生物醫學研究所

黃 幸 宜 (Hsing-I Huang)

學歷：美國紐澤西羅格斯大學微生物與分子遺傳學博士

任課科目：醫用生物技術學、醫檢概論

研究專長：腫瘤免疫學、細胞生物學

辦公室分機：3721

實驗室分機：3725

個人網頁：病毒暨幹細胞生物實驗室

E-mail：hihuang@mail.cgu.edu.tw

研究方向及研究室特色(Lab & Research Interest)

 我的實驗室主要是研究RNA病毒感染後在宿主細胞誘發之先天免疫反應，包括細胞自噬、干擾素暨細胞激素之分泌以及發炎小體之產生。並透過蛋白體學之分析，我們發現了RNA病毒感染後能影響RNA結合蛋白之表達，且進一步調控病毒之生長。利用人類上皮類器官作為模式，我們發現腸病毒能使用外泌體依賴方式離開上皮細胞，感染之腸上皮細胞釋放之外泌體能攜帶病毒蛋白暨核酸，甚至整顆病毒至其它細胞建立新的病毒感染。我們的實驗主題如下:

一、病毒感染在神經細胞引發之先天免疫反應

我們發現腸病毒能夠感染神經幹細胞並造成細胞凋亡,此一現象在小鼠腦中亦可發現,推測可能和感染造成的後遺症有關。此外,我們使用人類神經幹細胞分化成的神經細胞作為細胞模式,發現了腸病毒感染會誘發自噬現象，自噬的產生能促進腸病毒在神經細胞生長。我們的研究也指出腸病毒雖能夠透過模式識別受器TLR3，TLR8,以及MDA-5引發神經細胞產生第一型干擾素以抑制病毒快速生長,然而由於病毒蛋白能抑制後續干擾素合成，因此無法有效抑制病毒生長。

二、RNA結合蛋白對病毒生長之調控

為了進一步了解宿主細胞因子是否會影響病毒在神經細胞的複製,我們利用LC-MS/MS分析能和腸病毒5’UTR結合之宿主細胞蛋白質，發現有數個蛋白質能夠影響腸病毒在神經細胞的複製。其中FBP3在病毒感染後能自細胞核移動至細胞質，並調節腸病毒在細胞的生長。除了FBP3之外，我們亦發現了數個新穎的候選RNA結合蛋白具有調控細胞生長之能力。目前正針對其中一個在神經細胞能高度表達之RBP就其對病毒調控之機制深入探討中。

三、病毒感染對腸道上皮細胞造成之影響

 目前對於腸道病毒感染消化道上皮細胞的複製以及如何感染其他組織或器官仍不清楚。為了探討病毒在不同的宿主細胞是否採用不同的機制離開宿主細胞,我們使用了由人類多能幹細胞分化的腸道上皮類器官作為體外模式,實驗結果發現小RNA病毒科的成員在感染腸道上皮細胞後,能夠利用外泌體自宿主細胞中釋出。在分化後腸道上皮細胞,使用外泌體抑制劑能夠明顯抑制病毒的複製暨釋出,此一現象在小鼠實驗亦會發生,足證外泌體對於腸病毒的致病機轉有著重要的地位。

論文與著作(Publication)

