‘We’re trying to understand how and why obesity disrupts the immune system’

29 Nov 2022

Dr Andrew Hogan. Image: Maynooth University

A childhood fascination with lovebirds got Dr Andrew Hogan interested in biology. Now, he is working to reduce the risk of developing obesity-related diseases.

Dr Andrew Hogan completed his undergrad and postgrad studies at Maynooth University, before being awarded a Newman Fellowship in Obesity with Prof Donal O’Shea at University College Dublin and St Vincent’s Hospital. He returned to Maynooth as an assistant professor in immunology in 2017.

Hogan is now also principal investigator with the Metabolic Immunology Research Group. This group focuses on the impact of obesity on the immune system and the development of diseases such as type 2 diabetes and cancer.

‘We think it is absolutely critical to understand the impact obesity has on the body, in particular how it drives development of serious chronic conditions’

Tell us about the research you’re currently working on.

Our research group currently consists of 10 full-time researchers, including post-doctoral scientists, PhD fellows and clinical fellows with backgrounds in endocrinology, immunology and biochemistry.

Our focus is on obesity, a chronic, relapsing and progressive disease, which can lead to conditions such as heart disease, diabetes and cancer. We are trying to understand how and why obesity disrupts the immune system, and the effects this has on the development of these serious diseases.

For example, a major focus of the lab currently is on an unconventional subset of the immune system called the MAIT (mucosal-associated invariant T) cell. MAIT cells protect us from bacterial and viral infections and are found at high numbers in our blood, as well as our liver, gut, fat and lungs.

However, we have shown that in the setting of obesity these cells become harmful and can disrupt insulin working, leading to insulin resistance. We are currently trying to figure out what causes this change and have identified that altered nutrients in patients with obesity may impact how the MAIT cell fuels itself leading to cellular stress and the release of damaging proteins.

Understanding the role of the immune system in these diseases helps us to find targeted interventions, be that pharmaceuticals or surgery, which could help to reverse the defects, and thus reduce the risk of developing obesity-related diseases.

In our most recent study, we have demonstrated that a drug used for weight loss (Semaglutide) can reverse obesity-related defects in the body’s anti-cancer immune cell, the natural killer (NK) cell. Three months of treatment resulted in boosted NK cell anti-cancer activity, even in patients who did not lose weight, supporting their use beyond weight loss.

In your opinion, why is your research important?

Obesity is one of the most prevalent chronic diseases in the world with over 600m adults living with the condition. Furthermore, we know the damaging aspects of obesity start very early in life, putting children on a trajectory towards lifelong disease and, for the first time ever, a lower life expectancy than their parents.

Therefore, we think it is absolutely critical to understand the impact obesity has on the body, in particular how it drives development of serious chronic conditions such as heart disease, cancer and diabetes. Understanding the why and how these life-limiting diseases occur will allow us to develop targeted strategies to limit or reverse their progression, such as the use of the weight loss drug explained above. 

What inspired you to become a researcher?

Like most researchers, I have been very lucky to have had very influential and supportive teachers in my life.

But there was a distinct spark – as a child I kept lovebirds as pets and was intrigued by the various colours. My dad, who recently passed due to Covid-19, bought me a book which explained their genetics and how the different colours arose. I was hooked.

We set out on a very successful lovebird breeding programme and won numerous awards. From then on, I only wanted to study biology.

What are some of the biggest challenges or misconceptions you face as a researcher in your field?

Obesity is an extremely complex disease and has multiple contributing factors. It is also among the most stigmatised diseases, which is very evident in the language and images used in the media. A major misconception is that it is the individual’s ‘fault’ or that ‘they lack willpower’. This is point-blank wrong.

As we unravel the complexities around obesity, we are learning that the body is designed to protect against weight loss and sees it as a threat. We also know that once obesity is established, metabolism is rewired and calories in no longer equal calories out, again making sustained and successful weight loss very difficult for the majority.

These are the major challenges we need to tackle both as researchers and as a society.

Do you think public engagement with science has changed in recent years?

The Covid-19 pandemic has definitely had a positive impact on how researchers engage with the public. We have had to make our research more accessible and understandable, some with more success than others. It’s also helped scientists to understand that the research we do is not for ‘us’ but for the public.

Recently, Ireland’s first obesity patient group – Irish Coalition for People Living with Obesity – was launched. During that I heard one of the most pertinent lines from Karen Gaynor, programme manager with the HSE obesity programme: “Patients are experts in their lived experience of their disease and as researchers we need this expertise.”

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