CV Science

Cécile Delettre PhD, Molecular genetic

Course and current status

EDUCATION

2011         Accreditation diploma to supervise research

2013         Ph.D in Molecular Genetic and health, Montpellier University, France

1995         Postgraduate degree (DESS) in Neuropsychopharmacology and Toxicomany, Bordeaux University, France 

FUNCTIONS

2016-2021   Member of INSERM Scientific national committee for the Neuroscience (CSS4)

2016           Member of the scientific council of Fondation Groupama pour la Santé

2016           Member of the Biohealth Department Council of the University of Montpellier

2010           Nominated INSERM CR1, October 2010

2006           Nominated INSERM CR2, October 2006

WORK EXPERIENCE

 2006-Present  Research associates in Institute of Neurosciences of Montpellier, INSERM U1051  

• Identification and characterisation of gene involved in optic neuropathies.
• Characterisation of mouse models with optic neuropathies and development of therapeutic approaches for these diseases

2005-2006       Postdoctoral stage in Institute of Neurosciences of Montpellier, INSERM U583 

• Identification of a new gene for Dominant Optic Neuropathy and Deafness with promising therapeutic applications

2003-2005       Postdoctoral stage in Pasteur Institute, Apoptosis and Immune System - URA 1961 CNRS, headed by Dr S. Susin, Paris, France

• Characterization of two new AIF isoforms (AIFsh and AIFsh2)

1998-2002       Ph D thesis in preparation in the INSERM laboratory (U 254) Neurobiology of Audition, Synaptic Plasticity 

• Identification of genes involved in the blindness/deafness syndromes. Identification and characterization of OPA1 that causes dominant optic atrophy. Supervisor: Dr. C.Hamel

EXPERTISE

-        Molecular and cellular biology, genetics of inherited diseases, inherited optic neuropathies and mitochondrial disorders

-        Member of the club of hopes of Groupama Health Foundation

-        Member of ARVO (American association for research in vision and ophthalmology)

AWARDS and HONORS

-        Laureate « Futur Researcher 2015 » Languedoc Roussillon region

-        ARVO-International Travel Grant, 2013

-        Travel grant European Association for Vision and Eye Research, 2012

-        Prix de la Fondation de l’œil in 2011

-        Trofémina price 2011 in « Science, Recherche & Technologie »

-        Competitive recruitment “Young Confirmed Researchers” Inserm, 2005

Scientific summary

Inherited optic neuropathies (ION) characterized by the atrophy of the optic disc, are genetic disorders caused by the progressive loss of retinal ganglion cells (RGCs) and are major causes of blindness worldwide. These diseases are very interesting models for neurodegenerative diseases of the central nervous system, since many of them are associated with other neurological damage. The objective of the group is to continue the gene discovery in ION and evaluate the efficiency of novel therapies knowing that there is no treatment today.

 Genetics of inherited optic neuropathies

We recruit ION families in Maolya center (Montpellier) and perform targeted sequencing on genes involved in AODs, AORs, X-linked syndromic optic atrophy, mtDNA genes and optic nerve hypoplasia genes. Negative cases/families are subjected to NGS full exome to search for new genes. Five genes were thus discovered including two new AOR genes, RTN4IP1 and NDUFA13.

Pathophysiology and therapy of Wolfram syndrome

Wolfram syndrome (WS, MIM 222300, prevalence 1/200,000) is the association of diabetes mellitus and optic atrophy. In WS patients, the evolution of the optic atrophy is fast and severe, leading frequently to legal blindness before the age of 20. To date no treatment is available. WS is an autosomal recessive genetic disease caused by mutations in WFS1 encoding an ER protein predominantly expressed in RGCs and in beta-cells of Langerhans islets. Wolframin play a role in Ca²⁺ homeostasis and modulate ER stress. Yet, today, the roles of WFS1 in neurons remain unknown.

We have two goals. First, we investigate the role of WFS1 in neurons and study ER and mitochondrial consequences of WFS1 deficiency. Second, we test therapeutical approaches, by performing pharmacological and gene therapy in our preclinical models, including fibroblasts, stem cell–derived RGCs and animal models.

Pathophysiology and therapy of dominant optic atrophy

One of the most common form of ION is the dominant optic atrophy (DOA) causes by mutations in OPA1 gene. OPA1 is a mitochondrial membrane dynamin which modulates mitochondrial shape and maintains mitochondrial DNA. In the past, we demonstrated in vitro that mutations in OPA1 cause fission of mitochondria in small rounded units, altering the structure of the cristae and decreasing the respiratory chain efficiency. Later, we showed that Opa1delTTAG mice indeed undergo respiratory complex IV defect in the retina with associated mitophagy in the optic nerve. Further analysis of these mice suggests that sex steroids could play a role in this disease and could have a negative effect on Opa1 mutated RGCs.

Our goal is to explore how the steroid synthesis is altered in the Opa1 mutated Muller cells and what causes the increase in RGC death in Opa1 mutant female mice.