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|2001/08 – 2005/12||M.S.&Ph.D., Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA, U.S.|
|1997/08 – 1999/05||M.S., Molecular Microbiology, National Taiwan University, Taipei, Taiwan|
|1993/08 – 1997/05||B.S., Biology, National Cheng Kung University, Tainan, Taiwan|
|2014/4-Present||Associate Investigator, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan|
|2010/11 – 2014/3||Assistant Investigator, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan|
|2006/02 – 2010/10||Postdoctoral Research Fellow, Pharmacology, University of California, San Diego, CA, U.S.|
|2000/06 – 2001/07||Research Assistant, Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan|
|1999/05 – 2000/05||Research Assistant, Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan|
Honors & Awards
|2007 – 2010||Mentor-based Postdoctoral Fellowship, American Diabetes Association, U.S.|
The main theme in our research is to understand how RNA virus replication activates innate immunity and causes tissue damage and diseases. We try to establish small animal models for Hepatitis C Virus (HCV), Dengue virus, Zika virus, and SARS-CoV-2 in recent years. Current projects are:
- Identification of virulence determinants of Dengue virus with high epidemic potential: DENV is transmitted mainly from Aedes aegypti mosquitoes to humans and back to mosquitoes through mosquito bites. Approximately one-fourth of the infected Dengue cases show apparent typical manifestations, such as fever, rash, muscle pain, and hemorrhage. Dengue infection might lead to severe diseases including Dengue hemorrhage fever and Dengue shock syndrome. Small animal models have been a useful tool to understand the interaction between arbovirus, vector, and host and to evaluate DENV pathogenesis. We used both Stat1-/- and AGB6 (mice defective in type I and type II IFN signaling in C57BL/6 background) mice to establish a mosquito-mediated DENV transmission model with the TW2015 virus. We found that the TW2015 virus is highly pathogenic in mice and penetrates to secondary organs, such as the lung and small intestine, at later time points, which might contribute to organ failure and mouse death. We will further examine the TW2015 virus pathogenesis by pursuing the following directions: (1) Dissect the barrier disruption process during the DENV organ penetration; (2) evaluate therapeutic strategy targeting DENV-associated organ penetration.
- SARS-CoV-2 related research: SARS-CoV-2 belongs to the genus Coronavirus and family Coronaviridae and has a positive single-stranded RNA genome of 30 kb in length. The spike protein is located on the viral envelope and interacts with cell surface receptors during virus entry. The amino acid sequences encoding the S protein of SARS-CoV-1 and SARS-CoV-2 have ~76% identity, and there is ~67% identity in the RBD region [15,41]. Both viruses use ACE2 as the receptor for virus entry. The VSVdG vector was used to characterize S protein maturation and virus infectivity. The replication-competent recombinant VSVdG-S (SARS-CoV-2) was further established and applied as a vaccine against SARS-CoV-2 infection.
- The role of Type I interferon signaling in liver regeneration. IFN-I has a well-known function in controlling viral infections, but its contribution to hepatocyte proliferation and hepatocellular carcinoma (HCC) formation remains unclear. Mice deficient in IFN α receptor expression in whole mice or only in hepatocytes (Ifnar-/- and IfnarΔliver) were used to investigate the role of IFN-I signaling in cell proliferation and cancer formation in the liver. We found that Ifnar-/- mice were resistant to chemical-induced HCC formation in the absence of infection. Our results showed that low grade of IFN-I and interferon-stimulated gene (ISG) were expressed substantially in naïve mouse liver. The low level of IFN-I activation is constantly present in the mouse liver after weaning and negatively modulates Forkhead box O (FOXO) hepatic expression. The IFN-I signaling can be partially blocked by the clearance of lipopolysaccharide (LPS). Mice lacking IFN-I signaling have lower basal proliferation activity and delayed liver regeneration processes after two third partial hepatectomy. The activation of IFN-I signaling on hepatocyte controls glucose homeostasis and lipid metabolism to support proliferation potency and long-term tumorigenesis. Our results reveal a positive role of low-grade IFN-I singling to hepatocyte proliferation and HCC formation by modulating glucose homeostasis and lipid metabolism.
