Team Philippe LORY
Ion channels in neuronal excitability and diseases
Philippe
Lory
DR1, CNRS
The work in Lory’s team is dedicated to the study of voltage-gated calcium and sodium channels (Cav and Nav) and the ‘leak’ sodium channels (NALCN) in physiology and diseases. These ion channels are central in the electrophysiological activity of excitable cells, especially neurons. Dysfunction of these channels leads to a wide group of diseases known as “channelopathies”. Our goal is to decipher how these ion channels are involved in the disease mechanisms underlying severe neurodevelopmental disorders (Cav3.1 and NALCN) and neuromuscular disorders (Nav1.4). We develop in vitro, in vivo and in silico models of these conditions, and seek for new therapeutic strategies. Our work helps identifying further the physiological role of these ion channels in hormone secretion, muscle excitability and motor function in the cerebellum, among others.
The excitability of neurons, endocrine cells and muscle cells greatly depends on the ion channels studied by the team. While electrophysiology, in particular the patch-clamp technique, is favored for studying these ion channels, it is the complementarity of the diverse approaches and models we use in the lab (molecular and cellular biology, biochemistry, immuno-cytochemistry, animal and cellular models, etc.) that enables us to study as effectively as possible i) the intrinsic properties of ion channels, ii) their physiological roles, iii) their involvement in diseases. The team’s work on Cav3 calcium channels, Nav1.4 sodium channels and NALCN channels can be best appreciated through the reading of several review articles recently published by the team members, listed below:
- Lory P, Nicole S, Monteil A. Neuronal Cav3 channelopathies: recent progress and perspectives. Pflugers Arch. 2020 472(7):831-844. PMID: 32638069.
- Nicole S, Lory P. New Challenges Resulting From the Loss of Function of Nav1.4 in Neuromuscular Diseases. Front Pharmacol. 2021 12:751095. PMID: 34671263.
- Guérineau NC, Monteil A, Lory P. Sodium background currents in endocrine/neuroendocrine cells: Towards unraveling channel identity and contribution in hormone secretion. Front Neuroendocrinol. 2021 63:100947. PMID: 34592201.
- Monteil A, Guérineau NC, Gil-Nagel A, Parra-Diaz P, Lory P, Senatore A. New insights into the physiology and pathophysiology of the atypical sodium leak channel NALCN. Physiol Rev. 2024 104(1):399-472. PMID: 37615954.
The genetic homology between the ion channels studied by the team and associated pathologies.
Team leader
Philippe
Lory
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Philippe
Lory
DR1, CNRS
Team: Philippe Lory
EDUCATION
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1999Habilitation to Supervise Research (HDR) - University of Montpellier - France
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1990Ph.D. in Physiology - University of Montpellier - France
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1987Master Degree in Membrane Biophysics - University of Poitiers - France
POSITIONS HELD
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2020-Team leader of "Ion channels - Neuronal excitability and channelopathies" - IGF - Montpellier - France
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2015-2020IGF Deputy Director - Montpellier - France
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2003-CNRS Research Director (DR2)
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2005-2019Team leader of "Calcium channels: Structure-Function Studies & Channelopathies" - IGF - Montpellier - France
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2006-2010In charge of the coordination of the scientific activities at IFR3 - Montpellier - France
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1996Visiting Scientist, Dept of Cardiac Mol. Biology - University of California - San Diego - USA
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1992-2003CNRS Research scientist
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1991-1992Postdoc at Dept of Pharmacology & Cell Biophysics - University of Cincinnati - Ohio - USA
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1987-1990PhD Thesis - Centre de Recherche de Biochimie Macromoléculaire (CRBM) - Montpellier - France
HONORS / RESPONSABILITIES
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2005-Member of GIS "Résocanaux" for the study of neuromuscular rare diseases
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2008-Board member for CIC (Clinical Investigation Center) of Montpellier Hospital (CHRU)
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2011-Co-founder of the Electrophysiology school of Montpellier (E2M): 1 week/year
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2011-Frontiers in Pharmacology of Ion Channels and Channelopathies, Chief Editor
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2015-Scientific Committee of the FFRE (French Foundation for Epilepsy Research)
SKILLS / EXPERTISE
- Trained in electrophysiology, I am leading the team "Ion channels - Neuronal excitability and channelopathies" at IGF - CNRS, Montpellier (~ 10 members including 4 tenured CNRS and INSERM scientists).
