Ashley Mansell

The common factor in all disease

Dr Ashley Mansell views inflammation as the basis of nearly all disease, including cancer, heart disease and diabetes. Inflammation provides the body's first line of defence against disease. Recent discoveries show it is also critical in signalling the body to mount more sophisticated and long-term defences.

When this signalling goes wrong, disease follows.

Ashley studies the immune system and its most fundamental disease-fighting process - how the body first detects it is injured or under attack from microbes.

Despite decades of research, this mechanism was misunderstood until the discovery of a family of receptors - called the Toll-like receptors - that acts as the body's central alarm system. The receptors allow the body to mount a rapid response to disease in the form of inflammation. They also amount to a central mechanism that can determine the outcome of fights against many diseases.

Ashley was working with Professor Luke O'Neill in Dublin, Ireland, when the breakthrough happened. He was using his science degree 'to see the world' and the discovery launched him into a career in this important area of research, including a role with Monash University.

'Inflammation has a lot of firepower when it comes to fighting disease,' Ashley says. 'But it lacks subtlety or specificity. I jokingly call inflammatory responses the shock-and-awe arm of the immune system. It sees the problem and it just responds - a bit blindly and a bit violently - and in the process it causes collateral damage to the body.'

A typical example is the joint pain, headache and fever associated with fighting the influenza virus. But the problem can run deeper. Inflammation is known to overwhelm the body in a runaway reaction that results in auto-inflammatory disorders such as septic shock.

Even more critical is the growing evidence that more sophisticated immune responses, such as those needed to fight cancer, are initiated and guided by inflammation.

By studying inflammation, Ashley and other researchers in his field are shedding new light on why diseases such as cancer escape the immune system's efforts to control them. Inflammation is also a factor in more than 100 auto-immune diseases, including arthritis and asthma. These involve antibodies inappropriately attacking healthy tissue.

For these reasons, Ashley focuses on the genes that control the inflammatory response. Called pattern recognition receptors, they have stirred international interest from laboratories seeking better treatment for patients with specific diseases.

'Globally, we have realised that inflammation is probably the basis of nearly all disease. Cancer, heart disease and obesity included. That means inflammation is an emerging field with the potential to clinically redefine disease.'

Ashley is working in collaboration with a German heart disease laboratory that has detected cholesterol micro-crystals in blocked arteries. The crystals are suspected of triggering disease as they are proving to be potent inducers of self-harming forms of inflammation. Other collaborations see him assisting laboratories working on influenza virus, hepatitis B and asthma.

Internationally, the research is changing how pharmaceutical companies think about disease. Opportunities are being created to develop a new class of therapies and drugs. Such a prospect fascinates Ashley. 'I like to think my research can make a difference, that it can benefit humanity,' he says. 'I may ultimately provide just a small part of a solution. But the idea that I can contribute at all is very motivational.'