Mission
The research of the group of Modeling & Analysis of Physiological Systems (MAPS) combines mathematical modeling, computer simulation, and in vivo experimentation to quantify relationships between cellular metabolism and physiological responses of tissue-organ systems and the whole body. Primary emphasis is given to investigating the regulation of energy metabolism in cardiac and skeletal muscle. The tissue-organ systems are linked through circulating blood and integrated into a whole-body model. Physiologically based models incorporate cellular metabolic reactions and transport processes of a large number of chemical species. Such models allow quantitative evaluation of metabolic pathways and regulatory mechanisms under normal and abnormal conditions as well as disease states. Model simulations provide the basis for analyzing of physiological responses to perturbations such as decreased blood flow, reduced oxygen supply, increased demand, or short term alterations in circulating substrates. Experimentally validated models can be used to predict the effects of altering metabolic processes with pharmacological agents or test hypothesis in the contest of an integrated system.
Top-down and bottom-up approaches are used interactively to develop multi-scale mathematical models of oxygen transport and metabolism. This combined approach has the advantage that, while it preserves mass balances and thermodynamic feasibility, it incorporates experimentally derived mechanisms that operate in vitro into a multi-scale model of an in vivo system, which maintains the integrity of regulatory mechanisms. Published mathematical or computational models and experimental in-vitro data on biochemical kinetic; parameters, model equations, and reaction mechanisms associated with specific enzymes or transporters are primarily used for the development of cellular metabolic subsystems. Data from experiments conducted in our human and rodent exercise labs or labs of collaborators, are ideal for investigations of intact tissue or organ oxidative metabolism. Database developed from these sources are used in the development and validation of compartmental biophysical models of oxygen transport and metabolism, which will be the functional components of the multiscale model integrating cellular processes with intact tissue responses to increased energy demand.