Muscle Disorders and Regenerative Biology Laboratory
Directed by Mahasweta Girgenrath, Ph.D., the Muscle Disorders and Regenerative Biology Laboratory is at the forefront of the effort to develop treatment and therapies for muscle disorders, prolonging overall life, longevity, and quality of life for those with muscular dystrophy. The lab focuses on understanding the pathomechanisms of MDC1A that result from mutations in the gene that encodes for the alpha 2 chain of an indispensible extracellular matrix (ECM) protein known as laminin 211. This is the second-most prevalent form of the numerous congenital muscular dystrophies that have been identified. In many cases of this very aggressive disease, premature death of affected children occurs due to either respiratory complications or failure to thrive.
While significant progress has been made towards understanding the molecular and biochemical causes for MDC1A, there is no therapy that effectively treats this lethal form of muscular dystrophy. We study signal transduction pathways in neuromuscular diseases using in vivo and in vitro approaches to identify the different targets to ameliorate the disease pathology.
Our approach is to treat some of the secondary manifestations—such as inflammation, necrosis, apoptosis, autophagy, fibrosis, and inefficient regeneration of damaged muscle fibers—as they are also common to a host of neuromuscular degenerative diseases, thereby multiplying the potential benefits of an effective treatment. MDC1A, like many other dystrophies, has multiple disease drivers. We are working on a combinatorial strategy that aims to target more than one pathophysiological process that may be more beneficial in tackling the complexities of MDC1A pathology.
- Kumar A, Yamauchi J, Girgenrath T, Girgenrath M. (2011). Muscle-specific expression of insulinlike growth factor 1 improves outcome in Lama2Dy-w mice, a model for congenital muscular dystrophy type 1A. Hum Mol Genet. 20(12):2333–43.
- Beermann ML, Ardelt M, Girgenrath M, Miller JB. (2010). Prdm1 (Blimp-1) and the expression of fast and slow myosin heavy chain isoforms during avian myogenesis in vitro. PLoS One. Apr 1;5(4):e9951.
- Girgenrath, M., Beermann ML, Vishnudas VK, Homma S, Miller JB. (2009). Pathology is alleviated by doxycycline in a laminin-alpha2-null model of congenital muscular dystrophy. Ann Neurol. 65(1): 47–56.