Thesis: The effect of inflammatory mediators in skeletal muscle function and regeneration
Intrinsic skeletal muscle weakness and reduced muscle mass are major causes of the loss of function after muscle injury or disease. The inflammation that follows muscle injury plays a fundamental role in facilitating the repair and regeneration of damaged muscle fibres and the return of normal muscle strength. However, chronic inflammation may be deleterious to skeletal muscle function. Chronic inflammation plays an important role in the pathophysiology of skeletal muscle diseases, e.g. Duchenne muscular dystrophy (DMD), and other diseases which affect skeletal muscle, such as chronic heart failure, and may play a direct role in promoting the long term muscle weakness and atrophy associated with these diseases.
Recent reports suggest that activation of protease-activated receptors (PARs) may play an important role in the response of skeletal muscle to injury and disease. PARs are a family of G protein-coupled receptors located on the surface membrane of various cells, including skeletal muscle. They mediate a diverse range of cellular activities, especially during inflammation, and could be a major link between inflammation, post-injury skeletal muscle weakness and eventual regeneration. One focus of my research is to determine the role of PAR activation in the skeletal muscle weakness and regeneration that follows injury and disease.
Another focus of my research is to examine the ability of anti-inflammatory agents, such as curcumin, to prevent or ameliorate the damaging effects of inflammation on skeletal muscle function.
Why my research is important
Skeletal muscle is essential for respiration. Therefore, the consequences of muscle injury and disease can be life threatening. The findings from my research project could have important ramifications for the treatment of sports injuries and lethal skeletal muscle diseases, such as the muscular dystrophies, and other inflammatory conditions and diseases that result in skeletal muscle weakness.