FLORENCE FAUVELLE
Chercheur(e) (INSERM)
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Eq B.Lemasson/T.Christen
Coordonnées
Bâtiment : Grenoble Institut des Neurosciences
Bureau : GIN R/073
Batiment Edmond J. Safra
Chemin Fortuné Ferrini
38700 La Tronche
Thèmes de recherche
I am mainly involved in metabolomics studies of human and animal brain. My main research projects are on Parkinson’s disease and focal epilepsy.
Parkinson’s disease (PD), metabolic biomarker discovery
- We conducted a large translational study of the different phases of PD, in collaboration with S. Boulet from Carnicella’s team (team “physiopathology of motivation”). This study included three different animal models and two de novo PD patient cohorts. We discovered a new blood biomarker exhibiting a high accuracy for de novo PD diagnosis and may possibly predict early PD development, before motor symptoms. This biomarker is being patented.
- We are now recruiting late and de novo PD patients at CHUGA (Grenoble Alpes hospital) through the BIOPARK project (E. Moro). We are also comparing the metabolic profile of parkinsonian patient to those of Alzheimer patients (S-PARK projet, M. Sauvee and A. Le Gouellec)
- On the mechanistic side of the project, we are now trying to dysregulate/upregulate some metabolic pathways which could be involved in the metabolic perturbations observed (V. Millasseau PhD project).
This project has been funded by foundation France Parkinson, by the Parkinson’s Disease Biomarkers Program (PDBP) Consortium, supported by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, by CHUGA, by IXXI (Complex system institute), by Fondation de France (2023), Fondation pour la recherché sur le cerveau (2024), ANR (project PYPARK, 2024, PI Sabrina Boulet).
Focal epilepsy, biomarker of the epileptogenic zone
The main objective of my research is to better delineate the epileptogenic zone (EZ) using NMR spectroscopy. First, an unbiased strategy based in ex vivo NMR-based metabolomics, followed by in vivo NMR spectroscopy, has suggested that GABA was a biomarker that accurately define the epileptogenic zone (EZ) in a mouse model of focal epilepsy (the kainate mouse model). We have then developped, in collaboration with Vasile Stupar, in vivo spectroscopic imaging of GABA in the same animal model (Alicia Plaindoux thesis, May 2024).
This project has been funded by Fondation Française pour la Rercherche sur l'Epilepsie (FFRE, METAB-O-EPI project) and by France Life Imaging (FLI, GABA-MAP project).
Other metabolomics project, mainly to find specific biomarkers of:
- Addiction (collaboration with S. Carnicella, GIN), mainly to alcohol, pre-clinical and clinical studies,
- Encephalitis (Collaboration with M. Le Marechal), clinical study
Disciplines scientifiques
I am specialized in Nuclear Magnetic Resonance (NMR) spectroscopy of small molecules, mainly in biomedical research field.
► Metabolomics to investigate metabolism and to improve diagnosis
- HRMAS NMR (High Resolution Magic Angle Spinning) for unprocessed sample analysis,
- High resolution NMR (biofluids e.g. serum, cerebrospinal fluid, fecal water...)
- Multivariate statistics : PCA, OPLS-DA..
► NMR study of interactions
- Intercalation of heterocycles with synthetic oligonucleotides
- Complexation of small molecules with different cyclodextrins, using multi-nuclei NMR and mass spectrometry (thesis)
- Drugs-membranes interactions (phospholipidic Liposomes) using 1H, 31P, 2H NMR.
► Quantification of NMR signals
- Semi-automatic quantification of HRMAS NMR brain tissus, collaboration to the development of jMRUI/QUEST algorithm (collaboration D. Graveron, Université Lyon1, La Doua, Villeurbanne).
Enseignement
► Master 2, UFR Chimie biologie, UGA
- Master 2 “High throughput in biology”, “High throughput NMR: metabolomics” 3h/an depuis 2015.
- Master 2 “Cancer disease: experimental and therapeutic approaches”, “Metabolomics in cancer research” 3h/an 2015-2023.
► AI4OneHealth, UGA
- AI4 omics, “NMR-based metabolomics”, 2021-2023.
► DUT Mesures Physiques, UGA
- Initiation à la RMN, 8h/an, 1999 à 2009,
- Sectroscopie, 45h/an, 1999 à 2001.M
Curriculum vitae
Formation:
► Expérimentation animale pour les cadres (niveau I), Université Grenoble Alpes (juin 2011).
