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Guo Lab

The research lab of Haitao Guo, PhD  focuses on the viral pathogenesis of hepatitis B virus (HBV) and antiviral discovery. HBV is the etiologic agent of viral hepatitis B, a disease affecting approximately 350 million people worldwide who suffer the high risk of liver failure, cirrhosis and liver cancer.

Active Research

The Guo laboratory aims at understanding the molecular mechanisms of HBV DNA replication and morphogenesis, with special focus on the biosynthesis and regulation of HBV covalently closed circular (ccc) DNA, which is the persistent form of HBV infection, and is the culprit for the failure of current antiviral therapies.

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Making use of the HBV cccDNA reporter cell line systems, the Guo lab is screening small molecule compound libraries for cccDNA inhibitors in a high throughput fashion, and two identified cccDNA formation inhibitors are currently under preclinical development. In addition, the Guo lab is studying the innate immunity and oncogenic signaling pathways that regulate HBV replication, as well as identification and characterization of interferon stimulated genes and microRNAs that inhibit HBV infection and propagation.

Research Funding

  • Molecular mechanisms of HBV cccDNA formation
    NIH/NIAID R01AI110762, Guo (PI), 03/11/2016-02/29/2020
  • Development of an HTS Assay for Discovery of HBV cccDNA Inhibitors
    NIH/NIAID R01AI123271, Guo (PI), 12/01/2016-11/30/2019
  • Development of a novel drug candidate that inhibits HBV cccDNA establishment
    NIH/NIAID R01AI094474, Guo (PI), 05/05/2011-04/30/2018
  • Interplay between HBV and AKTmTOR Oncogenic Pathway
    IU Simon Comprehensive Cancer Center Pilot Fund, Guo (PI), 01/01/2017-12/31/2017
  • Study
    Showalter Scholarship Fund, Guo (PI), 07/01/2017-06/30/2020
  • Development of Novel HBV cccDNA Reporter Systems

    Alios Biopharma, Inc., Guo (PI), 04/01/2016-03/31/2018 

  • Characterization of Novel Small Molecule Inhibitors of HBV cccDNA Metabolism
    Arbutus Biopharma, Inc., Guo (PI), 08/01/2016-07/31/2018

Recent Publications

  • 2017
    Liu, Y., Nie, H., Mao, R., Mitra, B., Cai, D., Yan, R., Guo, J., Block, T., Mechti, N., Guo, H. Interferon-inducible Ribonuclease ISG20 Inhibits Hepatitis B Virus Replication through Directly Binding to the epsilon Stem-loop Structure of Viral RNA. PLoS Pathogens. 2017, 13: e1006296.

    Hong, X., Kim, E., Guo, H. Epigenetic Regulation of Hepatitis B Virus Covalently Closed Circular DNA: Implications for Epigenetic Therapy against Chronic Hepatitis B. Hepatology 2017 [Epub ahead of print]

    Iwamoto, M., Cai, D., Sugiyama, M., Suzuki, R., Aizaki, H., Ryo, A., Ohtani, N., Tanaka, Y., Mizokami, M., Wakita, T., Guo, H., Watashi, K. Functional association of cellular microtubules with viral capsid assembly supports efficient hepatitis B virus replication. Scientific Reports 2017, 7: 10620.

    Yan, R., Cai, D., Liu, Y., Guo, H. Detection of Hepatitis B Virus Particles Released from Cultured Cells by Particle Gel Assay. Methods in Molecular Biology: Hepatitis B Virus. Springer. 2017, 1540: 193-202.

  • 2016
    Liu, C., Cai, D., Zhang, L., Tang, W., Yan, R., Guo, H. , Chen, X. Identification of hydrolyzable tannins (punicalagin, punicalin and geraniin) as novel inhibitors of hepatitis B virus covalently closed circular DNA. Antiviral Research 2016, 134:97-107.

    Mitra, B., Guo, H. Hepatitis B Virus X Protein Crosses Out Smc5/6 Complex to Maintain cccDNA Transcription. Hepatology. 2016, 64:2246-49.

    Cai, D., Wang, X., Yan, R., Mao, R., Liu, Y., Ji, C., Cuconati, A., Guo, H. Establishment of an Inducible HBV Stable Cell Line that Expresses cccDNA-dependent Epitope-tagged HBeAg for Screening of cccDNA Modulators. Antiviral Research 2016, 132: 26-37.

  • 2015
    Yan, R., Zhao, X., Cai, D., Liu, Y., Block, T., Guo, J., Guo, H. Interferon-inducible Protein Tetherin Inhibits Hepatitis B Virus Virion Secretion. Journal of Virology 2015, 89: 9200-12.

    Yan, R., Zhang, Y., Cai, D., Liu, Y., Cuconati, A., Guo, H. Spinoculation Enhances HBV Infection in NTCP-Reconstituted Hepatocytes. PLoS One 2015, 10(6):e0129889.

    Guo, J.T., Guo, H. Metabolism and function of hepatitis B virus cccDNA: Implications for the development of cccDNA-targeting antiviral therapeutics. Antiviral Research. 2015, 122: 91-100.

Faculty Research Team

Junjie Zhang, PhD

Visiting Assistant Scientist in Medical & Molecular Genetics

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Additional Research Team Members

Other research team members in the Guo Lab include Quanxin Long, PhD (postdoctoral fellow), Sue Wang (research analyst II), Bidisha (Eshaani) Mitra (PhD student) and Alex Marchetti (PhD student).