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Could immune checkpoint signalling be important in the development of Barrett’s oesophagus?

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.

Diana Cooke AllCan

Are lifestyle interventions the key to battling Oesophageal diseases?

All About Me 

My name is Diana Cooke and I am a PhD candidate at Trinity College Dublin. I grew up in Clonmany, a very small village in Donegal, where I attended Carndonagh Community School. From a young age, I always knew I wanted to be able to help people in the future, which led me to studying Psychology at the University of Galway. During my undergraduate degree, I had the opportunity to work with the Irish Cancer Society on a project aiming to improve the quality of life of people living with hereditary cancer predispositions, which helped me to develop a passion for health psychology and its potential to improve the lives of people facing long-term health challenges. This interest ultimately led me to pursue a Master’s in Health Psychology also at the University of Galway.

My past research explored different aspects of life for people at high risk of developing cancer, such as managing uncertainty, emotional well-being, and the psychological impact of regular screenings and preventive measures. A key part of this research was also exploring how family, friends, and healthcare providers influence health decisions. This work revealed that the support and advice from loved ones and healthcare professionals play a critical role in helping individuals make informed decisions about their health, adopting healthier lifestyles, and managing the emotional burden of living with increased cancer risk. Through this work, I gained valuable insights into the resilience and coping mechanisms individuals develop when faced with such a daunting risk.

All of this led me to pursue my PhD, where I aim to develop a lifestyle intervention for individuals with Barrett’s Oesophagus to improve their quality of life and reduce cancer risk, under the supervision of Dr. Emer Guinan, Prof. Juliette Hussey, and Dr. Olinda Santin

When I’m not working, I’m likely strolling along a beautiful Donegal beach or lost in a book, with coffee in hand. When I’m indoors, I love to cook, as you might expect from my name, and I find it to be a relaxing way to unwind after a busy day, especially when making simple, comforting meals.

What are lifestyle interventions?

While medical treatments and surveillance play a key role in managing Barrett’s Oesophagus, lifestyle factors like what we eat, how much we move, and whether we actually get enough sleep (a rare achievement) can also have a significant impact. Lifestyle interventions are structured programs designed to help people make sustainable changes to their daily habits, ideally without feeling like they’ve signed up for a life of bland salads and endless treadmill sessions. These interventions often focus on key areas such as diet, physical activity, sleep, and stress management, aiming to reduce the risk of disease progression and improving quality of life. Instead of just relying solely on medical treatments, lifestyle interventions aim to empower people to take an active role in their health without making them feel like they need to become an overnight wellness guru.

It’s very easy to tell someone, “You need to exercise more” or “You should eat healthier”. In theory, this is great advice that we often hear from healthcare professionals, family members, or even friends. In practice? If making lasting lifestyle changes were that simple, we’d all be effortlessly fit and stress-free. The reality is that humans are complicated (and stubborn). We know what’s good for us, yet we often struggle to put it into action. Why? Well, life gets in the way or simply not knowing where to start.

Work, family responsibilities, stress, and the sheer exhaustion of existing can make it hard to prioritise things like exercise or meal planning. And let’s be honest sometimes, after a long day, the idea of cooking a nutritious meal is less appealing than eating the chocolate bar you know is hidden in the back of the cupboard. It’s not enough to simply provide information or make recommendations; we need to understand the underlying psychological, emotional, and social factors that influence decision-making. That’s where my research comes in it’s not just about knowing what’s good for us, it’s about finding ways to integrate these changes into our daily lives in a realistic and sustainable way.

For individuals with Barrett’s Oesophagus, these challenges can feel even more daunting. Managing acid reflux, coping with the side effects of medications, and adjusting to the reality of living with a condition that has cancerous potential make it harder to focus on things like exercise and nutrition. Studies show that keeping a healthy weight, eating well, and staying active can help with symptoms and might even reduce the risk of the condition getting worse. But knowing that and actually doing it are two very different things. Many people find it tough to keep a healthy weight, change their diet, or figure out an exercise routine that works for them. That’s why having support that’s right for you really makes a difference. My research attempts to identify these barriers to behaviour change and what kind of support would help most.

