Team Philippe MARIN
Neuroproteomics and signalling of brain disorders
The team is developing a multidisciplinary strategy combining genomics and proteomics approaches with pharmacological, biochemical, cell biology, electrophysiological and behavioral studies to decipher the neuronal mechanisms involved in various neurological and psychiatric disorders (mood disorders, psychoses, autism, Alzheimer’s disease, multiple sclerosis) and identify biomarkers of these pathologies.
Our research aims at characterizing the pathophysiological mechanisms of neurological (Alzheimer’s disease, multiple sclerosis, gliomas) and psychiatric (depression, schizophrenia, autism spectrum disorders) disorders, in order to identify targets for innovative therapies and biomarkers. It cover molecular mechanisms, with a focus on signaling networks associated with various G protein-coupled receptors that are potential targets for the pathologies studied (serotonin, glutamate and chemokine receptors), which we characterize using interactomic or phosphoproteomic screens, cellular mechanisms (intracellular trafficking, secretion and paracrine diffusion of pathological proteins), synaptic mechanisms (transmission and plasticity) and changes in brain connectivity and network activity, in particular alteration of the excitation/inhibition balance. Particular attention is paid to neurodevelopmental mechanisms and environmental factors (microbiota, diet, etc.). The team is also deeply involved in environmental issues and the impact of climate change on mental health.
Within this general framework, the team is developing the following lines of research under the direction of project leaders:
• Interactomics and neuropathologies
• Microbiota, serotonin and Alzheimer’s disease
• Protein trafficking and neurodegenerative diseases
• Signaling networks associated with antipsychotic targets
• Serotonin receptors, mood disorders and psychoses
• Serotonin receptors and neurodevelopmental pathophysiology
• Multiple sclerosis: environmental factors and biomarkers
Colocalization of ACKR3 and Connexin 43 (receptor’s partner identified by interactomics) in mouse brain astrocytes. ACKR3 (cyan), Cx43 (pink), GFAP (white). Adapted from Fumagalli et al. Nat. Commun. 2020.
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IGF Sud 219 04 34 35 93 23- Philibert CE, Disdier C, Lafon PA, Bouyssou A, Oosterlaken M, Galant S, Pizzoccaro A, Tuduri P, Ster J, Liu J, Kniazeff J, Pin JP, Rondard P, Marin P*, Vandermoere F*. TrkB receptor interacts with mGlu2 receptor and mediates antipsychotic-like effects of mGlu2 receptor activation in the mouse. Sci Adv. 2024 Jan 26;10(4):eadg1679. doi: 10.1126/sciadv.adg1679. PMID: 38277461.
- Hinsinger G, Du Trieu de Terdonck L, Urbach S, Salvetat N, Rival M, Galoppin M, Ripoll C, Cezar R, Laurent-Chabalier S, Demattei C, Agherbi H, Castelnovo G, Lehmann S, Rigau V, Marin P, Thouvenot E. CD138 as specific CSF biomarker of multiple sclerosis Neurol Neuroimmunol Neuroinflamm. 2024 May;11(3):e200230. doi: 10.1212/NXI.0000000000200230, PMID: 38669615
- Sekssaoui M, Bockaert J, Marin P*, Bécamel C*. Antidepressant-like effects of psychedelics in a chronic despair mouse model: is the 5-HT2A receptor the unique player? Neuropsychopharmacology 2024 Jan 11. doi:10.1038/s41386-024-01794-6. PMID: 38212441.
- Sengupta S, Mondal M, Prasasvi KR, Mukherjee A, Magod P, Urbach S, Friedmann- Morvinski D*, Marin P*, Somasundaram K*. Differentiated glioma cell-derived fibromodulin activates integrin-dependent Notch signaling in endothelial cells to promote tumor angiogenesis and growth. Elife 2022 Jun 1;11:e78972. doi:10.7554/eLife.78972. PMID: 35642785.
- Sheu SH, Upadhyayula S, Dupuy V, Pang S, Deng F, Wan J, Walpita D, Pasolli HA, Houser J, Sanchez-Martinez S, Brauchi SE, Banala S, Freeman M, Xu CS, Kirchhausen T, Hess HF, Lavis L, Li Y, Chaumont-Dubel S, Clapham DE. A serotonergic axon-cilium synapse drives nuclear signaling to alter chromatin accessibility. Cell 2022 Sep 1;185(18):3390-3407.e18. doi:10.1016/j.cell.2022.07.026. PMID: 36055200.