- We cloned and characterized the human T-type calcium channels in the early 2000s, especially Cav3.1 channels.
- My expertise covers ion channel physiology, regulation and channelopathies, especially for Cav3 calcium channels during the last decade. The calcium channelopathies we study include forms of epilepsy, cerebellar disorders, neuropathic pain and neurodevelopmental deficits.
- These recent years, my lab studies the pathogenic mechanisms underlying these neuronal channelopathies using in vitro, in vivo (animal models) and in silico strategies. We also investigate sodium channelopathies using similar approaches, especially the functional consequences of mutations in the sodium-leak channel NALCN.
Researchers
Nathalie
Guérineau
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Nathalie
Guérineau
DR1, CNRS
Team: Philippe Lory
EDUCATION
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1999Accreditation to supervise research - University of Montpellier - France
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1992PhD - Neurosciences - University of Bordeauxr - France
POSITIONS HELD
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2015-Research Director CNRS - Institute of Functional Genomics - Montpellier - France
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2010-2014Research Director CNRS - Laboratory of Integrated Mitochondrial and Neurovascular Biology - Angers - France
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2008-2009Research Director CNRS - Institute of Functional Genomics - Montpellier - France
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1995-2008CNRS Research Fellow - Institute of Functional Genomics - Montpellier - France
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1993-1995Postdoctoral Fellow - Brain Research Institute - University of Zurich - Switzerland
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1989-1992Thesis - Laboratory of Neurophysiology - Bordeaux - France
HONORS / RESPONSABILITIES
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2021-Deputy Director - Institute of Fonctional Genomics (IGF) - Montpellier - France
- Awards/Distinctions
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2011-2014Award for Scientific Excellence - CNRS
- Scientific appointments
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2020-Elected member of Scientific Council of the CBS2 Doctoral School (University of Montpellier)
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2018-2021Elected member of the Directorate of the French Society of Neuroscience and Secretary General (2020-2021)
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2018-2021Elected member of the Scientific Council of the French Society of Neuroendocrinology
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2015-2019 Assigned member of the National Council of Universities (section 69-Neurosciences)
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2012-2016Assigned member of the National Scientific Committee of the CNRS ("Physiology and Tumorigenesis" section)
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2010-2014Appointed member of the Laboratory Council - Laboratory of Integrated Mitochondrial and Neurovascular Biology - Angers
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2010-2013Elected member of the Scientific Council of the French Society of Neuroendocrinology
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2010-2013Elected member of the Directorate of the French Society of Neuroscience and Treasurer (2012-2013)
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2004-2008Assigned member of the National Scientific Committee of the CNRS ("Physiology" section)
SKILLS / EXPERTISE
- Study of the role of intercellular communication mechanisms (synaptic neurotransmission and gap junctional coupling) in the propagation of biological signals in endocrine/neuroendocrine tissues (anterior pituitary and adrenal medulla). Implication in hormone secretion.
- Investigation of the remodeling of stimulus-secretion coupling in the adrenal medullary tissue in response to stress and to stress-related disorders (arterial hypertension) Approach on acute adrenal slices and on organotypic cultures. Combined measurements of electrical signals (patch-clamp) and cytosolic calcium changes real-time confocal imaging), monitoring of secretory events (catecholamines secretion) by amperometry in acute slices.
- Study of the role of the sodium-leak channel NALCN in chromaffin cell excitability and stimulus-secretion coupling (electrophysiological approach on adrenal acute slices.
- Keywords: neuroendocrine network; stimulus-secretion coupling; adrenal medullary tissue; cholinergic synapses; gap junctions; hormone release; chromaffin cells; stress; development; electrophysiology; calcium imaging; amperometry; tissue slices.