Current lab members:
Postdoctoral Research Fellow: Chih-Feng Tien (田至峰), Yu-Siang Su (蘇煜翔)
Research Assistant: Wan-Ting Tsai (蔡宛庭), Yi-Ping Kuo (郭依萍), Shih-Syong Dai (戴世雄), En-Ju Lin (林恩如), Wei-Hsiang Tsai (蔡瑋祥)
Former lab members:
Postdoctoral Research Fellow: Chia-Yang Li (李佳陽), Ming-Sian Wu (吳明憲), Jhe-Jhih Lin (林哲志)
Research Assistant: Yu Tsai (蔡瑀), Kai-Chieh Chen (陳凱潔), Chih-Wen Hsu (徐志文), Mei-Ling Lai (賴玫伶), Yin-Chiu Lo (羅尹秋), De-Jiun Tsai (蔡德君), Pei-Jung Chung (鍾佩蓉), Yu-Feng Lin (林鈺峰)
Chai KM, Tzeng TT, Shen KY, Liao HC, Lin JJ, Chen MY, Yu GY, Dou HY, Liao CL, Chen HW, Liu SJ DNA vaccination induced protective immunity against SARS CoV-2 infection in hamsters Plos NTD 2021 May 27;15(5):e0009374.
Lin JJ, Chung PJ, Dai SS, Tsai WT, Lin YF, Kuo YP, Tsai KN, Chien CH, Tsai DJ, Wu MS, Shu PY, Yueh A, Chen HW, Chen CH*, Yu GY* Aggressive organ penetration and high vector transmissibility of epidemic dengue virus-2 Cosmopolitan genotype in a transmission mouse model PLoS Pathog. 2021 Mar 30;17(3):e1009480. *Correspondence
Wu MS, Kuo YP, Lo YC, Tsai DJ, Lai CY, Chuang TH, Lin SY, Tsai WT, Chung PJ, Yu GY* Type I interferon signaling accelerates liver regeneration by metabolic modulation in non-infectious conditions. Am J Pathol. 2021 Mar 19; S0002-9440(21)00110-3. *Correspondence
Chuang YC, Tseng JC, Yang JX, Liu YL, Yeh DW, Lai CY, Yu GY, Hsu LC, Huang CM and Chuang TH Toll-Like Receptor 21 of Chicken and Duck Recognize a Broad Array of Immunostimulatory CpG-oligodeoxynucleotide Sequences. Vaccines 2020, 8(4), 639;
Li HH, Cao Y, Li JC, Su MP, Cheng L, Chou SJ, Yu GY, Wang HD, Chen CH. C-Type Lectins Link Immunological and Reproductive Processes in Aedes aegypti. iScience 2020 Sep 25; 23(9):101486
Chiang CH, Lai YL, Huang YN, Yu CC, Lu C, Yu GY, and Yu MJ Sequential phosphorylation of the HCV NS5A protein depends on NS3-mediated auto-cleavage between NS3 and NS4A. J Virol. 2020 Jul 22
Pathak N, Kuo YP, Chang TY, Huang CT, Hung HC, Hsu JT, Yu GY, Yang JM. Zika Virus NS3 Protease Pharmacophore Anchor Model and Drug Discovery. Sci Rep. 2020 Jun 2;10(1):8929.
Simanjuntak Y, Ko HY, Lee YL, Yu GY, Lin YL. Preventive effects of folic acid on Zika virus-associated poor pregnancy outcomes in immunocompromised mice. PLoS Pathog. 2020 May 11;16(5):e1008521.
Chen MY, Chai KM, Chiang CY, Wu CC, Yu GY, Liu SJ, Chen HW. Recombinant lipidated Zika virus envelope protein domain III elicits durable neutralizing antibody responses against Zika virus in mice. J Biomed Sci. 2020 Apr 14;27(1):51.
Lai CY, Yu GY, Luo Y, Xiang R, Chuang TH. Immunostimulatory Activities of CpG-Oligodeoxynucleotides in Teleosts: Toll-Like Receptors 9 and 21. Front Immunol. 2019;10:179.
Hsu WC, Chen MY, Hsu SC, Huang LR, Kao CY, Cheng WH, Pan CH, Wu MS, Yu GY, Hung MS, Leu CM, Tan TH and Su YW DUSP6 connects T cell receptor-engaged glycolysis and restrains TFH cell differentiation. PNAS 2018 Aug 21;115(34):E8027-E8036.