Autophagy is a cellular process that controls the lysosomal degradation of proteins and organelles, essential for a broad range of cellular functions and tissue development. Dysregulation of autophagy is found or implicated in many human pathologies. An optimal level of autophagy is critical for skeletal muscle homeostasis and health, as well as muscle regeneration after injury. Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophies diagnosed in childhood, caused by mutations in the X-linked dystrophin gene with an estimated incidence of about 1 in 5,000 live male births. There is currently no cure or satisfactory therapy for DMD. A common cellular alteration underlying the DMD phenotypes is the impairment of autophagy. Unraveling molecular pathways involved in the inhibition of autophagy in DMD will contribute to our understanding of DMD pathology and potential identification of new therapeutic targets. Our recent work has led to unraveling of signaling pathways that impact autophagy in muscle regeneration and DMD, and this continues to be an active area of research in the lab.
J.-S. You, N. Singh, A. Reyes-Ordonez, N. Khanna, Z. Bao, H. Zhao, and J. Chen, (2021) ARHGEF3 regulates skeletal muscle regeneration and strength through autophagy. Cell Rep, 34, 108594. Link to article
J.-S. You and J. Chen, (2021) Autophagy-dependent regulation of skeletal muscle regeneration and strength by a RHOGEF. Autophagy, 17, 1044.
J.-S. You, Y. Kim, S. Lee, R. Bashir, and J. Chen, (2023) RhoA/ROCK signalling activated by ARHGEF3 contributes to autophagy-dependent muscle weakness in a mouse model for Duchenne muscular dystrophy. J. Cachexia, Sarcopenia and Muscle, 14, 1880. Link to article
J.-S. You, K. Karaman, A. Reyes-Ordoñez, S. Lee, Y. Kim, R. Bashir, and J. Chen, (2024) Leucyl-tRNA synthetase contributes to muscle weakness through mTORC1 activation and autophagy suppression in a mouse model of Duchenne Muscular Dystrophy. American Journal of Pathology, 194, 1571. Link to article