Skip to main content Skip to navigation
We care about your privacy. Read about your rights and how we protect your data. Get Details

Coronavirus Update:What patients and families need to know

The Children's National Research Institute

Muscle Biology and Diseases

Cell Biology of Myogenesis, Muscle Repair, Regeneration and Aging

This group led by Jyoti Jaiswal, Ph.D., focuses on understanding the cell biology of muscle and degenerative diseases. The group studies the cellular and molecular mechanisms involved in subcellular trafficking and the role played by this process in healing the injured cell membrane and identifying therapies to target diseases resulting from poor repair of injured muscles. Limb Girdle Muscular Dystrophies encompass diseases where ability of the wounded muscle cells to repair is compromised. These studies suggest a role of acid sphingomyelinase and a modified steroid drug – vamorolone, as a potential therapy for LGMD2B. In preclinical studies by Sen Chandra Sreetama, Ph.D., is providing evidence that use of these drugs improve myofiber repair, reduce muscle inflammation and prevent adipogenic conversion of muscle. It has also helped identify a novel role for mitochondria – facilitating repair of injured muscle fibers, deficit in this contributes to myofiber necrosis in Duchenne Muscular Dystrophy (Vila et al 2017). Extending this work further, Adam Horn has identified the molecular mechanism by which mitochondria sense and help repair myofiber injury, work was recognized as one of the top ten amongst the 850 articles published this year by Children’s National investigators (Horn et al 2017). Pursuing a career-development award funded by the Muscular Dystrophy Association Dr. Marshall Hogarth’s work is providing novel clues regarding how poor myofiber repair and chronic inflammation in LGMD2B is linked to adipogenic replacement of the muscle fibers, and has provided evidence supporting a role of inflammation in adipogenic replacement of muscle in LGMD2B (Defour et al 2017).

Work by Marie Nearing and Davi Mazala in the lab led by Terence Partridge, Ph.D., are investigating the differences in the mechanisms of muscle formation during the growth period immediately after birth from those that operate during subsequent regeneration in response to damage caused by muscular dystrophy. The team is exploring how the mechanisms that control satellite cell function during growth differ from those that operate during regeneration, and testing the responses of muscle to growth-promoting agents, such as Formoterol. These investigations are carried out in the mdx mouse, a model for human DMD. Understanding of these processes is important, because in boys with Duchenne, unlike mice, growth and repair mechanisms operate contemporaneously for much of the juvenile and pubertal growth period. It was recently shown that the DMD mutation on the DBA/2J mouse background results in an atrophic phenotype that more closely resembles that in DMD boys. Dr. Davi Mazala, together with James Novak, Ph.D., and Dr. Jaiswal, is now investigating the pathological differences between the DBA/2J model and the original mdx mouse, to identify the crucial factors underlying the distinct pathologies and refine the utility of the DBA/2J model for testing of therapeutic strategies such as exon-skipping.