About me and how I started this project.
Hi I’m Sam. I’m currently doing a masters of research funded by AllCaN. Growing up, I always knew I wanted to study Biology, glued to the latest David Attenborough documentary. Throughout my bachelor’s degree in Biomedical and Molecular Diagnostics I learned a great deal about diseases, how they develop, and how we are able to diagnose them. I continued to be fascinated with human biology, having learned a large breadth of topics from basic cell biology, to more detailed and complicated biological pathways and diseases. During this time, I began to realise that it’s difficult to think of a disease where the immune system isn’t an important part of the puzzle, especially when it comes to cancer. Once I started to learn about immunology in more detail and its translation into real treatments, I was hooked. I knew that I wanted to pursue my own research in cancer immunology. After this realisation, I reached out to my now primary supervisor Prof Joanne Lysaght who luckily had an exciting project starting with my now co-supervisor Dr Aideen Ryan.
How is immune system relevant to Barrett’s Oesophagus?
Barrett’s oesophagus is a precursor to oesophageal cancer. It is now widely recognised that Barrett’s oesophagus is driven by inflammation. This occurs as stomach acid goes back up the oesophagus (food pipe) and irritates the cells which line it, resulting in inflammation. This is not normally an issue, however when the cells are constantly or regularly exposed to stomach acid the oesophagus becomes chronically inflamed, damaging the cells, leading to Barrett’s oesophagus. Treatments for Barrett’s are mostly aimed at managing the symptoms such as proton pump inhibitors, however these don’t prevent the disease from progressing. Once Barrett’s progresses to cancer, only one 1 in 5 patients will live past 5 years. Given the poor treatment landscape for Barrett’s oesophagus and oesophageal cancer patients, there is a huge unmet need for research into these diseases. Further understanding how the immune system drives the development of Barrett’s and its progression into cancer, could offer new insights for translational treatment approaches in halting or slowing disease progression.
What am I researching?
My research hopes to understand how the immune system changes throughout the progression of Barrett’s oesophagus to oesophageal cancer. The Immune system is a finely tuned and delicate system which has multiple components ensuring proper function and an appropriate response. Signalling molecules on the surface of immune cells are vital in maintaining its normal function, known as ‘immune checkpoints’. These immune checkpoints are the target of immunotherapies which have seen great success in the treatment of cancer. Traditionally, research has been mostly focused on immune checkpoints within the context of immune cells. However, our research group has shown that immune checkpoints are also expressed on the surface of cells outside of the immune system, changing as Barrett’s oesophagus develops and progresses to cancer.
My research focuses on the role of immune checkpoint signalling in the development of Barrett’s oesophagus in cells outside of the immune system. Specifically, I’m interested in the cells which go on to become premalignant and cancerous known as ‘epithelial cells’, along with their surrounding supportive cells known as ‘stromal cells’. Given the vital role of immune checkpoints for immune cells, we believe they play an important role in non-immune cells, contributing to the progression and onset of inflammatory associated diseases such as Barrett’s oesophagus.
What do I hope hope to find?
The goal of my project is to explore the types of immune checkpoints that emerge as the disease progresses, specifically in both epithelial and stromal cells. I aim to understand how stromal cells influence immune checkpoint signalling in epithelial cells that eventually go on to become cancerous. Additionally, I aim to understand the role that immune checkpoints play in the development of Barrett’s oesophagus and its progression to cancer.
Ultimately, the broader objective of these aims is to generate translational outputs in improving patient outcomes. By understanding the role that immune checkpoints play in disease progression we will gain invaluable insights into the potential in targeting these pathways during premalignancy as a method to prevent disease progression.
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