Let’s face it, lasting change doesn’t happen overnight, and no one expects you to overhaul your life in a single afternoon. The key is starting small, making gradual changes that fit into your life and that you can realistically maintain. Whether it be a brisk 10-minute walk, opting for smaller, more frequent meals to reduce acid reflux, or swapping out acidic foods like citrus and tomatoes for gentler alternatives, these small changes can have a big impact over time.

Lifestyle interventions have the potential to bridge the gap between medical care and everyday health habits, giving people more control over their well-being. Ultimately, the goal is to improve not just physical health outcomes but also overall quality of life. Health is more than just the absence of illness. It’s about quality of life, emotional well-being, and the daily choices we make. That’s why my research focuses on making these choices more achievable and sustainable, because small, consistent changes can lead to meaningful, long-term improvements in health and well-being.

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Capsule sponge testing could improve the diagnosis of Barrett’s Oesophagus

All About Me 

My name is Orla Carney and I am currently a second year MPhil student based in the Centre for Public Health at Queens University Belfast. I completed my undergraduate medical degree at Queens and graduated in 2016. I then completed my foundation medical training rotating through various specialties including renal medicine, geriatrics, orthopaedics and oncology.  I have always loved travelling and after completing my foundation programme, I knew I wanted to spend some time working abroad to experience a different healthcare system. I opted for the sunny shores of Perth, Western Australia where I spent two years working in a busy emergency department. I gained such a wealth of experience during this time by assessing and treating a range of patients, from tiny newborn babies to the elderly patients presenting towards the end of life. I even gained skills in the management of snake bites, although these are skills that I thankfully haven’t had to use since returning to Ireland!

I think I adapted well to the Aussie way of life with my days off filled with road trips, sea swims and plenty of barbecues. However, my time there was also filled with uncertainty as we faced the challenges of the beginning of the COVID pandemic. In many ways, as Perth is the most isolated city in the world, there was no better place to be during this time. On the other hand, with my friends and family on the other side of the world, I knew that home was calling and so I made the decision to return to Belfast in 2021.

I began my general practice training in 2021 as I knew I wanted to work with a variety of patients regarding age, clinical presentation and complexity of medical problems. In my final year of GP training, I was given the opportunity to become involved in research through the GP Academic Research Training Scheme. Whilst I had no previous involvement or experience with research, I had always been interested in gaining research skills and knew this would be an invaluable opportunity. When considering my potential areas for research, I thought back to my time working in oncology in my foundation years. This is a speciality which I had always found interesting and with early diagnostics being such a rapidly evolving area, I felt that this would be an exciting area to begin my research journey.

Outside of work, I am a keen runner and completed my first half marathon last year. I am currently training for the Paris marathon in April 2025 in aid of Cancer Focus NI. I regularly run with various social running clubs in Belfast and find these a great way to meet people and destress after a busy clinic day.

My Project

My research project is focused on the potential uses for capsule sponge testing within primary care to improve diagnosis of Barrett’s Oesophagus. Barrett’s oesophagus is an inflammatory condition where the normal squamous cells lining the oesophagus, undergo changes and can become abnormal. These cells have the potential to develop into oesophageal cancer. Many patients with Barrett’s oesophagus are asymptomatic and identifying those at risk presents a challenge in primary care. The development of the capsule sponge test has presented an exciting opportunity to improve early diagnosis.

The capsule sponge test is a quick test which has the potential to be performed in a general practice or outpatient setting. The test involves swallowing a capsule attached to a string under the supervision of a doctor or nurse. Once swallowed, the capsule lining dissolves in the stomach to reveal a small sponge attached to the string. On removal of the sponge by pulling on the string, the sponge is able to collect cell samples from the oesophageal lining, which can then be tested to identify any changes suggestive of Barrett’s oesophagus. Clinical trials to date have shown that the capsule sponge is a safe and effective test, identifying up to ten times more cases of Barrett’s oesophagus than current standard care (which involves assessment by a GP and using history and examination to assess whether a patient would benefit from further investigation with upper GI endoscopy).

