TEAM B. Garmy-Susini / A-C. PRATS

Regulation of lymphangiogenic factors in cardiovascular diseases

The physiological role of the lymphatic system is to collect interstitial fluids, fats and immune cells before joining blood flow via the subclavian vein. In pathological conditions, the lymphatic system dysfunction generates formation of lymphedema, a disabling pathology related to accumulation of adipose tissue and fluids in limbs. More recently, a role of the lymphatic system has been identified in cardiac function. This system would be required to prevent and reabsorb heart edema and maintain a continuous flow of oxygen and nutriments in tissues. Furthermore, the lymphatic system constitutes the main metastasis site of solid tumors and provides a promising target for anti-cancerous therapies. All of these pathologies are associated to common stresses such as lack of oxygen (hypoxia) and heat shock which induce major changes in (lymph)angiogenic factor gene expression. Our work hypothesis is that restoration of lymphatic drainage in injured tissues will considerably accelerate healing by improving tissue homeostasis, regulating inflammation cell traffic and favoring edema draining. In this context, our group focuses onto pathologies characterized by a massive lymphatic dysfunction: secondary lymphedema and cardiac ischemia. Our objective is to associate approaches of basic and translational research in the field of lymphatic vessel biology.

TEAM Members

 
Tous / AllTeam leaderResearchersPost Doctoral fellowsStudentsTechnical staff
Team leader-Researcher

Barbara GARMY-SUSINI

Co-Team leader-Researcher

Anne-Catherine PRATS

Researcher

Florence TATIN

Associate professor

Eric LACAZETTE

Post-Doctoral fellow

Florent MORFOISSE

PhD Student

Audrey ZAMORA

PhD Student

Emilie ROUSSEL

PhD Student

Emmanuelle MARCHAUD

PhD Student

Florian DAVID

Phd Student

Leila DIALLO

Phd Student

Manon NOUGUE

Phd Student

Nathalie LAUGERO

Technician

Françoise PUJOL

Engineer

Ami Marie COULIBALY

Engineer

Maxime FAYEL

Engineer

Emeline BENUZZI

Team leader-Researcher

Barbara GARMY-SUSINI

Research director (INSERM)

Barbara GARMY-SUSINI graduated with a PhD from Toulouse III university. She performed her postdoc at the university of California San Diego (UCSD) and she obtained a permanent position at Inserm in 2009 at the Toulouse Cancer Research Center. In 2014, she moved to the I2MC to create a group dedicated to the study of the lymphatic system.

Main domains of expertise
Vascular biology, lymphatic, lymphedema, gene therapy

Co-Team leader-Researcher

Anne-Catherine PRATS

Research director (INSERM)

Anne-Catherine Prats obtained her PhD in molecular virology from the Paul Sabatier University UT3, in 1988. She has been a group leader since 1994 and has focused her research on translational control and gene therapy of cardiovascular diseases.

Main domains of expertise
Molecular and cell biology, RNA, translational control of gene expression, cardiovascular diseases, vectorology, gene therapy.

Researcher

Florence TATIN

Researcher (CRCN INSERM)

Florence Tatin received her PhD in cell biology from University of Bordeaux in 2006. She joined the team as post-doc in september 2014 and obtained her position in 2018 in the field of lymphatic valve development and diseases.

Main domains of expertise
Vascular development, valvulopathy, cell adhesion and signalisation.

Associate professor

Eric LACAZETTE

Associate professor

Eric Lacazette obtained his PhD in molecular biology at the Univ. of Clermont-Ferrand in 1999. He then completed a postdoctoral fellowship at the Biozentrum (Univ. of Basel). Since 2004 he is working as an Associate Professor in molecular biology at the Toulouse 3 Univ. He joined the team in 2016.

Main domains of expertise
Molecular biology, cellular biology, bioinformatics.

Post-Doctoral fellow

Florent MORFOISSE

Postdoctoral researcher

Florent Morfoisse received his PhD in Physiopathology from the Paul Sabatier University, Toulouse, France, in 2015. He focus his work on the interactions between the extracellular matrix and the lymphatic system, he joined our team in January 2020 to work on lymphedema-associated fibrosis.

Main domains of expertise
Lymphatic biology, lymphedema, extracellular matrix, fibrosis, translational regulations.

