“In a lot of projects I’m running, collaboration is key”

Our Youth Ambassador Eden sat down with Professor Shareen Forbes from the University of Edinburgh about her fascinating research exploring the role of antigens in improving islet transplant success rates, made possible through our global research programme. She tells us about the personal reasons driving her work and how her findings could help people with type 1 diabetes (T1D).

Why did you choose to focus on T1D research in your career? 

Members of my family, going back generations, have had diabetes. Many of them had it before the discovery of insulin. I used to hear a lot of stories of how they managed back then. It was remarkable to me that there was a treatment, whether it be tablets or insulin that came years later, that could actually control it. That made me keen to go into it as a research area because I felt that there was a way of making people’s lives better. 

What has your journey in the medical field looked like so far? 

I began by studying medicine, then specialised in diabetes and endocrinology before deciding to focus on T1D years later. It’s been an amazing journey and fantastic to see the new treatments that have evolved. That’s really what’s kept me in the field and kept my interest, and why I’ve gone into academia. It’s been so incredible to see the new therapies that can move us towards a cure, particularly over the past ten years. 

Exploring antigens

So, what are you researching? 

I am looking into if a specific kind of protein on the surface of cells called antigens, and if a certain type known as ‘HLA antigens’ impact the success of a transplant for people with T1D.  

People have a unique set of these antigens, which allow the body to recognise whether a cell belongs to them or not. This then affects the response of their immune system. In T1D, many of the people affected are more likely to also have a specific antigen called HLA-DQ8 – which is the antigen I am researching. 

What is the focus of your project? 

I have a long-standing collaboration with the Edmonton Islet Transplant Programme, which is the biggest islet transplant programme in the world. Islets are the small clusters of cells in the pancreas that contain the insulin-producing cells (beta cells) and an islet transplant (clusters of beta cells) replaces the insulin-producing function that’s been lost in T1D. 

The islets come from the pancreases of donors. These pancreases come to the lab, and we isolate the islets. We then put them into a bag, and we then transplant them into the recipient with T1D. What we did in this project was look at the HLA type in the recipients of those beta cells, as well as the donors. What we wanted to understand was whether the donor’s HLA type made any difference to how well the transplant went. 

The findings

So, how have HLA-DQ8 typings been studied in your research project? 

We asked the question: what happens if you receive islets from donors that are DQ8 positive? Because not everyone is DQ8 positive, and we wanted to see if this made a difference. We thought that these islets would actually worsen the condition of patients with T1D, but what we found was the opposite. People who received islets from donors who were positive for DQ8, which is an at-risk antigen for the development of T1D, actually did better. 

Just to be clear – those donors were positive for the antigen, but they didn’t have T1D themselves? 

Correct! That’s an important point, because just because you have the antigen doesn’t mean you develop T1D, you’re just at an increased risk to develop T1D.  

How did you measure that success of the transplants? 

We looked at the outcomes by measuring something called C-peptide, which is something we use to test the function of beta cells. We looked at it across all the transplants, so they had up to five transplants in the Edmonton islet transplant programme. It showed that anyone who received this DQ8 antigen seemed to have much better graft survival. This is what we call a ‘retrospective observational study’, so it’s not a randomised controlled trial. And we don’t really understand yet why it is that these people had significantly better transplant function. 

Unexpected results

What has surprised you most about this project? 

Well, you might expect that a recipient would do better if they were somehow matched to the donor. But that’s not what we found. Whatever their background – whether the recipient was DQ8 positive or DQ8 negative, they did well. That’s exciting, because that’s research! You set out expecting one thing, and you find another. 

Do you think beta cell transplants are the most viable option for finding a cure for type 1? 

I think it’s certainly a very promising avenue, but there are a couple of other things we need to think about. One of the main downsides at the moment, of all transplants, is the requirement for anti-rejection drugs. These drugs dampen down the immune system, otherwise, it recognises the cells as foreign and starts to attack them. If we can edit genes to avoid this process, we can then open up this idea to many more people, including children. There are some really exciting developments in this field across the globe. It really is the most exciting period for research in type 1.

Looking to the future

What does a typical day in the lab look like for you? 

There is no typical day, which is why it’s very exciting! A lot of my day is about meeting my research group. I have a big group of scientists from all sorts of backgrounds, and I really want to make sure I give credit to these people, because you’re as good as your team, and mine is amazing! 

I might talk to chemists, engineers or people doing clinical trials. It’s a very varied day, and in a lot of the projects I am running, collaboration is key. It’s very exciting, cutting-edge work that my whole team is doing. 

And what is the next step in your research going to look like? 

The overarching aim is to really understand why we are seeing these results. We’re going down many different avenues to try and understand that. This is a big project, so collaboration is everything. We’re working with the Edmonton transplant group, along with international specialists and lots of other people here at the university. We’re using a technique called next generation sequencing, which means we get a really good look at the genetic sequence of the recipients and the donors. We will have so much data that we’ll be working with specialists in the field to really get a good handle on it. 

Interview by Eden V.