Publication

1. Hsing-I Huang*, Chih-Chong Chio, Jhao-Yin Lin, Chia-Jung Chou, Chia-Chen Lin, Shih-Hsiang Chen, Liang-Sheng Yu. EV-A71 induced IL-1β production in THP-1 macrophages is dependent on NLRP3, RIG-I, and TLR3. Sci Rep. 2022 Dec 11;12(1):21425. (SCI, IF:4.996; Multidisciplinary:17/71)
2. Rei-Lin Kuo*, Yo-Tung Chen, Huan-An Li, Chih-Ching Wu, Hsiao-Chu Chiang, Jhao-Yin Lin, Hsing-I Huang, Shin-Ru Shih, Bertrand Chin-Ming Tan. Molecular determinants and heterogeneity underlying host response to EV-A71 infection at single-cell resolution. RNA Biol. 2021 Feb;1-13. (SCI, IF:4.652, Biochemistry and molecular biology: 106/205)
3. Jhao-Yin Lin, Hsing-I Huang*. Autophagy is induced and supports virus replication in Enterovirus A71-infected human primary neuronal cells. Sci Rep. 2020 Sep;10(1):15234. (*corresponding author) (SCI, IF: 4.380; Multidisciplinary:17/72)
4. Yu-Nong Gong, Kuo-Chien Tsao, Mei-Jen Hsiao, Chung-Guei Huang, Peng-Nien Huang, Po-Wei Huang, Kuo-Ming Lee, Yi-Chun Liu, Shu-Li Yang, Rei-Lin Kuo, Kuan-Fu Chen, Yen-Chin Liu, Sheng-Yu Huang, Hsing-I Huang, Ming-Tsan Liu, Ji-Rong Yang, Cheng-Hsun Chiu, Cheng-Ta Yang, Guang-Wu Chen, Shin-Ru Shih. SARS-CoV-2 genomic surveillance in Taiwan revealed novel ORF8-deletion mutant and clade possibly associated with infections in Middle East. Emerging Microbes and Infections 2020 Jun:1457-1466. (SCI, IF: 7.163; Infectious diseases: 14/118)
5. Hsing-I Huang*, Jhao-Yin Lin, Hsiao-Chu Chiang, Peng-Nien Huang, Qin-Dong Lin, Shin-Ru Shih. Exosomes facilitate transmission of Enterovirus A71 from human intestinal epithelial cells. J Infect Dis. 2020 Jul;222(3):456-469. (*corresponding author) (SCI, IF: 5.226; Infectious diseases: 18/93)
6. Jhao-Yin Lin, Rel-Lin Kuo, Hsing-I Huang*. Activation of type I interferon antiviral response in human neural stem cells. Stem Cell Res Ther. 2019 Dec;10(1):387. (*corresponding author) (SCI, IF:6.832; cell and tissue engineering: 8/31)
7. Hsing-I Huang*, Jhao-Yin Lin, Sheng-Hung Chen. EV71 Infection Induces IFNβ Expression in Neural Cells. Viruses 2019 Dec;11(12): 1121. (*corresponding author) (SCI, IF:5.084; Ranking: Virology 10/37)
8. Rei-Lin Kuo, Chi-Jene Chen, Robert Y.L.Wang, Hsing-I Huang, Ya-Han Lin, Ee-Hong Tam, Wen-Jung Tu, Sheng-En Wu, Shin-Ru Shih. Role of Enteroviral RNA-Dependent RNA Polymerase in Regulation of MDA5-Mediated Beta Interferon Activation. J Virol. 2019 May 1;93(10). (SCI) (IF:6.208; Ranking: Virology 13/66)
9. Hsing-I Huang*, Chi-Chong Chio, Jhao-Yin Lin. Inhibition of EV71 by curcumin in intestinal epithelial cells. PLoS One, 2018 Jan 25;13(1), e0191617. (*corresponding author) (SCI, IF:3.240; Ranking: Multidisciplinary sciences: 26/72)
10. Hsing-I Huang*, Ying-Ying Chang, Jhao-Yin Lin, Rei-Lin Kuo, Hao-Ping Liu, Shin-Ru Shih, Chih-Ching Wu. Interactome analysis of the EV71 5' untranslated region in differentiated neuronal cells SH-SY5Y and regulatory role of FBP3 in viral replication. Proteomics. 2016 Sep, 16(17):2351-62. (*corresponding author)
11. Hsing-I Huang, Shin-Ru Shih. Neurotropic Enterovirus Infections in the Central Nervous System. Viruses, 2015 Nov, 7(11):6051-66. (SCI, IF:5.084; Ranking: Virology 10/37)
