Chris JoplingInstitut de génomique fonctionnelle (IGF) - CNRS / Inserm / Université de Montpellier
Mes recherches
My research involves using a multidisciplinary approach to understand the moleclar mechanisms involved in cardiac development, disease and regeneration. In 2006 I obtained by PhD in developmental biology in the lab of Jeroen den Hertog at the Hubrecht Institute in the Netherlands. Following this I joined the Juan Carloz Belmonte’s team at the CMRB in Barcelona where I developed my interest in cardiac regeneration. I was a recipient of the ATIP AVENIR in 2011 and also obtained a CR1 position with INSERM in the same year. This allowed me to establish a team at the IGF in Montpellier in 2012.
Mon projet ATIP-Avenir
The molecular mechanisms of heart regeneration
Heart disease has now become one of the most common causes of fatality and disability in the western world 1. To understand how heart regeneration may be induced in humans we have chosen to analyse the zebrafish model organism in which heart regeneration does occur. Our previous findings have indicated that during heart regeneration in zebrafish, new cardiomyocytes are produced by the proliferation of existing differentiated cardiomyocytes 2, 3. Our main objective is to expand the relatively small list of genes known to regulate heart regeneration in zebrafish and thus provide candidates which can subsequently be manipulated in mammals. To determine suitable target genes we will make use of the substantial microarray data generated from studying heart regeneration in zebrafish 4, 5. Importantly this data has revealed that certain genes shown to be up-regulated during zebrafish heart regeneration have previously been shown to positively regulate cardiomyocyte proliferation in mammalian models. To further refine the selection of candidates from the microarray data we will target genes that are associated with specific processes that we have identified as being important for zebrafish heart regeneration. Key areas identified thus far include dedifferentiation, inflammation, proliferation, extra cellular matrix remodelling, signalling, transcription, chromatin remodelling and hypoxia amongst others. Subsequently, we will test the selected genes for their role during heart regeneration by either over-expressing or knocking down expression using the Cre/tamoxifen system to achieve tissue specific/temporal control.
Once candidates have been selected and confirmed in our zebrafish model system we will begin testing these in vitro in mammalian cardiomyocytes using a relatively simple and established protocol.
Achieving these goals should provide a framework for testing candidate genes by creating transgenic mouse models to determine whether they are capable of inducing myocardial regeneration after cardiac ischemia.