► Habilitation à Diriger les Recherches (HDR) diplôme de l’Université Grenoble Alpes (03 décembre 2010) intitulé « Application de la RMN HRMAS à l’étude du métabolisme et la métabolomique ».
► Doctorat de l'Université Grenoble Alpes, Grenoble (29 avril 1999) mention très honorable avec félicitations du jury, spécialité Génie Biologique et Médical. " Décontamination biologique des cations toxiques : la voie des cyclodextrines"
Plateforme IRMaGe, responsable métabolomique depuis 2013.
Responsable du parc RMN du CRSSA (2 spectromètres RMN Bruker), mise à niveau technologique, et gestion des budgets du laboratoire de RMN
Publications
Mallet D., Goutaudier R., Dufourd T., Barbier EL., Carnicella S., Colca JR., Fauvelle F.* Boulet S.* (* Co-senior authors). Re-routing metabolism by the mitochondrial pyruvate carrier inhibitor MSDC-0160 attenuates neurodegeneration in a rat model of Parkinson’s disease, Molecular Neurobiology, DOI: 10.1007/s12035-022-02962-9, 2022.
Mallet D., Dufourd T., Decourt M., Carcenac C., Bossù P., Verlin L., Fernagut PO., Benoit-Marand M., Spalletta G., Barbier EL., Carnicella S., Sgambato V., Fauvelle F.* Boulet S.* (* Co-senior authors). A metabolic biomarker predict Parkinson’s disease at early stages in patients and in animal models, Journal of Clinical Investigations DOI: 10.1172/JCI146400, 2022.
Guillon A. Diakite D., Cezard A., Baranek T., Bourgeais J., Picou F., Hervé V., Carballido J., Nadal Desbarats L., Auvet A., Dingli F., Turtoi A., Le Gouellec A., Fauvelle F., Crépin T., Hiemstra P.S., Paget C., Loew D., Herault O., Naffakh N., Le Goffic R. and Si-Tahar M. Host succinate inhibits influenza virus infection through succinylation and nuclear retention of the viral nucleoprotein, EMBO DOI: 10.15252/embj.2021108306, 2022.
Clement A., Doyen M., Fauvelle F., Hossu G., Chen B., Barbery-Heyob M., Hirtz A., Lamiral Z., Pouget C., Gauchotte G., Karcher G., Beaumont M., Verger A., Lemasson B. In vivo characterization of physiological and metabolic changes related to isocitrate dehydrogenase 1-mutation expression by multiparametric magnetic resonance imaging and spectroscopy in rat model with orthotopically-grafted human-derived glioblastoma cell lines. NMR biomed doi.org/10.1002/nbm.4490, 2021.
Lo Presti C., Fauvelle F., Jacob MC., Mondet J., Mossuz P. The metabolic reprogramming in acute myeloid leukemia patients depends on their genotype and is a prognostic marker, Blood Advances doi.org/10.1182/bloodadvances.2020002981, 2021.
Hamelin S., Stupar V., Maziere L., Guo J., Labriji W., Liu C., Bretagnolle L., Parrot S., Barbier EL., Depaulis A., Fauvelle F. In vivo GABA increase as a biomarker of the epileptogenic zone : an unbiased metabolomics approach, Epilepsia doi.org/10.1111/epi.16768, 2020.
Vial J., Huchedé P., Fagault S., Basset F., Rossi M., Geoffray J., Soldati H., Bisaccia J., Elsensohn M.H., Creveaux M., Neves D., Blay J.Y., Fauvelle F., Bouquet F., Streichenberger N., Corradini N., Bergeron C., Maucort-boulch D., Castets P., CARRE M., Weber K., CASTETS, M. Low expression of ANT1 confers oncogenic properties to rhabdomyosarcoma tumor cells by modulating metabolism and death pathways. Cell Death Discovery doi.org/10.1038/s41420-020-00302-1, 2020.
Lo presti C., Fauvelle F., Mondet J., Mossuz P. The differential activation of metabolic pathways in leukemic cells depending on their genotype and micro‑environmental stress. Metabolomics, doi.org/10.1007/s11306-020-1633-z, 2020
Sinniger V., Pellissier S., Fauvelle F., Trocmé C., Hoffmann D., Vercueil L., Cracowski J.L., David O. A 12-month pilot study outcomes of vagus nerve stimulation in Crohn’s disease. Neurogastroenterology & Motility., doi.org/10.1111/nmo, 2020
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