Chris O’Callaghan: Atherosclerosis & immunity
Atherosclerosis is the most important cause of death worldwide. It is caused by the accumulation of both fatty material and immune cells. Over time, these set up an inflammatory reaction which causes a lot of damage to the blood vessel wall. Although we do have good therapies designed to lower the levels of fatty material, we haven’t any therapies specifically designed to target the effect of the immune system. Professor O'Callaghan's group is working towards developing such therapies.
What is atherosclerosis?
Atherosclerosis is a narrowing of the arteries. Arteries are blood vessels that supply blood to tissues or organs and it's very common over time for those arteries to fur up, or to get narrowed inside. When that happens, blood, which is normally supplying oxygen and nutrients to the tissues can't get through so easily to those tissues – that might be the heart or the brain or the kidney, for example –and they become starved of oxygen and nutrients and then become damaged. In a heart, this could cause a heart attack, in the brain it might be a stroke, in a kidney it might cause the kidney not to work properly. So it's an important cause of disease.
What is the role of our immune system in vascular disease?
Well I think over time people have tended to think of atherosclerosis as a deposit of fatty material inside the wall of the artery – they say that there's a blob of butter or something like that, just inside the wall. There is certainly fatty material in the wall, but increasingly we've realised that it's not just fat which is deposited there. The narrowings in the arteries, which are essentially lumps that form in the wall of the artery, are stuffed full of little immune cells. Immune cells are white blood cells and they are designed, or they seem to have evolved, to fight infection and to protect the body from abnormal situations. It seems that in atherosclerotic deposits in the artery wall, they (the cells) are getting into those deposits and finding that tissue abnormal in some way, probably because of the fatty material. But then once that happens they set up an inflammatory reaction, a very irritant reaction, and that makes things worse. It's a vicious cycle that then starts to bring in more fatty material and cells, which creates more irritation and causes a lot of damage to the blood vessel wall. So the immune system plays a really important role in the development of atherosclerosis in the artery.
What scope is there for developing new therapies?
We've got some quite good therapies now that are designed to lower the levels of fatty material, but we haven't really got any therapies that are specifically designed to target the effect of the immune system in atherosclerosis. I think an increased understanding of how the immune system plays a role in the development of these furring up of the arteries, the atherosclerotic legions, will help because that's an area we just haven't really targeted any treatments to. We now know that it's very important, so I think it will help over time.
What are the most important lines of research that have developed in the past 5 or 10 years?
I think there has been an increasing appreciation of the role of the immune system in the development of atherosclerosis. I think also, over more recent years, the development of technologies that allow us to do a lot of DNA sequencing, to look at which bits of DNA are important in giving people a risk of atherosclerosis. Those have allowed us to make quite significant advances in our understanding of the disease, and we're certainly applying them in our own group now.
Why does your line of research matter, why should we put money into it?
I think, first of all, atherosclerosis is a very important cause of disease. It's the major cause of death in the UK and in almost all other countries around the world, apart from one or two Sub-Saharan African countries. It's far and away the most important cause of death, so I don't think that's difficult to justify – we clearly need more treatments for atherosclerosis. Our own research is studying the immune system, and I think that's an area that is increasingly recognised as important in this condition, but nevertheless, I think we haven't yet got good treatments that have come out of that research and we're keen to do that. We're now deploying some very modern approaches, using high throughput DNA sequencing to look at the effects of the atherosclerotic environment on immune cells and to try and understand how they respond, what their response is, and therefore which aspects of those cells we might want to target with treatment in the future.
How does your research fit into Translational Medicine within the Department?
Our group spans quite a wide range of technologies: we are using basic science in the laboratory but we also run some clinical trials. We have a whole spectrum of activity and quite a lot of our work does involve patients, but some is just done in the laboratory. We're acutely aware of the need to translate basic laboratory science into new treatments, and we're trying to identify new targets for drug treatment and new pathways for drug treatment in the laboratory, and then spot those which may be translatable, and bring them forward. So we're very much involved in translational activity in the department.