Systems Biology Laboratory
Systems Biology of Angiogenesis
Angiogenesis (the growth of new blood vessels) is important in such diverse areas as cancer, cardiovascular disease, arthritis, diabetes, wound healing, and tissue engineering. We are interested in quantitative understanding of the mechanisms of microvascular network formation under different conditions. Using methods of computational and mathematical biology and bioinformatics, we analyze the signaling pathways leading to angiogenesis, and the cellular mechanisms governing capillary sprouting and network formation. Our current focus is on Vascular Endothelial Growth Factor (VEGF) and its interactions with endothelial cell receptors, Matrix Metalloproteinases (MMPs) and their role in the extracellular matrix proteolysis and release of growth factors, and a transcription factor Hypoxia Inducible Factor HIF-1alpha; we are constructing multiscale models of angiogenesis spanning several levels of biological organization. We use bioinformatics for discovery of novel agents that affect angiogenesis and use in vitro and in vivo experiments to test these predictions.
Blood Flow and Molecular Transport in the Microcirculation
We are formulating computational models of the microcirculation based on anatomical, biophysical, and physiological experimental data, spanning from the molecular to the tissue levels. These include detailed models of microcirculatory blood flow and molecular transport (e.g., oxygen and nitric oxide) and their regulation.