91猫先生

研究方向及研究室特色(Lab & Research Interest)

我的实验室主要是研究RNA病毒感染后在宿主细胞诱发之先天免疫反应，包括细胞自噬、干扰素暨细胞激素之分泌以及发炎小体之产生。并透过蛋白体学之分析，我们发现了RNA病毒感染后能影响RNA结合蛋白之表达，且进一步调控病毒之生长。利用人类上皮类器官作為模式，我们发现肠病毒能使用外泌体依赖方式离开上皮细胞，感染之肠上皮细胞释放之外泌体能携带病毒蛋白暨核酸，甚至整颗病毒至其它细胞建立新的病毒感染。我们的实验主题如下:

一、 病毒感染在神经细胞引发之先天免疫反应 

我们发现肠病毒能够感染神经干细胞并造成细胞凋亡,此一现象在小鼠脑中亦可发现,推测可能和感染造成的后遗症有关。此外,我们使用人类神经干细胞分化成的神经细胞作為细胞模式,发现了肠病毒感染会诱发自噬现象，自噬的产生能促进肠病毒在神经细胞生长。我们的研究也指出肠病毒虽能够透过模式识别受器TLR3，TLR8,以及MDA-5引发神经细胞产生第一型干扰素以抑制病毒快速生长,然而由於病毒蛋白能抑制后续干扰素合成，因此无法有效抑制病毒生长。

二、 RNA结合蛋白对病毒生长之调控

為了进一步了解宿主细胞因子是否会影响病毒在神经细胞的复製,我们利用LC-MS/MS分析能和肠病毒5’鲍罢搁结合之宿主细胞蛋白质，发现有数个蛋白质能够影响肠病毒在神经细胞的复製。其中FBP3在病毒感染后能自细胞核移动至细胞质，并调节肠病毒在细胞的生长。除了FBP3之外，我们亦发现了数个新颖的候选RNA结合蛋白具有调控细胞生长之能力。目前正针对其中一个在神经细胞能高度表达之RBP就其对病毒调控之机制深入探讨中。

叁、病毒感染对肠道上皮细胞造成之影响

 目前对於肠道病毒感染消化道上皮细胞的复製以及如何感染其他组织或器官仍不清楚。為了探讨病毒在不同的宿主细胞是否採用不同的机制离开宿主细胞,我们使用了由人类多能干细胞分化的肠道上皮类器官作為体外模式,实验结果发现小RNA病毒科的成员在感染肠道上皮细胞后,能够利用外泌体自宿主细胞中释出。在分化后肠道上皮细胞,使用外泌体抑制剂能够明显抑制病毒的复製暨释出,此一现象在小鼠实验亦会发生,足证外泌体对於肠病毒的致病机转有着重要的地位。

论文与着作(笔耻产濒颈肠补迟颈辞苍)

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.

研讨会论文

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)

4.    Jhao-Yin Lin and Hsing-I Huang*.  Autophagy in enterovirus 71-infected neuron. Europics 2016, Les Diaberetes, Switzerland.

5.    Hsing-I Haung* Permissiveness of neural stem cell and their neuronal progeny for EV71 infection, 2013  ASV 32nd Annual Meeting, State College, PA, USA

Books

1.    Isolation and Differentiation Potential of Fibroblast-Like Stromal Cells Derived from Human Skin. Hsing-I Huang* and Chung-Zu Wu. Somatic Stem Cells: Protocol for Methods in Molecular Biology (2011), Humana/Springer press

2.    Huang HI*. Isolation of Placenta-Derived Multipotent Cells from Human Placenta and In Vitro Differentiation into Hepatocyte-Like Cells. Current Protocols in Stem Cell Biology. Unit 1H.1, Wiley Interscience.

3.    Chan MM, Huang HI, Mattiacci JA, Fong D. 2002, Jul, Modulation of cytokine gene expression by curcumin.  In “Food factors for disease prevention and health promotion” edited by Shahidi F, Ho CT, and Watanabe S. American Chemical Society Press, Washington DC.

Patents

1.    具多分化能力的胎盘干细胞及其製备方法。陈耀昌,顏伶汝,简志诚,黄幸宜 (I299752)

2.    胎盘干细胞及其製备方法。陈耀昌,顏伶汝,简志诚,黄幸宜 (I307717)

3.    Y.C. Chen, L.J. Yen, C.C. Chien, H.I. Huang “Multipotent Stem Cell and Methods Thereof” U.S. Patent Pending, 2004. (60/535502)