Team L. Martinez

Lipoproteins and Mitochondrial adaptations in Age-related vascular & metabolic diseases (LiMitAging)

Our project aims to study the mechanism of action and the function of some players involved in lipoprotein metabolism and mitochondrial function, in different physiopathological contexts (aging, atherogenic dyslipidemia, hepatic and vascular dysfunctions).
Our objectives are to explore the physiological and pathophysiological roles of those molecular actors that regulate:
1) The oxidative phosphorylation, in particular the mitochondrial ATP synthase
2) The autophagy, in particular the mitophagy, and the involvement of this process in inter-organelle crosstalk
3) The cell surface ATP synthase and G protein-coupled P2Y receptors signaling pathways
Our research has led to the development of original drug candidates and biomarkers that are currently being validated on preclinical models (cells, organoids, animals) and human cohorts, to be used for early detection and resolution of mitochondrial dysfunctions and metabolic disorders in elderly with risk of functional decline or in population at high risk of cardiometabolic diseases.

Team members

 
Tous / AllTeam leaderResearchersPost Doctoral fellowsStudentsTechnical staff
Team leader

Laurent MARTINEZ

Maître de conférence (MCU)

Cendrine CABOU

MCU-PH

Annelise GENOUX

Researcher, Inserm

Souad NAJIB

PhD, professor emeritus

Bertrand PERRET

Post-doctoral fellow

Thibaut DUPARC

Post-doctoral fellow

Emilia GORE

Student

Jules MERIAN

Engineer

Vanessa BOUGUETOCH

Engineer Assistant, Inserm

Guillaume COMBES

Cécile INGUENEAU
Associate professor, Hospital Practitioner

Cécile INGUENEAU

Céline VERDIER
PhD, Hospital Practitioner

Céline VERDIER

Team leader

Laurent MARTINEZ

PhD, Director of research, Group leader

Laurent Martinez received his PhD degree in physiopathology from Paul Sabatier University (Toulouse, France). He is Director of research at Inserm and head a research team at I2MC since 2011.

Career path
After his PhD, Laurent Martinez did a post-doc at Columbia University (NYC, USA) in the laboratory of Pr. Alan Tall, working on the role of ABC transporters in lipoprotein metabolism. He did a second post-doc at the Mitochondrial Biology Unit in Cambridge (former Dunn Human Nutrition Unit, UK) in the team of Sir John Walker. He then integrated the CPTP research Institute in Toulouse, heading first an Inserm Avenir Team then his team moved to I2MC in 2011.

Main area of expertise
Lipoproteins, mitochondria, purinergic receptor, biomarkers, metabolic and cardiovascular disorders.

Email:laurent.martinez@inserm.fr

Tél/phone:+33 (0)5 31 22 41 47

Maître de conférence (MCU)

Cendrine CABOU

PhD, Associate Professor, Principal investigator

Cendrine Cabou is a pharmacist and received her phD degree (Paul Sabatier University, Toulouse), in 2008. She joined our team in Janvier 2012, as assistant professor from the faculty of pharmacy (Toulouse). Her projects aimed at to study the role of P2Y endothelial receptors and cell signaling in endothelial protection.

Career path
During her thesis, and before joining our team, she worked in Pr. Remy Burcelin’s team at Inserm / I2MC (from 2004 to 2011). Her projects aimed at to study the effects of central infusions of insulin and GLP-1 both on vascular function and insulinsensitivity in the awake mouse.

Main area of expertise
Endothelium, diabetes and dyslipidemia, lipoproteins, microsurgery, measurement of blood flow and heart rate in awake mouse by using transonic flowprobes, Insulin clamps, myography and immunohistochemistry.

Email:cendrine.cabou@inserm.fr

Tél/phone:+33 (0)5 61 32 56 36

MCU-PH

Annelise GENOUX

PhD, Associate Professor – Hospital Practitioner (MCU-PH), Principal investigator

Annelise Genoux has held a position of MCU-PH since 2013. She works in the Biochemistry and Molecular Biology laboratory of the Purpan Hospital (Institut Fédératif de Biologie), in teaching at the Faculty of Medicine of Toulouse and in research at the I2MC.

Career path
Annelise Genoux obtained her PharmD and her DES in Medical Biology at the Faculty of Pharmacy of Lille in 2005 and her PhD in Biochemistry and Molecular Biology at the University of Lille II in 2006. Since her arrival in Toulouse in 2006, she has been working as an AHU, PHU and MCU-PH with a shared activity between the Biochemistry and Molecular Biology laboratory of the Purpan Hospital and the research team of Laurent Martinez.

Main area of expertise
hormonal biochemistry and biomarkers of cardiovascular risk

Researcher, Inserm

Souad NAJIB

PhD, Researcher Inserm, Principal investigator

Souad Najib obtained her PhD in Clinical Biochemistry, option Medical Biochemistry and Molecular Biology, at Seville University, Spain, in 2004. She joined our team in 2014 as an Inserm Research Investigator in the field of autophagy, mitochondria and cardiovascular and metabolic diseases.

