Professor at Institut Biology de Valrose, Université de Nice Parc Valrose
Invited Talk Title: RNA-mediated epigenetic heredity : mouse models of an acquired pathology
In the recent years, our laboratory introduced a new, and for some colleagues disturbing concept, a mode of heredity distinct from the Mendelian paradigm, mediated by sperm noncoding RNAs (Rassoulzadegan et al., Nature 2006; Wagner et al., Dev Cell 2008; Grandjean et al, Development 2009). Experimental proofs were provided by microinjection into naive embryos of a variety of mRNA fragments and microRNAs. It led in three independent instances to the mitotically and meiotically stable transcriptional upregulation of the sequence-homologous target locus (paramutation). In the most recent period, the notion was not only validated, but extended by others to animal models of heritable pathologies ranging from diabetes to psychiatric diseases. Thus, it is now highlighted a way to search for unexplained hereditary characters and diseases. We ourselves further documented RNA-mediated heredity by evidencing a requirement for the methylation of the vector and the target transcript (Kiani et al, PLoS Genetics, 2013). Our present projects comprising the evaluation of a possible generalized model of epigenetic determinations by sperm RNAs; and the pursuit of a role of RNA methylation in development and heredity, joining our own expertise in genetics and the generation of animal models.
1979-1985 Attaché de Recherche, then Chargé de Recherche (CNRS) -Since 1986 Directeur de Recherche (CNRS)- 2004-2011 Directrice Unité 636 Inserm- Group leader, Institut de Biologie Valrose since 2012.
Elected EMBO Member (2009)
Chevalier of Légion d’Honneur (2016)
Scientific Leadership Profile
A permanent CNRS scientist since 1980, I was trained on the manipulation of mouse embryos during a stay at the Cold Spring Harbor Laboratory (1984). Since that time, I worked on mouse genetics as a group leader, with the development of several tools to study early embryos, male germ cells development, differentiation and tumorigenesis. Observer and experimenter in mouse genetics, through various approaches to dissect meiosis and germ cell differentiation, I have recently discovered and defined with my colleagues the modes of hereditary epigenetic variation known in other models systems as transvection (EMBO J. 2002, 21:440) and paramutation (Nature. 2006, Dev.Cell. 2008, Development 2009). The latter work led us to propose, with the description of the first phenotypic marker modified by paramutation in the mouse, a role of RNA in the heredity of the epigenetic regulation. Among other implications in fundamental research, our results may provide new models for a number of instances of familial recurrence of diseases in humans not explained by a clear Mendelian determination. We are currently working on the definition of the molecular mechanisms underlying RNA-mediated heredity.
Recent publications (Research ID O-7939-2016)
Ghanbarian, H., Wagner, N., Polo, B., Baudouy, D., Kiani, J., Michiels, J.F., Cuzin, F., Rassoulzadegan, M., and Wagner, K.D. (2016). Dnmt2/Trdmt1 as Mediator of RNA Polymerase II Transcriptional Activity in Cardiac Growth. PLoS One 11, e0156953.
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