12. Kuo-Feng Wong, Po-Ting Hsieh, Hsing-I Huang, Shin-Ru Shih. Mammalian RNA virus-derived small RNA: biogenesis and functional activity. Microbes Infect. 2015, 17(8):557-63. (SCI)
13. Rei-Lin Kuo, Ya-Han Lin, Robert Yung-Liang Wang, Chia-Wei Hsu, Yi-Ting Chiu, Hsing-I Huang, Li-Ting Kao, Jau -Song Yu, Shin-Ru Shih, Chih-Ching Wu. Proteomics analysis of EV71-infected cells reveals the involvement of host protein NEDD4L in EV71 replication. J Proteome Res. 2015, 14(4):1818-30. (SCI)
14. Kuo-Feng Weng, Chuan-Tien Hung, Po-Ting Hsieh, Mei-Ling Li, Guang-Wu Chen, Yu-An Kung, Peng-Nien Huang, Rei-Lin Kuo, Li-Lien Chen, Jing-Yi Lin, Robert Yung-Liang Wang, Shu-Jen Chen, Petrus Tang, Jim-Tong Horng, Hsing-I Huang, Jen-Ren Wang, David M Ojcius, Gary Brewer, Shin-Ru Shih. A cytoplasmic RNA virus generates functional viral small RNAs and regulates viral IRES activity in mammalian cells. Nucleic Acids Res. 2014, 42(20):12789-805.
15. Hsing-I Huang *, Jhao-Yin Lin, Hsin-Hsu Chen, Shiou-Bang Yeh, Rei-Lin Kuo, Kuo-Feng Weng, Shin-Ru Shih. Enterovirus 71 infects brain-derived neural progenitor cells. Virology. 2014, 468-470:592-600. (*corresponding author)
16. Hsing-I Huang *, Shao-Kuan Chen, Robeert Yung-Liang Wang, Chia-Rui Shen, Yu-Che Cheng. Human foreskin fibroblast-like stromal cells can differentiate into functional hepatocytic cells. Cell Biol Int. 2013, 37(12):1308-19. (*corresponding author)
17. Robert Y L Wang, Rei-Lin Kuo, Wei-Chieh Ma, Hsing-I Huang, Jau-Song Yu, Sih-Min Yen, Chi-Ruei Huang, Shin-Ru Shih.Heat shock protein-90-beta facilitates enterovirus 71 viral particles assembly. Virology. 2013, 443(2):236-47.
18. Chiann-Chyi Chen, Hsing-I Huang*, Cassandra L Louis, Kao-Tien Lin, Yacov Ron. Isolation of multilineage progenitors from mouse brain. In Vitro Cell Dev Biol Anim. 2013 May, 49(5):307-14. (*corresponding author)
19. Hsing-I Huang, Kuo-Feng Weng, Shin-Ru Shih. Viral and host factors that contribute to pathogenicity of enterovirus 71. Future Microbiol. 2012, 7(4):467-79.
20. Shih-Hsin Tu, Hsing-I Huang, Su-I Lin, Hsin-Yu Liu, Yuh-Pyng Sher, Sheng-Kuo Chiang, Pele Chong, Steve Roffler, Guan-Chin Tseng, Hsin-Wei Chen, Shih-Jen Liu A novel HLA-A2-restricted CTL epitopes of tumor associated antigen L6 could inhibit tumor growth in vivo. J Immunother. 2012, 35(3):235-44. (co-first author)
21. Peng-Nien Huang, Jing-Yi Lin, Nicolas Locker, Yu-An Kung, Chuan-Tien Hung, Jhao-Yin Lin, Hsing-I Huang, Mei-Ling Li, Shin-Ru Shih. 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, 39(22):9633-48.
22. Hsing-I Huang*, Shao-Kuan Chen, Qing-Dong Ling, Chih-Cheng Chien, Hsiao-Tung Liu, Shu-Hui Chan. Multilineage differentiation potential of fibroblast-like stromal cells derived from human skin. Tissue Engineering Part A. 2010, 16(5):1491-501.
23. CA Chung, Tze-Hung Lin, Shih-Di Chen, Hsing-I Huang. Hybrid cellular automaton modeling of nutrient modulated cell growth in tissue engineering constructs. J Theor Biol. 2010 Jan; 262(2):267-78.
24. B Linju Yen, Chih-Cheng Chien, Yao-Chang Chen, Jen-Tse Chen, Jing-Shan Huang, Fa-Kung Lee, Hsing-I Huang*. Placenta-derived multipotent cells differentiate into neuronal and glial cells in vitro. Tissue Engineering Part A. 2008, 14(1):9-17.
