Yan Laboratory
Molecular
Exercise Physiology

Center for Skeletal Muscle Research
Robert M. Berne Cardiovascular Research Center
University of Virginia School of Medicine
409 Lane Road, MR4 - 6031A
Charlottesville, VA 22908
Phone: 434-982-4477
Fax: 434-982-3139
E-mail:
zhen.yan@virginia.edu

Research Topics in Yan Lab

Molecular mechanism of exercise training-induced skeletal muscle adaptation (Learn more)
Mitochondrion, the power plant in the cell, is a dynamic organelle that plays critical roles in metabolism and disease. Research in this laboratory has focused on two opposite processes: addition (biogenesis) and removal (mitophagy) of mitochondria in skeletal muscle. We have revealed that mitogen-activated protein kinase (MAPK) p38γ isoform, but not p38α or p38b isoform, is critical for exercise training-induced mitochondrial biogenesis through peroxisome proliferator activated receptor γ co-activator-1α (Pgc-1α). We have developed a novel mitochondrial reporter gene, MitoTimer, and an inducible MitoTimer reporter mouse and have found that exercise training activates mitophagy through AMPK-Ulk1 regulatory axis. (NIH R01). Consistent with our interest in exercise-induced improvement of mitochondrial quality in skeletal muscle, we take advantage of different models of exercise to study the impacts of exercise training in preventing the onest of Friedreich's ataxia (FA) (funded by FARA). An improved understanding of mitochondrial maintenance and remodeling in skeletal muscle will facilitate the development of new interventions for numerous medical conditions, such as FA heart failure, cachexia and type 2 diabetes.
Exercise benefits in protection against diseases (Learn more)
Exercise training is the most effective intervention against chronic diseases; however, much less is known about the underlying mechanisms. We have found that an endogeneous antioxidant, extracellular superoxide dismutase (EcSOD), is highly induced by exercise training. We tested the hypothesis that endurance exercise training-induced EcSOD expression in skeletal muscle provides protection against oxidative damage in skeletal muscle and other peripheral tissues/organs. We are specifically interested in the roles of exercise-induced EcSOD in protection against catabolic muscle wasting induced by heart failure, diabetic cardiomyopathy and multiple organ dysfunction syndrome induced by sepsis and trauma (NIH R01). The findings will provide novel insights into the moledular mechanism by which regular exercise elicits profound protection against many other disease conditions, such as diabetes, atherosclerosis, heart failure and peripheral arterial disease.
Exercise in prevention of parent-offsping disease transmission (Learn more)
Parental obesity and pro-diabetic conditions predisposit the offspring to the metabolic syndrome, whereas exercise during pregnancy can mitigate it; however, the underlying mechanism is unknown. Peroxisome proliferator activated receptor g co-activator-1α (PGC-1α) gene, a master regulator of mitochondrial biogenesis and oxidative metabolis, has been shown to be hypermethylated under the condition of diabetes in skeletal muscle. We hypothesize that exercise during pregnancy prevents hypermethylation of the Pgc-1a gene in offspring skeletal muscle, preventing age-dependent metabolic dysfunction. We use powerful molecular genetics combined with diet-induced obesity and exercise training to test the hypothesis. The studies will likely provide mechanistic insights into the prevention of parental-offspring transmission of the metabolic syndrome.