Local Signals and Macromolecular Architecture in Heart

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Heart Failure

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T. B. Rogers
R. J. Bloch
W. J. Lederer

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Molecular Genetics
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Project 3: Lederer

Subcellular Organization and Ca2+ Signaling in Heart Failure

W. J. Lederer, MD, PhD

Seeks to characterize quantitatively Ca2+ signaling defects that occur in cardiac ventricular myocytes and to investigate the causes of the dysfunction.

Ca2+ signaling dysfunction occurs in heart muscle cells under many conditions and is associated with diverse cardiac pathologies. The project seeks to characterize quantitatively Ca2+ signaling defects that occur in cardiac ventricular myocytes and to investigate the underlying causes of this dysfunction. New results from our group suggest a central hypothesis: disruption of the cellular machinery of excitation-contraction coupling may underlie the Ca2+ signaling defects that have been observed. Such remodeling may involve reorganization of cytoskeletal proteins, or mislocalization of important proteins targeted to specialized structures, called transverse tubules, in the cardiac cell.

Our research team is addressing four questions. 1. How do acute changes in cytoskeletal proteins affect calcium signaling? 2. How is Ca2+ signaling changed in animal models of heart disease? 3. How does modulation of the transverse tubule organization and function affect cardiac Ca2+ signaling? 4. Can Ca2+ signaling abnormalities be rescued by gene transfer? Our work is not only broadening our understanding of Ca2+ signaling in the heart but will clarify how this cascade is dysfunctional in disease.

 

 

Heart Cells
Heart cells.

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