25. Men-Luh Yen, Chih-Cheng Chien, Ing-Ming Chiu, Hsing-I Huang, Yao-Chang Chen, Hsin-I Hu, B Linju Yen. Multilineage differentiation and characterization of the human fetal osteoblastic 1.19 cell line: a possible in vitro model of human mesenchymal progenitors. Stem Cells. 2007, 25(1):125-31.
26. Chih-Cheng Chien, Wen-Mei Fu, Hsing-I Huang, Yeur-Hur Lai, Yun-Fang Tsai, Shu-Lin Guo, Tzong-Jeng Wu, Qing-Dong Ling. Expression of Neurotrophic Factors in Neonatal Rats After Peripheral Inflammation. J Pain. 2007, 8(2):161-7.
27. Chun-Jung Chang, Men-Luh Yen, Yao-Chang Chen, Chih-Cheng Chien, Hsing-I Huang, Chyi-Huey Bai, B Linju Yen. Placenta-derived multipotent cells exhibit immunosuppressive properties that are enhanced in the presence of interferon-gamma. Stem Cells. 2006, 24(11):2466-77.
28. Chih-Cheng Chien, Betty Linju Yen, Fa-Kung Lee, Tsung-Hsuan Lai, Yao-Chang Chen, Shu-Hui Chan, Hsing-I Huang*. In vitro differentiation of human placenta-derived multipotent cells into hepatocyte-like cells. Stem Cells. 2006, 24(7): 1759-1768.
29. B Linju Yen, Hsing-I Huang, Chih-Cheng Chien, Hsiang-Yiang Jui, Bor-Sheng Ko, Ming Yao, Chia-Tung Shun, Men-Luh Yen, Meng-Chou Lee, Yao-Chang Chen. Isolation of Multipotent Cells from Human Term Placenta. Stem Cells. 2005, 23(1):1-6. (Co-first author)
30. Hsing-I Huang, Ping-Yi Wu, Chin-Yee Teo, Min-Nan Chen, Yi-Chau Chen, Dmytro Silin, Mi-Hua Tao. Improved immunogenicity of a self tumor antigen by covalent linkage to CD40 ligand. Int. J Cancer. 2004 Feb, 108(5):696-703.
31. Hsin-Wei Chen, Hsing-I Huang, Yi-Ping Lee, Li-Li Chen, Hsiung-Kun Liu, Mei-Lien Cheng, Jy-Ping Tsai, Mi-Hua Tao, Chou-Chik Ting. Linkage of CD40 to a self-tumor antigen enhances the antitumor immune responses of dendritic cell based treatment. Cancer Immunol Immunother. 2002 Jun,51(6):341-8.
32. Tzu-Hsuan Huang, Pin-Yi Wu, Chin-Nien Lee, Hsing-I Huang, Shie-Liang Hsieh, John Kung, Mi-Hua Tao. Enhanced antitumor immunity by fusion of CTLA-4 to a self tumor antigen. Blood 2000 Dec; 96(12):3663-70.
33. Marion Man-Ying Chan, Hsing-I Huang, Merilyn Ruth Fenton, Dunne Fong. In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with anti-inflammatory properties. Biochem Pharmacol. 1998, 55(12):1955-62.
34. Marion Man-Ying Chan, Dunne Fong, Chi-Tang Ho, Hsing-I Haung. Inhibition of inducible nitric oxide synthase gene expression and enzyme activity by epigallocatechin gallate, a natural product from green tea. Biochem Pharmacol. 1997 Dec; 55(12):1281-6.
35. Marion Man-Ying Chan, Chi-Tang Ho, Hsing-I Huang. Effects of three dietary phytochemicals from tea, rosemary and turmeric on inflammation-induced nitrite production. Cancer Lett. 1995 Sep; 4;96(1):23-9.

研討會論文

1. Hsing-I Huang*, Jhao-Yin Lin. The roles of autophagy in EV71 infection of neuronal cells. Positive-strand RNA viruses meeting. Keystone Symposium. 2019 Killarney, Ireland
2. Hsing-I Haung* and Sheng-Hung Chen. EV71 infection enhances IFNb expression in neuronal cells. Europics 2018, Egmond aan Zee, The Netherlands.
3. Hsing-I Huang^＊ Recognition of enterovirus 71 by toll-like receptor 8 and RIG-I activate the inflammasome in human myeloid cells. Europics 2016, Les Diaberetes, Switzerland. (oral presentation)

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