Our lab studies the biology of muscle stem cells to understand how they work in making muscle. We also try to find out how muscle stem cells can be “encouraged” to perform better in aging and in disease such as muscular dystrophy. In our research we use many approaches, from cell biology, to biochemistry, molecular biology, systems biology and animal models.  We are especially interested in understanding how the extracellular environment regulates intracellular “business”, from signal transduction to gene expression, cell functions, cell metabolism and cell fate.

Skeletal muscle is the largest “organ” of the body and serves many functions in addition to movement, including: breathing, blood pressure control, metabolism regulation and vision. Muscles have a remarkable regenerative capacity if injured, and are also very plastic, meaning that they can grow or shrink in size depending on whether they are used a lot or not. Muscle regenerative capacity and plasticity largely rely on a population of muscle stem cells also known as satellite cells.

ACTIVE PROJECTS

  1. Are neutrophils the Prince Charming of muscle regeneration?  In intact (uninjured) muscle, muscle stem cells are mitotically quiescent. However, upon injury, they quickly become activated and re-enter the cell cycle. Muscle stem cell activation temporarily coincides with infiltration of damaged tissue by neutrophils. The overall hypothesis at the basis of this project is that neutrophils communicate with quiescent muscle stem cells and participate in the process of muscle stem cell activation. We are currently testing this hypothesis and investigating the molecular mechanisms the underly the  communication between neutrophils and muscle stem cells.
  2. Syndecan-3 in myogenesis: a tale of many functions. Myogenesis is the process of muscle formation from progenitors. Syndecan-3 is a transmembrane proteoglycan expressed by muscle stem cells and involved in several signalling pathways that play crucial in the regulation of muscle stem cell fate and homeostasis. This project aims to identify how syndecan-3 orchestrates these many signalling pathways simultaneously, and how syndecan-3 signalling might be involved in a range of muscle diseases.
  3. New horizons in the monitoring and treatment of Duchenne Muscular Dystrophy. DMD is a genetic disorder affecting approximately 1 in 3,000 boys. It develops in childhood and leads to progressive and widespread muscle weakening and loss, eventually causing loss of ambulation, independent breathing and premature death. We have recently identified novel players in the pathogenesis of DMD, and we are now testing whether they can be used as biomarkers to monitor DMD progression and/or therapeutic targets.
  4. To be, or not to be [..] to die – to sleep. The tumor suppressor p53 is a key cell cycle controller that inhibits cell division. Cells in G0 phase of the cell cycle can undergo at least four different fates: differentiation, quiescence, senescence or death. the function of p53 is often associated with induction of cell death, since p53 is mutated in a large fraction of human cancers and indeed, p53 knockout mice spontaneously develop tumours. However, we have recently shown that a sustained increase in p53 levels leads myoblasts to downregulate MyoD, which is the main transcritption factor driving muscle differentiation, and become quiescent. Therefore, it appears that in myoblasts p53 drives a “sleep state” rather than a “die” state. Now, we need to find out: what this means for muscle stem cell biology and the underlying molecular mechanisms.

 

PROJECTS UNDER DEVELOPMENT

These projects are currently in “stand-by” due to our recent move across the Atlantic, but will resume as soon as new staff (students or postdocs) interested in them becomes available.

  1. Extracellular matrix in 3D. Dystrophic muscle is characterized by increased extracellular matrix deposition to the extent of tissue fibrosis. We have developed a method based on confocal microscopy that allows us to take 3D images of the muscle extracellular matrix and use them to quantitatively compare, using mathematical modelling, the 3D structure of dystrophic muscle matrix to healthy muscle matrix.