Group leader, Research Director (DR1), Unit Director (Genetics and Developmental Biology, UMR3215), Professor at the Collège de France
Curie Institute, Paris, France CNRS, France
X-inactivation is a process by which one of the two X chromosomes is transcriptionally silenced during early development in female mammals. It allows for dosage compensation between XX females and XY males. Edith Heard is studying this paradigm for developmental epigenetics to gain insights into the fundamental mechanisms that underlie the dynamics of gene expression during development and cellular differentiation, as well as during tumorigenesis.
During development, specialized cell types emerge from a common single progenitor thanks to the expression of specific sets of genes, and the silencing of other genes. The differences between cell types are not due to DNA sequence differences but rather to what is often referred to as epigenetic variation.
The aim of the group of Edith Heard is to understand how cells can express their genomes differentially and in a stable, although sometimes reversible, manner during development, using X-chromosome inactivation as our model. X inactivation is a normal process, entailing the silencing of one of the two X chromosomes in female mammals. Once established the silent state is stably maintained through cell divisions and throughout the adult life, but can be reversed at certain stages of development, in the germ line and possibly in cancer cells. The inactive X provides a unique model of chromosome-wide epigenetic silencing.
Studying the process of X chromosome inactivation allows to unveil molecular mechanisms involved in establishing, maintaining and reversing heterochromatin. Edith Heard and her team are interested in four principal questions :
To analyse the early steps of X-chromosome inactivation Edith Heard and her group study mouse embryos and mouse embryonic stem cells. In parallel, they also use human cancer cell lines, as well as breast tumor samples in collaboration with doctors at the Curie Hospital, to investigate the mechanisms underlying epigenetic instability in the context of tumor development.
Edith Heard and her team couple classic molecular approaches with the analysis of cellular behavior at the single-cell level, in fixed or live samples, thanks to the the Institut Curie’s imaging platform and the state-of-the-art microscopy tools and expertise available within the Genetics and Developmental Biology department. These approaches are combined with large-scale genomic and epigenomic techniques made possible thanks to the various technological departments of the Institut Curie. Their work is especially focused on changes in chromatin structure and nuclear organization associated with heterochromatin formation, as well as the role of non-coding RNAs such as the remarkable Xist RNA which is expressed specifically from the inactive X and underlies the initiation of X inactivation.
Understanding the regulation of gene expression during normal development is crucial for our comprehension of the alterations that can lead to cancer. Using the process of X-chromosome inactivation as a model system, Edith Heard and her group are developing approaches that allow us to gain insights into the fundamental mechanisms that underlie the dynamics of gene expression during development and cellular differentiation, as well as during tumorigenesis.
• 1990 : Ph. D. Imperial Cancer Research Fund laboratory, London, United Kingdom, Mike Fried’s lab
• 1990-1993 : Post-doctoral fellow, Pasteur Institute, Paris, France, Philip Avner's lab
• 1993 : Appointed CNRS staff scientist, Pasteur Institute, Paris, France, Philip Avner's lab
• 2001 : Appointed Group leader at the Curie Institute, Paris, France
• 2010 Nommée Directrice de l'UMR3215/U934 à l’Institut Curie, Paris, France
• 2013 Nommée Professeur au Collège de France, Paris, France
• La Ligue Prize “René et Andrée DUQUESNE”, 2017
• European Society of Human Genetics Award, 2017
• Elected Fellow of the Royal Society, 2013
• Grand Prize of the Allianz Foundation, Institut de France, 2013
• Grand Prize of the Foundation for Medical Research (FRM), 2012
• Advanced Grant from the European Research Council (ERC), 2010
• Silver Medal (Best Confirmed Researchers), CNRS, 2008
• Elected as an EMBO member, 2005
Mar 2017, Nat Struct Mol Biol.
Jul 2016, Nature