PhD Student

Audrey ZAMORA

PhD student

Audrey received her master degree in health biology option biochemistry, cellular and molecular biology from the Université of Orléans, France, in 2017. She joined our team in January 2019 as a PhD student in the field of inflammation resolution in vascular disease.

Main domains of expertise
Animal experiments, histology, cellular & molecular biology

PhD Student

Emilie ROUSSEL

PhD Student

Emilie Roussel received her master degree in biology option virology, gene therapy and vectorology from the Paul Sabatier University, Toulouse in 2019. She joined our team in September 2019 as PhD student working on the translation regulation by specialized ribosomes in lymphatic endothelial cells.

Main domains of expertise
Translation, lymphatic desease, cellular and molecular biology.

PhD Student

Emmanuelle MARCHAUD

PhD Student

Emmanuelle Marchaud received her engineer degree in biology from INSA Toulouse in 2019. After an ERASMUS at KTH (Stockholm) on molecular biology, immunology, she worked at DIVA Expertise (Toulouse) on a 3D-model of human adipocytes.

Main domains of expertise
She joined our team as a PhD student on the characterization of adipose tissue remodeling on vascular and lymphatic structure in the context of lymphedema and obesity.

PhD Student

Florian DAVID

PhD Student

Florian DAVID received her master degree in health biology option virology, gene therapy and vectorology from the Paul Sabatier University, Toulouse, France, in 2018. He joined our team in September 2018 as a PhD student in the field of translational control in heart disease.

Main domains of expertise
Cellular and molecular biology, cell fractionation, IRES activity.

Phd Student

Leila DIALLO

Phd Student

Leïla Halidou DIALLO joined the team in 2017 as a trainee and received her master degree in health biology option oncology from the Paul Sabatier University, Toulouse, France, in 2018. She obtained a grant from the BSB doctoral school for a thesis on circular RNAs in the Lab.

Main domains of expertise
Cellular and molecular biology

Phd Student

Manon NOUGUE

Phd Student

Manon Nougué received her master degree in health biology option physiopathology from the Paul Sabatier University, Toulouse, France, in 2020. She joined our team in September 2020 as a PhD Student in the field of lymphatic vessels in breast cancer.

Main domains of expertise
Animal experiments, histology, lymphatic system physiology, cancer biology.

Phd Student

Nathalie LAUGERO

Phd Student

Nathalie received her master degree in health biology option virology, gene therapy and vectorology from the Paul Sa-batier University, Toulouse, France, in 2020. She obtained a grant from the BSB doctoral school for a thesis on the role of long non coding RNAs in lymphatic system.

Main domains of expertise
Cellular & molecular biology, vectorology.

Technician

Françoise PUJOL

Technician/Lab manager

Françoise was recruited in Inserm in 2000 and is a founding member of our team.

Main domains of expertise
Cell biology, molecular biology, animal experiments.

Engineer

Ami Marie COULIBALY

Engineer

Ami-Marie received her master degree in cancer biology from Paul Sabatier Uni-versity, Toulouse, France, in 2017. She later on worked for a year at the Tumor Microenvironment Laboratory in POSTECH, Pohang, South Korea. She joined our team in January of 2021 as an engineer in the field of lymphatic diseases.

Main domains of expertise
Animal experiments, cancer biology (breast), cell culture.

Engineer

Maxime FAYEL

Engineer

Maxime Fayel received his master degree in health biology option vectorology, gene therapy and vaccinology from the Paul Sabatier University, Toulouse, France, in 2020. He joined our team in february 2021 as an engineer in the field of heart disease.

Main domains of expertise
Vectorology, gene therapy, cellular & molecular Biology.

Engineer

Emeline BENUZZI

Pathophysiology of lymphedema

Coordinator: Barbara Garmy-Susini

Barbara Garmy-Susini studies the pathophysiology of lymphedema, a disabling disease presently incurable. We focus to both risk factors and biomarkers of this pathology. Using OMICS approach-es (lipidomics, RNAseq), we have identified potential therapeutic targets to restore lymphatic flow in an injured limb. The “Theralymph” project financed by the European Call H2020 will allow us to achieve a phase I/II clinical trial in patients presenting a lymphedema, using a novel technology based on RNA vectors. We are also studying how the fibrotic microenvironment of lymphatics can aggravate lymphedema and render it irreversible.

