin JY, Huang PN, Shih SR. Development of antiviral agents for enteroviruses. J Antimicrob Chemother. 2008 Dec;62(6):1169-73. doi: 10.1093/jac/dkn424. Epub 2008 Oct 18. Review. PubMed PMID: 18931391.

4.      Tsao KC, Huang CG, Huang YL, Chen FC, Huang PN, Huang YC, Lin TY, Shih SR, Chang SC. Epidemiologic features and virus isolation of enteroviruses in Northern Taiwan during 2000-2008. J Virol Methods. 2010 May;165(2):330-2. doi: 10.1016/j.jviromet.2010.03.001. Epub 2010 Mar 7. PubMed PMID: 20214926.

5.      Weng KF, Chen LL, Huang PN, Shih SR. Neural pathogenesis of enterovirus 71 infection. Microbes Infect. 2010 Jul;12(7):505-10. doi: 10.1016/j.micinf.2010.03.006. Epub 2010 Mar 27. Review. PubMed PMID: 20348010.

6.      Huang PN, Lin JY, Locker N, Kung YA, Hung CT, Lin JY, Huang HI, Li ML, Shih SR. Far upstream element binding protein 1 binds the internal ribosomal entry site of enterovirus 71 and enhances viral translation and viral growth. Nucleic Acids Res. 2011 Dec;39(22):9633-48. doi: 10.1093/nar/gkr682. Epub 2011 Aug 31. PubMed PMID: 21880596; PubMed Central PMCID: PMC3239202.

7.      Huang CH, Chen CJ, Yen CT, Yu CP, Huang PN, Kuo RL, Lin SJ, Chang CK, Shih SR. Caspase-1 deficient mice are more susceptible to influenza A virus infection with PA variation. J Infect Dis. 2013 Dec 1;208(11):1898-905. doi: 10.1093/infdis/jit381. Epub 2013 Jul 30. PubMed PMID: 23901080.

8.      Huang PN, Shih SR. Update on enterovirus 71 infection. Curr Opin Virol. 2014 Apr;5:98-104. doi: 10.1016/j.coviro.2014.03.007. Epub 2014 Apr 12. Review. PubMed PMID: 24727707.

9.      Liu YC, Kuo RL, Lin JY, Huang PN, Huang Y, Liu H, Arnold JJ, Chen SJ, Wang RY, Cameron CE, Shih SR. Cytoplasmic viral RNA-dependent RNA polymerase disrupts the intracellular splicing machinery by entering the nucleus and interfering with Prp8. PLoS Pathog. 2014 Jun;10(6):e1004199. doi: 10.1371/journal.ppat.1004199. eCollection 2014 Jun. PubMed PMID: 24968230; PubMed Central PMCID: PMC4072778.

10. Weng KF, Hung CT, Hsieh PT, Li ML, Chen GW, Kung YA, Huang PN, Kuo RL, Chen LL, Lin JY, Wang RY, Chen SJ, Tang P, Horng JT, Huang HI, Wang JR, Ojcius DM, Brewer G, Shih SR. A cytoplasmic RNA virus generates functional viral small RNAs and regulates viral IRES activity in mammalian cells. Nucleic Acids Res. 2014 Nov 10;42(20):12789-805. doi: 10.1093/nar/gku952. Epub 2014 Oct 28. PubMed PMID: 25352551; PubMed Central PMCID: PMC4227785.

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 Pathog. 2017 May;13(5):e1006375. doi: 10.1371/journal.ppat.1006375. eCollection 2017 May. PubMed PMID: 28545059; PubMed Central PMCID: PMC5435352.

12. 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. 2020 Apr;17(4):608-622. doi: 10.1080/15476286.2020.1722448. Epub 2020 Feb 6. PubMed PMID: 32009553; PubMed Central PMCID: PMC7237135.

13. Huang PN, Wang HC, Hung HC, Tseng SN, Chang TY, Chou MY, Chen YJ, Wang YM, Shih SR, Hsu JT. Antiviral Activity of a Llama-Derived Single-Domain Antibody against Enterovirus A71. Antimicrob Agents Chemother. 2020 Apr 21;64(5). doi: 10.1128/AAC.01922-19. Print 2020 Apr 21. PubMed PMID: 32152074; PubMed Central PMCID: PMC7179613.

14. 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. J Clin Microbiol. 2020 Jul 23;58(8). doi: 10.1128/JCM.01068-20. Print 2020 Jul 23. PubMed PMID: 32518072; PubMed Central PMCID: PMC7383522.

