Stem Cell Mechanobiology
Muscle stem cells, or ‘satellite cells’, are a rare population of cells in skeletal muscle tissue that sit on top of the long muscle fibers and beneath a blanket of proteins in their ‘niche’. For the most part, muscle stem cells are inactive, or ‘quiescent’, until they are called to action in response to tissue injury. It’s rather counterintuitive that a population of cells can remain quiescent in such a metabolically and mechanically active tissue like muscle!
We love to think about how physical features of the niche like tissue softness, topography, interstitial flow, or tensile strain influence satellite cell gene expression and their decision to remain quiescent or to divide and make more copies of themselves (self-renewal). Since these physical features change dynamically during regeneration and are altered in the course of aging and disease, our research program is poised to provide a unique picture of the biomechanical basis of skeletal muscle health and degeneration and identify novel therapeutic avenues to restore muscle strength.
3D Skeletal Muscle Models
Skeletal muscle is organized into a beautiful three-dimensional tissue. When the organization is disrupted, by injury or by other means, resident muscle stem cells are called to action to repair the damage and restore three-dimensional order. Using a histological approach on transgenic animal models, researchers capture a snap shot of the events that occur during tissue repair and the genes that mediate each stage. However, to date no one has ever watched skeletal muscle regeneration in real time, so our understanding of the process is really quite limited. To overcome this challenge, we develop and characterize 3D models of normal, injured and diseased skeletal muscle tissue. In addition to establishing unique platforms to expand fundamental knowledge of muscle stem cell-mediated skeletal muscle regeneration, we hope one day to make engineered replacement skeletal muscle a translational reality.