Current lab members:

• Véronique Paquis-Flucklinger, PU-PH (EC), PI
• Mélanie Abou-Ali, PhD student
• Samira Ait El Mkadem-Saadi, IR CHU
• Gaelle Augé, technician CHU
• Sylvie Bannwarth, PU-PH
• Aurore Bernardin, postdoc
• Annabelle Chaussenot, PH CHU
• Konstantina Fragaki, IR CHU
• Emmanuelle Genin, CRCN Inserm
• Justine Labory, PhD student 
• Alessandra Mauri-Crouzet, IA UniCA
• Anna Requena, IE Inserm
• Cécile Rouzier, PH CHU
• Loan Vaillant-Beuchot, postdoc

Links:

https://www.chu-nice.fr/offre-de-soins/maladies-rares/maladies-mitochondriales

https://www.chu-nice.fr/patients-visiteurs/accompagnement-patients-et-familles/Maladies-rares-plateforme-resilience

The goal of the team concerns the identification of new genes and mechanisms responsible for mitochondrial diseases (MD), rare disorders characterized by an energy defect. Patients with MD develop a wide spectrum of severe disorders including early-onset symptoms in children and late-onset neurodegenerative pathologies. MD are caused by pathogenic variants in nuclear-encoded mitochondrial genes (>400 reported disease genes) or in mitochondrial DNA (mtDNA). Today, the responsible gene is unknown in one patient out of 2 leading to diagnosis deadlock, despite the development of Next Generation Sequencing (NGS) technologies.

Our attention also focuses on aging-associated mitochondrial dysfunction and its involvement in neurodegenerative disorders. Ten years ago, the identification of a point mutation (p.S59L) in the CHCHD10 gene,  encoding a mitochondrial protein, was the first genetic evidence that mitochondrial dysfunction can trigger motor neuron disease (MND), leading to amyotrophic lateral sclerosis (ALS). In CHCHD10-related disease, we demonstrated that instability of the MICOS complex, responsible for mitochondrial cristae junction maintenance, contributes to neuronal death via disorganization of the inner mitochondrial membrane (IMM). This discovery led us to identify repositionable molecules (nifuroxazide (NFX) and analogues) able to rescue defects found in in vitro models generated from patient cells.

The work of the team is performed in close collaboration with the CHU of Nice : the Reference Centre for Mitochondrial Diseases “CALISSON”, the Department of Medical Genetics and the Rare Diseases Expertise Plateform “RESILIENCE”. This collaboration enables us to build a continuum between upstream and clinical research, with the aim of fighting diagnostic and therapeutic deadlocks in mitochondrial defects, particularly those responsible for neurodegenerative disorders.

Research Teams

IRCAN has a diverse research teams, tackling a wide range and resolution of topics in ageing and cancer.