BMedSc (Hons), DPhil
Post-Doctoral Research Fellow
Understanding the interplay between hypoxia signalling and hepatitis B virus replication
James attained his undergraduate degree in Medical Science, at the University of Birmingham in 2017. During his time there, he completed a summer vacation studentship in the laboratory of Professor Jane McKeating, winning funding from the Lister Institute of Preventative Medicine. This project sought to understand the relationship between APOBEC mediated cytidine-deamination and Hepatitis C Virus sequence diversity and pathogenesis.
James returned to Professor McKeating's group at Oxford in October 2017 to begin his DPhil studies on a NDM Prize Studentship funded project. James' project is investigating how the cellular microenvironment can influence viral replication. The liver is the site of replication for hepatitis B virus (HBV), and presents a naturally low oxygen environment for the virus to manipulate and exploit. The cellular response to low oxygen is orchestrated predominantly by hypoxia inducible factors (HIFs), which are heterodimeric transcription factors that regulate gene expression by binding to a hypoxia response element in the promoter of genes. James' DPhil project largely looked to understand the relationship between HIFs and HBV replication at physiological oxygen levels, to try to identify how viral gene expression is regulated. As well as HIFs, there are many other factors which regulate the response to low oxygen, covering a range of roles in: gene expression, DNA methylation, protein function and epigenetic modifications.
James is now beginning to explore how oxygen sensing mechanisms may define a cell as permissive to viral infection. The microarchitecture of the liver is defined by an oxygen gradient, and a cell's position on the radial axis of the liver lobule may determine whether a virus can successfully infect and propagate. James is working in collaboration with colleagues in Oxford and London to employ spatial transcriptomic technology to address the interplay between infected and uninfected hepatocytes, as well as infiltrating immune cells and liver parenchyma.
An enrichment protocol and analysis pipeline for long read sequencing of the hepatitis B virus transcriptome
Ng E. et al, (2023), Journal of General Virology, 104
17β-Oestradiol Protects from Hepatitis C Virus Infection through Induction of Type I Interferon.
Barbaglia MN. et al, (2022), Viruses, 14
Reply to: ‘Active HBV replication in hypoxic pericentral zone 3 is upregulated by multiple host factors including HIF-1α’
Harris JM. et al, (2022), Journal of Hepatology, 77, 267 - 268
Inflammatory Gene Expression Associates with Hepatitis B Virus cccDNA- but Not Integrant-Derived Transcripts in HBeAg Negative Disease
Magri A. et al, (2022), Viruses, 14, 1070 - 1070
Circadian control of hepatitis B virus replication
Zhuang X. et al, (2021), Nature Communications, 12