Team Chris JOPLING

PRINCIPAL INVESTIGATOR

Chris Jopling

CRCN, Inserm

IGF staff involved
Jourdano MANCILLA ABAROA
PhD Student INSERM
Adèle FAUCHERRE
CRCN CNRS
Thomas MOORE MORRIS
CRCN INSERM
Aurélien DROUARD
IE CNRS
Crystal GUILLEMIN
IE CNRS

Mechanisms driving cardiomyocyte renewal are largely unknown. Among recently identified signaling pathways, the Hippo pathway, myocardial O₂ exposure and cardiomyocyte metabolic status are described to dramatically determine cardiomyocyte proliferation abilities and thus are essential for heart regeneration. Nevertheless, how the hypoxic and metabolic status of cardiomyocytes are controlled remains to be determined. Our principal hypothesis is that the interplay between hypoxic and metabolic signaling is of crucial importance for adult heart regeneration.

Macrophages play an important role during cardiac regeneration. Our analysis of the macrophage population revealed that the inflammatory response of resident macrophages followed by the invasion of recruited macrophages appears to be remarkably similar to the response observed in adult mammals after injury, albeit more rapid. Furthermore, we found that recruited macrophages require Mmp14 in order to invade the wound region and promote cardiac regeneration.

Myocardial damage caused, for example, by cardiac ischemia leads to ventricular volume overload resulting in increased stretch of the remaining myocardium. In humans, these changes trigger cardiomyocyte hypertrophy resulting heart failure. Conversely, in response to extensive myocardial damage, cardiomyocytes in regenerative species proliferate and completely regenerate the damaged myocardium. Our aim is to determine how changes in mechanical forces due to myocardial damage can be detected by mechanosensors which in turn can trigger cardiac regeneration.

Recent evidence indicates that environmental pollutants such as Bisphenol A and perfluorinated acids can potentially impact human development and health. Our goal is to determine whether environmental pollutants can cause disrupt cardiac development and physiology. To achieve this, we use in vivo models in conjunction with cutting edge optical mapping and high throughput cardiac and behavioural tests.