Our laboratory studies inflammation generated by the innate immune system. This can happen in many different contexts, including during infection, when cells die, or when genetic mutations activate innate immune pathways causing autoinflammatory disease. Inflammation contributes to the development of many chronic inflammatory diseases including rheumatoid arthritis, inflammatory bowel disease, amyotrophic lateral sclerosis (ALS) and type 2 diabetes.
Previously we have made discoveries relevant to all of these areas. We maintain close links to industry and the clinic to make sure our discoveries can continue to have a direct effect on human health in the future.
A particular focus for our laboratory is a family of innate immune receptors known as Nod-like receptors (NLRs). Many of these have the capacity to form intracellular protein complexes called inflammasomes. These biological structures process the pro-inflammatory cytokines IL-1b and IL-18 into their mature forms. Our research has identified substances that activate the inflammasome, and mechanisms by which this inflammation causes disease.
Activation of the inflammasome also triggers an inflammatory form of cell death known as pyroptosis. This programmed form of cell death is a way by which an infected cell can prevent the spread of a micro-organism, but it can also contribute to inflammatory pathology during disease. We are researching the triggers and effectors for this new form of cell death.
This is a particularly exciting time to be working on inflammation because so many new drugs are coming to the clinic. We have the diverse research tools to determine where and why these new drugs can provide benefit.
The mystery of a rare, debilitating disease that has afflicted generations of European families – and long baffled their doctors – has been solved.