Bio


I am fascinated by the sensorimotor system and by how do we perceive touch, pain and movement. I want to understand the molecular pathways involved in neurodegeneration and to find treatments for diseases affecting the nervous system.

Professional Education


  • Doctor of Philosophy, Montpellier University, France, Molecular Pathology of Amyotrophic Lateral Sclerosis (2021)
  • Master of Science, University of Strasbourg, France, Integrated molecular and cell biology (2017)
  • Bachelors of Science, University of Science and Technology Lille 1, Biochemistry (2015)

Stanford Advisors


Current Research and Scholarly Interests


I am part of the wormsense lab where we study the molecular and biophysical mechanisms endowing sensory neurons with the capacity to perceive mechanical and thermal stimuli. I study the mechanisms involved in the regulation of degeneration and regeneration of sensory endings. Using genetics, in vivo imaging, electrophysiology and behavioral assays in C.elegans I screen for small molecules that restore touch sensation following chemotherapy and I validate their therapeutic potential in mice.

Lab Affiliations


All Publications


  • Theme 4 In vivo experimental models. Amyotrophic lateral sclerosis & frontotemporal degeneration Chudinova, A. V., Rossel, M., Vergunst, A., Le-Masson, G., Camu, W., Raoul, C., Lumbroso, S., Mouzat, K. 2019; 20 (sup1): 160-187

    Abstract

    Background: In 90% of Amyotrophic Lateral Sclerosis (ALS) cases, the disease is sporadic, the remaining 10% being familial. Many genes have been associated with the disease. The use of next generation sequencing has allowed increasing the number of genes analysed in routine diagnostics. However, this increase raises the issue of genetic variants interpretation within a growing number of ALS-associated-genes. Variant classification is based on a combinatory analysis of multiple factors. Among them, functional analyses provide strong arguments on pathogenicity interpretation.Objectives: We developed a simple animal model, the Zebrafish, for the functional analysis of candidate variants pathogenicity identified by routine genetic testing.Methods: Transient overexpression of different ALS associated genetic variants has been performed by mRNA injection in 1-cell stage zebrafish eggs. Validation of protein overexpression has been done by western blot. Embryos mortality, developmental delay and morphological abnormalities have been assessed within the first two days of development. Cellular phenotype has been investigated by the analysis of axonal length of 2-days old larvae with confocal microscopy. Motor phenotype of 5-days old larvae has been explored by touched-evoked response assay.Results: The model has been validated by the analysis of well-described ALS mutations, SOD1-Gly93Ala and OPTN Glu478Gly. Overexpression of this mutated protein was shown to provoke a shortening of axons and a premature axonal branching, as well as an impairment of motor performances as expected. We did not observe these aberrations in SOD1-WT injected fishes. Two candidate variants observed in ALS-patients have been explored with our model: SOD1 NM_000454.4:c.400_402del, p.Glu134del and OPTN NM_021980.4:c.1475T > G, p. Leu492Arg. Overexpression of both variants induced morphological abnormalities and motor impairment, suggesting a pathogenic involvement of these variants in ALS-patients.Discussion and conclusions: We developed for the first time a simple animal model, the Zebrafish, useful for the functional analysis of variant pathogenicity in order to assist ALS molecular diagnosis. Our model has been used to assess the pathogenicity of SOD1 and OPTN candidate variants, allowing to improve genetic testing interpretation.

    View details for DOI 10.1080/21678421.2019.1646992

    View details for PubMedID 31702459

  • Regulation of Brain Cholesterol: What Role Do Liver X Receptors Play in Neurodegenerative Diseases? INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Mouzat, K., Chudinova, A., Polge, A., Kantar, J., Camu, W., Raoul, C., Lumbroso, S. 2019; 20 (16)

    Abstract

    Liver X Receptors (LXR) alpha and beta are two members of nuclear receptor superfamily documented as endogenous cholesterol sensors. Following conversion of cholesterol in oxysterol, both LXR isoforms detect intracellular concentrations and act as transcription factors to promote expression of target genes. Among their numerous physiological roles, they act as central cholesterol-lowering factors. In the central nervous system (CNS), cholesterol has been shown to be an essential determinant of brain function, particularly as a major constituent of myelin and membranes. In the brain, LXRs act as cholesterol central regulators, and, beyond this metabolic function, LXRs have additional roles such as providing neuroprotective effects and lowering neuroinflammation. In many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and multiple sclerosis (MS), dysregulations of cholesterol and oxysterol have been reported. In this paper, we propose to focus on recent advances in the knowledge of the LXRs roles on brain cholesterol and oxysterol homeostasis, neuroinflammation, neuroprotection, and their putative involvement in neurodegenerative disorders. We will discuss their potential use as candidates for both molecular diagnosis and as promising pharmacological targets in the treatment of ALS, AD, or MS patients.

    View details for DOI 10.3390/ijms20163858

    View details for Web of Science ID 000484411100015

    View details for PubMedID 31398791

    View details for PubMedCentralID PMC6720493