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專任教師

楊宏志 副教授

聯絡電話:02-2312-3456 轉 88299

E-mail: hcyang88@ntu.edu.tw

個人資料

專長:

肝臟學、分子生物學、病毒學、病毒免疫學

學歷:

Johns Hopkins University, School of Medicine, Baltimore, Maryland 2003-2008
Ph.D. Graduate Program in Immunology
National Taiwan University School of Medicine, Taipei, Taiwan 1988-1995 M.D. College of Medicine

經歷:

Resident: National Taiwan University Hospital, Department of Internal Medicine (1997-2000)
Fellowship: National Taiwan University Hospital, Department of Internal Medicine, Subdivision of Gastroenterology and Hepatology (2000-2002)
Postdoctorate: Johns Hopkins School of Medicine(2008-2009)
Visiting staff: Department of Medical Research, National Taiwan University Hospital (2009/7-2010/8)
Assistant professor: Department of Microbiology, National Taiwan University College of Medicine (2010/8~2015/7)
Associate professor: Department of Microbiology, National Taiwan University College of Medicine (2015/8~now)
Visiting staff: Department of Internal Medicine, National Taiwan University Hospital (2010/8~now)

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目前進行研究

My laboratory is interested in understanding the interaction between virus and host. Currently, we study two clinically important viruses, hepatitis B virus (HBV) and influenza virus. We explore how HBV persists within hosts under the antiviral therapy and host immune pressure. Current antiviral therapy, nucleos(t)ide analogues (NAs) and interferon, seldom cures chronic hepatitis B (CHB), due to the persistence of covalently closed circular (ccc) DNA, the replicative template of HBV. CccDNA persists within infected hepatocytes even after years of NA treatment. Therefore, it is critical to understand the mechanisms regulating the activity and stability of cccDNA. Curing CHB may need elimination of all infected hepatocytes or disruption/silencing of cccDNA. My laboratory aims to explore the mechanisms regulating the formation and activity of cccDNA and all the potential strategies that can cure CHB. In addition, we investigate how HBV evolves under antiviral therapy and immune pressure by utilizing the advanced sequencing technology, like next-generation sequencing, to understand how virus and host interact with each other. This will provide important information for designing novel antiviral strategy.

We are also interested in exploring the role of T cell immunity against influenza virus infection. Although current inactivated influenza vaccine induces robust neutralizing antibodies against the surface viral proteins HA and NA, it often requires annual reformulation because of the high mutation rate of these viral proteins resulting from antigenic drift and antigenic shift. In contrast, T cell immunity targeting the more conserved internal viral proteins can exhibit cross-reactivity against wider ranges of influenza virus strains. It has been shown that T cell immunity can reduce morbidity and mortality caused by influenza viruses. Therefore, we aim to investigate the determinants in generation and maintenance of robust and effective T cell immunity against influenza viruses in hoping to design better vaccination strategy to combat pandemic influenza.

Curing chronic hepatitis B: therapeutic strategies for eradication of cccDNA or killing of the infected hepatocytes

