We are interested in studying the natural systems which shape and guide the processes of the natural world.
Our long-term goal is to identify and characterize the scientific mechanisms specific to our principal areas of research.
Muscle stem cells in the forefront of myogenesis
We have a long-standing interest in understanding the regulatory networks of developmental and adult myogenesis, with a specific focus on muscle stem cells (termed satellite cells). Through large-scale screens we have identified the transcriptional and epigenetic shift that is manifested at the quiescence-to-activation switch. We are following up on several factors and pathways that regulate quiescence, activation, differentiation, self-renewal, and the epigenetic landscape of satellite cells. Furthermore, we are investigating the adaptive response of satellite cells to environmental stress. Finally, we have developed a novel protocol that permits the isolation of truly quiescent satellite cells, avoiding the artefacts introduced by current isolation protocols. Using this protocol we are launching a series of high throughput and single cells experiments to uncover the major players of the quiescence and activation networks.
Elucidating the networks that command satellite cell quiescence and activation is a major challenge and a requirement to comprehend the remarkable regenerative capacity that muscle displays.
Interactions of stem cells with their environment
We seek to address how muscle stem cells are controlled by their niche, the specialized microenvironment that signals to them affecting their homeostasis and activation. In terms of cellular input, we focus on perivascular cells (e.g. endothelial cells, pericytes) and inflammatory cells (e.g. macrophages) that influence postnatal muscle growth and regeneration. Following up on our findings about coordinated myo-angiogenesis, we aim to address the effect of hypoxia in orchestrating these processes. Our studies on the non-cellular nature of the niche focus on secreted growth factors and the extracellular matrix. We recently unveiled a Notch/COLV/CALCR cascade that cell-autonomously maintains the satellite cell quiescent state.
Identifying diverse factors of the niche and their modes of interaction is a prerequisite for the use of muscle stem cells in regenerative medicine.
Pathogenesis and Therapy of neuromuscular disorders
Our prime biomedical goal is to understand and treat neuromuscular disorders, notably Duchenne Muscular Dystrophy. Our capacity to bring new therapies to the market is conditioned by the rate of successful therapy translation from animal models to human patients. Thus, a strong transversal objective for our team is to establish novel and accurate preclinical models. We confirm the relevance of these models by deep phenotyping (natural history, histology, inter-disciplinary functional evaluation) before integrating them in innovative genome-editing therapeutic schemes.
The use of spontaneous and engineered preclinical models in fundamental myology provides a valuable tool for the exploratory steps from proof-of-principle to clinical applications in human.