Interview with a Researcher

Image Credit: Fran Veale

Jana Joha sits down with Professor Patricia Maguire to talk about platelets—the little sensors in our blood

Professor Patricia Maguire, a lecturer and researcher in the School of Biomolecular and Biomedical Science at UCD has recently been awarded the Nova UCD’s Invention of the Year 2021 alongside Professor Fionnuala Ní Aínle, UCD School of Medicine and Dr Paulina Szklanna, UCD School of Biomolecular and Biomedical Science, for their discovery of blood biomarkers that can determine and diagnose pre-eclampsia risk in pregnant women. 

In an interview with The University Observer, Prof Maguire explained that she has been fascinated with platelets for a long time and started working with them nearly twenty years ago. She referred to platelets as the “conductor of an orchestra” and called them “our body’s first responders”. Platelets are small, cell fragments in our blood that function to form clots and prevent bleeding but they can also tell us a lot about disease. Platelets are fundamentally involved in many diseases, including cancer and they store important information, which Prof Maguire has been cataloguing and investigating for almost twenty years. "I wonder are things different in that information that platelets are storing, is disease changing it in some way? We hypothesised that this information… that [the platelet] stores might be different in disease".

Seven years ago, Prof Maguire and her team set out to prove if the information stored by platelets truly changes in disease. This information exists in the form of proteins and other molecules, such as lipids and mRNAs. "We started off a project looking at this information that a platelet stores, which we call the platelet releasate, we looked at this in 100 people" and "it was called the 100 Platelet Releasate Project (PREP)". Prof Maguire told the University Observer that they first studied the information stored in platelets from healthy individuals and found that among these individuals the information was similar, the platelets seemed to have a particular "signature". "Then we could show… that in healthy pregnant women this signature, if you like, of this information is different but it all looks the same in a healthy pregnant woman". The study found that platelets and the information they store "is different in pregnancy" compared to healthy individuals who are not pregnant. Specific platelet signatures can be found depending on the physiological state of an individual. 

These findings were published and it made Prof Maguire and her team "believe that what we were onto, was something here". It inspired them to start thinking "a bit differently about looking at diagnostics" as they believe "there is not huge innovation" in that area. This led Prof Maguire and her team to investigate how the information stored in platelets changes in disease, specifically in pre-eclampsia. As a disease, it’s "actually unbelievable because it affects 1 in every 10 pregnancies" and "it can be very mild or it can be really severe". Pre-eclampsia is a disease that affects pregnant women and is usually characterised by high blood pressure and organ damage most often being the liver and kidneys. Prof Maguire remarks that "it’s just frightening because every year 50,000 women and 500,000 babies, half a million babies, across the world die of pre-eclampsia". She also believes that those numbers are most likely an underestimation because in other parts of the world, especially in "lower-income countries women may not even make it to a hospital". In addition, approximately five million babies are born prematurely which is in part due to one of the biggest issues associated with pre-eclampsia as it "can happen any time" during the pregnancy, usually after 20 weeks.

Unfortunately, the only cure for pre-eclampsia is to deliver the baby and this also highlights another key issue which is that there is currently no diagnostic test for pre-eclampsia. This fact has driven Prof Maguire and her team to study how the information in platelets changes in pre-eclampsia to not only better understand the disease but to be able to provide a test that can help in diagnosing both the occurrence and risk of this devastating disease. As part of the 100 PREP project, blood samples were taken from pregnant women who had pre-eclampsia and were processed in order to find a specific signature for the disease. Prof Maguire notes that "it was a huge undertaking". Dr Szklanna, a PhD student at the time, worked on this project and showed "unbelievable commitment" according to Prof Maguire. "She really committed to this, she was working, extracting this information from this blood within an hour... sometimes in the middle of the night". Prof Maguire emphasised how lucky and grateful she feels for having "amazing people in our team". 

From that project, Prof Maguire and her team were able to uncover the information stored by platelets that is specific for pre-eclampsia. This led to the development of a test that not only determines whether a pregnant woman has pre-eclampsia or not but also predicts how severe the disease will be. "We’re very hopeful for our test because our test does a couple of different things…… What's built into our test is a predictor tool. Not only do we say ‘yes’, ‘no’ for pre-eclampsia, we help the clinician predict the future". Prof Maguire explained that this predictor tool helps the clinician determine how the disease will progress which is crucial in determining if an immediate delivery is needed or, in less severe cases, can the delivery be delayed to allow for the baby to continue developing inside the womb. Prof Maguire stated that "it can just make so much of a difference that extra time". This test developed by Prof Maguire and her team is a combination of their patented biomarker testing and all the clinical data that was available on those pregnant women, which was melded into one "risk stratification tool" that uses machine learning models to predict patient outcomes. It’s called AI_PREMie, and was the runner-up project in the Science Foundation Ireland AI for Societal Good Challenge in 2020. "It’s such a complex disorder, you almost need a complex solution unfortunately and that’s what we tried to do with this AI_PREMie". Prof Maguire also noted that AI_PREMie was "a project we managed to actually pull off during lockdown" which involves an interdisciplinary team of collaborators where "everybody is playing such an important part". 

The impact of this research and diagnostic test is substantial as it "will mean that less women, babies will die and also less babies will be born prematurely… you can see the benefit to both the baby and the mother, the clinician, their families….and their wider communities". However, with all the incredible work done by Prof Maguire, she remarked that there is still a long way to go and that there is room for improvement. Even though they were able to expand this project into numerous hospitals that cover 50% of all births in the country, Prof Maguire and her team hope to "expand that out now into a thousand women in those hospitals". Their motto, Prof Maguire explained, is that they want to get their test to every single pregnant woman who needs it, "we want to be able to get it to her". In order to achieve this Prof Maguire explained that they will "spin out at some point" and will "go down the commercial route" and hope to "drive that money back into making sure that this test gets to everyone who needs it".