Using Adult Stem Cells to Engineer the Microcirculation

Human adipose-derived stem cells (hASCs) can be easily acquired from fat during routine liposuction procedures. We are developing cell-based therapies for diabetic retinopathy that use hASCs to control microvascular growth. By using a combination of pre-clinical models and in vitro assays, we are determining the cellular and molecular mechanisms that ASCs use to regulate microvascular growth and support, and with a better understanding of their mechanism of action, we can move this therapy closer to clinical application. FUNDING: NIH-NEI

Manipulating Macrophage and Microvessel Dynamics for Tissue Regeneration

Immune cells play an important role in modulating vascular growth and remodeling, and the microcirculation is the conduit for immune cell entry into tissues during acute and chronic inflammation. We study how macrophages, in particular, affect angiogenesis and arteriogenesis and how their phenotype decisions affect degeneration and regeneration in tissues, such as the eye, skin, and skeletal muscle. We combine experimental models with computational models to understand (and therapeutically manipulate) the dynamics of macrophage recruitment and their impact on microvascular adaptations and tissue remodeling in settings of acute and chronic inflammation throughout the body. FUNDING: The Hartwell Foundation, AstraZeneca

Multiscale Modeling of Skeletal Muscle Adaptations for Treatment Discovery in Muscular Dystrophy and Exercise Training for Astronauts

We are collaborating with the Blemker laboratory at UVA to develop multi-scale, predictive computational models of growth and remodeling of skeletal muscle to study how molecular mechanisms and biomechanical forces contribute to Duchenne Muscular Dystrophy. This project combines finite element models with agent-based models to span molecule-to-organ level functional adaptation. We are also using these models to simulate muscle atrophy during long-duration space flight. FUNDING: NIH-NIBIB, NIH-NIAMS, and NASA

Multi-cell Interactions in Macrophage Infection

In collaboration with the Covert Lab and other Salmonella researchers at Stanford University, we are developing a computational model of macrophage infection by Salmonella. This project is part of the Allen Discovery Center for “Modeling Macrophage Infection as a Multiscale System,” based at Stanford University. The vision of the Center ‐ is to open an unprecedented window into infections of macrophages by the global pathogen Salmonella, integrating cutting‐edge modeling, computation and experimental measurements of both host and pathogen into a combined systems approach. Our project therefore stands at the nexus of modeling, measurement and immunology ‐ all of which were recently identified by the Allen Family Foundation as critical interest areas ‐ and lays the foundation for predictive systems medicine based on whole‐cell and multiscale mechanistic modeling. FUNDING: Paul Allen Foundation