Angiogenesis in Health and Disease: In-vivo and in-silico

Angiogenesis, the process of generating new vessels from pre-existing vasculature, is essential for the growth, repair and function of all vertebrate tissues and a hallmark of cancer. The mechanisms that regulate the process of angiogenesis have been greatly deconstructed at the molecular and signaling level, however, although acknowledged, the contribution of physical forces, including essential flow related phenomena, are poorly understood. More importantly, the integration of molecular and physical information, on the predicted vascular pattern and structure is inefficient when performed experimentally one step at the time. We propose an integrative computational/experimental study to investigate the role of multi-scale flows in angiogenesis through High Performance Computing. The success of this project relies on the capability of mapping effectively multiscale numerical methods to efficient software of massively parallel computer architectures so as to access the multitude of spatiotemporal scales inherent to angiogenesis. The integration of simulations with in vitro experiments will be performed through a Bayesian uncertainty quantification framework. The present computational+experimental approach aims to accelerate scientific discovery and to elucidate the role of physical forces in angiogenesis and it is envisioned that it will have an impact on regenerative medicine. We aim to develop software that will find broad utility for scientists in Computational Life Sciences, while making fundamental contributions that can be incorporated in other projects in the PASC network.