Thesis work
Thesis title: Understanding the persistence of Hepatitis B virus covalently closed circular DNA
Supervisors: Thomas Tu, Mark Douglas
Thesis abstract:
«p»Chronic infection with Hepatitis B virus (HBV) is a global health issue and causes liver injury over many decades. This disease progression eventually leads to cirrhosis and hepatocellular carcinoma, killing >600,000 people each year. Chronic HBV infections are generally lifelong due to the intrahepatic persistence of HBV covalently closed circular (ccc)DNA, which is the blueprint for all viral transcripts. cccDNA is stable within the nucleus of hepatocytes and is only cleared from the infected cells when targeted for cell death or during cell mitosis. Here, I aim to identify host factors that affect cccDNA synthesis and stability as novel targets to develop cures for Hepatitis B infections. Moreover, I investigate the mechanisms by which cccDNA is maintained despite significant liver turnover during a chronic infection. In particular, I characterise and target a sub-population of liver cells that act as a potential viral reservoir. By understanding how cccDNA persists, I intend to develop ways to therapeutically interrupt these specific pathways and thereby cure chronic HBV infection.«/p»
Publications
Journals
- Zhang, H., Tu, T. (2023). Targeting Hepatitis B Virus DNA Using Designer Gene Editors. Clinics in Liver Disease, 27(4), 895-916. [More Information]
- Zhang, H., Tu, T. (2022). Approaches to quantifying hepatitis B virus covalently closed circular DNA. Clinical and Molecular Hepatology, 28(2), 135-149. [More Information]
- Tu, T., Zehnder, B., Wettengel, J., Zhang, H., Coulter, S., Ho, V., Douglas, M., Protzer, U., George, J., Urban, S. (2022). Mitosis of hepatitis B virus-infected cells in vitro results in uninfected daughter cells. JHEP Reports, 4(9). [More Information]
2023
- Zhang, H., Tu, T. (2023). Targeting Hepatitis B Virus DNA Using Designer Gene Editors. Clinics in Liver Disease, 27(4), 895-916. [More Information]
2022
- Zhang, H., Tu, T. (2022). Approaches to quantifying hepatitis B virus covalently closed circular DNA. Clinical and Molecular Hepatology, 28(2), 135-149. [More Information]
- Tu, T., Zehnder, B., Wettengel, J., Zhang, H., Coulter, S., Ho, V., Douglas, M., Protzer, U., George, J., Urban, S. (2022). Mitosis of hepatitis B virus-infected cells in vitro results in uninfected daughter cells. JHEP Reports, 4(9). [More Information]
- Tu, T., Zhang, H. (2022). Viral integrations in chronic hepatitis B infection: Purposeless passenger or problematic promoter of persistence? Hepatology, 76(1), 15-17. [More Information]
2021
- Zhang, H., Tu, T. (2021). A River From the Liver: Detecting Hepatocyte Genomic DNA in Urine. Hepatology Communications, 5(10), 1629-1631. [More Information]
- Tu, T., Zhang, H., Urban, S. (2021). Hepatitis B Virus DNA Integration: In Vitro Models for Investigating Viral Pathogenesis and Persistence. Viruses, 13(2), 180. [More Information]