Mechanisms regulating myogenesis, myofiber growth and muscle fibrosis
We use mammalian skeletal myogenesis as a powerful system with which to study the molecular regulation of genesis, activation, proliferation and differentiation of muscle stem cells during adult muscle regeneration and growth.
Specific objectives:
A- To gain insight into the signal transduction-coupled transcriptional mechanisms regulating muscle cell proliferation versus differentiation.
We focus on two key regulators of myogenesis, the p38 MAPK signaling pathway and the bHLH family of myogenic regulatory factors (MRFs), using cellular and molecular biology in vitro approaches and the Cre-LoxP system in mice.
B- To gain understanding of the mechanisms regulating growth of adult skeletal muscle, by identifying extracellular and intracellular mediators of this process.
We devote a particular emphasis to the mechanisms underlying satellite cell-mediated hypertrophic growth and the contribution of inflammatory cytokines to this process. This goal is relevant for combating disorders associated to loss of muscle mass, such as cachexia provoked by cancer or AIDS, and aging-associated muscle wasting.
C- To decipher the mechanisms leading to fibrosis development in Duchenne Muscular Dystrophy (DMD).
Besides progressive muscle degeneration and inflammation, fibrotic transition of muscle tissue is critical in DMD as it progressively deteriorates locomotor capacity and the vital function of cardiac and respiratory muscles. Yet, the underlying mechanisms of fibrosis development within dystrophic muscle remain largely unknown.