Arnaud
Monteil
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Arnaud
Monteil
CRHC, CNRS
Team: Philippe Lory
EDUCATION
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2012-2013HDR - University of Montpellier - France
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1996-2000Thesis/PhD - Molecular Biology - University of Montpellier - France
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1995-1996DU - Immunology - University of Montpellier - France
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1994-1995Master 2 - Molecular Biology - University of Montpellier - France
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1993-1994Master 1 - Molecular Biology - University of Montpellier - France
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1991-1993Licence - Molecular Biology - University of Montpellier - France
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1989-1991DEUG B - Biology - University of Montpellier - France
POSITIONS HELD
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2005-Permanent Researcher (CRCN - CNRS) - Team "Ion Channels in Neuronal Excitability and Diseases"(Dir. P. Lory) - Institut de Génomique Fonctionnelle - Montpellier - France
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2003-2005Permanent Researcher (CR2 - CNRS) - Team "Ion Channels: Structure-fonction and channelopathies" (Dir. P. Lory) - Institut de Génomique Fonctionnelle - Montpellier - France
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2001-2002Permanent Researcher (CR2 - CNRS) Dir. J. Nargeot - Institut de Génétique Humaine - Montpellier - France
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2000-2001Research associate (Dir. Pr. R.J. Miller) - Department of Pharmacology, Neurobiology and Physiology - University of Chicago - USA
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1996-2000Graduate Student (Dir. J. Nargeot) - Institut de Génétique Humaine - Univ. Montpellier - France
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1995-1996Master Student Univ. Montpellier (Dir. Pr. J. Clot) - Hôpital St. Eloi – Department of Immunology - Montpellier - France
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1994-1995Master Student Univ. Montpellier (Dir. Pr. J. Haiech) - Laboratoire de Chimie Bactérienne - CNRS - Marseille - France
HONORS / RESPONSABILITIES
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2022-2025Coordinator of the RestoreLeak consortium (https://www.neuron-eranet.eu/projects/RestoreLeak)
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2015-President of the French Ion Channel society (https://www.canaux-ioniques.fr)
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2020-2023Libellas foundation : President of the scientific committee (https://fundacionlibellas.org)
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2021-2026Elected member of the National Committee of the CNRS (Sub-committee #24 "Aging, Tumorigenesis, Physiology")
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2016-2021Idem
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2008-Head of the Vectorology facility of Montpellier - France (UAR BioCampus, https://www.biocampus.cnrs.fr )
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2020-Associate Editor - AllLife
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2020-Review Editor - Frontiers in Molecular Neuroscience
SKILLS / EXPERTISE
- Ion channels / Physiology / Neurosciences / Human Diseases
- Gene Transfer / Viral Vectors / Genome Editing
Sophie
Nicole
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Sophie
Nicole
CRHC, Inserm
Team: Philippe Lory
EDUCATION
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2009Habilitation à diriger des recherches (HDR) in Neurogenetics, UFR medicine - Université Pierre et Marie Curie (UPMC) - Paris - France
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1999PhD in Human Genetics - UPMC - Paris - France
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1995Master II (DEA) in Human Genetics - UPMC - Paris - France
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1994UE in Genetics - UPMC - Paris - France
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1993Master I in Cell Biology (Université Reims Champagne-Ardennes, Reims - France
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1992Licence in Biochemistry (Université Reims Champagne-Ardennes, Reims - France
POSITIONS HELD
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2019-Principal investigator in the "Ion Channels, Neuronal Excitability and Channelopathies" team, Institute of Functional Genomics (IGF) - Montpellier - France
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2015-2019Coordinator of the Inserm collective expertise on Fibromyalgia, Pôle Expertise Collective Inserm, thematic institute "Public Health" - Paris - France
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2014-2018Co-leader of the "Neurogenetics and Physiology" team, Brain and Spine Institute (ICM), Inserm, CNRS, Sorbonne Université - Paris - France
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2009-2013Principal investigator, research center of ICM (CRICM) - Paris - France
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2002-2008Principal investigator, research unit "Myelin and Muscle Ion Channel Disorders", Inserm, UPMC - Paris - France
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2000-2002Postdoctoral researcher, research unit "Molecular Neurogenetics", Inserm, Université d’Evry - Evry - France.
