Team 9- Signaling Pathways & Striated Muscles

Co-team leaders: Fabien Le Grand & Antoine Muchir

Striated muscles comprise approximately 40% of total body weight, contain 50–75% of all body proteins and contribute significantly to multiple bodily functions. Two types of striated muscles exist: skeletal and cardiac muscles. They share a common architecture characterized by a very particular and well-described arrangement of muscle cells and associated connective tissue.

 

The team SPaSM is composed of the Le Grand and Muchir’s research groups that assemble complementary expertise in both heart and skeletal muscle basic cell biology and translational research. The focal point of the team will be the dissection of mechanisms leading to striated muscle dysfunction using an integrated multi-scale approach.


Our goal is to identify specific targets for therapeutic development, which will be the basis for future clinical trials to treat muscular dystrophies and cardiomyopathies and develop personalized medicine.

Our research will revolve around three aims:

  • Using single-cell technologies, we will dissect the cell type composition (RNA-sequencing; Mass Cytometry) of striated muscles during development, regeneration, ageing and in disease.
  • We will study intracellular cytoskeleton dynamics as an endpoint of extracellular signaling pathways and decipher the cues that regulate skeletal myoblasts fusion and cardiac myocyte contractility.
  • We found aberrant Wnt/Erk target gene expression in both cardiomyopathy and muscle dystrophies. We aim to understand the functional consequences of these mis-regulations in muscle cells.

 

Major projects

While most myopathies cannot be cured, symptoms can be alleviated. Development of therapeutic advances to ameliorate patient symptoms and life is a priority in our society. Knowledge of the molecular mechanisms that control the muscle stem cell pool or the homeostasis of differentiated cardiomyocytes will help to identify molecules able to modulate muscle cell fate in vivo, with an outcome for regenerative medicine. We study animal models of both muscular dystrophy and cardiomyopathy and develop novel pharmacological therapies based on our discoveries.

Our research revolve around 3 axes:

  • Tissue organization of striated muscles in health and disease
  • Signaling pathways regulating structure-function relationships in striated muscles
  • Control of striated muscles gene expression by signaling pathways

 

Team members

Fabien LE GRAND DR CNRS, Team Leader
Antoine MUCHIR CR INSERM, Team Leader
Nicolas VIGNIER CR AIM
Lorenzo GIORDANI Post-doc Fellow
Cécile PECATTE IE AIM
Anissa TALEB IE ANR
Francesco GIRARDI PhD student
Nicolas ROSE PhD student
Deborah CARDOSO PhD student