Epigenetic mechanisms in inflammatory disease
Programme Grant funded by Arthritis Research UK
Project reference 20522
We aim to systematically identify epigenetic mechanisms that underlie and control the complex stem cell and inflammatory environment in bone that leads to destruction of bone tissue in arthritis and other musculoskeletal conditions.
Recent research has provided strong evidence that epigenetics is a central mechanism which controls stem cell physiology and inflammation. Epigenetics also provides possible means to manipulate the complex interactions that occur in inflammatory disease, for example to suppress cytokine production, alter senescence behaviour, control differentiation and thereby understand and manipulate disease. Despite this progress a detailed picture and systematic understanding about which epigenetic factors are important are missing and we attempt to address this impasse in our program.
We will systematically analyze epigenetic factors using targeted screening platforms consisting of antisense as well as unique small molecule inhibitors, and ex vivo model systems to understand stem cell ageing in relation to bone formation and inflammation. We propose that a more detailed understanding of the epigenetic inter-relationships within the bone environment, and the effects of ageing and the ability of mesenchymal stem cells to differentiate to osteoblasts in an inflammatory milieu will provide novel insights into disease mechanisms and identify innovative strategies for the development of unique anabolic and anti-inflammatory therapies needed in inflammatory arthritis.