Dr. Rachelle Crosbie's research program focuses on determining the pathogenetic mechanisms of muscular dystrophy. Members of Dr. Crosbie's lab examine the muscle function using biochemical, molecular and cellular approaches. There are many forms of muscular dystrophy caused by primary genetic mutations within different muscle genes. For instance, mutations in dystrophin are responsible for causing Duchenne muscular dystrophy while mutations in any of the four sarcoglycan genes cause limb-girdle muscular dystrophy. Congenital and Emery-Dreyfus muscular dystrophies are caused by mutations in laminin and emerin, respectively. These muscle diseases differ based on the types of muscles that are affected, clinical progress of the disease and mode of inheritance.
Dr. Crosbie's lab is interested in why these proteins are critical for normal muscle function, creating animal models for specific forms of muscular dystrophy using transgenic and knockout mouse technology and developing new therapeutic agents. They are in the process of developing novel animal models for cytoplasmic muscle proteins that are known to cause muscular dystrophy. By this method, they can examine the progress of muscle disease in a mouse at the molecular, cellular and tissue levels. Finally, they can determine how molecular changes within myofibers result in aberrant muscle function. They will compare murine models of muscular dystrophy with current mouse models for Duchenne muscular dystrophy and congenital muscular dystrophy.
During Dr. Crosbie's postdoctoral research, she identified and characterized a novel muscle protein, which she named "sarcospan" based on its multiple SARCOlemma-SPANning domains. This 25-kDa protein has four transmembrane domains and is associated with dystrophin at the muscle plasma membrane. Sarcospan is absent in patients with Duchenne and Limb-Girdle muscular dystrophies. Together with the sarcoglycans, sarcospan is important for maintaining stability of the plasma membrane during muscle contraction. Dr. Crosbie's lab is currently examining whether genetic mutations in sarcospan are responsible for causing other forms of muscular dystrophy. In addition, their researchers are investigating the role of sarcospan in cellular signaling and communication.