Currently, the BEST4 trial is seeking to understand whether mortality from oesophageal cancer can be reduced through use of the capsule sponge test. This trial also includes parallel studies which are focusing on patient experience and their willingness to undertake a capsule sponge test. However, one key group which has not been involved in this research are general practitioners. As a GP trainee, I feel that I am uniquely placed to fill this research gap.

This qualitative study seeks to understand GP perspectives regarding current management of dyspepsia and upper GI symptoms in primary care. It also seeks to understand views on the potential uses of the capsule sponge and any barriers and enablers to its implementation. Through the use of semi-structured interviews, a group of GP volunteers from across the UK and Ireland will be given the opportunity to discuss their opinions. The data obtained from these interviews will be vital for policymakers to consider when developing any new potential pathways in primary care. 

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The Role of Diet in Inflammation: A Researcher’s View Point

I am Pousali Chatterjee, and I am from West Bengal, India. I completed my undergradate and postgraduate courses in Human Physiology from Burdwan University and the latter from Calcutta University. I specialised in Endocrinology and got exposure to working with the pancreas and the associated inflammation of this organ that is caused by certain lifestyle choices, like Bisphenol-A, that can be found in the lining of canned food and all the plastic boxes or polycarbonate tableware that we use on a daily basis. I was intrigued by how our environment and food choices affect inflammation in our bodies and our overall health. Inflammation is associated with the development of many chronic diseases including heart disease, diabetes and cancer. The mechanisms driving this inflammation, however, are poorly understood and this is a major focus of my PhD project.

After I graduated from Calcutta University, I worked as a lecturer and lab instructor in my undergraduate college. I held this position for a year before moving to University College Dublin (UCD) in 2018 to undertake an MSc in Biotechnology and Business. I know it sounds off-track, ‘human physiology’ and suddenly ‘business?’, I get this question a lot! Biotechnology is revolutionising the healthcare sector, so I really wanted to learn more about the latest technologies out there. In addition, business training gave me a much more holistic understanding of problem-solution fit and how to go about asking the right questions in my research. Currently, I am pursuing my PhD under the supervision of Dr Fiona McGillicuddy and Prof. Helen Roche at UCD, exploring the role of dietary factors in driving inflammation, and possible causal role in mediating the transition of Barrett’s Oesophagus (an inflammatory disease) to Oesophageal Adenocarcinoma (cancer).

I used the term ‘Inflammation’ a couple of times, so what is it?

In simple words, inflammation is the response of the body to protect itself from injury, infection, and diseases. They can be classified as acute or chronic: acute inflammation begins following a tissue injury and lasts for a few days whereas chronic inflammation is a response to an unresolved issue within our body causing constant flaring, indicating that something adverse is going on and needs attention. Acute inflammation can go away by taking prescribed medications such as antibiotics for bacterial infections, NSAIDs, or painkillers. But for chronic inflammation, it is more challenging. This inflammation is often low-grade inflammation which can be very difficult to detect systemically. Some biomarkers like C-reactive protein, Erythrocyte Sedimentation Rate, and plasma viscosity can be helpful, however, more sensitive biomarkers to detect low-grade inflammation and associated adverse effects on health are still an unmet need.  This is one area that I am studying within my PhD. If chronic inflammation is suspected, many medications can be utilised to help alleviate the inflammation, such as corticosteroids or biologics.

Continuous overstimulation of the immune system causes chronic low-grade inflammation. This can occur in an individual because of low-level continuous exposure to industrial chemicals, dietary factors (saturated fats), autoimmune disorders, or autoinflammatory diseases. The risks associated with chronic low-grade inflammation are also increased by smoking, obesity, older age, and eating food with unhealthy fat and sugar. Simple tasks such as eating right, having a proper diet, and exercising can help manage chronic inflammation. One particular disease that I am working on at the moment is Barrett’s Oesophagus – an inflammatory condition that heightens the risk of developing oesophageal cancer.

