Team M. LAFFARGUE

Cell Responses in Arterial Stress : Impact on cardiovascular diseases (CREATED)

Our team groups together experts in cell signalling dedicated to the understanding of molecular mechanisms involved in vascular homeostasis (PI3K/mTOR pathways) and modulated by various stresses in pathologic conditions or related to aging (mechanical, oxydative or metabolic stresses, inflammation). In collaboration with clinicians from the hospital Toulouse Rangueil, we develop original pre-clinical models of arterial lesions with the aim to improve actual treatments of atherosclerosis and the prevention of transplant vasculpathies causing organ rejection.

Team members

 
Tous / AllTeam leaderResearchersCliniciansPost Doctoral fellowsStudentsTechnical staff
Team leader

Muriel LAFFARGUE

Principal scientist

Nathalie AUGE

Principal scientist

Stéphanie GAYRAL

Emeritus scientist

Anne NEGRE-SALVAYRE

Principal scientist

Damien RAMEL

Principal scientist

Natalia Smirnova

Clinician

Caroline CAMARE

Didier CARRIE
Clinician

Didier CARRIE

Clinician

Robert SALVAYRE

Post-doctoral fellow

Amandine WAHART

PhD Student

Lucile GRZESIAK

PhD student

Marie-Kerguelen SARTHOU

Technician

Nicole MALET

Engineer

Audrey SWIADER

Team leader

Muriel LAFFARGUE

Principal scientist

Nathalie AUGE

INSERM researcher

Her current researches focus on understanding the pathophysiological mechanisms that make diabetes a risk factor for atherosclerosis. Currently, she studies the cellular and molecular mechanisms observed on smooth muscle cells in a hyperglycemic and hyperlipemic context.

Career path
Master’s degree in Biology of Aging (Toulouse III / Paris V; 1993) and Ph.D. in Medical Biochemistry, Paul Sabatier University (1993-1996), Post-doctorate in Atlanta, Emory university (1997-1998), Joined M. Laffargue team in 2021. INSERM recruitment in 1999, team of Prof. R. Salvayre. HDR (2005)

Main domains of expertise
Signaling, vascular pathophysiology, sphingolipids, lipoproteins.

Principal scientist

Stéphanie GAYRAL

INSERM researcher

Her research focuses on the integration of mechanical signals induced by blood flow by the endothelium in normal and physiopathological conditions.

Career path
Master’s degree and PhD in Biology and Pharmacology of Hemostasis and Vessels at Paris VII (2003-2007). Postdoc position at Brussels (Belgium, 2007-2010). Joined Laffargue’s team in 2010. Obtained a permanent position at INSERM in 2014.

Main domains of expertise
Cell signaling, Endothelium, Vascular physiology, Mechano-biology.

Emeritus scientist

Anne NEGRE-SALVAYRE

Emeritus research Director (CNRS)

Pharmacist-biologist, Doctorate in pharmaceutical science, Doctorate in human biology (Paul Sabatier University, Toulouse). Post-doctorate at Hadassah Medical School, Jerusalem, Israel. Research director at CNRS, team leader INSERM from 2006 to 2020. Researcher emeritus in Laffargue’s team since 2021.

Main domains of expertise
Lipids, lipoproteins, lipid peroxidation, post-translational modifications. Role of oxidative stress in cardiovascular physiopathology (apoptosis, angiogenesis, inflammation). Endothelial permeability (endocytosis, transcytosis) during atherosclerosis and transplant arteriosclerosis.

Principal scientist

Damien RAMEL

CNRS researcher

Cellular and molecular biologist. His research focuses on the study of molecular determinants of vascular smooth muscle cells biology in normal and physiopathological conditions.

Career path
Master’s degree and PhD in cancerology at Paul Sabatier university, Toulouse (2004-2009), Post-doc experience at University of Montréal (Canada, 2010-2013). Permanent position at CNRS (CBI, Toulouse) in 2013. Joined Laffargue’s team in 2017.

Main domains of expertise
Cell signaling, Endocytosis, cell migration, cytoskeleton, small GTPases, phosphoinositides, cellular imaging (FRET, Optogenetics, spectral imaging).

