Dr Edward Jarman
How does Cox2 recruit and pattern local immune neighborhoods to promote PSC-CCA transition?
Awarded to Dr Edward Jarman, University of Leicester
The total grant awarded is £49,928
Duration of award: 27 months
Research title: How does Cox2 recruit and pattern local immune neighborhoods to promote PSC-CCA transition?
This project builds on Dr Jarman's previous work funded by PSC Support.
Summary
PSC Support has awarded £49,928 to Dr Edward Jarman to investigate the mechanisms through which PSC promotes risk of bile duct cancer (cholangiocarcinoma, or CCA). He aims to identify specific cell populations within the liver that they believe are particularly prone to changing and becoming high risk for cancer due to inflammation.
Dr Jarman will use a technology called spatial transcriptomics to zoom in on this population of cells (which express a protein called COX2) in tissue from people with PSC and understand exactly how these cells react to PSC inflammation.
Dr Jarman will use animal models to functionally verify whether COX2 is involved in these changes and whether its actions can be reduced or turned off, and if this can reduce the cancer risk. He hopes that this research will inform future strategies for targeted cancer prevention in people with PSC.
Aims
This study looks at how CCA first starts in the bile ducts in some people with PSC. Dr Jarman wants to understand exactly how having PSC increases the risk of developing CCA. He will investigate whether cells of the PBGs are the starting point for tumours in PSC. He will compare PBGs from people with and without PSC, and then he will see if he can stop 'cross-talk' between immune cells and the PBGs to lower the risk of cancer, ultimately helping us find the best medicines to protect patients.
What will Dr Jarman do?
Dr Jarman will compare liver samples from people with and without PSC to see exactly how their cells differ. Using a high-tech tool called 'spatial transcriptomics,' he can create a detailed map showing how bile duct cells and immune cells behave when there is inflammation. He will then look at this data (and data from his previous work) to see if PSC inflammation 'pushes' bile duct cells to act like cancer cells.
Finally, Dr Jarman will use animal models to recreate how these cells behave. He will look at how immune cells and bile duct cells react to the very first signs of cancer. By doing this, he can test if he can stop cancer from developing by 'blocking the conversation' between these two types of cells.
Why is this study important?
While rare, the impact of CCA is severe for people with PSC. even though therapies for patients with cancer are improving, preventing people from getting cancer in the first place is a much better option. The Asp-PSC Study is looking at whether aspirin can reduce this risk. By studying the earliest triggers of cancer, Dr Jarman wants to find out why aspirin works for some but not others. This knowledge will allow us to tailor treatments to the individual and develop new ways to block the transition from PSC to cancer.
How might this study improve lives?
Dr Jarman is looking for the 'warning signs' that show when a liver is more likely to develop a tumour. By identifying these signals, we can develop better ways to monitor patients based on their individual risk. Dr Jarman is also investigating why aspirin helps some people but not others. By understanding the link between aspirin and immune cells, scientists will be able to target the right treatment to the right person at the right time. Ultimately, this will help us find new ways to block cancer that don't rely on inflammation alone.
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