Lorraine lab pic

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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