Acid reflux happens when the contents of our stomach flow up to the tube connecting our mouth to the stomach, called the oesophagus. The lower oesophageal sphincter weakens, relaxes, and lets the acid pass up to the oesophagus. Lying down after heavy meals contributes to continuous and repetitive irritation of acid to the oesophagus leading to gastroesophageal reflux disease (GORD) which can affect 10%-20% of the population. Over time, the inner cell lining of the oesophagus can change with constant acid reflux exposure, and increasing the chances of cancer forming in the oesophagus. GORD is a major risk factor for the development of Barrett’s Oesophagus.

Can diet play a role in preventing BO to OAC progression?

We hope so, as this is the major area of focus for my PhD.

Dietary fat-derived energy comes from saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs). Fast food and ultra-processed foods cooked in hydrogenated oil, deep-fried meat, and vegetables that are consumed by us are the most common forms of SFAs. It causes coronary artery disease and increases low-density lipoprotein levels (‘bad’ fats). SFAs are also major stimulators of inflammation, while MUFAs are not.

Managing GORD can be stressful but introducing high levels of dietary fibre, cutting down on extremely processed food, consuming low dietary fat content, increasing exercise, and waiting for 2-3 hours after dinner before going to bed and elevated sleeping will help control the acid reflux. Evidence from one particular study shows that GORD decreases significantly with weight loss. 81% had a GORD-reduced score, 65% had complete resolution and 15% had partial resolution for reflux in the study. A simple intervention like this can bring a significant change in our lives. Adding more PUFAs to our diet, like walnuts, seafood, salmon, tofu, and olive oil, can also help reduce the inflammation. In my PhD research project, we aim to establish whether modulating the nutritional microenvironment of Barrett’s Oesophagus cells can help reduce inflammation and prevent Barrett’s Oesophagus transitioning to OAC, to further understand how we can reduce cancer risk through specific nutritional approaches.

Author: Ms. Pousali Chatterjee (AllCaN PhD Candidate)

Image: Made with Biorender.com

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Calcium electroporation as a novel therapy for Barrett’s Oesophagus.

All About Me

I’m Lorraine, a first year PhD student based in the Trinity Translational Medicine Institute (TTMI) on the St James’s Hospital campus, Dublin. I’m originally from Ballybofey in Donegal and I attended St Columba’s College in Stranorlar. I was always fascinated by science in school, it was my favourite subject, and my teachers were hugely inspirational. I chose to study Biology, Chemistry and Home Economics for Leaving Certificate and these were both my favourite and strongest subjects. I wasn’t sure what to choose to study in college but after much thought and deliberation I chose General Science in Trinity as this offered a lot of choice throughout. I thoroughly enjoyed the first two years where I studied many different subjects. I chose to specialise in Molecular Medicine in my final years as I was captivated by human immunology and disease mechanisms and this course provided a broad base of knowledge on a wide range of topics. After college, I worked as a Research Assistant with Prof. Jacintha O’Sullivan, who is now my PhD supervisor, in the Department of Surgery at TCD. I really enjoyed working in her lab, I found it endlessly fascinating, mentally stimulating and it provided a strong sense of purpose, which prompted me to pursue a PhD.

Outside of the lab, I love running, especially in the mornings, I find it hugely energising and also a great way to clear my head and destress. I am currently training for my second half- marathon and hope to run my first marathon later this year. In the evenings, I love reading, especially fiction, or watching TV with my flatmates. At the weekends, I spend time with my friends and family, we enjoy going for long walks together especially by the coast and trying new restaurants and coffee shops.

What is Barrett’s Oesophagus and why should we study it?

