Modulating Tregs in liver disease for therapeutic benefit

Regulatory T cells (Tregs) are important for maintaining tolerance to self and are known to contribute to appropriate priming in the case of foreign challenges, however, their role in liver homeostasis and disease remains to be determined.

Liver disease represents a significant global health issue with Hepatitis B Virus (HBV), Metabolic dysfunction-associated Steatotic Liver Disease (MASLD), and Hepatocellular Carcinoma (HCC) resulting in considerable morbidity and mortality worldwide and limited treatments are available to address these conditions.

This project aims to identify novel mechanisms of targeting Tregs in liver disease to suggest methods to manipulate these cells for therapeutic benefit.

Cutting-edge mouse models of HBV, MASLD, and HCC will be used to determine the phenotypes, kinetics, and localisation of Tregs in the liver under homeostasis and during disease.

High parameter flow cytometry, spatial transcriptomics, and state-of-the-art intravital imaging will allow us to investigate high-resolution spatiotemporal dynamics of liver Tregs to identify novel molecules, interactions, and functions of these cells.

Tissue samples from human patient HBV and HCC cohorts are available to the host lab and can be used to screen and refine the molecules of interest identified in mouse liver Tregs to focus further investigation on clinically relevant molecules.

The role of Tregs in T cell priming in HBV, and effects on MASLD progression, and HCC development will be determined using mouse models to specifically deplete Tregs, or delete molecules of interest in Tregs, at defined disease stages.

Overall, this project will significantly advance our understanding of Tregs in the liver and has the potential to reveal promising clinical targets.

The training in experimental techniques, research communication, and transfer of knowledge my career will be developed towards my goal of becoming an independent researcher.