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Research in the Campbell lab investigates the dynamic mechanical properties of skeletal and cardiac muscle. We are particularly interested in the molecular components of muscle stiffness and are currently funded by the National Institutes of Health and the American Heart Association to determine the molecular mechanisms underlying diastolic heart failure.
Diastolic dysfunction occurs when not enough blood is able to enter the ventricles between heart beats. The condition affects about 40% of heart failure patients and is particularly prevalent in elderly, obese and diabetic populations. We already know that failing hearts are excessively stiff but we don't yet know why. One of our main aims is to determine whether the increased stiffness reflects 'passive' structural components (such as titin molecules and collagen filaments) or elevated cross-bridge cycling.
We are also interested in how cellular architecture affects contractile properties. Since actin and myosin molecules are localized in separate lattice structures within striated muscles, acto-myosin kinetics are determined as much by the spatial arrangement of the molecules as they are by the mechano-chemistry of individual bonds. We use computer models to investigate this behavior and test our predictions using a wide variety of experimental techniques.
We have active collaborations with many other UK faculty including Drs. Andrade, Esser and Reid in the Department of Physiology and Dr. Bonnell in the Department of Surgery. Experimental techniques commonly used in the lab include: gel electrophoresis, western blotting, histology, computer modeling and biophysical assays of muscle properties.
MITOV, M.I., HOLBROOK, A.M. & CAMPBELL, K.S. (2009) Myocardial short-range force responses increase with age in F344 rats. Journal of Molecular and Cellular Cardiology.46, 39-46. PMC2633371.
MITOV, M.I., GREASER. M.L. & CAMPBELL, K.S. (2009) GelBandFitter: a computer program for analysis of closely spaced electrophoretic and immunoblotted bands. Electrophoresis. 30(5), 848-851. PMC2742644.
CAMPBELL, K.S. (2009) Interactions between connected half-sarcomeres produce emergent mechanical behavior in a mathematical model of muscle. PLoS Computational Biology. 5(11), e1000560. PMC2770126.
CAMPBELL, S., LIONETTI, F.V., CAMPBELL, K.S. & McCULLOCH, A.D. (2010) Evidence that tropomyosin overlap potentiates cross-bridge activation of the cardiac thin filament. Biophysical Journal. 98:2254-2264. PMC2872217.
CAMPBELL, K.S. (2010) Distorting the sarcomere. Journal of General Physiology. (In press).
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