Barrett’s Oesophagus is an inflammatory disease where cells in the oesophagus, or food pipe, undergo abnormal changes. This occurs in response to long-term acid reflux where acid from the stomach flows back up into the oesophagus. Symptoms include persistent and severe heartburn, difficulty swallowing and indigestion. Treatments include medications which limit the production of acid from the stomach and ease the symptoms of indigestion. If the disease has progressed, surgery can be performed to remove the abnormal cells using a modified endoscope. Alternatively, a therapy called radio frequency ablation is administered. This involves the use of radio waves, and the heat the radio waves generate to kill abnormal cells. Often this is performed in conjunction with surgery. One further treatment option is a procedure called Nissen fundoplication where the valve connecting the stomach and oesophagus is strengthened to prevent acid migrating up the oesophagus.

People with Barrett’s Oesophagus undergo routine endoscopes to monitor disease progression. This is important as approximately 1 in 100 of people with Barrett’s Oesophagus will develop oesophageal cancer (OAC). This is a poor prognosis cancer, but early detection significantly improves survival rates. However, stopping and/or delaying its progression to OAC through novel treatment interventions could also be key in combating this cancer.

What is electroporation and could calcium help treat Barrett’s Oesophagus?

Electroporation is the term used when small electrical pulses are applied to a cell. This creates pores in the cell’s exterior. These pores allow substances into the cell which otherwise cannot enter. Electroporation can be combined with chemotherapy (electrochemotherapy), in what is now emerging as a promising anticancer therapy. Combining electroporation with chemotherapy increases the toxicity of chemotherapies by several thousand times. During electrochemotherapy, the drug is injected into the tumour, then an electric field is applied. Thus, toxic systemic effects of chemotherapy are reduced. Interestingly, calcium has also been investigated as a combination therapy for several malignancies such as melanoma, colorectal cancer, and head and neck cancer. It has been shown to display the same efficacy as various chemotherapies, does not damage surrounding tissues and is inexpensive, making it an attractive treatment option better tolerated by patients. Therefore, combining calcium with electroporation for the treatment of Barrett’s Oesophagus could be a plausible treatment option.

How will we examine if calcium electroporation is a viable treatment option for Barrett’s Oesophagus?

Mr Cian Gargan is the Barrett’s Biobank manager in Trinity’s Department of Surgery. He identifies people living with Barrett’s Oesophagus attending their endoscopy appointments and invites them to participate in the Department of Surgery’s research programme. If the patient consents, the clinical team can take additional blood and tissue samples. Their samples are pseudonymised (to adhere with GDPR) and given to the researchers. When I receive the tissues from consenting patients, I treat them with calcium electroporation using the “ePORE Electroporator” (developed by Mirai Medical). After treatment, I will measure the levels of secreted inflammatory markers in the tissues. In collaboration with Dr Sharon McKenna and Dr John Mackrill in UCC in Cork, I will investigate how calcium electroporation treatment impacts calcium handling within cells and will determine how the treatment affects various signalling pathways in Barrett’s Oesophagus.

How does examining calcium electroporation link in with other projects in AllCaN?

My project within AllCaN will be the first human ex vivo study to examine how human Barrett’s tissues respond to calcium electroporation therapy and if this treatment boosts immunity and/or alters cellular signalling. This could have profound implications in the clinic where the addition of electroporation treatment could be applied in outpatients. I hope that the data generated from my project will accelerate the introduction of this treatment for people with Barrett’s Oesophagus in the clinic; In fact, Mirai Medical have already developed a device which can be attached to the end of an endoscope to treat gastrointestinal malignancies, so the technology to do so is already in place.

Author: Ms. Lorraine Smith (AllCaN PhD Candidate)

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Get to Know AllCaN Oesophageal Better with a Word Search.

The AllCaN programme represents a new, focused effort to implement advances in Oesophageal Cancer research as rapidly as possible through the creation of a collaborative, translational cancer research network using the most talented and promising researchers across various All-Ireland institutions.

Get to know the AllCaN team better using the link below, or if that’s enough, grab a beverage and get to know the whole team including the principal investigators, the academic institutions, the charity partners, the industry partners and all the AllCaN collaborators by doing a word search solely based on AllCaN (choose between easy, normal and hard).