- Fumagalli A, Heuninck J, Pizzoccaro A, Moutin E, Koenen J, Séveno M, DurrouxT, Junier MP, Schlecht-Louf G, Bachelerie F, Schütz D, Stumm R, Smit MJ, Guérineau NC, Chaumont-Dubel S, Marin P. The atypical chemokine receptor 3 interacts with Connexin 43 inhibiting astrocytic gap junctional intercellular communication. Nat Commun. 2020 Sep 25;11(1):4855. doi: 10.1038/s41467-020-18634-y. PMID: 32978390.
- Berthoux C, Hamieh AM, Rogliardo A, Doucet EL, Coudert C, Ango F, Grychowska K, Chaumont-Dubel S, Zajdel P, Maldonado R, Bockaert J, Marin P*, Bécamel C*. Early 5-HT6 receptor blockade prevents symptom onset in a model of adolescent cannabis abuse. EMBO Mol Med. 2020 May 8;12(5):e10605. doi:10.15252/emmm.201910605. Epub 2020 Apr 24. PMID: 32329240.
- Pujol CN, Dupuy V, Séveno M, Runtz L, Bockaert J, Marin P*, Chaumont-Dubel S*. Dynamic interactions of the 5-HT6 receptor with protein partners control dendritic tree morphogenesis. Sci Signal. 2020 Feb 11;13(618):eaax9520. doi: 10.1126/scisignal.aax9520. PMID: 32047117.
- Rochais C, Lecoutey C, Hamidouche K, Giannoni P, Gaven F, Cem E, Mignani S, Baranger K, Freret T, Bockaert J, Rivera S, Boulouard M, Dallemagne P, Claeysen S. Donecopride, a Swiss army knife with potential against Alzheimer’s disease. Br J Pharmacol. 2020 May;177(9):1988-2005. doi: 10.1111/bph.14964. PMID: 31881553.
- Murat S, Bigot M, Chapron J, König GM, Kostenis E, Battaglia G, Nicoletti F, Bourinet E, Bockaert J, Marin P*, Vandermoere F*. 5-HT2A receptor- dependent phosphorylation of mGlu2 receptor at Serine 843 promotes mGlu2 receptor-operated Gi/o signaling. Mol Psychiatry. 2019 Nov;24(11):1610-1626. doi: 10.1038/s41380-018-0069-6. PMID: 29858599.
Microbiota, serotonin and neurodegenerative diseases
Principal investigator
Sylvie CLAEYSEN
GPCR signaling, compartmentalization and pathophysiological roles
Principal investigator
Séverine CHAUMONT-DUBEL
Protein trafficking and neurodegenerative diseases
Principal investigator
Julien VILLENEUVE
Identification and functional analysis of multiple sclerosis biomarkers
Principal investigator
Eric THOUVENOT
Normal and pathological functions of Tau / Eco-emotions and mental health
Principal investigator
Marie-Laure PARMENTIER
Regulations and signaling of metabotropic glutamate receptor mGlu2, the target of a new generation of antipsychotics
Principal investigator
Franck VANDERMOERE
PhD students
Lucie PELLISSIER
2004 – 2009
CRCN CNRS, Tours, France – ERC Starting Grant 2019 –CNRS Bronze Medal 2022
Gaëlle CARRAT
2007 – 2010
Clinical Research Associate, Medpace, Londres, Angleterre, Royaume-Uni
Julie MEFFRE
2007 – 2011
Postdoc, LNC, Marseille, France
Samah KARAKI
2008 – 2011
Founder of the Social Brain Institute, Paris, France
Maud COCHET
2007 – 2011
Pedagogical coordinator Lyon, France
Alexander BARRE
2009 – 2013
Patch Clamp engineer, Neuroservices, Aix en Provence, France
Romain DONNEGER
2010 – 2014
Lead Clinical Operations, Roche, Paris, France
Fanny DUHR
2011 – 2015
MD, France
Geoffrey HINSINGER
2013 – 2016
Psychiatric intern, AP-HM, Marseille, France
Coralie BERTHOUX
2013 – 2017
Staff scientist, Albert Einstein College of Medicine, NY, USA
Camille PUJOL
2014 – 2018
Psychiatric intern, CHRU Strasbourg, France – Madeleine Lecoq Award from Académie des Sciences 2022
Samy MURAT
2014 – 2018
Intern in Geriatrics, CHU Nîmes, France
Amos FUMAGALLI
2015 – 2019
