1. Mechanism of skeletal muscle wasting Our lab and others have shown that inflammatory mediators that activate NF-ºB and p38 MAPK play an important role in mediating muscle protein loss associated with many diseases. We investigate the signaling mechanisms of inflammatory mediator stimulation of the ubiquitin-proteasome pathway and the autophagy-lysosome pathway which are responsible for accelerated muscle protein degradation. We also conduct experimental therapy using animal models of muscle wasting and try to translate the basic research into clinical interventions for human patients.

2. Regulation of skeletal muscle regeneration Skeletal muscle adapts to various stresses (injury, disease and training) by regenerating to make new muscle (myogenesis). Muscle regeneration is the function of muscle stem cells (also known as satellite cells) that have the capacity to proliferate, differentiate and fuse to form new muscle fibers when stimulated by myogenic cues. We study how these cells sense chemical or mechanical cues of myogenesis via their plasma membrane and activate specific intracellular signaling pathways that initiate muscle specific gene expression. We are particularly interested in the role of some membrane proteins including TNF-± converting enzyme (TACE) and integrins in regulating muscle gene expression.

3. Signaling mechanism of cardiac muscle adaptation to mechanical stress. Cardiac muscle responds to chronic hemodynamic overloading (mechanical stress) by developing hypertrophy (adaptation) that leads to left ventricle dilation (maladaptation). We study the mechanotransduction mechanism that mediates cardiac muscle response to overloading with the purpose of identifying ways to prevent the maladaptation specifically without blocking adaptation. Particularly, we focus on the mechanism that mediates TACE activation by overloading.