Prof Fiona McGillicuddy of UCD is trying to find what happens to ‘good cholesterol’ in patients with obesity and diabetes.
After graduating with a science degree from University College Dublin (UCD), Prof Fiona McGillicuddy went on to complete a PhD in the field of cardiovascular disease. Afterwards, she travelled to the University of Pennsylvania in the US where she worked as a postdoctoral researcher for three years, before moving back to UCD in 2009.
In 2012 she was awarded a Wellcome Trust Research Career Development Fellowship to establish her own research group within the UCD School of Medicine at the Conway Institute, where she is an assistant professor.
What inspired you to become a researcher?
From an early age I wanted to go into medicine; however, when a very close neighbour of mine was diagnosed with cystic fibrosis, I swiftly learned that medicine does not yet have the answers to numerous diseases. This prompted me to pursue a career in biomedical sciences, which in hindsight was an excellent choice for me.
Can you tell us about the research you’re currently working on?
I am currently looking at what happens to ‘good cholesterol’ particles within obese and diabetic patients. These particles are best known for their ability to take cholesterol from cells within the body and bring the cholesterol back to the liver to be eliminated in the faeces. These particles also exert ‘anti-inflammatory’ effects in healthy individuals.
However, these particles are very complex – consisting of more than 100 proteins and 200 types of fat – and have to date been grossly oversimplified. In turn, it was assumed that simply raising the amount of ‘good cholesterol’ would protect against heart disease. This turns out not to be true, as was evident from the very expensive pharmaceutical trials with cholesterylester transfer protein (CETP) inhibitors.
My group is more interested in the ‘quality’ of high-density lipoprotein (HDL) cholesterol rather than the ‘quantity’ of HDL. One way to assess quality is to measure the proteins that are on the HDL particles. We have identified very particular changes in the proteins that associate with HDL in unhealthy obese individuals compared to healthy obese individuals.
In your opinion, why is your research important?
I believe HDL has hormonal characteristics which are dependent upon the proteins it carries, and that changes in these proteins would alter its activities. This essentially would mean that not all HDL is created equally and would certainly explain why raising HDL is not effective in high-risk patients where the quality of the particles may be reduced.
Secondly, moving cholesterol out of the body in the faeces is the only way for our bodies to handle excess cholesterol. We cannot use cholesterol for energy purposes, so it’s different to our traditional fats (fatty acids) that we find in food.
My research has shown that under both acute inflammation – such as having the flu – and chronic inflammation (obesity), the movement of cholesterol through the liver to the faeces is blocked. We are currently trying to understand the mechanism of this blockage and target identified pathways pharmacologically to re-establish cholesterol movement.
Raising HDL in the setting of an inflamed liver where cholesterol cannot be removed from the body is likely a futile approach to reducing heart disease burden.
What commercial applications do you foresee for your research?
I have recently been awarded just under €120,000 by Science Foundation Ireland (SFI) through the Technology Innovation Development Award (TIDA) programme to explore the commercial opportunities associated with my research outputs.
In this regard, a major finding from my group is that we can effectively identify metabolically unhealthy obese individuals by measuring the proteins on their HDL particles. HDL picks up a lot of proteins from the liver, and in individuals with an inflamed liver the number of pro-inflammatory proteins on HDL increases substantially. At the same time, the number of anti-inflammatory proteins is reduced. Therefore, it is quite possible the measurement of HDL-associated proteins will identify those individuals with inflamed livers without necessitating more invasive liver biopsies.
Chronic inflammation increases a person’s risk of numerous diseases that are associated with obesity, including heart disease and cancer. We thus suspect that measuring HDL-associated proteins will provide a mechanism to sub-classify obese individuals into risk categories.
We are currently developing a high-throughput, diagnostic-grade test with Prof Stephen Pennington – founder and chief scientific officer of Atturos, a UCD spin-out company – that will measure approximately 100 HDL-associated proteins from serum.
What are some of the biggest challenges you face as a researcher in your field?
Time, money and trying to keep up! Some of the biggest challenges are trying to manage my time effectively to fulfil my academic teaching commitments and research commitments as well as raise a young family.
Secondly, applying for funding is always stressful and the constant sound of a ticking clock over your current funding as the money runs out is always present. Writing grants that don’t get funded is very disheartening.
Finally, just trying to keep up with what is going on internationally is very challenging – particularly in an era where medicine is moving at such a fast pace!
Are there any common misconceptions about this area of research?
I think one of the biggest challenges for the obesity field is the perception of obesity and lack of recognition by many that obesity is a disease with many different underlying causes. There is a lot of ‘fat-shaming’ associated with obesity and I hope in years to come the era of self-blame will have passed and obesity will be recognised and treated as the disease it is.
Blame and shame is even worse for patients with type 2 diabetes who constantly have the media telling them it’s their fault they developed the disease because of the lifestyle they have chosen. The truth of the matter is we do not fully understand why some people gain weight and develop type 2 diabetes, and others don’t.
Much greater research into this area is critical and, in particular, how a person’s genes interact with their diet to affect disease risk. I think the official recognition of obesity as a disease by all European countries will be an important step to start changing the perceptions around obesity.
What are some of the areas of research you’d like to see tackled in the years ahead?
In health, I think understanding the link between obesity and cancer will be very important given our population’s current weight trajectory.
Beyond that, I think research around sustainable energy and novel ways to deal with our plastic pollution crisis and global warming are all critical areas.
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