BBS Faculty Member - Alan Beggs

Alan Beggs

Department of Pediatrics

Boston Children's Hospital
Division of Genetics, CLSB 15026
3 Blackfan Circle
Boston, MA 02115
Tel: 617-919-2170
Fax: 617-730-0786
Email: beggs@enders.tch.harvard.edu
Lab Members: 5 postdoctoral fellows, 2 graduate students
Visit my lab page here.



The fundamental goals of the Beggs Laboratory are to understand the molecular biology of skeletal muscle and to use this information to study inherited disorders of muscle function. Our laboratory is taking three complementary approaches. The first is to identify and characterize new muscle-specific genes and proteins and learn as much as possible about their basic biology. The underlying assumption is that these new genes are likely to include ones that are defective in patients with various congenital myopathies. Much previous work has concentrated on the a-actinins which are essential Z-line proteins. Current studies include several new sarcomeric proteins identified through interactions with a-actinin as well as several proteins involved in congenital myopathies including the myotubularins and selenoprotein N.

After learning about the cell biology and biochemistry of normal genes and proteins, we are then in a position to look for abnormalities of these genes in patients with muscle weakness. Thus, the second major approach is to find and enroll patients and families with various congenital myopathies and then study their DNA and muscle to find and understand the causes of their disorders. In the past few years, we have made much progress in understanding the basis of nemaline myopathy, including the identification of four thin filament proteins involved in this disorder. Current studies are also focusing on myotubular/centronucluclear myopathy, multi/minicore myopathies and other forms of congenital myopathy, including undefined cases without firm diagnoses. Knowing the genetic basis for each disorder will be critical to designing specific and effective treatments for some of these diseases.

The third approach is to learn as much as possible about the physiologic state of diseased muscle from patients with congenital myopathy. One frustrating aspect of medical genetics today is that knowing the exact genetic defect has often not allowed us to fully understand how the disease is caused and, more importantly, how we can treat it. Utilizing high-throughput genomic methods, we are studying global gene expression patterns to determine the "downstream" or secondary consequences of particular genetic mutations and to identify novel muscle genes for further study. These genomic, together with newer proteomic, approaches are yielding important new insights into basic muscle biology as well as into the pathophysiology of inherited muscle diseases. Studies of zebrafish and mouse models for some of these disorders are now leading to development of novel molecular therapies.



Last Update: 3/25/2014



Publications

For a complete listing of publications click here.

 


 

Beggs AH, Böhm J, Snead E, Kozlowski M, Maurer M, Minor K, Childers MK, Taylor SM, Hitte C, Mickelson JR, Guo LT, Mizisin AP, Buj-Bello A, Tiret L, Laporte J, Shelton GD. MTM1 mutation associated with X-linked myotubular myopathy in Labrador Retrievers. Proc Nat’l Acad Sci, USA, 2010; 107:14697-14702. PMC2930454

Lawlor MW, Read BP, Edelstein R, Yang N, Pierson CR, Stein MJ, Wermer-Colan A, Buj-Bello A, Lachey JL, Seehra JS, Beggs AH. Inhibition of activin receptor type IIB increases strength and lifespan in myotubularin-deficient mice.
Am J Pathol, 2011, 178:784-793. PMC3069865.

Gupta V, Kawahara G, Gundry SR, Chen AT, Lencer WI, Zhou Y, Zon LI, Kunkel LM, Beggs AH. The zebrafish
dag1 mutant: A novel genetic model for dystroglycanopathies. Hum Molec Genet, 2011, 20:1712-1725. PMC3071669.

Ottenheijm CAC, Lawlor MW, Stienen GJM, Granzier H, Beggs AH. Changes in cross bridge cycling underlie muscle weakness in patients with tropomyosin 3-based myopathy.
Hum Molec Genet, 2011, 20:2015-2025. PMC3080611.



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