Team C. Galés/JM. Sénard

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Molecular and clinical determinants of cardiac architecture (ARCHI-CARD)

The physiologic response of an organ relies on a complex interplay between the different cell types structuring the tissue. At the cellular level, the response arises from the plasma membrane through different receptors, channels, pumps… that integrate and proceed the extracellular stimuli (chemical, mechanical). Alteration of the plasma membrane response is a hallmark of number of patho-physiological situations. Now, how the plasma membrane and the overall cell architecture behave in such pathologies, what is the impact on the surface organization and functions of the proteins inserted in the plasma membrane and more largely what is the impact on the neighboring cells still remain poorly understood.
In this context, the research program of our team focuses on understanding the clinical/molecular determinants of the cardiac architecture/function.
Our team is highly interdisciplinary integrating people from basic and medical research in pharmacology, cellular biology, cardiology and neurology. As a consequence, our approach also relies on a high interdisciplinarity starting from the identification of the molecular/cellular mechanisms to the integration in animal models but also in humans thanks to our collaboration with the Toulouse CHU hospital.

Team members

Co-team leader / PUPH
Jean-Michel SÉNARD

Associate professor and researcher
Thomas FARGE

PUPH, Faculty investigator
Frédérique SAVAGNER

Faculty investigator
Jean-Philippe MAURY

Associate professor and researcher
Varravaddheay ONG-MEANG

Team leader

Céline GALÉS

Research director INSERM

Career path.
She received her PhD in Pharmacology (GPCRs) at Paul Sabatier University (Toulouse, France) in 2001, and completed her postdoctoral training (GPCRs) in the lab of Michel Bouvier at Montreal University (Canada). She got a permanent position at INSERM in 2005 as research PI, co-chairs the team Archi-Card since 2011 that she runs now since 2021.

Main domain of expertise
Pharmacology, G protein-coupled-receptors (GPCRs), Signaling, Biased agonism, Intracellular trafficking, cardiology, cardiomyocyte surface architecture, heart failure.

Email:celine.gales@inserm.fr

Tél/phone:+33(0)5 31 22 40 75

Co-team leader / PUPH

Jean-Michel SÉNARD

MD, PhD

Career path
JM Senard is Prof of Clinical Pharmacology at the school of Medicine of Toulouse University and a MD specialist in neurocardiology. He chaired the European Federation of Autonomic Societies and is the current chair of the SOOM1 IRB. He currently cochair with C Galés the team he founded in 2011.

Main domain of expertise
Pharmacology, autonomic nervous system.

Email:jean-michel.senard@inserm.fr

Tél/phone:+33(0)531224075

MCU-PH

Céline GUILBEAU-FRUGIER

Medical Doctor, Physician-scientists doctor

Career path
Céline is a pathologist, a forensic medical doctor and the director of an electron microscopic platform. She obtained her PhD degree in pharmacology in 2012 at the university of Toulouse. She joined our team in 2013 wherein she developed the use of electron microscopy to explore the cardiac tissue.

Main domain of expertise
Myocardial morphology, electron microscopy, histology

Email:celine.guilbeau-frugier@inserm.fr

Tél/phone:+33(0)561323622

Faculty investigator

Clément KARSENTY

Faculty investigator

Career path
Clement is a pediatric cardiologist. He received his Master degree in Biology option heart and circulation from the Paris Diderot University in 2015. He joined our team in 2015 as a master student, now finishing his thesis in the field of heart diseases.

Main domain of expertise: Pediatric cardiology, Cardiac postnatal development, Congenital heart defect, Heart failure, Animal experimentation.

Email:karsenty.cl@chu-toulouse.fr

Tél/phone:+33(0)531224075

Researcher, Inserm

Véronique PONS

INSERM researcher

Career path.
She received her PhD in Physiopathology at Toulouse University (2003) followed by a postdoctoral training in intracellular trafficking at Geneva University. In 2014, she got a permanent position at INSERM and joined the team to develop projects on GPCR pharmacology/biased agonism.

Main domain of expertise
Pharmacology, G protein-coupled-receptor, Signaling, Biased agonism, Intracellular trafficking

Email:veronique.pons@inserm.fr

Tél/phone:+33(0)531224072

Associate professor and researcher

Thomas FARGE

Associate professor and researcher

Career path
With a background in hemato-oncology, Thomas now focuses his research on cardio-oncology. As an Associate Professor in Physiology at the Faculty of Pharmacy and a researcher at I2MC, he investigates metabolic dysregulations at the interface between the heart and cancer.

Main domain of expertise
Cardio-oncology, Metabolism, Mitochondria, Preclinical Models

Email:thomas.farge@inserm.fr

Tél:0561325616

Associate profesor

Yannis SAINTE-MARIE

Associate Professor in physiology at the Faculty of Pharmaceuticals sciences, Toulouse

In vivo studies, in preclinical models, of cardiac remodeling associated with various cardiac pathologies, of its molecular actors and of the means of intervention on the identified therapeutic targets.

