Team 4 – Integrative Biology of Atherosclerosis

Team headed by P. Lesnik

Team 4 focuses its research on the lipido-inflammatory dimension of atherosclerotic vascular disease, the structure, metabolism and function of lipoproteins, the molecular genetics of cholesterol transport and homeostasis, and the systemic biomarkers of cardiometabolic diseases. This research has three main objectives: (i) to determine how lipids and immune cells crosstalk to influence atherogenesis, (ii) to determine the clinical relevance of novel mechanisms, genes, and biomarkers by studies of human diseases, and (iii) to evaluate and develop novel therapeutic approaches for inflammatory and metabolic disorders and atherosclerosis.

This team is attached to the “école doctorale” 394 “Physiologie et Physiopathologie”.

 

Principal investigators’ groups:

  • In team 4, Emmanuel Gautier‘s group works on the diversity and functionality of mononuclear cell subsets in cardiometabolic diseases.
    His group is interested in delineating the role of mononuclear phagocytes (monocytes, macrophages and dendritic cells) in chronic inflammatory conditions such as cardiometabolic diseases (atherosclerosis, obesity, NASH).
    More specifically, we study how dendritic cell subsets, tissue resident and monocyte-derived macrophages impact on cardiometabolic diseases development, and developed tools to target these subsets in vivo. Our studies are based on integrated approaches combining molecular, cellular biology and animal models. Particular attention is given to the interactions between inflammatory stimuli, mononuclear phagocytes, lipid and carbohydrate metabolisms as well as the gut microbiota.

  • In team 4, Wilfried Le Goff’s group works on mechanisms controlling lipid homeostasis and inflammation in tissue macrophages in cardiometabolic diseases.
    Tissue macrophages (resident and inflammatory) play a central role in the chronic lipid-inflammatory dimension of cardiometabolic diseases (CMD). Alteration of lipid metabolism in those disorders allows macrophages to engulf excess of cellular material and to handle large amounts of lipids. Interestingly, the fate of such lipids within macrophages is a key sensor in the activation of those cells. Indeed, in response to a lipid-stress, tissue macrophages trigger an adaptive program to resolve the local inflammation and restore lipid homeostasis in the tissue altered. In this context, his group is interested in decrypting the adaptive program triggered by tissue macrophage in response to lipid stress. To achieve this goal, Omic approaches (lipidomic and transcriptomic) are combined in order to identify interaction networks in tissue macrophages in CMD and to propose potential new therapeutic targets. His studies are based on integrated in vitro and in vivo approaches combining molecular and cellular biology investigations, studies in mouse models and translation in CMD patients.