Catherine Coirault MD-PhD Mechanobiology in muscular disorders

Course and current status

Academic Position

Senior Researcher: DR2  INSERM

Center of Research for Myology directed by Bertrand Fontaine, UMRS_974 Inserm Sorbonne Université, Institut de Myologie, 47 bld de l’Hôpital, GH Pitié-Salpétrière, Paris, France.

Member of Team 2 Organisation de la cellule musculaire et thérapie de la myopathie centronucléaire autosomique dominante.

Education

1993: Doctor in Medicine (MD degree). Faculty of Medicine, Paris 11. 

1993: Specialization obtained in Cardio-Vascular Pathologies (Cochin-Port Royal Faculty, Paris).

1995: Doctor of Science (PhD) "Mechanics and energetics of the diaphragmatic muscle". Paris 11

1997: HDR (Habilitation to lead research programs), Physiology, Paris 11.

 

Scientific Research Experiences

1991-1992: Sabbatical year of research

1992-1995: Doctorat en Sciences: Mechanics and energetics of diaphragm muscle.

1996-1998: Post doctoral fellow: INSERM, Ecole Polytechnique, Palaiseau). “Regulation of actin-myosin interactions in striated and smooth muscles”

1998: Research Associate CR1 INSERM

1999: Post-doctorant fellow in York (GB): Justin Molloy’s Muscle Lab.

2000-2003: Head of the Inserm biomedical team “Actin-myosin interactions and contractile dysfunction”, Inserm U451, Palaiseau. Lab. director: Prof JL Martin.

2003–2006: Head of the Inserm team “Actomyosin interactions in chronic heart failure”, Inserm U572, Lariboisière Hospital, Paris. Lab Director: Dr JL Samuel.

2003-2006: Principal coordinator of a French multidisciplinary project on ARVD (rare disease project granted by GIS-INSERM-AFM) including 10 hospital departments (clinical, genetics and researchers).

2006-July 2007: Head of Inserm team “Cellular & molecular Physiopathology in heart failure” in U689, CRCIL- U689 (Hôpital Lariboisière, Paris). Laboratory director: Prof. B. Levy.

2007-present: Leader of the group “Mechanobioly and muscle disorders”, Center of Research for Myology, Myology Institute, Paris, France

 

-          Membership of research committee

2020-present

2019- présent

2018-present

2019-présent

2019-présent

2015-2018

2013-2015 

CNU 66: National council of University, Physiology committee

Member of Steering committee Science, Culture and Society, Sorbonne University

Member board of Medical School, Sorbonne University

Member board of the Inserm Technical committee

 Member board of the Inserm joint administrative commission for Research Director

Research Committee Paris University 6

Member board of Medical School, Sorbonne University

2012-2016 

Member of INSERM Scientific committee CSS4

2012-2020 

Evaluating committee of HDR de la faculté de Médecine, Sorbonne Université

2009-2012 

Scientific committee IFR14, Univ Paris 6

2004-2015

2003-2007

2002-2003

Scientific committee of animal physiology INRA

National council of University, Thoracic and cardiovascular surgery

Scientific committee Medical School, University Pars 7

Awards

Recipient of the award of the Assistance Publique-Hôpitaux de Paris (Médaille d'or) – 1993.

Scientific summary

Since 2008, my group is focusing on the mechanobiology defects in muscular disorders. Our rationale is that whereas the primary function of skeletal muscle is to produce force and movement, mechanical forces in turn are critical to control muscle cell decisions and tissue homeostasis. We aim to explore how mechanical stress affect muscle mass and function in normal and pathological conditions and particularly in two different conditions:

ð Muscular dystrophies related to nuclear envelope protein mutations. We aim to determine the mechanisms of mechanosensing defects in the pathophysiology of muscular dystrophies related to mutations in nuclear envelop proteins. Using 3D cellular model we set up (Chiron et al. 2012), we revealed defective mechanosensing of human lamin mutant myoblasts due to abnormal YAP signaling, and emphasized the crucial role of the biophysical attributes of the cellular microenvironment (Bertrand et al 2014). We further investigate i) the role of defective dynamic actin-mediated cellular functions and YAP signaling (Fischer et al, 2016; Owens et al 2020), ii) the dynamic response of cell-matrix adhesion, cytoskeleton components including measurement of traction force, nuclear deformations, and mechano-transduction signaling (Schwartz/Fischer et al, 2017); iii) the influence of varying matrix stiffness on the mechanosensitive responses of myoblasts and iv) the role of lamin in skeletal muscle plasticity in vivo (Owens et al, BioRxiv 2020) . We aim obtaining detailed description of the molecular events taking place within the nucleus after application of a mechanical stress on a cell, in order to understand i) how a mechanical force is transformed into biochemical signal, ii) how these signals impact the interactions involved in nuclear envelope architecture that may regulate nuclear rigidity/deformability, iii) how they modify interactions between nuclear envelope and chromatin that may regulate mechanosensitive gene expression and iv) how these defects contribute to muscle disorders.

ð Regulation of mechanosensing in sarcomeric muscle: by analyzing the effects of mechanical inactivity/passive shortening (controlled mechanical ventilation) in diaphragm muscle. Based on our expertise in diaphragm function, we are analyzing the molecular mechanisms leading to ventilation-induced diaphragm dysfunction, an adverse effect present in a broad-based population of mechanically, critically ill ICU patients, in both in human (Demoule et al 2013) and animal models (Masmoudi et al 2013; Carreira et al 2014; Michelet et al 2015; De Jong et al 2017).

ð Science, Culture and Society: In parallel to my scientific research activity, I am committed in the interconnections between Science, Culture and society. My aims are to contribute to a fruitful dialogue between Science, culture and society, through for instance, contributions to Declics (Cercle FSER, http://www.cerclefser.org/en/), to Steering committee Science, Culture and Society, Sorbonne University, Paris and implications in patients’association.

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