Career path
Yannis Sainte-Marie has a PhD in Biology from the Paris VII University, France, in 2006 for his work on new roles for the mineralocorticoid receptor in physiopathology. After a post-doctoral project on molecular actor of heart failure, he was recruited as assistant professor in Physiology at the Faculty of Pharmaceuticals sciences and joined the team in 2010.

Main domains of expertise
Cardiac physiopathology, animal model design and phenotypic characterization.

Email:yannis.sainte-marie@inserm.fr

PUPH, Faculty investigator

Frédérique SAVAGNER

PUPH, Faculty investigator

Career path
Doctor of Pharmacy and Science, specializing in Cell and Molecular Biology (Angers), with a specialized diploma (DES) in Medical Biology. Hospital Practitioner (PH) in Biochemistry (1996–2002), Associate Professor–Hospital Practitioner (MCU-PH) from 2003 to 2013 in Angers, then Full Professor–Hospital Practitioner (PU-PH) in Toulouse since 2014.
Research field: energy metabolism in endocrine tumor pathologies, transcriptional and epigenetic regulation of metabolism. Link between differentiation/dedifferentiation and metabolism.

Main domain of expertise
Energy metabolism, epigenetics, cardiac microenvironment, stromal cells, exosomes, cell therapy

Email:frederique.savagner@inserm.fr

Enseignant-Chercheur

Daniel CUSSAC

Email:daniel.cussac@inserm.fr

Tél/Phone:05 31 22 41 21

Engineer Assistant

Nicolas PATALUCH

Engineer Assistant

Nicolas obtained his master degree in Biotechnologies options Neurology & Applied Physiology from the Faculty of Sciences of Nancy (France) in 2019. He Joined the team in September 2020 as an t Engineer Assistant in the field of cardiac imaging.

Main field of expertise
Animal experimentation, Biotechnologies, Tissue Clearing, Photonic microscopies, Physiology/animal experimentation.

Email:nicolas.pataluch@inserm.fr

Tél/phone:+33(0)632026712

Research Engineer

Amandine WAHART

Research Engineer

Her current research focuses on the study of the mechanisms responsible for the phenotype of smooth muscle cells during neoatherosclerosis in the context of restenosis during hyperglycemia.

Career path
Master in Biology (2014, Reims), Engineer in pre-clinical imaging (2014-2013, Reims), Thesis in biochemistry and cell biology (2015-2019, Reims), Post-doctoral fellow (2019-2022, Toulouse) in the team of Muriel Laffargue.

Main domains of expertise
Cell biology, Animal experimentation, Microsurgery, Pre-clinical imaging, histology.

Email:amandine.wahart@inserm.fr

Technician

Sabrina BENAOUADI

PhD Student

Emma DUPONT

After obtaining a bachelor’s degree in Biochemistry and Biology at the Jean Perrin Faculty in Lens, Emma went on to complete a Master’s 1 in Biology and Health at the University of Lille. She then completed her second year of a Master’s degree in Integrative Biology and Physiology, specializing in Cardiovascular, Metabolic, and Nutritional Regulation, at Claude Bernard Lyon 1 University. She is currently working on her thesis in the team led by Céline Galés and Céline Guilbeau-Frugier, funded by the 2025 Jeanne-Philippe Béziat Cardiology Prize from the Foundation for Medical Research. Her research project focuses on the impact of obesity on cardiac maturation and diastolic function in juvenile/adolescent mice.

Email:emma.dupont@inserm.fr

Technical staff

Emma BERNARD

Emma obtained her BTS Anabiotec degree in 2024 at Beauregard High School in Villefranche de Rouergue in the Aveyron region. She joined the team in October 2024 as a laboratory technician on a three-year contract.

Email:emma.bernard@inserm.fr

Faculty investigator

Fabien DESPAS

Faculty Investigator

Career path
Fabien is a Pharmacist, MCU-PH of Pharmacology at the Faculty of Health of the University of Toulouse, specializing in the exploration of the autonomic nervous system. He joined the team in 2021 to develop the pharmacoepidemiology of the cardiovascular effects of anticancer drugs, in particular protein kinase inhibitors.

Main domain of expertise
Adverse drug reactions, anticancer drugs, cardiovascular pharmacology, protein kinase inhibitors

Email:fabien.despas@univ-tlse3.fr

Tél/phone:+33(0)56114595940

Faculty investigator

Jean-Philippe MAURY

Faculty Investigator

Career path
Jean-Philippe is Prof of Cardiology at the school of Medicine of Toulouse University and a MD specialist in interventional rhythmology. He is member of the electrophysiology working group of the french society of Cardiology. He joined our team in 2016 and develop in vivo rhythmology in mice.

Main domain of expertise
Electrophysiology, cardiac Arrhythmias

Email:maury.p@chu-toulouse.fr

Tél/phone:+33(0)561325054

Maxime BENEYTO

Yoann ZELMAT

Associate professor and researcher

Varravaddheay ONG-MEANG

Researcher

Career path
Doctor of Neurophysiology (Paris VI); researcher (private sector) on Alzheimer’s disease then on the production of anti-sperm antibodies involved in human sterility; assistant-professor since 1999 at the University of Toulouse in STAPS in the field of adapted physical activity.