Career path
During her PhD., Souad studied insulin signalling. Throughout her postdoctoral training in Toulouse, she worked on pancreatic and colon cancer progression. She is currently exploring how mitochondria/plasma membrane axis contributes to cellular and organismal metabolic homeostasis.

Main area of expertise
Cell Biology, Mitochondria, Autophagy, Metabolic Homeostasis, Cancer, Metabolic and Cardiovascular Diseases.

Email:souad.najib@inserm.fr

Tél/phone:+33 (0)5 31 22 40 82

PhD, professor emeritus

Bertrand PERRET

PhD, professor emeritus

Graduated as an MD in 1979 and as a PhD in Biochemistry and Molecular Biology in 1985. Joined the team at its beginning in 2011. He became professor emeritus as of January 2020. He is involved in the team projects in clinical investigation regarding inhibitory factor 1 (IF1) or selected lipoprotein markers, with respect to the cardiovascular risk.

Career path
Bertrand Perret performed several post-doctoral periods, particularly in Israël. Became professor in Biochemistry and Molecular Biology and Hospital Biologist in 1995. His main field of investigation concerns the search of new biomarkers of cardiovascular risk, related either to mitochondrial functions or to lipoprotein metabolism.

Post-doctoral fellow

Thibaut DUPARC

PhD, post-doctoral fellow

Thibaut Duparc received his PhD degree in Pharmacological Innovation from Paul Sabatier University (Toulouse, France) in 2012. He joined the team in 2016 as a post-doctoral fellow, and is studying the mechanisms involved in the development of metabolic diseases.

Career path
After his PhD, Thibaut Duparc achieved a first post-doc in Belgium (Louvain Drug Research Institute, Brussels). His current research focuses on the role of the mitochondrial ATPase Inhibitory factor in energy metabolism and cardiometabolic dysfunctions.

Main area of expertise
Lipid and glucose metabolism, energy metabolism, nonalcoholic steatohepatitis, cellular and molecular biology

Email:thibaut.duparc@inserm.fr

Tél/phone:+33 (0)5 31 22 40 85

Post-doctoral fellow

Emilia GORE

PhD, post-doctoral fellow

Emilia Gore received her PhD degree in Pharmaceutical Technology and Biopharmacy from the University of Groningen, The Netherlands, in 2019. She joined the team in 2020 as a post-doc researcher in the field of metabolic diseases, with a focus on nonalcoholic steatohepatitis.

Career path
Emilia Gore obtained her Master in Pharmacy from the University Carol Davila, Bucharest, Romania, in 2011. She worked as a community pharmacist (2011-2012). In 2014 she obtained a second Master degree in Medical Pharmaceutical Sciences from the University of Groningen, The Netherelands. Between 2014-2019 she worked on her PhD.

Main area of expertise
Animal experiments, Liver disease (fibrosis, nonalcoholic steatohepatitis), Precision-cut tissue slices, Histology, Cellular and molecular biology, Gene and pathways analysis

Student

Jules MERIAN

PhD Student

Jules Mérian received his Master Degree in Cellular Biology option Vascular Biology, Atherosclerosis, Thrombosis, Hemolysis from the Descartes University, Paris, France, in 2018. He joined the team as a PhD student in October 2018, and has been focusing his work on autophagy and liver metabolism.

Career path
In 2015, Jules Mérian worked on Human predisposition for mycobacterial infection at the IMAGINE institute in Paris. Then, during his Master internships, he studied  liver sinusoidal autophagy in context of NASH development at the PARCC. He is now fully involved in his PhD research in our team.

Main area of expertise
autophagy, liver pathophysiology, glucose and lipid metabolism, cardiovascular diseases

Email:jules.merian@inserm.fr

Tél/phone:+33 (0)5 31 22 40 82

Engineer

Vanessa BOUGUETOCH

Engineer (INSERM)

Vanessa Bouguetoch joined the team in 2021 as an engineer.

Career path
Vanessa graduated with a master’s degree in Health Biology from the University of Nîmes in 2010. After a first experience at Firalis, specializing in the research and development of biomarkers, she joined the Center for Developmental Biology (CBD, Toulouse ) where she worked on the role of glial cells during embryonic development in the zebrafish model. In 2018, she joined the Institute in the Adipolab team to set up the zebrafish model for the different projects. In July 2021, she joined the LimitAging team to participate to the Respimitaging project.

Main area of expertise
Molecular and cellular biology, biochemistry, histology

Email:vanessa.bouguetoch@inserm.fr

Tél/phone:+33 (0)5 61 32 56 36

Engineer Assistant, Inserm

Guillaume COMBES

Engineer Assistant (Inserm)

Guillaume is specialized in biochemistry and animal physiology. He participates to the technical training of newcomers to the laboratory and is the lab manager of the team. He is also involved in the implementation and compliance with health and safety rules within the team, but also within the institute.

Career path
Guillaume Combes obtained a professional master’s degree in Gene Expression and Recombinant Proteins from Paul Sabatier University (Toulouse) in 2004. He joined our team in 2016 following his recruitment at INSERM as an assistant engineer in biological techniques.

Main area of expertise
Protein production and analysis, biochemistry, animal experimentation, cell culture (cell lines and primary cultures).

