Alan Beggs, PhD
|Hospital Title||Director, The Manton Center|
|Academic Title||Sir Edwin and Lady Manton Professor of Pediatrics|
300 Longwood Avenue
Boston MA 02115
Our research aims to understand the structures and function of proteins that make up skeletal muscle fibers, and to use this information to develop methods to diagnose and treat neuromuscular diseases in children.
Our laboratory is taking several complementary approaches to meet these goals. The first involves identification and characterization of new skeletal muscle genes and proteins that we think are important for normal muscle function. The second is to examine these genes for mutations that may cause human neuromuscular disease, and to study how these mutations lead to weakness in affected individuals. Finally, by correlating our basic muscle biology findings with our studies on DNA and muscle tissue of affected individuals, we are able to design and test more effective therapies for these diseases.
Specifically, we are looking into the genetic causes of the congenital myopathies, a group of related disorders of muscle weakness caused by defective genes and proteins in skeletal muscle. Over the past few years, we have identified gene mutations affecting a series of muscle contractile proteins shown to cause nemaline myopathy, a disease characterized by muscle weakness, respiratory problems and the presence of "nemaline rods" (abnormal rod-shaped structures) in muscle fibers.
Our current projects include the identification of new nemaline myopathy genes, understanding the basis of the variability of patients' symptoms and the determination of how these mutations affect muscle function and lead to weakness.
Click image to learn more about nemaline myopathy.
More recently, we have used gene expression studies (microarrays), cell culture experiments, and mouse models to characterize the defective components of muscle fibers in children with multiminicore myopathy. Based on these studies, we are now working to develop therapies that target the underlying defect responsible for muscle weakness. Related projects focus on other congenital myopathies, including: congenital fiber type disproportion (CFTD), myotubular myopathy, and centronuclear myopathy, as well as congenital myopathies with nonspecific muscle findings.
A cytochrome oxidase stained section of muscle from a patient with multiminicore myopathy. Note the patchy white areas, called minicores.
To read more about our work, visit our lab web site.
- Beggs AH et al. MTM1 mutation associated with X-linked myotubular myopathy in Labrador Retrievers. Proc Natl Acad Sci USA 2010 Aug 3. [Epub ahead of print]
- Lawlor MW et al. Mutations of tropomyosin 3 (TPM3) are common and associated with type 1 myofiber hypotrophy in congenital fiber type disproportion. Hum Mutat 2010 Feb; 31(2):176-83.
- Ottenheijm CA et al. Thin filament length dysregulation contributes to muscle weakness in nemaline myopathy patients with nebulin deficiency. Hum Mol Genet 2009 Jul 1; 18(13):2359-69.
- Buj-Bello A. et al. AAV-mediated intramuscular delivery of myotubularin corrects the myotubular myopathy phenotype in targeted murine muscle and suggests a function in plasma membrane homeostasis. Hum Mol Genet 2008 Jul 15; 17(14):2132-43.
- Agrawal PB et al. Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2. Am J Hum Genet 2007 Jan; 80(1):162-7.
- To see a complete list of Dr. Beggs' publications in PubMed, click here.
About Alan Beggs
Alan Beggs is director of The Manton Center for Orphan Disease Research at Children's Hospital Boston and the Sir Edward and Lady Manton Professor of Pediatrics at Harvard Medical School. He received his AB in biology at Cornell University and his PhD in human genetics at Johns Hopkins University. He then completed postdoctoral fellowships in medical genetics at Johns Hopkins University and in clinical molecular genetics at Harvard Medical School, and has directed an independent research laboratory in the Genetics Division at Children's Hospital since 1992.