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From Trinity to Harvard: Trinity PhD student heads to the US

School of Medicine PhD candidate Maria Davern is heading Stateside to take up a post-doctoral research position at the prestigious Dana-Farber Cancer Institute, Harvard Medical School with Professor Anthony Letai. Maria is currently completing her PhD studies with Dr Joanne Lysaght in the Department of Surgery in the Trinity St. James’s Cancer Institute, Trinity College Dublin. We spoke to Maria about her current high-impact research, her impending move, and her advice to young researchers.

Can you describe your current research topic?

My research focuses on an aggressive type of cancer that affects the lower part of the oesophagus, known as oesophageal adenocarcinoma. This type of cancer is increasing rapidly in Western countries due to rising obesity levels, which greatly increases the risk of developing this type of cancer. The current treatment options for these patients include conventional chemotherapy and/or radiation followed by surgical removal of the tumour. However, the majority of patients don’t respond well enough to these treatments to achieve a complete recovery. Therefore, new and better treatment options are required to enhance the success of conventional treatments.

Immune checkpoint inhibitors are an emerging cancer treatment option. They are a type of immunotherapy that gives the patient’s natural immune system a ‘boost’ or ‘releases the brakes’ on anti-cancer immune responses. Immune checkpoint inhibitors have garnered a lot of attention in the cancer research field due to their transformative results in treating advanced stages of melanoma and lung cancer. However, this type of immunotherapy doesn’t benefit everyone, and current research is now focussed on identifying 1) what therapies would be suitable and 2) when to combine immunotherapy with chemotherapy and radiotherapy to improve outcomes and to extend the benefits of this transformative medicine to more patients.

The research I have been conducting throughout my PhD focuses on examining the effects of chemotherapy on the immune system in oesophageal adenocarcinoma patients. In addition, my research also focuses on understanding how effective immune checkpoint inhibitors are when used in combination with chemotherapy in 1) stimulating the immune system and in 2) improving the effectiveness of chemotherapy. The main goal of this work is to help guide the selection of rational immunotherapy and chemotherapy combinations and to inform the scheduling of immune checkpoint inhibitors with chemotherapy regimens.

What got you interested in this area of research?

I have had an interest in health care from a young age, and then throughout secondary school my interest in science grew so I decided to do a science degree in Maynooth University. I received lectures in immunology and oncology from Dr Martina Schroeder, Dr Conor Breen, Dr Sinéad Miggan and Dr Marion Butler in the final years of my undergraduate degree which is where my love for research and the field of immuno-oncology developed. My final year research projects during my undergraduate degree provided me with my first experience of research which I thoroughly enjoyed, and I carried out these projects in Dr Paul Dowling’s lab and Dr Rob Elmes’s lab, which helped foster my enthusiasm for research. My passion and interest grew even more during my master’s degree in Translational Oncology which I carried out in the Trinity Translational Medicine Institute to help deepen my understanding of the immuno-oncology field and to help prepare me to undertake a PhD afterwards.

What is your proudest achievement?

My proudest achievement was when I was awarded the European Association for Cancer Research (EACR) Junior Investigator Award 2020 by the Irish Association for Cancer Research for my PhD research on the immune-independent functions of immune checkpoint inhibitors in oesophageal adenocarcinoma and the potential implications for overcoming chemoresistance to first-line chemotherapy regimens.

Tell us a little about the post-doctoral position, how it came about, what your role/research will be, and about the lab itself.

I first learned about Professor Anthony Letai’s research during my MSc in Translational Oncology where I learnt about BH3 profiling - a patented technology developed by Professor Letai’s lab in the Dana-Farber Cancer Institute in Harvard Medical School. BH3 profiling is a functional assay which profiles cancer cells in a patient’s tumour and reveals how easily/difficult tumour cells will die after chemotherapy treatment. This assay also identifies specific ‘pro-survival’ molecules that tumour cells rely on to protect themselves from chemotherapy and there are several drugs in clinical trials and that are FDA approved that can block these ‘pro-survival’ factors, re-sensitising resistant tumours to chemotherapy and boosting response rates.

In the first year of my PhD I attended a keynote talk delivered by Professor Letai at the annual Irish Association for Cancer Research in Dublin where he presented some of the cutting-edge, exciting research from his lab, and I thoroughly enjoyed his talk. The year after at the same annual conference I attended an early career researcher’s networking event where early career researchers are paired up with established Principal Investigators. It is an excellent opportunity to extend your research network and contacts and to receive valuable advice from Principal Investigators who successfully run their own labs. While I was at the networking event, I was very lucky to be paired up with Dr Tríona Ní Chonghaile who leads her own research group in Royal College of Surgeons, Ireland and had carried out her post-doctoral training in Professor Letai’s lab. Dr Ní Chonghaile gave me excellent advice for my future career and also spoke very highly of Professor Letai, highlighting the positive and encouraging research environment that he fosters in his lab. It turned out to be great timing as a post-doctoral position in cancer immunotherapy was advertised in Professor Letai’s lab earlier this year and I applied for it immediately. I was very fortunate to be invited for an interview in the lab a few months later and was then offered a position as a post-doctoral Research Fellow, starting in November 2021. An important strand of research in Professor Letai’s lab focusses on how the tumour microenvironment mediates responses to immunotherapy and on identifying therapeutic strategies to overcome these mechanisms of resistance. The translational research I will be conducting in Professor Letai’s lab addresses both of these clinically relevant questions.

What is your best advice to those thinking of taking on a PhD?

If a PhD is definitely what you want to do then absolutely go for it! I would recommend contacting supervisors or lecturers who are carrying out the kind of research that you have an interest in early in your undergraduate or post-graduate degree. There are a lot of opportunities to carry out summer projects in labs over the course of 6-8 weeks which is a very valuable experience for students personally, but also for their CVs. It will also give you an insight into what academic research and the PhD process is really like. I would advise reaching out to lecturers about a year in advance of doing a summer project as these applications often need to be filled out 6-12 months in advance. But you also don’t need to do a PhD to be involved in research, there are a lot of exciting opportunities in industry as well.