Thomas Jefferson University - Carol Beck
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Carol Beck
Pharmacology and Experimental Therapeutics
Assistant Professor, Pharmacology & Experimental Therapeutics
Assistant Dean, Jefferson College of Graduate Studies
Ph.D. Vanderbilt University, 1993
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Mailing Address
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1100 Walnut Street, 811 MOB
Philadelphia, Pennsylvania 19107
United States
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Expertise and Research Interests
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Mutations in the skeletal muscle chloride channel gene (CLCN-1) have been implicated in the human diseases myotonia congenita and recessive generalized myotonia and in animal models of myotonia in mouse, goat and dog. Myotonia is characterized by delayed relaxation of muscle secondary to sarcolemmal hyperexcitability and is the result of diminished chloride conductance in the muscle cell membrane. When chloride conductance (GCl) is reduced, either by drugs or dysfunctional channels, the repetitive myotonic contractions characteristic of the disease occur. These hereditary mutations are significant links between the pathology of these diseases and the basic physiology of skeletal muscle. We are using a combination of approaches to further our understanding of structure-function relationships of the affected voltage-gated ion channels and of the skeletal muscle diseases.
We want to understand how the molecular structure of ion channels contributes to their function. The carboxyl terminus of the ClC-1 chloride channel surrounding the mutation identified in myotonic goats contains multiple praline residues. Proline-rich domains have been found to participate in protein-protein interactions with specific binding motifs such as Src homology and WW domains. We hypothesize that the carboxyl terminus of ClC-1 participates in protein-protein interactions and that these interactions are important for proper channel function.
In other research in the laboratory, we are studying a new chloride channel family, the calcium-activated chloride channel CLCA.
Laboratory Staff
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Keywords
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pharmacology, voltage-gated ion channels; chloride channels; calcium-activated chloride channels; skeletal muscle; myotonia congenita
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Publications
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- Evans SR, Beck CL. Cloning and Characterization of mClCa5 and mClCa6. Biophysical Society Annual Meeting, 2004.
- Dunn SL, Beck CL. Effects of Fyn and Src on the human skeletal muscle chloride channel (hClC-1). Biophysical Society Annual Meeting, 2003.
- Mankodi A, Takahashi MP, Jiang H, Beck CL, Bowers WJ, Moxley RT, Cannon SC, Thornton CA. Expanded CUG repeats trigger aberrant splicing of ClC-1 pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy. Molecular Cell, 10: 35-44, 2002.
- Beck, CL, George AL, Jr. Protein-protein interactions between skeletal muscle proteins and the ClC-1 chloride channel. Biophys J., 78:117A (abstract), 2000.
- Pierno S, DeLuca A, Beck CL, George AL, Jr., Conte Camerino D. Aging-Associated down-regulation of ClC-1 expression skeletal muscle: phenotypic-independent relation to the decrease in chloride conductance. FEBS Lett., 449:12-16, 1999.
- Fahlke CH, Yu HT, Beck CL, Rhodes TH, George AL, Jr. Pore forming segments in voltage-gated Cl-channels. Nature, 390:529-532, 1997.
- Fahlke Ch, Beck CL, George AL, Jr. A mutation in autosomal dominant myotonia congenital affects pore properties of the muscle chloride channel. Proc.Natl.Acad.Sci.USA, 94: 2729-2734, 1997.
- Beck CL, Fahlke CH, George AL, Jr. Molecular basis for decreased muscle chloride conductance in the myotonic goat. Pro.NatlAcad.Sci.USA, 93:11248-11252, 1996.
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Individual Expertise profile of
Carol Beck, Copyright © Carol Beck.
Last Updated
by Carol Beck : Thursday, March 13, 2008 4:59:05 PM
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