Our lab focuses on systematic investigations into the underlying physiology, biology, and genetics of skeletal muscle diseases and disorders, with an emphasis on the following three aspects:
- Cerebral Ischemic Stroke: Stroke is a sudden interruption in the blood supply of the brain, caused by either an abrupt blockage of arteries leading to the brain (ischemic stroke) or bleeding into brain tissue when a blood vessel bursts (hemorrhagic stroke). Regardless of type, all strokes cause more serious long-term disabilities in patients than any other disease. Since skeletal muscle is the main target organ (after the brain) of stroke that induces severe muscle wasting and weakness, most stroke patients experience serious physical disabilities in daily activities. At present, no pharmacological drugs are available to prevent or reduce stroke-induced muscle loss. Rehabilitative therapy is the only available alternative to improve muscle function in stroke survivors. However, higher muscle fatigability and lower muscle strength due to muscle wasting provide poor rehabilitation outcomes in stroke patients. The major barrier in developing drugs for the treatment of muscle wasting in stroke is the lack of our understanding of the cellular and/or molecular mechanisms that underlie the post-stroke muscle atrophy program. Currently, we are investigating the intrinsic skeletal muscle signaling mechanisms by which stroke initiates muscle wasting and associated weakness so that therapeutic strategies that prevent/minimize the loss of muscle mass in stroke survivors can be developed.
- Skeletal Muscle Regeneration: Mammalian skeletal muscle composes 40% of total body mass and has a remarkable ability to regenerate itself on a daily basis as well as in response to exercise, muscle growth, muscle injury, or other myogenic stimuli. Skeletal muscle regeneration is a highly orchestrated process that involves the activation, proliferation, and differentiation of quiescent muscle stem cells, called satellite cells (SCs). During this process, the activated/proliferating SCs (ASCs/PSCs) give rise to the myogenic committed SCs (MSCs) that will differentiate into a new myofiber or fuse with an existing myofiber. This process also occurs with functional overload/exercise-induced muscle growth. As part of the process, some of the ASCs/PSCs will also return to a quiescence state, which serves to replenish the in vivo SC pool (SC self-renewal). This occurs by both symmetric and asymmetric cell divisions. While symmetric division yields identical SCs, the asymmetric division will generate both SC and MSC. However, the molecular mechanisms that regulate SC self-renewal in a timely manner remain unknown. Understanding the mechanisms has enormous potential for the development of novel therapies for treating various genetic and acquired degenerative muscle disorders and preventing loss of muscle mass in many catabolic conditions. At present, we are studying the role of different cell polarity proteins in the regulation of SC division because cell polarity proteins have been proposed to act as potential regulators of asymmetric cell division, allowing a stem cell to generate a daughter cell that self-renews and another that undergoes differentiation.
- Skeletal Muscle Metabolic Disorders: Skeletal muscles compose the largest metabolic tissue in the body and are a major site of lipid and glucose oxidation. Thus, the maintenance of muscle metabolic activity is critical for whole-body energy homeostasis and for preventing metabolic disorders like diabetes and obesity. Mitochondria are important sub-cellular organelles that play a central role in glucose and lipid oxidation, especially in skeletal muscles. It has been shown that mitochondrial impairment significantly contributes to skeletal muscle metabolic dysfunction. Our lab currently investigating the specific signaling pathways that regulate the metabolic components of mitochondria in skeletal muscle.
To address our research questions, we use several state-of-the-art genetic, cell and molecular biology techniques, bioinformatics tools, in vitro and in vivo experiments, and mouse models of human diseases. We also use microarray and next-generation sequencing technologies to determine the molecular origin of muscle disease and disorders.