Yan Laboratory
Exercise Physiology

Center for Skeletal Muscle Research
Robert M. Berne Cardiovascular Research Center
University of Virginia School of Medicine
409 Lane Road, MR4 - 6041A
Charlottesville, VA 22908
Phone: 434-982-4477
Fax: 434-982-3139

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 (mitochondrial 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 are ascertaining the isoform-specific p38 signaling and function in contractile and metabolic functions (NIH R01 supported). We also found that exercise training promotes mitophagy. We now study the functional importance of exercise training-induced mitophagy in metabolic and contractile adaptations, focusing on autophagy related genes, Atg1, Atg6 and Atg7 (ADA Basic Research Award). Meanwhile, we have developed a novel mitochondrial reporter gene, MitoTimer, for mitochondrial quantity and quality, and we are developing conditional transgenic MitoTimer reporter mice for assessing mitochondrial quantity and quality in vivo. (NIH R21 pending). Using this technology, we currently study the exercise impacts on mitochondria and muscle function in 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.

Signaling-transcription coupling in exercise-induced muscle adatpation (Yan et al. J Appl Physiol, 2010)

Exercise benefits in protection against diseases (Learn more)
It is well known that exercise training is the most effective intervention against chronic diseases; however, much less is known about the underlying mechanism for the benefits of exercise training. We have found that an endogeneous antioxidant, extracellular superoxide dismutase (EcSOD), is inducible in a nitric oxide (NO)-dependent manner in skeletal muscle. EcSOD is highly induced by exercise training in a mouse model of exercise. We test the hypothesis that endurance exercise training-induced EcSOD expression in skeletal muscle provides profound protection against oxidative damage in skeletal muscle and other peripheral tissues/organs. We are specifically interested in the roles of endurance exercise training-induced EcSOD expression in protection against catabolic muscle wasting induced by congenital heart failure (NIH R21 supported), diabetic cardiomyopathy(AHA Post-doctoral Fellowship supported) and multiple organ dysfunction syndrome induced by sepsis and trauma (NIH R01 pending). 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 trainin-induced EcSOD in protecting peripheral tissues/orgains from oxidative damage.

Maternal exercise in prevention of disease in offsping (Learn more)
Pro-diabetic conditions in pregnancy cause predisposition of the offspring to the metabolic syndrome, whereas maternal exercise has profound positive impacts on the offspring; 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 maternal exercise 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 by maternal exercise.

The overall strategy and the central hypothesis that exercise traing during pregnancy modifies the epigenome and lead to reduced susceptibility to insulin resistance in the offspring. Red color depicts insulin resistance.