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.
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.
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.
Tél/phone:+33 (0)5 31 22 41 47
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.
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.
Tél/phone:+33 (0)5 61 32 56 36
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.
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
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.
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.
Tél/phone:+33 (0)5 31 22 40 82
PhD, Associate Professor – Hospital Practitioner (MCU-PH)
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.
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.
PhD, Hospital Practitioner (PH, Toulouse University Hospital)
Julie PIRES DA SILVA
PhD, post-doctoral fellow
Julie Pires da Silva received her PhD degree in Molecular and Cellular Pathophysiology from the University of Paris-Saclay, France, in 2018. She joined the Team LiMitAging in February 2022 as a post-doc researcher in the field of metabolic diseases, with a focus on heart failure.
Julie obtained her Master in Integrative and Molecular Biology from the University of Versailles Saint Quentin-en-Yvelines, France, in 2015. Between 2015-2018, she worked on her PhD in the field of cardiovascular pathophysiology. In 2018, she became a post-doc researcher at the University of Colorado Anschutz Medical Campus, Colorado, U.S.A in the field of pediatric cardiovascular disease.
Main area of Expertise:
Mitochondrial metabolism, Cardiovascular disease, Cellular and molecular biology, Multi-omic analyses, Human clinical data interpretation, Pharmacologically and genetically engineered animal models
Mohamad NASSER works in the team as a post-doctoral researcher in the cardiovascular disease. In particular, he is studying the protective effect of different peptides on the cytotoxicity of human endothelial cells under different stress conditions, and the endothelial dysfunction in mice.
Mohamad NASSER obtained his PhD in Pathophysiology, Pharmacology, and Neuroscience from the University of Limoges, France, in 2011. His work focused on the effect of Angiotensin IV and the Angiotensin AT1 receptor blocker on type 1 diabetes-induced endothelial dysfunction in mice and traumatic brain injury in rats.
Main domains of expertise
Atherosclerosis, Ischemia, Hypoxia, Diabetes, and Traumatic brain injury.
Vanessa Bouguetoch joined the team in 2021 as an engineer.
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
Tél/phone:+33 (0)5 61 32 56 36
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.
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).
Tél/phone:+33 (0)5 31 22 40 85
PhD student in Team 3 – LiMitAging
Zichun CAI received her Master Degree in Internal Medicine option cardiovascular diseases from Nanjing Medical University, Nanjing, China, in 2022. She joined the team as a PhD student in October 2022, and has been focusing her work on metabolism of lipid and cardiovascular diseases.
Career Path :
From 2014 to 2019, Zichun CAI studied in Nanjing Medical University majoring in Clinical Medicine and in the last one and half years, she got internship in The Second Affiliated Hospital of Nanjing Medical University. During her master, she did research in Key Laboratory of Arrhythmias of Ministry of Education of China, Shanghai Heart Failure Research Centre in Shanghai, China and mainly focused on the mechanism of circRNA in heart failure. She is now fully involved in her PhD research in our team.
Domain of Expertise :
CircRNA, Cardiovascular diseases
Océane Roussel works as a technician to assist the team on our various projects.
Océane obtained her BTSA ANABIOTEC in 2021 at LEGTA d’Auzeville-Tolosane. She then went on to deepen her knowledge and skills by completing a professional bachelor’s degree in Biotechnology Research and Development at Paul Sabatier University. This final year of study was spent on a sandwich course at the Toulouse Cancer Research Center (CRCT) in the Sarcoma Oncogenesis team (ONCOSARC). She joined our team in October 2023.
Domain of expertise
Molecular and cellular biology
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 (Grant from Région Occitanie n°19014226 – HEPATOCARE and Région Occitanie / ERDF MP0022856 – Inspire RESPIMITAGING & MITOENERGY).
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 and cell therapy approaches that target nucleotide signaling to restore endothelial function (Grant from Région Occitanie / ERDF MP0018003 – THERANOVASC).
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.
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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