Dr Anthony George
Predicting Progression in PSC
Awarded to Dr Anthony George, University of Oxford
The total grant awarded is £52,500
Duration of award: 2 years
Research title: Predicting Progression in PSC
Summary
PSC Support has awarded £52,500 to Dr Anthony George to uncover the processes that drive inflammation and damage in PSC.
The team will use state of the art technologies to analyse liver biopsy samples from people with PSC, giving us unprecedented insights into how the disease develops and progresses.
One of the most difficult aspects of living with PSC is the uncertainty associated with its unpredictable nature. Dr George’s work could lead to the development of tools to accurately predict who will develop more advanced disease and allow doctors to tailor care to individuals’ needs.
Background
A new diagnosis of PSC can be a frightening prospect, made worse by the uncertainty of how the disease will progress over time and the fact that there are no effective treatments for PSC.
One of the most difficult emotional aspects of dealing with PSC for patients is not knowing how the disease may progress. Many people can remain relatively stable with few symptoms, but sadly for some, the disease can rapidly progress to serious symptoms that may ultimately lead to liver failure. What’s more, when someone is diagnosed with PSC, doctors do not have the tools to tell them what damage their PSC will cause or how quickly. People with PSC say that not knowing how serious it will get or when is like living under a ‘ticking time bomb’.
We do not fully understand the mechanisms that cause inflammation and scarring in the liver. Dr George will use cutting-edge research technologies that have never previously been applied to PSC to seek out markers of disease severity, potential targets for future drugs and the processes involved in how PSC develops.
What will Dr George do?
Dr George will look at the genetic make-up of individual clusters of cells at a microscopic level in liver biopsy samples from people with PSC and compare them to those of people with other liver diseases.
To do this, Dr George’s team will use a new technology called spatial transcriptomics to identify different types of cells and map out where they are. The location of the cells helps us to understand their function, and ultimately unlock information about how PSC develops and progresses at the cellular level.
Why is this study important?
One of the most difficult aspects of living with PSC is the uncertainty associated with its unpredictable nature. We simply don’t have the tools today to accurately predict who will get worse and how quickly, nor do we have an effective treatment to control the disease.
This study aims to use state of the art research technologies that have never previously been applied to PSC to seek out biological markers of disease severity and improve our understanding of how PSC forms and causes disease. Uncovering these pathways will provide new targets for drugs that can interrupt these processes - and help us predict who will develop more advanced disease, allowing doctors to personalise care to individual patients.
Progress Report
We are pleased to share that we have made substantial progress in the next phase of our research exploring the immune and molecular mechanisms underpinning primary sclerosing cholangitis (PSC).
We have now selected and requested 16 carefully chosen liver tissue samples from the local biobank. These samples will undergo spatial transcriptomic analysis, a cutting-edge technique that allows us to visualise which genes are active in individual cells and where those cells are located within the liver tissue. Importantly, these samples come from people with PSC who have had more than one liver biopsy over time, allowing us to study how the disease changes as it progresses.
Some of the samples are from individuals who later developed cholangiocarcinoma (a type of bile duct cancer), which gives us a unique opportunity to explore what changes in the liver may precede the development of cancer.
For comparison, we have also included samples from people who have a different condition called IgG-4 related sclerosing cholangitis. People with this condition also develop inflammation of the bile ducts but have a very different response to steroids then people with PSC.
Alongside this, we have developed a bespoke panel of genetic probe molecules tailored specifically to liver and bile duct diseases. These molecules lock on specific target regions of a cell’s DNA and can tell us what molecules and proteins a single cell is producing. This gene panel was designed using both published literature and our own data to ensure it includes the most relevant markers for immune cells, scar-forming (stromal) cells, and key pathways involved in inflammation, tissue damage, and cancer risk. This allows us to get the most useful information possible from the tissue samples, particularly when trying to distinguish between harmless inflammation and early signs of more serious disease.
To support this tissue work, we are also building an atlas of gene-expression from liver cells collected by fine-needle liver aspirates.
A fine-needle liver aspirate (FNLA) is a simple, quick medical procedure used to collect a small sample of cells from the liver for examination under a microscope. It's often referred to as a fine-needle aspiration (FNA) or fine-needle biopsy. These single-cell datasets help us understand the types of immune cells involved in PSC and how their activity compares to other chronic liver conditions, such as viral infections and fatty liver disease.
Our early findings suggest some interesting differences:
- Tolerant (protective) liver-resident macrophages, called Kupffer cells, are better preserved in PSC compared to other diseases. These cells play a key role in regulating inflammation and may contribute to how PSC behaves differently from other liver diseases.
- We have also observed a higher number of cytotoxic CD8 T cells in PSC. These are immune cells that can damage liver tissue if overly active. These cells express markers such as GZMK and GZMB, which are associated with cell-killing activity.
These results provide new insight into how the immune environment in PSC differs from other chronic liver diseases and may help us better understand why PSC progresses the way it does, and how progressive disease might be detected better and earlier in the future.
Dr Anthony George, July 2025
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