Unravelling the molecular mysteries of leaky guts

Research Lives: Prof Declan McCole, professor of biomedical sciences at University of California, Riverside

You are looking at a gene linked to inflammatory bowel disease and leaky guts – can you explain what that entails?

A lot of our work focuses on a gene called PTPN2. My lab showed that if this gene doesn’t work as normal – called a loss of function – it increases the leakiness or permeability of the gut lining, which is believed to be an early marker of inflammatory disease in the gut, including Crohn’s disease.

We have been looking at how losing the function of this gene compromises the junctions between cells in the gut lining, and we have just had a study published that teases out that mechanism.

How might that help people with inflammatory disease?

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We spend a lot of time looking at the genes and biochemical pathways that are affected by PTPN2 and, excitingly, we have identified an existing medicine that could potentially help to compensate for the loss of PTPN2 and its downstream effects, so that’s something we are looking at now.

You have recently been exploring the PTPN2 gene in Covid-19 too.

When Covid-19 came about I recalled there perhaps being some association in the data between the PTPN2 gene and ACE-2, which is the part of the cell that the Covid-19 virus latches on to. Since then we have found that losing PTPN2 function is linked to having more ACE-2, and if this bears up then it might offer a future way for clinicians to identify people at greater risk of infection.

What sparked your interest in science?

I grew up in Burtonport, Co Donegal, where my granny had been the local maternity nurse – people there still come up to me and say that she delivered them – my Mum was a nurse and my Dad was a teacher. I now see my job – influenced by each of them – as an amalgamation of science and medicine and teaching because I carry out biomedical research and I lecture to medical students.

How did you get to where you are now?

I studied pharmacology in University College Dublin, and I did my PhD there too. Even before I started to write up my thesis I went up and talked to a senior scientist from the US at an international meeting after I had presented my research, and I ended up going to work with him after my PhD.

I moved to more senior roles after that, and eventually I secured a big research grant from the National Institutes of Health in the US. At the same time UC Riverside were looking to set up a new school of medicine, so I went for it. I ended up being one of the first four researchers recruited here, and it has been a great experience to help build a new school from the start.

What is the key to a successful research lab?

Your research won’t get anywhere unless you have talented, hardworking people in your lab and good collaborators. I am lucky to have both.

How do you take a break from all that?

Up until a few years ago I was heavily involved in Gaelic football, which is a sport I played since I was a kid. But then between increased administrative commitments – I’m chair of the faculty in the school of medicine now – and having our daughter, there was less time for me to do sport.

But as this is California, and the weather is great. It is pretty easy to get outside and be active, and we love to get outdoors as a family.

Claire O'Connell

Claire O'Connell

Claire O'Connell is a contributor to The Irish Times who writes about health, science and innovation