Broad summaries of several active research areas are given below. If you have interest in learning more about specific research, please see our group publication list or contact Dr. Dan Beard.
- Biochemical Networks
Predicting the behavior of large-scale biochemical networks is an important challenge of research in bioinformatics and computational biology. We have introduced a thermodynamic formalism for the study of metabolic biochemical reaction (open, nonlinear) networks in both time-dependent and time-independent nonequilibrium states. These theoretical and computational tools for enforcing the first and second laws of thermodynamics in biochemical network simulations are used to generate physically realistic simulations, and to reveal insight into the regulatory and control mechanisms operating in complex large-scale systems. The developed tools are applied in profiling metabolic responses to various perturbations (e.g., chemical inhibition, or gene knockout), in understanding network interactions between gene products, and in profiling the mechanisms involved in drug metabolic interactions.
- Cardiac Oxygen Transport and Energetic Metabolism
This research is focused on developing computational models of the transport and biochemical reaction of metabolites and other substances in the myocardium systems. We have developed efficient computational method for simulating transport (advection, permeation, diffusion) in tissues containing microvascular structures of arbitrary complexity, providing a feasible approach for studying a general class of transport problems in the context of realistic representations of vascular anatomy.
- Multiscale Modeling of the Heart in Health and Disease
Large scale integrated systems models are required to understand the pathophysiology of complex diseases. For example, the progression of substrate imbalances (hyperglycemia and dislipidemia), hypertension and vascular hyper-reactivity, and insulin resistance and the onset of type II diabetes in the metabolic syndrome involves metabolic and cardiovascular interaction of several organs across multiple time and space scales. Similarly, the development of a mechanistic understanding of the long-term and short-term responses of the myocardium to ischemia and hypoxia requires the development of a model that can predict the effects of modulating expression and activity of mitochondrial and sarcolemmal ion channels on whole-heart mechanical function. This work involves building integrated models of cardiac energetics, mitochondrial ion handling, and microvascular oxygen transport. The resulting large-scale model is validated by comparison to multiple independent data sets and is used to investigate possible mechanisms of cardiac ischemic preconditioning.
