Mechanisms of Muscle Disease
As the gatekeepers of the sarcoplasmic reticulum (SR) intracellular Ca2+ reservoir, ryanodine receptors (RyR) play a central role in many Ca2+ dependent signaling pathways. Our use of animal models of RYR1-linked diseases such as malignant hyperthermia and central core disease allow us to determine how mutations that cause opposing effects on RyR1 function affect muscle performance. These studies have revealed novel features of the mechanisms underlying these diseases and will be important in the development of new therapeutic options for RYR1-linked disease.
Muscle Metabolism
Evidence shows that changes in muscle energy expenditure have a systemic effect, altering whole body metabolism. Skeletal muscle represents ~40 percent of total body mass in mammals and contributes about 30% of the resting metabolic rate in adult humans, therefore changes in muscle activity and muscle metabolism are likely to be important in the pathogenesis of obesity and diabetes. We study the molecular and cellular mechanisms of Ca2+ dependent signaling pathways that regulate muscle metabolism and modulate whole body metabolism. We are assessing the impact of exercise and pharmacological compounds on these pathways and aim to develop novel therapeutic strategies for people who are unable to exercise to maintain optimal muscle function and metabolism.