Principal scientist

Natalia Smirnova

INSERM researcher

Interested in understanding the mechanisms underlying transplant vasculopathy after solid organ transplantation, in particular those related to antibody-mediated rejection.

Career path
Master degree (Pathophysiology and Biology) in Toulouse and Cachan (2009), Ph.D. and post-doc in Toulouse, France (2009-2014), post-doc in Munich, Germany (2014-2018), Assistant Professor at the University of Colorado, USA (2018-2020). Joined the group of M. Laffargue in 2020.

Main domains of expertise
In vivo microsurgery (mouse graft rejection models), histology, flow cytometry, scRNA-seq.

Clinician

Caroline CAMARE

MD-PhD

Career path
MD, general medicine specialty, Toulouse-Rangueil University 2008. Master’s Degree, Cellular mechanisms of aging and associated pathologies, René Descartes Paris 5 university, 2009. PhD, Biology, Heath, Biotechnology, Paul Sabatier university Toulouse 3, 2014. Assistant lecturer 2009-2013, Assistant lecturer and medical practitioner 2013-2017. Hold a permanent MD-lecturer and medical practitioner position since 2017 in Anne Negre-Salvayre’s Team of I2MC. Joined Laffargue’s team in 2021.

Main domains of expertise
Endothelium, Sphingolipids signaling, oxydative stress, angiogenesis and atherosclerosis. General medical biochemistry, Biochemistry of nutrition and digestive pathologies exploration, energetic metabolism.

Clinician

Didier CARRIE

MD-PhD

Career path

MD, Cardiologist, expert in interventional cardiology. Head of the cardiology unit B of Toulouse Rangueil Hospital since 2008. Dean of the faculty of medicine of Toulouse Purpan since 2016.

Clinician

Robert SALVAYRE

Emeritus MD-PhD

Career path
MD and pediatric speciality (1965-1971, Univ Toulouse-3 et Aix-Marseille), Master’s in biochemistry (1971, Toulouse-3), Medical biology speciality (1974-80, Aix-Marseille, Montpellier, Toulouse-3). Medical doctorate (1976, Toulouse-3), PhD (1982, Toulouse-3). Post-docs and short rotations (1983-1992, Hadassah, Jerusalem; Mount Sinaï, New-York; Ste Justine, Montréal). Profesor and medical pratitioner form 1988. Unit director of U-466 (1996-2006). Head of biochemistry unit of Rangueil CHU (2000-2016) and of the Biology unit of Toulouse CHU (2004-2012), vice dean of the medicine university of Rangueil (2000-2016). Profesor emeritus since 2017.

Main domains of expertise
Biochemistry, molecular and cell biology of lipids, lipoproteins, lipid metabolism dysfunctions, oxydative stress, lipid peroxydation. Cell signalliing. Cellular (proliferation, apoptosis, inflammation) and physiological impact of lipid metabolism dysfunctions (atherosclerosis, hereditary lipdosis)

Post-doctoral fellow

Amandine WAHART

Post-doctoral fellow

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, Toulouse) in the team of Muriel Laffargue.

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

PhD Student

Lucile GRZESIAK

PhD Student (MNRT Grant)

During her PhD, she is working on identifying new molecules involved in the development of vascular calcification.

Career path
Bachelor in Biosciences completed at Robert Gordon University in Scotland in 2016. Master of integrative biology and physiology obtained at Sorbonne University in 2018 (speciality in human pathophysiology)

Main domain of expertise
Cellular biology, vascular calcification and histology

PhD student

Marie-Kerguelen SARTHOU

PhD Student (FRM Grant)

Marie-Kerguelen Sarthou’s thesis project focuses on the molecular mechanisms involved in the phenotypes of vascular smooth muscle cells, under normal and pathological conditions.

Career path
Master in Genes, Cells and Development at the University of Toulouse (2017-2018). PhD student since October 2018.

Main domains of expertise
Cellular and molecular biology, signaling, cell imaging and histology.