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1999-2000Postdoctoral researcher, research unit "Myelin Diseases", Inserm, CNRS, UPMC - Paris - France
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1995-1999PhD student - research unit "Cellular, Molecular and Clinical Neurobiology", Inserm, CNRS, UPMC - Paris - France
HONORS / RESPONSABILITIES
- Awards/Distinctions
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2009Senior Price, Association for the Research on Paediatric Diseases, France
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2009Contrat d’interface hospitalier individuel fellowship (2 years), AP-HP, Pitié-Salpêtrière hospital, Paris
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2006Contrat d’interface hospitalier individuel fellowship (3 years), AP-HP, Pitié-Salpêtrière hospital, Paris
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1999Postdoctoral fellowship of the French Association for myopathies
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1998Research fellowship of the French Academy of Medicine
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1995Research fellowship of the French Ministry of Research ( 3 years)
- Interventions at general assemblies of patients associations (AFM-Téléthon, Association Française contre l’Hémiplégie Alternante (AFHA)).
- Master lessons on "Scientific Integrity" and "Skeletal Muscle Excitability and Channelopathies" for Masters II (Université Claude Bernard Lyon I, Université de Montpellier)
- Organization of international meetings ( "Journée Recherche Maladies Rares Montpellier", 2019, Montpellier, France; "Channelopathies Meeting", 2016, Paris, France; 21st "Ion Channel Meeting", 2010, Presqu’île de Giens, France; 20th "Ion Channel Meeting", 2009, Presqu’île de Giens, France; ENMC international meeting on Schwartz-Jampel syndrome, 2001, Naarden, The Netherlands.
SKILLS / EXPERTISE
- I am a human neurogeneticist whose master words for doing research are interdisciplinarity and translational work. I have acquired strong expertise in congenital neuromuscular diseases due to abnormal myofiber excitability.
- Starting from the medical genetics of these rare diseases, my main research interests lie now on their physiology by modelling them to eventually develop innovative therapeutic approaches toward precision medicine.
- My experimental know-how and techniques used are multiple, including molecular biology, cell and tissue biology, physiology and behavior.
Nattaya
Thongsepee
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Nattaya
Thongsepee
Accueil scientifique, CNRS
Team: Philippe Lory
EDUCATION
POSITIONS HELD
HONORS / RESPONSABILITIES
SKILLS / EXPERTISE
Technicians and engineers
Claire
Bernat
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Claire
Bernat
IECN, CNRS
Team: Philippe Lory
EDUCATION
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2004DU - Research and Development in Biotechnology - Pierre and Marie Curie University Paris VI - France
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2003Master - Cellular Biology and Physiology - Pierre and Marie Curie University Paris VI - France
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2002Licence - Cellular Biology and Physiology - Pierre and Marie Curie University Paris VI - France
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2000Higher technician certificate (BTS) - Biology Analysis - Lycée ESTBA - Paris - France
POSITIONS HELD
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2018-CNRS Engineer - Institute of Functional Genomics - Montpellier - France
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2017-2018CNRS Engineer INSERM (CDD) - MIVEGEC - Montpellier - France
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2016-2017CNRS Assistant Engineer (CDD) - Biocampus - Montpellier - France
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2010-2016AMU Engineer - CEFOS Aix-Marseille University - Marseille - France
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2008-2009CNRS Engineer (CDD) - Centre d’Immunologie Marseille Luminy (CIML) - Marseille - France
