Name: Partner 11: Institut Imagine, France

Address: 24 Boulevard du Montparnasse, 75015 Paris, France

Link: https://www.institutimagine.org/en

Summary: First European center of research, care and education on genetic diseases, the Imagine Institute aims to understand them and cure them. The Institute brings together 1000 of the best doctors, researchers and healthcare personnel in a creative architecture of synergies. Today Imagine is focused on its ambition to change the lives of families affected by genetic diseases.

Neural crest and Waardenburg syndrome: Research projects developed in our group mainly focus on the understanding of molecular and cellular bases of Waardenburg syndrome (WS), a rare genetic disorder due to abnormal development of the Neural crest. We pay particular attention to the SOX10 transcription factor, the endothelin”/EDNRB signaling pathway functions, their interactomes and to post-transcriptional RNA modification.

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 the distal gastrointestinal tract which results in 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, PCWH, isolated HSCR and Kallmann syndrome). We developed in vitro tools to test functional consequences of mutations identified in WS genes or their regulatory sequences. Since 2003, we also use mouse models to study genetic interactions taking place between Sox10, Edn3/Ednrb 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.

Dr Nadège Bondurand and Dr. Veronique Pingault are principle contributing researchers from Partner 11. Institut Imagine will be hosting a young researcher ESR14, who will be looking into the cell and molecular bases of Waardenburg syndrome via exome sequencing, hiPSCs and NC-GRN.

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