Molecular Mechanisms of Calcium Signaling in Striated Muscle

The overall focus of the Dirksen laboratory is to characterize the cellular and molecular mechanisms that control intracellular calcium dynamics in skeletal and cardiac muscle in health and disease. Current projects involve elucidating the mechanisms by which muscle function is controlled by proteins involved in coordinating:

1. Excitation-contraction coupling
2. Store-operated calcium entry
3. Mitochondrial calcium uptake and energy production
4. The molecular mechanisms for skeletal and cardiac dysfunction in myotonic dystrophy

The laboratory also investigates the pathophysiological mechanisms by which defects in these three key calcium signaling mechanisms lead to muscle dysfunction and disease. The laboratory approaches these projects through integration of a broad range of approaches including generation of transgenic/knock-in/knock-out mouse models, electrophysiology, fluorescence photometry, molecular biology, biochemistry, muscle histology, confocal microscopy, high-speed digital imaging of intracellular Ca²⁺ dynamics, in vitro measurements of muscle contractile properties, and behavioral measures of in vivo muscle performance (rota-rod, treadmill, wire hanging, grip strength).

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