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2005-2007CNRS Engineer (CDD) - Institut Gustave Roussy - Villejuif - France
HONORS / RESPONSABILITIES
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2022-Responsible for implementing airflow controls - Institute of Functional Genomics - Montpellier
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2021-Member of the IGF shop Committee - Institute of Functional Genomics - Montpellier
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2020-Responsible for L2 - Institute of Functional Genomics - Montpellier
SKILLS / EXPERTISE
- Laboratory techniques
- Cell line cultures, primary cultures
- Molecular biology: DNA and RNA extraction, PCR, qPCR, design PCR HRM and competition, cloning and plasmid transformation
- Biochimistry: Protein extraction, Western Blot, protein assay
- Bacteriology: bacterial culture and transformation
- Immunohistology: Cryostat section and immunostaining
- Work in BSL2 sector
- Flow cytometry
- Level I and surgery
- Data analysis
- GraphPad Prism
- Mastery of Pack office
- Image J
Postdoctoral researchers and doctoral students
Kachaporn
Jintana
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Kachaporn
Jintana
Doctorant(e), UM
Team: Philippe Lory
EDUCATION
POSITIONS HELD
HONORS / RESPONSABILITIES
SKILLS / EXPERTISE
Alexandra
Typou
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Alexandra
Typou
Doctorant(e), UM
Team: Philippe Lory
EDUCATION
POSITIONS HELD
HONORS / RESPONSABILITIES
SKILLS / EXPERTISE
Fixed term contract technicians and engineers
Théo
Petrizzelli
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Théo
Petrizzelli
IE CDD, Inserm
Team: Philippe Lory
EDUCATION
POSITIONS HELD
HONORS / RESPONSABILITIES
SKILLS / EXPERTISE
Tanya
Phamban
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Tanya
Phamban
AI CDD, CNRS
Team: Philippe Lory
EDUCATION
POSITIONS HELD
HONORS / RESPONSABILITIES
SKILLS / EXPERTISE
Trainees
Marion
Lefevre
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Marion
Lefevre
Master 2, CNRS
Team: Philippe Lory
EDUCATION
POSITIONS HELD
HONORS / RESPONSABILITIES
SKILLS / EXPERTISE
Sixte
Sagnol
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Sixte
Sagnol
Master 1, Inserm
Team: Philippe Lory
EDUCATION
POSITIONS HELD
HONORS / RESPONSABILITIES
SKILLS / EXPERTISE
- Monteil A, Guérineau NC, Gil-Nagel A, Parra-Diaz P, Lory P, Senatore A. New insights into the physiology and pathophysiology of the atypical sodium leak channel NALCN. Physiol Rev. 2024 Jan 1;104(1):399-472. doi: 10.1152/physrev.00014.2022. Epub 2023 Aug 24. PMID: 37615954.
- Nicole S, Lory P. New Challenges Resulting From the Loss of Function of Nav1.4 in Neuromuscular Diseases. Front Pharmacol. 2021 Oct 4;12:751095. doi: 10.3389/fphar.2021.751095. PMID: 34671263; PMCID: PMC8521073.
- Impheng H, Lemmers C, Bouasse M, Legros C, Pakaprot N, Guérineau NC, Lory P, Monteil A. The sodium leak channel NALCN regulates cell excitability of pituitary endocrine cells. FASEB J. 2021 May;35(5):e21400. doi: 10.1096/fj.202000841RR. PMID: 33793981.
- Guérineau NC, Monteil A, Lory P. Sodium background currents in endocrine/neuroendocrine cells: Towards unraveling channel identity and contribution in hormone secretion. Front Neuroendocrinol. 2021 Oct;63:100947. doi: 10.1016/j.yfrne.2021.100947. Epub 2021 Sep 27. PMID: 34592201.
- Milman A, Ventéo S, Bossu JL, Fontanaud P, Monteil A, Lory P, Guérineau NC. A sodium background conductance controls the spiking pattern of mouse adrenal chromaffin cells in situ. J Physiol. 2021 Mar;599(6):1855-1883. doi: 10.1113/JP281044. Epub 2021 Jan 29. PMID: 33450050; PMCID: PMC7986707.
- Lory P, Nicole S, Monteil A. Neuronal Cav3 channelopathies: recent progress and perspectives. Pflugers Arch. 2020 Jul;472(7):831-844. doi: 10.1007/s00424-020-02429-7. Epub 2020 Jul 7. PMID: 32638069; PMCID: PMC7351805.
- Bouasse M, Impheng H, Servant Z, Lory P, Monteil A. Functional expression of CLIFAHDD and IHPRF pathogenic variants of the NALCN channel in neuronal cells reveals both gain- and loss-of-function properties. Sci Rep. 2019 Aug 13;9(1):11791. doi: 10.1038/s41598-019-48071-x. PMID: 31409833; PMCID: PMC6692409.