15. 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, Hsu JT. Discovery of M Protease Inhibitors Encoded by SARS-CoV-2. Antimicrob Agents Chemother. 2020 Aug 20;64(9). doi: 10.1128/AAC.00872-20. Print 2020 Aug 20. PubMed PMID: 32669265; PubMed Central PMCID: PMC7449189.

16. 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(9):e1008857. doi: 10.1371/journal.ppat.1008857. eCollection 2020 Sep. PubMed PMID: 32936838; PubMed Central PMCID: PMC7521691.

17. Huang KA, Zhou D, Fry EE, Kotecha A, Huang PN, Yang SL, Tsao KC, Huang YC, Lin TY, Ren J, Stuart DI. Structural and functional analysis of protective antibodies targeting the threefold plateau of enterovirus 71. Nat Commun. 2020 Oct 16;11(1):5253. doi: 10.1038/s41467-020-19013-3. PubMed PMID: 33067459; PubMed Central PMCID: PMC7567869.

18. Gong YN, Tsao KC, Hsiao MJ, Huang CG, Huang PN, Huang PW, Lee KM, Liu YC, Yang SL, Kuo RL, 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 ORF8-deletion mutant and clade possibly associated with infections in Middle East. Emerg Microbes Infect. 2020 Dec;9(1):1457-1466. doi: 10.1080/22221751.2020.1782271. PubMed PMID: 32543353; PubMed Central PMCID: PMC7473175.

19. 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;24:100860. doi: 10.1016/j.bbrep.2020.100860. eCollection 2020 Dec. PubMed PMID: 34095549; PubMed Central PMCID: PMC8164134.

20. 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). doi: 10.1128/AAC.00695-20. Print 2020 Dec 16. PubMed PMID: 33139286; PubMed Central PMCID: PMC7927848.

21. 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). doi: 10.1128/mSphere.00104-21. PubMed PMID: 33789940; PubMed Central PMCID: PMC8546686.

22. 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). doi: 10.3390/ijms22084146. PubMed PMID: 33923724; PubMed Central PMCID: PMC8074035.

23. Kiew LV, Chang CY, Huang SY, Wang PW, Heh CH, Liu CT, Cheng CH, Lu YX, Chen YC, Huang YX, Chang SY, Tsai HY, Kung 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. Biosens Bioelectron. 2021 Jul 1;183:113213. doi: 10.1016/j.bios.2021.113213. Epub 2021 Apr 3. PubMed PMID: 33857754; PubMed Central PMCID: PMC8018905.

24. 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. 2021 Oct 13;95(21):e0089721. doi: 10.1128/JVI.00897-21. Epub 2021 Aug 11. PubMed PMID: 34379497; PubMed Central PMCID: PMC8513470.

25. 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 Nov 4;81(21):4467-4480.e7. doi: 10.1016/j.molcel.2021.10.003. Epub 2021 Oct 22. PubMed PMID: 34687604; PubMed Central PMCID: PMC8628313.

26. 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 Feb 22;13(1):e0271721. doi: 10.1128/mbio.02717-21. Epub 2022 Jan 18. PubMed PMID: 35038927; PubMed Central PMCID: PMC8764547.

27. 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. 2022 Feb 23;7(1):e0088321. doi: 10.1128/msphere.00883-21. Epub 2022 Feb 2. PubMed PMID: 35107336; PubMed Central PMCID: PMC8809379.

28. Liu KT, Han YJ, Wu GH, Huang KA, Huang PN. Overview of Neutralization Assays and International Standard for Detecting SARS-CoV-2 Neutralizing Antibody. Viruses. 2022 Jul 18;14(7). doi: 10.3390/v14071560. Review. PubMed PMID: 35891540; PubMed Central PMCID: PMC9322699.

29. 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). doi: 10.3390/ijms232112967. PubMed PMID: 36361757; PubMed Central PMCID: PMC9653933.

30. 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. 2023 Jan-Feb;25(1-2):105044. doi: 10.1016/j.micinf.2022.105044. Epub 2022 Sep 9. PubMed PMID: 36096357; PubMed Central PMCID: PMC9461341.

31. Huang PN, Hsia SH, Huang KA, Chen CJ, Wang ET, Shih SR, Lin TY. Reflecting on the 1998 enterovirus outbreak: A 25-year retrospective and learned lessons. Biomed J. 2024 Mar 14;:100715. doi: 10.1016/j.bj.2024.100715. [Epub ahead of print] Review. PubMed PMID: 38492637.