Translational control and gene therapy of cardiovascular diseases

 

Coordinator : Anne-Catherine Prats

A.C. Prats studies the regulation of mRNA translation during cell stress. She is searching for modi-fications of the translation machinery leading to formation of specialized ribosomes able to specifi-cally translate IRES-containing mRNAs. Internal ribosome entry sites (IRESs) are RNA structure able to activate mRNA translation during stress. The study is performed in stressed cardiomyocytes and in cardiac ischemia (mouse model), as well as in lymphatic endothelial cells submitted to anti-cancerous chemotherapy, an aggravating factor of lymphedema. This project will have an impact on understanding gene expression control in cardiovascular diseases. A.C. Prats also develops trans-lational research with combined gene therapy using IRES-based multicistronic lentivectors that co-express several therapeutic molecules. These projects are financed by ANR as well as by Europe-an projects CARDIOPATCH and THERALYMPH.

Circular RNAs : biogenesis and functions in lymphangiogenesis

 

Coordinatror : Eric Lacazette

Eric Lacazette is interested in deciphering and characterizing the functions of a novel RNA family in lymphatic endothelial cells: circular RNAs (CircRNAs). CircRNAs have been identified by RNAseq with a dedicated bioinformatics approach, then characterized functionally in models in vitro and in vivo. Our data show that certain circRNAs are translated via an alternative mechanism of transla-tion initiation and code proteins whose functions are presently unknown. CircRNAs would participate to mechanisms of fine adaptation of gene expression in endothelial cells, in response to microenvi-ronment. This project also aims to better know the impact of circRNAs in pathophysiological con-texts such as lymphedema. Collaboration: C. Gaspin and J. Mariette (Unit of applied mathematics and bioinformatics in Toulouse, INRAE).

Incompetence of lymphatic valves in conditions of obesity and aging

 

Coordinator : Florence Tatin

Florence Tatin is interested in understanding the consequences of lymphatic valve in-competence during the development of metabolic diseases. Valve incompetence can be congenital or acquired due to environmental factors such as obesity or aging, and repre-sents a major risk for cardiovascular and metabolic complications. Our hypothesis is that lymphatic valve incompetence may induce vessel permeability and local remodeling of adipose microenvironment towards a pro-inflammatory phenotype, exacerbated in obesi-ty conditions. To answer this question, we develop new approaches of 3D imaging by light sheet microscopy (IMACTIV-3D) and single cell RNAseq analysis of endothelial cells. These projects are funded by European and regional grants as well as by Inserm.

Selected publications

Sex Hormones in Lymphedema. Morfoisse F, Zamora A, Mar-chaud E, Nougue M, Diallo LH, David F, Roussel E, Lacazette E, Prats AC, Tatin F, Garmy-Susini B.. Cancers 2021. Pubmed

Circular RNA, the Key for Translation.
Prats AC, David F, Diallo LH, Rous-sel E, Tatin F, Garmy-Susini B, Lacazette E.
. Int J Mol Sci 2020.
Pubmed

Vasohibin1, a new mouse cardi-omyocyte IRES trans-acting fac-tor that regulates translation dur-ing early hypoxia..
Hantelys F, Godet AC, David F, Tatin F, Renaud-Gabardos E, Pujol F, Diallo LH, Ader I, Ligat L, Henras AK, Sato Y, Parini A, Lacazette E, Garmy-Susini B, Prats AC. 
Elife 2019. Pubmed

Lymphatic vasculature requires estrogen receptor alpha signaling to protect from lymphedema.
Morfoisse F, Tatin F, Chaput B, Therville N, Vaysse C, Métivier R, Malloizel-Delaunay J, Pujol F, Godet AC, De Toni F, Boudou F, Grenier K, Dubuc D, Lacazette E, Prats AC, Guillermet-Guibert J, Lenfant F, Garmy-Susini B.
Arterioscler Thromb Vasc Biol. 2018. Pubmed

Therapeutic Benefit and Gene Network Regulation by Combined Gene Transfer of Apelin, FGF2, and SERCA2a into Is-chemic Heart.
Renaud-Gabardos E, Tatin F, Hantelys F, Lebas B, Calise D, Kunduzova O, Masri B, Pujol F, Sicard P, Valet P, Roncalli J, Chaufour X, Garmy-Susini B, Parini A, Prats AC.
Mol Ther. 2018. Pubmed

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