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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: 劉志猷、余欣樺、黃駿涵、侯佩君、梁潔瑜、馬元策
博班學生: 楊于嬋、林品宏
研究助理: 吳芳儀
博士後研究員:林素如

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研究成果

1.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).
2.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)
3.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 3, e64; doi:10.1038/emi.2014.64, Published online 17 September, 2014
4.Tseng TC, Liu CJ, Yang HC, Chen, CL, Yang, WT, Tsai, CS, et al. Higher proportion of viral basal core promoter mutant increases the risk of liver cirrhosis in hepatitis B carriers. Gut. 2014 Apr 24. doi: 10.1136
5.Kim, M., Hosmane, N. N., Bullen, C. K., Capoferri, A., Yang, H. C., Siliciano, J. D., Siliciano, R. F. A primary CD4(+) T cell model of HIV-1 latency established after activation through the T cell receptor and subsequent return to quiescence. Nature protocols 9, 2755-2770, doi:10.1038/nprot.2014.188 (2014)
6.Liang, CC, Liu, CH, Chung, CS, Lin, CK, Su, TH, Yang, HC, et al. (2014). Advanced Hepatic Fibrosis and Steatosis Are Associated With Persistent Alanine Aminotransferase Elevation in Chronic Hepatitis C Patients Negative for Hepatitis C Virus RNA During Pegylated Interferon Plus Ribavirin Therapy. The Journal of infectious diseases. 2014 Nov 11. [Epub ahead of print]
7.Wu HL, Kao JH, Chen TC, Wu WH, Liu CH, Su TH, Yang HC, et al. Serum Cytokine/Chemokine Profiles in Acute Exacerbation of Chronic Hepatitis B: Clinical and Mechanistic Implications. Journal of gastroenterology and hepatology. 2014 Apr 15. doi: 10.1111
8.Tseng TC, Liu CJ, Yang WT, Chen CL, Yang HC, Su TH, et al. (2014). Hepatitis B surface antigen level complements viral load in predicting viral reactivation in spontaneous HBeAg seroconverters. Journal of gastroenterology and hepatology 29: 1242-1249.
9.Su TH, Liu CJ, Yang HC, Jeng YM, Cheng HR, Liu CH, et al. (2014). Clinical significance and evolution of hepatic HBsAg expression in HBeAg-positive patients receiving interferon therapy. Journal of gastroenterology 49: 356-362.
10.Shan L, Xing S, Yang HC, Zhang H, Margolick JB, and Siliciano RF (2014). Unique characteristics of histone deacetylase inhibitors in reactivation of latent HIV-1 in Bcl-2-transduced primary resting CD4+ T cells. The Journal of antimicrobial chemotherapy 69: 28-33.
11.Liu CH, Huang CF, Liu CJ, Dai CY, Liang CC, Huang JF, Hung PH, Tsai HB, Tsai MK, Chen SI, Lin JW, Yang SS, Su TH, Yang HC, Chen PJ, Chen DS, Chuang WL, Yu ML, Kao JH. Pegylated Interferon-α2a With or Without Low-Dose Ribavirin for Treatment-Naive Patients With Hepatitis C Virus Genotype 1 Receiving Hemodialysis: A Randomized Trial. Ann Intern Med. 2013 Dec 3;159(11):729-38. doi: 10.7326/0003-4819-159-11-201312030-00005.
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 JC, Yang HC, Shun CT, Wang TH, Chien CT, Kao JY. Catechins and Sialic Acid Attenuate Helicobacter pylori-Triggered Epithelial Caspase-1 Activity and Eradicate Helicobacter pylori Infection. Evid Based Complement Alternat Med. 2013;2013:248585.
14.Su TH, Liu CJ, Tseng TC, Liu CH, Yang HC, Chen CL, Chen PJ, Kao JH, Chen DS. Longitudinal change of HBsAg in HBeAg-negative patients with genotype B or C infection. PLoS One. 2013 Feb;8(2):e55916.
15.Yu ML, Lee CM, Chen CL, Chuang WL, Lu SN, Liu CH, Wu SS, Liao LY, Kuo HT, Chao YC, Tung SY, Yang SS, Kao JH, Su WW, Lin CL, Yang HC, Chen PJ, Chen DS, Liu CJ; Taiwan Liver-Net Consortium. Sustained hepatitis C virus clearance and increased hepatitis B surface antigen seroclearance in patients with dual chronic hepatitis C and B during posttreatment follow-up. Hepatology. 2013 Jun;57(6):2135-42.
16.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
17.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.
18.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.
19.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)
20.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
21.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
22.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
23.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
24.Yang H.C. (2011) Primary cell models of HIV latency. Curr Opin HIV AIDS. 6: 62-67.
25.Xing S, Bullen CK, Shroff NS, Shan L, Yang HC, Manucci JL, Bhat S, Zhang H, Margolick JB, Quinn TC, Margolis DM, Siliciano JD, Siliciano RF. (2011) Disulfiram reactivates latent HIV-1 in a bcl-2-transduced primary CD4+ T cell model without inducing global T cell activation. J Virol, 85: 6060-6064
26.Lin YJ, Huang LR, Yang HC, Tzeng HT, Hsu PN, Wu HL, Chen PJ, Chen DS (2010) Hepatitis B virus core antigen determines viral persistence in a C57BL/6 mouse model. Proc. Natl. Acad. Sci. U. S. A. 107: 9340–9345.
27.Szeto GL, Brice AK, Yang HC, Barber SA, Siliciano RF, Clements JE. (2010) Minocycline attenuates HIV infection and reactivation by suppressing cellular activation in human CD4+ T cells. J. Infect. Dis. 201: 1132-1140
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