Main domain of expertise
Cardiac microenvironment, stromal cells, exosomes, polyunsaturated lipids, inflammation resolution.

Email:varravaddheay.ong-meang@inserm.fr

Architecture of the lateral membrane of cardiomyocytes

Coordinators : Céline Galés & Jean-Michel Sénard

Defects in cardiomyocyte (CM) signaling are a hallmark of heart failure (HF) from all origins. However, most of the studies have focused on the end-stage pathology. Whether these modifications are causes or consequences still remain to be answered and are essential for the development of new efficient therapeutics. However, the intracellular signaling outcome of a cell is tightly dependent on its origin, i.e. the cell surface. How the architecture of the CM surface is temporally modified upon cardiac stresses and how this can impact the 3D heart structure, the CM response and the overall heart function remain fundamental questions in cardiology.

Thanks to high resolution microscopies (AFM, MET) we optimized during these last years, we previously reported and accurately characterized in the cardiac tissue the architectural organization of the lateral membrane of adult CMs with periodic crests related to the presence of subsarcolemmal mitochondria (SSM) whose role is unknown and that are rapidly lost after myocardial infarction before T-Tubule disorganization, a common HF hallmark. Our goal is now to better understand the crest loss: i/ is it specific or generic to all HF origins? ii/ what is the trigger? iii/ what are the crest determinants/ modulators?, iv/ how to prevent the crest loss?

G protein coupled receptor (GPCR) organization at the cell surface and its role in ligand efficacy

Coordinators : Véronique Pons & Céline Galés

GPCRs represent the major pharmaceutical drug target. However, many drugs are associated with harmful side-effects and a poor clinical benefit-risk ratio that limit their use.
Recently, the concept of biased-agonism (ligand selecting some receptor-signaling pathways) paved the way for the development of pathway-specific drugs with higher efficacy and lower adverse events. Now, understanding the link between GPCR at the cell surface and the signaling/physiological outcome remains a major challenge for a more rational design of biased ligands.
By multiplexing high-resolution tools (FRET/BRET probes) to dissect and image the spatiotemporal GPCR signaling in living cells and 3D tissues, our goal is to identify the molecular basis underlying biased agonism/ligand efficacy at multiple cardiovascular GPCR drug targets (AT₁-R, b₂-AR, P₂Y-R) by taking into account the existence of multiple receptor populations and different membrane architectures at the cell surface.

Selected publications

Cardiac sensory afferents modulate susceptibility to anxio-depressive behaviour in a mouse model of chronic heart failure. KERMORGANT M, BEN SALEM J, IACOVONI J, CALISE D, DAHAN L, GUIARD BP, LOPEZ S, LAIREZ O, LASBORIES A, NASR N, PAVY-LE TRAON A, BEAUDRY F, SENARD JM, ARVANITIS DN. Acta Physiol (Oxf). 2021 Apr;231(4):e13601. doi: 10.1111/apha.13601. PMID: 33316126

Deciphering biased inverse agonism of cangrelor and ticagrelor at P2Y₁₂ receptor. GARCIA C, MAUREL-RIBES A, NAUZE M, N’GUYEN D, MARTINEZ LO, PAYRASTRE B, SENARD JM, GALES C, PONS V. Cell Mol Life Sci. 2019 Feb;76(3):561-576. doi: 10.1007/s00018-018-2960-3. PMID: 30406277

Structural evidence for a new elaborate 3D-organization of the cardiomyocyte lateral membrane in adult mammalian cardiac tissues.GUILBEAU-FRUGIER C, CAUQUIL M, KARSENTY C, LAIREZ O , DAMBRIN C, PAYRE B, CASSARD H, JOSSE C, SEGUELAS MH, ALLART S,BRANCHEREAU M, HEYMES C, MANDEL F, DELISLE MB, PATHAK A, DAGUE E, SENARD JM, GALES C. Cardiovasc Res. 2018 Oct 17. doi: 10.1093/cvr/cvy256. PMID: 30329023

Cardioprotective Angiotensin-(1-7) Peptide Acts as a Natural-Biased Ligand at the Angiotensin II Type 1 Receptor GALANDRIN S, DENIS C, BOULARAN C, MARIE J, M’KADMI C, PILETTE C, DUBROCA C, NICAISE Y, SEGUELAS MH, N’GUYEN D, BANÈRES JL, PATHAK A, SÉNARD JM, GALÉS C. Hypertension. 2016 Dec;68(6):1365-1374. doi: 10.1161/HYPERTENSIONAHA.116.08118. PMID: 27698068

Dual agonist occupancy of AT1-R-α2C-AR heterodimers results in atypical Gs-PKA signaling. BELLOT M, GALANDRIN S, BOULARAN C, MATTHIES HJ, DESPAS F, DENIS C, JAVITCH J, MAZÈRES S, SANNI SJ, PONS V, SEGUELAS MH, HANSEN JL, PATHAK A, GALLI A, SÉNARD JM, GALÉS C. Nat Chem Biol. 2015 Apr;11(4):271-9. doi: 10.1038/nchembio.1766. PMID: 25706338

Plus de publications

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CNES

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fondation bettencourt schueller

fondation d efrance

hopitaux de toulouse

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