James Bassingthwaighte, ProfessorAdjunct with Biomathematics and Radiology Thrust Areas Education |
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Research Interests Contact Information Research Description Understanding the relationships among different cell types within an organ requires integration of observations at the subcellular level, and on cells, organs, and the whole organism. In my laboratory the main focus is on the heart, but we also study liver, lung, and skeletal muscle. One program concerns the kinetics of energy metabolism, ATP, and adenosine and its metabolic products in endothelial and muscle cells. At times of stress, such as during oxygen deprivation or low flow, ATP is broken down, and adenosine concentration rises dramatically, causing vasodilation. We use multiple radioactive tracers simultaneously to measure reactions of adenosine and its metabolites and to determine their rates of transport across membranes. Models describe the kinetics in a precise way, allowing us to understand the regulation. A second program concerns the spatial distribution of blood flow in the heart and its temporal fluctuation. Obstruction of large coronary arteries is partially compensated for by vasodilation in smaller arterioles. Fractal statistics are useful for characterizing the spatial variation in flow; branching of the vascular tree is fractal. Chaotic dynamics of arterial diameters appear due to cellular and biochemical cycling. A third program, using PET imaging, allows us to appraise cellular metabolism in vivo and study regional myocardial blood flows and metabolism together. Tracers labeled with positrons are injected to give sequences of images. The regional concentrations change with time and the data are then analyzed via models for endothelial cell and cardiac cell metabolism. A National Simulation Resource Facility for Circulatory Mass Transport and Exchange supports the modeling analyses. We develop models and numerical techniques and new methods for optimizing the parameters of model solutions to fit data from PET images or other laboratory studies. The long range goal is to provide clinical cardiologists with tools to link various aspects of cardiac physiology and disordered functions. Dr. Bassingthwaighte is the originator of the Human Physiome Project, a large-scale international program for developing databasing and biological systems modeling for understanding genomic and pharmaceutic effects on human physiology. His program is highly collaborative, involving co-investigators at a dozen U.S. universities, several in Europe, and in 14 departments at the University of Washington. Some of these are involved in the Physiome Project, in particular the Cardiome Project. The Cardiome Project, to define a functional heart in mathematical terms, extends from the biochemistry and the signalling, to the mechanics and energetics of the three-dimensional visualizable heart. Selected Publications
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