LAURÉATE 2017, 2018 § 2019 

Pr. Laurence OLIVIER-FAIVRE

Laurence Olivier-Faivre est Professeur des Universités et Praticien hospitalier au CHU Dijon Bourgogne.

Elle est Responsable du Centre de Génétique pour le diagnostic des maladies rares d'origine génétique et les prédispositions génétiques au cancer, Coordinatrice du Centre de Référence « Anomalies du Développement et Syndromes Malformatifs de l'Est », Coordinatrice des Centres de Compétence « Maladie de Marfan », « Maladies Mitochondriales », « Retard Mental et Malformations Cérébelleuses »

Responsable de l' équipe EA 4271, conception des stratégies de l'équipe, constitution et phénotypage des cohortes des patients, description de nouveaux syndromes avec anomalies du développement, identification de nouveaux gènes impliqués dans les anomalies du développement

THÈME DE RECHERCHE : 

« Characterization of Cohen syndrome’s ocular defects in Vps13b-/- mice and identification of the molecular mechanisms involved in its pathogenesis. » 

SUBVENTIONS JED : 99.000 € 

OBJECTIF DU PROJET : 

This project started in October 2017, thanks to the grant provided by the foundation JED. 

Patients with Cohen syndrome (CS, OMIM 216550) suffer from many symptoms including developmental delay, intellectual disability, severe myopia and progressive loss of vision due to retinal degeneration. Patients and their families highlighted that the major issue for them was the loss of vision. Our project was submitted to patients’ families and it created great hope for them as it is the first time a research group attempts to solve, in a preclinical study, the major issue they face. So far, there is no therapeutic approach to prevent or slow down the loss of vision of those patients. We wish to provide such a treatment andthrough this achievement improve the patients’ life quality and relieve part of the burden that lay upon them and their families.

VPS13B is the causative gene associated with CS (Kolehmainen et al. 2003). VPS13B is located to the cis- Golgi apparatus where it is required for maintaining its integrity (Seifert et al. 2011) and interacts with Rab6 (Seifert et al. 2015). Despite these observations, nothing is known about VPS13B cellular functions. Studies in the GAD team have showed that mutations in VPS13B are associated with tissue-specific protein glycosylation defect (Duplomb et al. 2014), a process that could to be the starting point of the retinal degeneration in CS. Some of our preliminary data in acrosome formation during spermatogenesis also suggest a role for VPS13B in endosome-lysosome trafficking (Da Costa et al. 2019). Both academics and non-academics, working on understanding how glycosylation affects the retina and on developing treatments for retinopathies associated with Congenital Disorders of Glycosylation (CDG) and diabetic retinopathies, may find new ways to approach their research in our results.

 

Our long-term objective is to translate our research into a clinical trial to test therapies that would be shown safe and efficient in mice.