- Chemin J, Siquier-Pernet K, Nicouleau M, Barcia G, Ahmad A, Medina-Cano D, Hanein S, Altin N, Hubert L, Bole-Feysot C, Fourage C, Nitschké P, Thevenon J, Rio M, Blanc P, Vidal C, Bahi-Buisson N, Desguerre I, Munnich A, Lyonnet S, Boddaert N, Fassi E, Shinawi M, Zimmerman H, Amiel J, Faivre L, Colleaux L, Lory P, Cantagrel V. De novo mutation screening in childhood-onset cerebellar atrophy identifies gain-of-function mutations in the CACNA1G calcium channel gene. 2018 Jul 1;141(7):1998-2013. doi: 10.1093/brain/awy145. PMID: 29878067.
- Coutelier M, Blesneac I, Monteil A, Monin ML, Ando K, Mundwiller E, Brusco A, Le Ber I, Anheim M, Castrioto A, Duyckaerts C, Brice A, Durr A, Lory P, Stevanin G. A Recurrent Mutation in CACNA1G Alters Cav3.1 T-Type Calcium-Channel Conduction and Causes Autosomal-Dominant Cerebellar Ataxia. Am J Hum Genet. 2015 Nov 5;97(5):726-37. doi: 10.1016/j.ajhg.2015.09.007. Epub 2015 Oct 8. PMID: 26456284; PMCID: PMC4667105.
- Cochet-Bissuel M, Lory P, Monteil A. The sodium leak channel, NALCN, in health and disease. Front Cell Neurosci. 2014 May 20;8:132. doi: 10.3389/fncel.2014.00132. PMID: 24904279; PMCID: PMC4033012.
Deciphering the role of calcium channels in neurodevelopemental diseases
Principal investigator
Philippe LORY
Stimulus-secretion coupling in the adrenal medullary tissue: pathophysiology of the adaptive response to stress and associated disorders
Principal investigator
Nathalie GUERINEAU
Therapeutics of muscle weakness related to the sodium channel Nav1.4
Principal investigator
Sophie NICOLE
TECHNOLOGIES
The schematic « ion channel toolkit » used in the team to encover the role of ion channels in physiology and diseases.
FUNDING
• FMR (Fondation Maladies Rares) “High throughput screening” grant (2024-2026)
• ANR PRC ‘CaCh-Investigation’ project (2023-2027)
• LabEx ICST ‘Ion Channels Science & Therapeutics’, partner and scientific council (2012-2024)
• AFM Telethon “ActNavLOF” project (2023-2024)
• Fondation CSC (Connaitre les Syndromes Cérébelleux), grant (2023-2024)
• ERA-NET NEURON ‘Neurodevelopmental Disorders’, projet RestoreLeak (2022-2025)
• FMR (Fondation Maladies Rares) “High throughput screening” grant (2022-2023)
• FRC (Fédération pour la Recherche sur le Cerveau), EET (2022)
• ANR PRCE ‘NeuroCard’ project (2022-2025)
• Hubert Curien Siam exchange program (2020-2021)
• Equipe FRM (Fondation Recherche Médicale) grant (2017-2020)
• FMR (Fondation Maladies Rares) “animal models” grant (2019-2020)
• AFM Telethon (2018-2020)
• PHENOMIN appel d’offre 2020 ‘modèle animal’ (2020)
• PRC CNRS – University of Toronto exchange program (2018)
Team members
From left to right (permanent staff in bold): Sophie Nicole, Claire Bernat, Zoe Servant, Nathalie Guérineau, Hathaichanok Impheng, Arnaud Monteil, Auemphon Mordmuang, Philippe Lory, Clément Marchal, Amaël Davakan.
ALUMNI
Past contributors to the team’s work:
Postdoctoral fellows
Lidiane Pereira Garcia (2022-2023)
Maud Cochet (2012-2015)
Iulia Blesneac (2011-2015)
PhD students
Hathaichanok Impheng (2016-2020)
Alexandre Milman (2015-2018)
Malik Bouasse (2014-2017)
Tiphaine Voisin (2012-2016)
Technician – Engineers
Zoé Servant (2018-2020)
Andie Godo (2016-2017)
Master students
Sujira Chedsadavitayakul (2023)
Marion Chevallier (2023)
Romain Baudat (2022)
Youssef Issa (2022)
Julien Grelaud (2021)
Adrien Lesage (2019)
