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Investigating the immunomodulatory signature of TAGLN+ fibrosis-associated endothelial cells in progressive fibrotic liver disease

Code: BC-DTP_2026_41

Title: Investigating the immunomodulatory signature of TAGLN+ fibrosis-associated endothelial cells in progressive fibrotic liver disease

Primary Supervisor: Neil Dufton

Email: n.dufton@qmul.ac.uk

Institute: William Harvey Research Institute

Secondary Supervisor: Will Alazawi

Email: w.alazawi@qmul.ac.uk

Institute: Blizard Institute

Lay Summary:

Metabolic-dysfunction associated steatotic liver disease (MASLD) is the most common form of liver disease and is estimated to affect up to 30% of the adult population. Notably, the rising prevalence of MASLD is paralleled by an alarming increase in patient mortality rates, which have doubled in the UK over the last 20 years. There are three key factors driving the acceleration of this disease. First, rising levels of obesity across the UK, particularly in hot spots such as the boroughs of East London, are contributing to increasing disease incidence. Second, the lack of sensitive diagnostic tools limit early detection, and consequently many patients are identified only at the later, more severe stages of the disease. Third, there remains an urgent need for effective anti-fibrotic therapies in patients with late-stage tissue scarring, with no therapeutics currently licensed for clinical use. Therefore, the field requires new early-stage disease markers that can identify patients before they suffer irreparable liver fibrosis.                                                 

Our research has identified excessive expression of a protein called Transgelin (TAGLN) in the blood vessels of MASLD patients. Crucially, patients with the highest expression of TAGLN are more likely to have worst disease outcomes. In this project, we will investigate how TAGLN- expressing cells within blood vessels interact with circulating immune cells to induce an inflammatory response. Ultimately, we hope to discover new diagnostic and therapeutic targets in patient blood that will enable us to mitigate the pro-inflammatory effect of TAGLN in blood vessels and, in turn, improve patient outcomes.

Aims and Objectives:

  1. Profile how T-cell phenotype and activation status is affected by TAGLN expression in patients with chronic liver disease and compared to loss of function/expression of TAGLN in individuals within the London Genes and Health cohort.
  2. Determine specific TAGLN+ FAEC-T-cell interaction partners and their effect on T-cell activation in vitro.                                                                        
  3. Investigate the impact of inhibition of TAGLN+ FAEC-T-cell in pre-clinical murine models of liver fibrosis.

References:

Dufton et al., 2017 Nat. Comms https://doi.org/10.1038/s41467-017-01169-0, Gkantsinikoudi et al., 2026 Pre-print Biorxiv, Kumar et al., 2026. Pre-print Biorxiv, Sawada et al., 2024 Cell Metab. doi: 10.1016/j.cmet.2023.10.009.

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