Postdoc The Netherlands Cancer Institute, Amsterdam, Netherlands – Recipient of 2 bourses Marie Curie
Bérénice HATAT
2016 – 2019
Odontology student, Montpellier, France
Hugo PAYAN
2016 – 2020
Postdoc, Duke-NUS Medical School, Singapour
Angelina ROGLIARDO
2017 – 2021
Postdoc, INM, Montpellier, France
Vincent DUPUY
2017 – 2021
Postdoc, IINS, Bordeaux, France
Caroline ISMEURT
2017 – 2021
Postdoc, IGMM, Montpellier, France
Lucile DU TRIEU DE TERDONCK
2017 – 2021
Postdoc, INP, Marseille, France
Clémentine PHILIBERT
2018 – 2022
Postdoc, Boston University School of Medicine, Boston, USA
Ophélie BENTO
2020 – 2023
Postdoc, IGF, Montpellier, France
Manon GALOPPIN
2020 – 2023
Postdoc, PhyMedExp, Montpellier, France
Alessandro RABBITO
2020 – 2024
Postdoc, USA
Lucy KUNDURA
2023 – 2024
R&D project manager, Ciloa, Montpellier, France
Tomas DEL OLMO
2020 – 2025
Postdoc IGH, Montpellier, France
Post-doctoral fellows
Elena MARCELLO
2011 – 2012
Associate Professor, Univ. Milano, Italy
Paul DELERIS
2012 – 2014
Associate Professor, Univ. Nantes, France
Pascal SEYER
2012 – 2015
Associate Professor Univ. Montpellier, France
Patrizia GIANNONI
2011 – 2016
Associate Professor, Univ. Nîmes, France
Al Mahdy HAMIEH
2015 – 2016
Clinical and preclinical studies manager, Virbac, PACA, France
Simon NICOT
2017 – 2018
Post-doc EFS, Montpellier, France
Émilie DOUCET
2016 – 2020
Laboratory Manager Nervosave Therapeutics, Montpellier, France
Clinical studies conducted by the team
MICMALZ – Analysis of the microbiota’s blood signature as a diagnostic marker for Alzheimer’s disease in its early stages: Pilot study
S. Claeysen (IGF) / A. Gabelle & K. Bennys (CMRR, CHU Montpellier)
The aim of this study is to characterize the composition of the microbiota, in stool and blood, of patients with Alzheimer’s disease (AD, Alzheimer’s group) and people with memory complaints unrelated to AD (Control group). Participants without memory defects are also included in the study (Neurotypical group).
To date, we have included 116 subjects and are continuing recruitment for the Neurotypical group.
D-Lay MS – Efficacy of Cholecalciferol (Vitamin D3) for Delaying the Diagnosis of MS After a Clinically Isolated Syndrome
E. Thouvenot (IGF, CHU Nîmes)
This is the largest randomized, double-blind clinical trial to assess the clinical efficacy of high-dose vitamin D versus placebo in reducing multiple sclerosis (MS) activity after a first clinical attack of the disease.
In 35 centers in France, we included 316 patients followed for two years and studied the impact of vitamin D on the clinical and MRI evolution of MS.
VDSS – Peripheral Immunological Effects of High-dose Vitamin D Treatment in Healthy Subjects
E. Thouvenot (IGF, CHU Nîmes)
The aim of this study was to clarify the immunomodulatory effects of Vitamin D (3 months treatment with cholecalciferol 100,000 IU) on lymphocytes from healthy subjects, to establish a normal regulatory profile and thus define potential pathological regulations in MS patients included in D-Lay MS. To this end, we randomized 56 healthy subjects to vitamin D or placebo for 3 months and collected blood samples (PBMC) at inclusion and at 3 months.
We also took stool samples at 3 months to characterize the composition of the microbiota, in stool and blood, of healthy subjects, to study the effects of vitamin D and to serve as a reference for other studies by the team.
