“Regulating Myofiber Connection to the Extracellular Matrix in Health and Disease”

Welcome to the Crosbie Lab Homepage.

Loss of appropriate connections and contact between the sarcolemma and the extracellular matrix has emerged as a critical initiating event of muscle pathology in the muscular dystrophies. Many of these cell contacts and adhesion events are regulated by glycosylation of cell surface glycoproteins on muscle. Dystroglycan is a receptor for components within the extracellular matrix and is is associated with a group of peripheral and transmembrane proteins called the dystrophin-glycoprotein complex. The dystrophin-glycoprotein complex provides a physical linkage between the actin cytoskeleton and the extracellular matrix, which protects the muscle sarcolemma from contraction-induced damage. It is well-established that stable interactions amongst the integral membrane proteins are critical for muscle function and prevention of muscular dystrophy.

Our laboratory is focused on understanding the function of the dystrophin-glycoprotein complex and how perturbation of this complex causes many forms of muscular dystrophy. In particular, we are interested in identifying mechanisms to increase expression of compensatory proteins that ameliorate dystrophic pathology. We have shown that sarcospan, a component of the dystrophin-glycoprotein complex, is an important determinant in regulating levels of several adhesion proteins within muscle. Our data support a rationale for identifying compounds that modulate sarcospan expression as a therapy for muscular dystrophy. Our studies are applicable to a wide range of dystrophies resulting from loss of cell-extracellular matrix contact.

Our lab is also focused on advancing STEM education by creating and testing inclusive online learning communities and by bringing students into the real world challenge of muscular dystrophy.  Our team consists of biochemists, physiologists, physical therapists, molecular biologists, statisticians, and education specialists.  Our STEM education research and muscle cell biology research are funded by grants from the National Institutes of Health, Muscular Dystrophy Association USA, Parent Project Muscular Dystrophy, LGMD2i Research Fund, and UCLA ILTI.

Figure: Muscle cell adhesion complexes.  Laminin-binding complexes that connect the actin cytoskeleton to the extracellular matrix to protect the sarcolemma from injury.