The Univeristy of Melbourne The Royal Melbourne Hopspital

A joint venture between The University of Melbourne and The Royal Melbourne Hospital

  • Research Groups

    Current Projects

    • Identifying novel biomarkers of HBV treatment response

      Peter is lead investigator on multiple studies interrogating novel biomarkers of treatment response in the setting of antiviral therapy. His team utilises next generation sequencing (Illumina miseq) to sequence the complete HBV genome, to determine the impact of sequence diversity and identify specific mutations associated with adverse or successful treatment. Peter also has an interest in the role of the innate immune response in treatment response, with his team showing that some innate immune responses are predicative of response in the setting of interferon treatment. Importantly, the ability of HBV to down-regulate innate immune responses varies by HBV genotype.

    • Novel approaches to HBV cure

      HBV is currently incurable. The HBV X protein is critical for transcription of viral cccDNA, the nuclear form of HBV, which represents a major impediment to HBV cure, as it is not targeted by current antiviral therapies. Peter’s team will utilise cell culture models to investigate the role of the HBx protein in HBV infection, replication and cccDNA stability, to assess the feasibility of HBx as a novel therapeutic target that may lead to HBV cure.

    • The emergence of African HBV genotypes in Australian pediatric patients

      Although HBV is mostly transmitted by “mother to baby” worldwide, there have been few studies of HBV in the pediatric setting. HBV chronically infects over 75 million people in Africa where novel genotypes are associated with rapid progression to liver cancer in young males (subtype A1) or reduced vaccine efficacy (genotype E). In collaboration with Associate Professor Winita Hardikar and Dr Liz Bannister at the Royal Children’s Hospital, Peter’s team is investigating the distribution, natural history and molecular virology of African HBV genotypes in a pediatric setting.  

    • The role of genotype in HBV pathogenesis

      HBV exists as nine major genotypes, one minor genotype, and over 40 subtypes globally.  HBV natural history, disease progression and treatment response varies markedly for many genotypes and subtypes, for reasons that are unclear. Peter’s team has established an extensive panel of replication competent cDNA clones of all major genotypes and many important subtypes, enabling direct comparison of HBV replication, using cell culture and more recently (in collaboration with Dr Marc Pellegrini at the Walter and Eliza Hall Institute) murine models. He has also established collaborations with international investigators using these clones to interrogate the role of genotype in treatment response.  

    • The role of splicing in HBV pathogenesis

      At least 14 different splice-derived RNA or DNA variants have been identified to date in cells or serum obtained from persons with chronic HBV, or from cell cultures transfected with infectious HBV cDNAs. The most frequently detected HBV spliced RNA/DNA is a 1.9 kb molecule termed Sp1, generated by removal of a 1.3 kb intron from the pre-genomic RNA.  We have shown that the presence of spliced variants in patient serum is predictive of liver cancer. Peter is interested to determine the mechanisms by which this occurs and whether spliced variants can be specifically targeted for removal using RNAi.

    Lab Team

    • Tina Sozzi
      Senior Research Assistant
    • Dr Liz Bannister
      PhD candidate
    • Dr Zina Valaydon
      PhD candidate
    • Miss Thao Huynh
      Honours student
    • Mr Hugh Mason
      Research Assistant

    Clinical Research

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    Current projects

    • Hepatitis HIV

      A surveillance program for the detection of hepatitis B virus (HBV) resistance to tenofovir (TDF) in HIV-HBV co-infected patient

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    • Hepatitis

      Characterising Hepatitis B in northern Australia through Molecular epidemiology - longitudinal cohort study

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    • Hepatitis

      Liver Cancer Prevention: linking viral hepatitis diagnosis, treatment and outcomes

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    • Hepatitis HIV

      Long-term persistence of HIV in the liver and the clinical impact on HIV-HBV co-infection (CHHANEL)

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    • Hepatitis HIV

      Towards a Functional cure for HBV: exploiting lessons from HBV-HIV co-infection

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