Education & Training
- Postdoc, virology, Fox Chase Cancer Center 2004
- Ph.D., microbiology, Wuhan University 2001
- B.S., virology, Wuhan University 1996
Research Interest Summary
Research Categories
Research Interests
My research is focused 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. My 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. Making use of the HBV cccDNA reporter cell line systems recently established by us, we are 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, we are studying the innate immunity and oncogenic signaling pathways that regulate HBV replication, as well as identification and characterization of host restriction factors that inhibit HBV infection and propagation in human hepatocytes. We are also investigating the molecular mechanisms of HBV-induced liver cancer and finding therapeutic targets.
Representative Publications
Mitra B, Wang J, Kim E, Mao R, Dong M, Liu Y, Zhang J, Guo H. Hepatitis B Virus Precore Protein p22 Inhibits Interferon-alpha Signaling by Blocking STAT Nuclear Translocation. Journal of Virology 2019, 93: e00196-19 PubMed PMID: 31019054.
Liu S, Zhou B, Valdes J, Sun J, Guo H. Serum HBV RNA: a New Potential Biomarker for Chronic Hepatitis B Virus Infection. Hepatology 2019, 69: 1816-1827. PubMed PMID: 30362148.
Long Q, Yan R, Hu J, Cai D, Mitra B, Kim E, Marchetti A, Zhang H, Wang S, Liu Y, Huang A, Guo H. The Role of Host DNA ligases in Hepadnavirus Covalently Closed Circular DNA Formation. PLoS Pathogens 2017, 13: e1006784. PubMed PMID: 29287110.
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, 66: 2066-77. PubMed PMID: 28833361.
Liu Y, Nie H, Mao R, Mitra B, Cai D, Yan R, Guo JT, Block TM, 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. PubMed PMID: 28399146.
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. PubMed PMID: 27185623.
Yan R, Zhao X, Cai D, Liu Y, Block TM, Guo JT, Guo H. Interferon-inducible Protein Tetherin Inhibits Hepatitis B Virus Virion Secretion. Journal of Virology 2015, 89: 9200-12. PubMed PMID: 26109732.
Mao R, Nie H, Cai D, Zhang J, Liu H, Yan R, Cuconati A, Block TM, Guo JT, Guo H. Inhibition of Hepatitis B Virus Replication by the Host Zinc Finger Antiviral Protein. PLoS Pathogens 2013, 9: e1003494. PubMed PMID: 23853601.
Cai D, Mills C, Yu W, Yan R, Aldrich CE, Saputelli JR, Mason WS, Xu X, Guo JT, Block TM, Cuconati A, Guo H. Identification of the Disubstituted Sulfonamides as Specific Inhibitors of Hepatitis B Virus Covalently Closed Circular DNA Formation. Antimicrobial Agents and Chemotherapy 2012, 56: 4277-88. PubMed PMID: 22644022.
Mao R, Zhang J, Jiang D, Cai D, Levy J, Cuconati A, Block TM, Guo JT, Guo H. Indoleamine 2, 3-dioxygenase mediates the Antiviral Effect of Gamma Interferon against Hepatitis B Virus in Human Hepatocyte-derived Cells. Journal of Virology 2011, 85: 1048-57. PubMed PMID: 21084489.