Nadege Bondurand PhD human genetics and development, HDR

Course and current status

Since December 2013- Research Director (DR2), INSERM U955, IMRB Team11. Group leader “Molecular and cellular bases of neurocristopathies” 

2007-2013 Research scientist (CR1). INSERM U654 and U955, IMRB, Young group leader within the team “molecular genetics and development” headed by Pr. M. Goossens. Research interest: SOX10 and Edn3 network: from WS4 to ENS development

2003-2007 Research scientist (CR2) INSERM U468 and 654. Research interest: Interactions between SOX10 and other ENS genes  

2001–2003 Postdoctoral position, National Institute of Medical Research, Division of Molecular Neurobiology, Pr. V. Pachnis. EMBO fellowship. Research interest: role of SOX10 and endothelin-3 during enteric nervous system development.

1996– 2000 PhD in Human Genetics, INSERM U468. PhD supervisor Pr. M. Goossens. Research interest: Role of the SOX10 transcription factor in different neurocristopathies.

Student’s training and coordination:

2003-present -Training of 4 PhD students (L.Stanchina, PhD defended 11/05/09; A. Chaoui, PhD defended 11/30/2013 + 2 ongoing) and master (M1 and M2) students.

-  Reviewer for several journals including Am J Med Genet, Clin Genet, JCMM, GIM, Orphanet Journal of Rare diseases, PlosOne, Clin Genet.

- Coordinator of ANR Young researcher grant 2010-2013.

5 main publications over the last 5 years: 

1-Lecerf L, Kavo A, Ruiz-Ferrer M, Baral V, Watanabe Y, Chaoui A, Pingault V, Borrego S and Bondurand N. An impairment of long distance SOX10 regulatory elements underlies isolated Hirschsprung disease. Hum Mutat, 2014, 35(3):303-7

2- Pingault V, Bodereau V, Baral V, Marcos S, Watanabe Y, Chaoui A, Fouveaut C, Leroy C, Vérier-Mine O, Francannet C, Dupin-Deguine D, Archambaud F, Kurtz FJ, Young J, Bertherat J, Marlin S, Goossens M, Hardelin JP, Dodé C, and Bondurand N. Loss-of-function mutations in SOX10 cause Kallmann syndrome with deafness.Am. J. Hum. Genet. 201392(5):707-24

3- Watanabe Y, Broders-Bondon F, Baral V, Paul-Gilloteaux P, Pingault V, Dufour S and Bondurand N. Interaction between Sox10 and Itgb1 controls enteric neural crest cells migration. Dev Biol, 2013, 379(1):92-106

4- Chaoui A, Watanabe Y, Touraine R, Baral V, Goossens M, Pingault V, and Bondurand N.Identification and functional analysis of SOX10 missense mutations in different subtypes of Waardenburg syndrome. Hum Mutat, 2011, 32(12):1436-49. 

5- Pingault V, Ente D, Dastot-Le Moal F, Goossens M, Marlin S, Bondurand N. Mutation update: Waardenburg syndrome. Hum Mutat, 2010, 31(4):391-406.

Scientific summary

Research projects developed in our group mainly focus on the understanding of molecular and cellular bases of Waardenburg syndrome (WS), a a rare genetic disorder due to abnormal development of the Neural crest.  We pay particular attention to the SOX10 transcription factor function and "interactome".

In 1998, we identified the first mutations of SOX10 in patients presenting with Waardenburg syndrome type 4 (WS4) which is defined by the association of intestinal aganglionosis characteristic of Hirschsprung disease (HSCR, absence of enteric ganglia along a variable portion of the distal gastrointestinal tract which results in the contraction of the aganglionic gut segment and functional intestinal obstruction) with the pigmentation defects and deafness characteristic of WS. Since then, we have been at the heart of genetic studies highlighting involvement of this gene in endophenotypes or related disorders (WS2, PCW, PCWH, isolated HSCR and more recently in Kallmann syndrome).

Since 2003, we also developed in vitro tools required to test functional consequences of each mutation identified in the SOX10 gene or its regulatory sequences. In parallel, we use mouse models to study genetic interactions taking place between Sox10 and other genes known to play key roles during enteric nervous system (ENS) development and have developed cellular models allowing the study of the role of ENS factors/signaling pathways in proliferation, migration, apoptosis and/or differentiation of enteric progenitors in a step by step procedure.

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