Harvard Neuromuscular Disease Project
The Beggs Laboratory
Gene Expression and Biochemical Analysis of Muscle Development in Myotubular Myopathy.
The goal of this Project is to understand the molecular basis for X-linked myotubular myopathy (XLMTM) by determining the effects of myotubularin mutations on gene expression. Pathologically, XLMTM is characterized by incomplete muscle maturation caused by defects in myotubularin, a dual specificity protein phosphatase. This study entails the developmental characterization of global gene expression of known genes and novel expressed sequence tags (ESTs) in XLMTM and related disorders from the SP stem cell stage through to mature muscle. Understanding perturbations in gene expression will shed light on the function of myotubularin and its role in normal muscle development and may allow identification of therapeutic targets to stimulate normal muscle development in patients with XLMTM and related disorders of muscle development.
- To ascertain and characterize fresh muscle, muscle cell cultures and frozen muscle biopsies from patients with XLMTM and CTNM.
- To isolate and characterize muscle stem cells (SP cells) from myotubularin-deficient patients. To use chip-based mRNA expression arrays to analyze perturbations of gene expression associated with abnormalities of myotubularin in cultured muscle cells.
- To use chip-based mRNA expression arrays to analyze/compare XLMTM and CTNM human muscle to identify disease-specific and nonspecific changes in muscle gene expression.
- To validate results of expression arrays and characterize genes whose expression is specifically perturbed by myotubularin dysfunction.
|If you are interested in participating in this project or learning more about our research, please visit the Beggs Laboratory website.|