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研究室成員

碩班學生: 侯佩君、梁潔瑜、馬元策、余欣樺、景琦、潘慶輔、黃桂鈺
博班學生: 楊于嬋
研究助理: 吳芳儀、陳昱翔
博士後研究員:林林品

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研究成果

1.Yang, H. C., Tsou, H. H., Pei, S. N., Chang, C. S., Chen, J. H., Yao, M., Lin, S. J., Lin, J., Yuan, Q., Xia, N., Liu, T. W., Chen, P. J., Cheng, A. L., Hsu, C*. and Taiwan Cooperative Oncology, Group. (2018) Quantification of HBV core antibodies may help predict HBV reactivation in lymphoma patients with resolved HBV infection. J Hepatol. 2018 Mar 15. pii: S0168-8278(18)30171-5. doi: 10.1016/j.jhep.2018.02.033. [Epub ahead of print]
2.Lin, P.H., Wong, W.I., Wang, Y.L., Hsieh, M.P., Lu, C.W., Liang, C.Y., Jui, S.H., Wu, F.Y., Chen, P.J., and Yang, H.C., (2018) Vaccine-induced antigen-specific regulatory T cells attenuate the antiviral immunity against acute influenza virus infection. Mucosal Immunol, 2018 Feb 21. doi: 10.1038/s41385-018-0004-9. [Epub ahead of print] (Corresponding author )
3.Yang HC, Chen PJ. The potential and challenges of CRISPR-Cas in eradication of hepatitis B virus covalently closed circular DNA. Virus Research, 2018 Jan 15; 244:304-310..
4.Shan, L., Deng, K., Gao, H., Xing, S., Capoferri, A.A., Durand, C.M., Rabi, S.A., Laird, G.M., Kim, M., Hosmane, N.N., Yang H.C., et al. (2017). Transcriptional Reprogramming during Effector-to-Memory Transition Renders CD4(+) T Cells Permissive for Latent HIV-1 Infection. Immunity 47, 766-775 e763.
5.Liu WL, Yang HC, Hsu CS, Wang CC, Wang TS, Kao JH*, Chen DS. (2016) Pegylated IFN-α suppresses hepatitis C virus by promoting the DAPK-mTOR pathway. Proc Natl Acad Sci U S A. 2016, 113:14799-14804.
6.Yang, HC, and Kao, JH (2016). Looking into the crystal ball: biomarkers for outcomes of HBV infection. Hepatology international 10: 99-101.
7.Yang HC, Shih YF, Liu CJ. Viral factors affecting the clinical outcomes of chronic hepatitis B. J Infect Dis. 2017 Nov 16;216(suppl_8):S757-S764
8.Tseng, TC, Liu, CJ, Yang, HC, Chen, CL, Yang, WT, Tsai, CS, et al. (2015). Higher proportion of viral basal core promoter mutant increases the risk of liver cirrhosis in hepatitis B carriers. Gut 64: 292-302.
9.Yang, H.C. and Kao J.H. (2015) HBV cure—can we pin our hopes on immunotherapy? Nature reviews. Gastroenterology & hepatology, doi:10.1038/nrgastro.2015.8 (2015).
10.Lin, S. R., Yang, H. C., Kuo, Y. T., Liu, C. J., Yang, T. Y., Sung, K. C., Lin, Y. Y., Wang, H. Y., Wang, C. C., Shen, Y. C., Wu, F. Y., Kao, J. H., Chen, D. S. and Chen, P. J. (2014). "The CRISPR/Cas9 System Facilitates Clearance of the Intrahepatic HBV Templates In Vivo." Mol Ther Nucleic Acids 3: e186. (Corresponding Author)
11.Yang, H.C. and Kao J.H. (2014) Persistence of hepatitis B virus covalently closed circular DNA in hepatocytes: molecular mechanisms and clinical significance. Emerging Microbes & Infections 2014 Sep;3(9):e64; doi:10.1038/emi.2014.64, Published online 17 September 2014
12.Tseng TC, Liu CJ, Chen CL, Yang HC, Su TH, Wang CC, Yang WT, Kuo SF, Liu CH, Chen PJ, Chen DS, Kao JH. Risk stratification of hepatocellular carcinoma in hepatitis B virus e antigen-negative carriers by combining viral biomarkers. J Infect Dis. 2013 Aug 15;208(4):584-93.
13.Yang HC, Chen CL, Shen YC, Peng CY, Liu CJ, Tseng TC, Su TH, Chung WL, Yu ML, Dai CY, Liu CH, Chen PJ, Chen DS, Kao JH. (2013) Distinct evolution and predictive value of hepatitis B virus precore and basal core promoter mutations in interferon-induced HBeAg seroconversion. Hepatology. 57(3): 934-43
14.Tseng TC, Liu CJ, Su TH, Yang HC, Wang CC, Chen CL, Kuo SF, Liu CH, Chen PJ, Chen DS, Kao JH. Young chronic hepatitis B patients with nucleos(t)ide analogue-induced hepatitis B e antigen seroconversion have a higher risk of HBV reactivation. J Infect Dis. 2012 Nov 15;206(10):1521-31.
15.Tseng TC, Liu CJ, Yang HC, Su TH, Wang CC, Chen CL, et al. Serum hepatitis B surface antigen levels help predict disease progression in patients with low HBV loads. Hepatology 2013 Feb;57(2):441-50. doi: 10.1002/hep.26041. Epub 2012 Dec 6.
16.Liu WL, Yang HC*, Su WC, Wang CC, Chen HL, Wang HY, Chen DS, Lai MY. (2012) Ribavirin enhances the action of Interferon-α against hepatitis C virus by promoting the p53 activity through the ERK1/2 pathway. PLoS One 7(9):e43824 (co-corresponding author)
17.Shan L, Deng K, Shroff NS, Durand CM, Rabi SA, Yang HC, Zhang H, Margolick JB, Blankson JN, Siliciano RF. (2012) Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity 36(3):491-501
18.Tseng TC, Liu CJ, Yang HC, Su TH, Wang CC, Chen CL, Kuo SF, Liu CH, Chen PJ, Chen DS, Kao JH. (2012) High Levels of Hepatitis B Surface Antigen Increase Risk of Hepatocellular Carcinoma in Patients With Low HBV Load. Gastroenterology 142(5):1140-1149
19.Tseng TC, Liu CJ, Yang HC, Su TH, Wang CC, Chen CL, Kuo SF, Liu CH, Chen PJ, Chen DS, Kao JH. (2012) Determinants of spontaneous surface antigen loss in hepatitis B e antigen-negative patients with a low viral load. Hepatology 55(1):68-76
20.Shan L, Yang HC, Rabi SA, Bravo HC, Shroff NS, Irizarry RA, Zhang H, Margolick JB, Siliciano JD, Siliciano RF (2011) Influence of host gene transcription level and orientation on HIV-1 latency in a primary-cell model. J. Virol. 85: 5384-5393
21.Yang HC, Xing S, Dinoso J, Zhou Y, Han Y, Liu JO, Zhang H, Margolick JB, Siliciano RF. (2009) Small-molecule screening using a human primary cell model of HIV latency identifies compounds that reverse latency without cellular activation. J. Clin. Invest. 119: 3473-3486
22.Yang HC, Shen L., Siliciano RF, Pomerantz JL. (2009) Isolation of a cellular factor that can reactivate latent HIV-1 without T cell activation. Proc. Natl. Acad. Sci. U. S. A. 106: 6321–6326.
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