The goal of the Gilbert Lab is to find ways to restore skeletal muscle function by harnessing the potential of muscle stem cells. We do this by working to understand what controls muscle stem cells in health, and how this changes in disease, and then we test potential treatments -discovered in our research - in miniature culture models of human skeletal muscle that we engineer in a dish.
We define the interactions between muscle stem cells and their dynamic extracellular milieu that serve to orchestrate the elegant process by which a muscle stem cell switches between states of quiescence, activation, proliferation, differentiation, and self-renewal in health and in disease. The native stem cell niche is a three-dimensional entity. While conceptually it is accepted that dimensionality is a critical feature of tissues that defines the location and timing of cellular events, understanding how dimensionality exerts such a powerful influence on stem cell biology is not well understood. Our specific emphasis is on evaluating how biomechanical stresses of the niche, like compressive forces, shear stress, or extracellular matrix stiffness, synergize with niche proteins to drive stem cell behavior. By quantifying in vivo biomechanical stresses presiding over the quiescent and regenerating adult skeletal muscle niche, and engineering three-dimensional culture models of skeletal muscle regeneration, we aim to uncover how the native three-dimensional tissue exerts spatiotemporal control over muscle stem cell fate.
3D skeletal muscle models
Using biofabrication and tissue engineering techniques we deconstruct and reconstruct miniaturized versions of human skeletal muscle tissue in a dish for drug discovery efforts
and for fundamental studies
of skeletal muscle biology. Project focus areas include aging, Duchenne muscular dystrophy, muscle stem cell mediated repair, exercise, intensive care unit acquired weakness, and neuromuscular biology.