Technician

Nicole MALET

Technician University

Expert in molecular biology, cell biology and signaling. She is involved in research projects on vascular cells and participate to the development of new techniques.

Career path
Bachelor’s degree in Cell biology and physiology (Paul Sabatier University, Toulouse, 2015). Hired at university in 1994. Joined Laffargue’s team in 2010.

Main domains of expertise
Signaling, molecular and cellular biology.

Engineer

Audrey SWIADER

Engineer INSERM

Expert in Cell biology and imaging technics. She develops tools allowing the study of signaling pathways on cultured vascular cells and tissues.

Career path
Master’s degree in cell biology and physiology (2003-2004). Hired at Paul Sabatier University in 2005 and at INSERM in 2012.

Main domains of expertise
Signalisation, Biologie cellulaire et moléculaire, Imagerie, Cytométrie en flux

Control of endothelial homeostasis in response to mechanical stress : Impact on arterial diseases

 

Coordinators : Stéphanie GAYRAL, Caroline CAMARE, Anne NEGRE-SALVAYRE, Muriel LAFFARGUE

Environnemental hemodynamic milieu controls endothelial cell activation and their maintenance of their barrier function. Study of the perturbations of mechanosensors able to integrate these bio-mechanics stimuli and their associated signalling pathways associated with pathological conditions, will allow us to propose new therapeutic avenues to prevent endothelial dysfunction.

Cell signaling in vascular smooth muscle cells in normal and pathological conditions

 

 

Coordinators : Nathalie AUGE, Damien RAMEL, Natalia SMIRNOVA, Anne NEGRE-SALVAYRE, Muriel LAFFARGUE

Smooth muscle cells are at the center stage of the arterial responses in normal and pathological conditions. We investigate their signaling pathways to decipher the molecular mechanisms leading to their deregulation found in cardiovascular diseases such as atherosclerosis or explant rejection but also in disturbed metabolic conditions such as diabetes.

New therapeutic strategies for arterial diseases : Pre-clinical models and translational approaches towards patients

 

 

Coordinators : Didier CARRIE, Natalia SMIRNOVA, Anne NEGRE-SALVAYRE et Muriel LAFFARGUE

With the aim to test new therapeutic strategies to prevent vascular damages, we have developed original mice models of arterial lesions (mechanical injury of carotids, humanized model of aorta transplantation) found in cardiovascular diseases and in transplant vasculopathies. In collaboration with industrial partners and clinicians, we plan to test various chemicals compounds targeting PI3K/mTOR signaling pathways in these pre-clinical models and eventually develop a translational approach towards patients.

SELECTED PUBLICATIONS

Smooth muscle cells-derived CXCL10 prevents endothelial healing through PI3Kγ-dependent T cells response. Lupieri A, Smirnova NF, Solinhac R, Malet N, Benamar M, Saoudi A, Santos-Zas I, Zeboudj L, Ait-Oufella H, Hirsch E, Ohayon P, Lhermusier T, Carrié D, Arnal JF, Ramel D, Gayral S, Laffargue M. Cardiovasc Res. 2020. Pubmed

PI3KC2α-dependent and VPS34-independent generation of PI3P controls primary cilium-mediated autophagy in response to shear stress. Boukhalfa A, Nascimbeni AC, Ramel D, Dupont N, Hirsch E, Gayral S, Laffargue M, Codogno P, Morel E. Nat Comm. 2020. Pubmed

A non-catalytic function of PI3Kγ drives smooth muscle cell proliferation after arterial damage. Lupieri A, Blaise R, Ghigo A, Smirnova N, Sarthou MK, Malet N, Limon I, Vincent P, Hirsch E, Gayral S, Ramel D, Laffargue M. J. Cell. Science. 2020. Pubmed

Immune and Smooth Muscle Cells Interactions in Atherosclerosis: How to Target a Breaking Bad Dialogue? Ramel D, Gayral S, Sarthou MK, Augé N, Nègre-Salvayre A, Laffargue M. Front Pharmacol. 2019. Pubmed

FUNDINGS

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Inserm/UPS UMR 1297 - I2MC Institut des Maladies Métaboliques et Cardiovasculaires

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