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 leaderResearchersCliniciansPost Doctoral fellowsStudentsTechnical staff
Team leader-Researcher

Barbara GARMY-SUSINI

Co-Team leader-Researcher

Anne-Catherine PRATS

Associate professor

Eric LACAZETTE

Principal scientist

Florent MORFOISSE

Post-doctoral fellow

Halyna LOI

Phd Student

Nathalie LAUGERO

Engineer

Léna VERDU

Xavier CHAUFOUR
Clinician

Xavier CHAUFOUR

Benoît LEBAS
Clinician

Benoît LEBAS

Julie MALLOIZEL-DELAUNEY
Clinician

Julie MALLOIZEL-DELAUNEY

Hervé ROUSSEAU
Clinician

Hervé ROUSSEAU

Fatima MOKRANE
Clinician

Fatima MOKRANE

Ramiro MORENO
Clinicien

Ramiro MORENO

Aurélien HOSTALRICH
Clinician

Aurélien HOSTALRICH

Elisa BALZAN

Ana ALVAREZ

Pierre-Jean BORDIGNON

Doctorante

Roxane SYLVESTRE

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.

Associate professor

Eric LACAZETTE

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.

Principal scientist

Florent MORFOISSE

Principal scientist

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.

Post-doctoral fellow

Halyna LOI

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.

Engineer

Léna VERDU

Clinician

Xavier CHAUFOUR

Clinician

Benoît LEBAS

Clinician

Julie MALLOIZEL-DELAUNEY

Clinician

Hervé ROUSSEAU

Clinician

Fatima MOKRANE

Clinicien

Ramiro MORENO

Clinician

Aurélien HOSTALRICH

Elisa BALZAN

Ana ALVAREZ

Pierre-Jean BORDIGNON

Doctorante

Roxane SYLVESTRE

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).

Selected publications

15-Lipoxygenase promotes resolution of inflammation in lymphedema by controlling Treg cell function through IFN-β. Zamora A, Nougué M, Verdu L, Balzan E, Draia-Nicolau T, Benuzzi E, Pujol F, Baillif V, Lacazette E, Morfoisse F, Galitzky J, Bouloumié A, Dubourdeau M, Chaput B, Fazilleau N, Malloizel-Delaunay J, Bura-Rivière A, Prats AC, Garmy-Susini B.  Nat Commun. 2024. Pubmed

Apelin-VEGF-C mRNA delivery as therapeutic for the treatment of secondary lymphedema. Creff J, Lamaa A, Benuzzi E, Balzan E, Pujol F, Draia-Nicolau T, Nougué M, Verdu L, Morfoisse F, Lacazette E, Valet P, Chaput B, Gross F, Gayon R, Bouillé P, Malloizel-Delaunay J, Bura-Rivière A, Prats AC, Garmy-Susini B. EMBO Mol Med. 2024. Pubmed

Specific Circular RNA Signature of Endothelial Cells: Potential Implications in Vascular Pathophysiology. Diallo LH, Mariette J, Laugero N, Touriol C, Morfoisse F, Prats AC, Garmy-Susini B, Lacazette E. Int J Mol Sci. 2024. Pubmed 

Coordinating Effect of VEGFC and Oleic Acid Participates to Tumor Lymphangiogenesis. Morfoisse F, De Toni F, Nigri J, Hosseini M, Zamora A, Tatin F, Pujol F, Sarry JE, Langin D, Lacazette E, Prats AC, Tomasini R, Galitzky J, Bouloumié A, Garmy-Susini B. Cancers (Basel). 2021. Pubmed

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

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