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

Team leader

Muriel LAFFARGUE

Email:muriel.laffargue@inserm.fr

Tél/Phone:05 31 22 41 46

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.

Email:nathalie.auge@inserm.fr

Tél/Phone:05 61 32 56 32

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.

Email:stephanie.gayral@inserm.fr

Tél/Phone:05 31 22 41 45

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).

Email:damien.ramel@inserm.fr

Tél/Phone:05 31 22 41 45

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.

Email:natalia.smirnova@inserm.fr

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.

Email:caroline.camare@inserm.fr

Tél/Phone:05 61 32 56 32

Doctorante

Anne Darmon

PhD Student

Career path

Main domains of expertise

Email:anne.darmon@inserm.fr

PhD Student

Honora Labrana

PhD Student

Honora Labrana’s thesis project focuses on the study of the role of hyperglycemia in the formation of foamy smooth muscle cells with the aim of identifying new therapeutic targets for atherosclerotic complications in diabetic patients.

Career path
Master in Integrated Preclinical and Clinical Pharmacology at the University of Paris (2020-2021). PhD student since October 2021.

Main domains of expertise
Cell biology, signaling, cell imaging

Email:labrana.honora@inserm.fr

Laura Mickiewicz

Email:laura.mickiewicz@inserm.fr

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.

Email:nicole.malet@inserm.fr

Tél/Phone:05 31 22 41 41

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

Email:audrey.swiader@inserm.fr

Tél/Phone:05 31 22 41 41

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.

Email:anne.negre-salvayre@inserm.fr

Tél/Phone:05 61 32 20 59

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)

Email:robert.salvayre@inserm.fr

Tél/Phone:05 61 32 31 48

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.

Ingineer

Kevin CORMIER

Email:kevin.cormier@inserm.fr

Arnaud DEL BELLO

MD-PhD

Career path
Doctorate in Medicine obtained in 2011, PhD in Immunology in 2021. Appointed hospital practitioner in 2015. Joined M Laffargue’s team in 2022. Member of the Paris Transplant Group. Member of the French Society of Transplantation.

Main domains of expertise
Nephrology and solid organ transplantation. Precision medicine in transplantation. Prevention and treatment of rejection after renal or liver transplantation. Long-term consequences of immunosuppressive drugs.

Email:delbello.a@chu-toulouse.fr

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

Doctor with a stethoscope in the hands and hospital background

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

Single-cell transcriptome mapping identifies a local, innate B cell population driving chronic rejection after lung transplantation. Smirnova N, Riemondy K, Bueno M, Collins S, Suresh P, Wang X, Patel K.N, Cool C, Königshoff M, Sharma N.S, and Eickelberg O. JCI Insight. 2022. Pubmed

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

More publications

FUNDINGS

FEDER

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

1 avenue Jean Poulhès - BP 84225 - 31432 Toulouse Cedex 4

Tél. : 05 61 32 56 00

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