email: rcrosbie@physci.ucla.edu
phone: (310) 794-2103
office: Rm 5804 Life Science Bldg
homepage: http://www.physci.ucla.edu/research/crosbie
research interests: Molecular Basis of Muscle Function and Muscular Dystrophy
Research Interests
My research program focuses on determining the pathogenetic mechanisms of muscular dystrophy. Members of the lab are examining 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 (DMD) 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. My lab is interested in 1) determining why these proteins are critical for normal muscle function 2) creating animal models for specific forms of muscular dystrophy using transgenic and knockout mouse technology and 3) developing new therapeutic agents. We are in the process of developing novel animal models for cytoplasmic muscle proteins that are known to cause muscular dystrophy. By this method, we can examine the progress of muscle disease in a mouse at the molecular, cellular, and tissue levels. Finally, we can determine how molecular changes within myofibers result in aberrant muscle function. We will compare our murine models of muscular dystrophy with current mouse models for Duchenne muscular dystrophy and congenital muscular dystrophy. During my postdoctoral research, I identified and characterized a novel muscle protein, which we 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. We are currently examining whether genetic mutations in sarcospan are responsible for causing other forms of muscular dystrophy. In addition, we are investigating the role of sarcospan in cellular signaling and communication.
Selected Publications
Peter, A.K., Ko, C.Y., Kim, M.H., Hsu, N., Ouchi, N., Rhie, S., Izumiya, Y., Zeng, L., Walsh, K. and R.H. Crosbie. 2009. Myogenic Akt signaling upregulates the utrophin-glycoprotein complex and promotes sarcolemma stability in muscular dystrophy Human Mol. Genetics 18 318-327 .
Colantonio, J.R., Bekker, J.M., Kim, S.J., Morrissey, K.M., Crosbie, R.H., and K.L. Hill. 2006. Expanding the Role of the Dynein Regulatory Complex to Non-Axonemal Functions: Association of Gas11 with the Golgi Traffic 7 538-548 .
Peter, A.K. and R.H. Crosbie. 2006. Hypertrophic response of Duchenne and limb-girdle muscular dystrophies is associated with activation of Akt pathway Exp. Cell Res 312 2580-2591 .
Peter, A.K. and R.H. Crosbie. 2006. Hypertrophic response of Duchenne and limb-girdle muscular dystrophies is associated with activation of Akt pathway Exp. Cell Res 312 2580-2591 .
Yi, C.E., Bekker, J.M., Miller, G., Hill, K.L. & R.H. Crosbie. 2003. Specific and Potent RNA Interference in Terminally Differentiated Myotubes J. Biol. Chem 278 934-939 .
Crosbie, R.H., Barresi, R., and K.P. Campbell. 2002. Loss of Sarcolemma nNOS in Sarcoglycan-Deficient Muscle J. Biol. Chem 16 1786-1791 .
Crosbie, R.H., Dovico, S.A., Cohn, R.D., Flanagan, J.D., Chamberlain, J.S., Ownby, C.L., and K.P. Campbell. 2001. Characterization of Aquaporin-4 in Muscle and Muscular Dystrophy FASEB J 16 943-949 .
Crosbie, R.H.. 2001. News and Views: NO Vascular Control in Duchenne Muscular Dystrophy Nature Med 7 27-29 .
Holt, K.H., Crosbie, R.H., Venzke, D.P., and Campbell, K.P.. 2000. Biosynthesis of Dystroglycan: Processing of a Precursor Propeptide FEBS Lett 468 79-83 .
Crosbie, R.H., Lim, L.E., Moore, S.A., Hirano, M., Hays, A.P., Maybaum, S.W., Collin, H., Stolle, C.A., Fardeau, M., Tomé, F.M.S., and Campbell, K.P.. 2000. Complexity of Sarcoglycan-Sarcospan Expression in Limb-Girdle Muscular Dystrophy: Insights into Sarcoglycan Domains Hum. Mol. Gen 9 2019-2027 .