Email:guillaume.combes@inserm.fr

Tél/phone:+33 (0)5 31 22 40 85

Associate professor, Hospital Practitioner

Cécile INGUENEAU

PhD, Associate Professor – Hospital Practitioner (MCU-PH)

PhD, Hospital Practitioner

Céline VERDIER

PhD, Hospital Practitioner (PH, Toulouse University Hospital)

High Density Lipoproteins (HDL) and ATP synthases in metabolic and cardiovascular dysfunctions 

 

Coordinator : Laurent MARTINEZ

ATP synthase is a mitochondrial enzyme complex that we have also found expressed at the plasma membrane of several cell types as a receptor for apoA-I, the main HDL protein.
In this project, we explore the cellular functions and signaling pathways associated to the enzymatic activities of mitochondrial and cell surface ATP synthases. We are also studying the mechanisms regulating their activities. We develop original pre-clinical models and innovative pharmacological approaches to study their role in the process of aging and in different metabolic and cardiovascular dysfunctions such as dyslipidemias, atherosclerosis, diabetes and nonalcoholic steatohepatitis (HEPATOCARE and Inspire RESPIMITAGING grants). 

 

Lipoproteins and purinergic signaling in the vascular endothelium

 

Coordinators : Cendrine CABOU, Laurent MARTINEZ

Endothelial cells, which line the surface of blood vessels to form the endothelium, largely contribute to the homeostasis of the cardiovascular system. It has been established that a dysfunction or damage to the vascular endothelium is the cause of cardiovascular pathologies and complications.
Extracellular nucleotides such as ADP and ATP activate signaling pathways involved in endothelial function (vasomotricity, permeability, cell adhesion, etc.)
In this project, we are studying the nucleotide signaling of the vascular endothelium, in particular the one mediated by High Density Lipoprotein and involving cell surface ATP synthase, whose hydrolytic activity generates extracellular ADP which activates P2Y purinergic receptors.
In translational research, we are developing a novel family of molecules that target nucleotide signaling to restore endothelial function (THERANOVASC project).

Degradative/secretory autophagy and inter-organelle crosstalk in health and disease

 

 

Coordinator : Souad NAJIB

Autophagy is an essential catabolic process to maintain cellular homeostasis program. Increasing evidences suggest a role of autophagy machinery in anabolic processes such as a plasma membrane targeting of soluble and transmembrane proteins.
In this project, we explore this versatile role of autophagy, analyse its interconnection with mitochondrial metabolism, and study the consequence of its dysfunction on the development of metabolic and cardiovascular diseases.

Biomarkers associated with lipid and energy metabolism

 

 

Coordinators : Annelise Genoux, Bertrand Perret and Laurent Martinez

This project aims to discover novel biomarkers of cardiovascular risk and metabolic syndrome, associated to mitochondrial functions or  lipoprotein metabolism. Our goal is to develop diagnostic tools that will allow accurate and early risk stratification. Our work is based on a consortium comprising clinicians, epidemiologists and private companies and the use of local, national and international cohorts.

Selected publications

A reference measurement of circulating ATPase inhibitory factor 1 (IF1) in humans by LC-MS/MS: Comparison with conventional ELISA,Genoux A, Duparc T, Ruidavets JB, Ingueneau C, Najib S, Ferrières J, Perret B, Croyal M, Martinez LO.,Talanta, 2020. Pubmed

Pharmacological inhibition of the F 1 -ATPase/P2Y 1pathway suppresses the effect of apolipoprotein A1 on endothelial nitric oxide synthesis and vasorelaxation, Cabou C, Honorato P, Briceño L, Ghezali L, Duparc T, León M, Combes G, Frayssinhes L, Fournel A, Abot A, Masri B, Parada N, Aguilera V, Aguayo C, Knauf C, González M, Radojkovic C, Martinez LO.,Acta Physiol (Oxf)., 2019. Pubmed

Liraglutide improves hepatic steatosis and metabolic dysfunctions in a 3-week dietary mouse model of nonalcoholic steatohepatitis.Cabou C, Honorato P, Briceño L, Ghezali L, Duparc T, León M, Combes G, Frayssinhes L, Fournel A, Abot A, Masri B, Parada N, Aguilera V, Aguayo C, Knauf C, González M, Radojkovic C, Martinez LO., Acta Physiol (Oxf)., 2019. Pubmed

Ectopic adenine nucleotide translocase activity controls extracellular ADP levels and regulates the F1-ATPase-mediated HDL endocytosis pathway on hepatocytes.Cardouat G, Duparc T, Fried S, Perret B, Najib S, Martinez LO.Biochim Biophys Acta Mol Cell Biol Lipids., 2017. Pubmed

Serum levels of mitochondrial inhibitory factor 1 are independently associated with long-term prognosis in coronary artery disease: the GENES Study. Genoux A, Lichtenstein L, Ferrières J, Duparc T, Bongard V, Vervueren PL, Combes G, Taraszkiewicz D, Elbaz M, Galinier M, Nassar B, Ruidavets JB, Perret B, Martinez LO. BMC Med. 2016. Pubmed

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