The laboratory is a Joint Research Unit (UMR) Inserm - Lille University - Lille University Hospital and Pasteur Institute of Lille.

UMR 1011 studies the biological and molecular mechanisms controlling the development and progression of type 2 diabetes and its cardiovascular complications, in order to develop preventive and therapeutic strategies. We study the regulation of the genes involved in these pathologies and the consequences of their deregulation, with a particular interest in specific transcription factors: nuclear receptors which constitute potential therapeutic targets. Our previous studies have characterised nuclear receptors, such as PPARs and LXRs, as metabolic regulators and pharmacological targets, and have led to a better understanding of the side effects of synthetic ligands of nuclear receptors currently used in therapy or under development. In recent years, we have made significant contributions to :

    Demonstrating the involvement of nuclear receptors in metabolic and energy balance disturbances: disturbances characteristic of type 2 diabetes;
    demonstrate the regulatory role of nuclear receptors in inflammatory processes in adipose tissue and the vascular wall;
    to better understand the molecular mechanisms by which nuclear receptors modulate the progression of type 2 diabetes.

Nevertheless, the molecular mechanisms of action of nuclear receptors, as well as their exact role in the pathophysiology of early (metabolic syndrome) and late stages of type 2 diabetes, obesity and cardiovascular disease, are still imperfectly understood.

The current objectives of our laboratory are to understand the contribution of nuclear receptors - as regulators of gene expression - in the pathophysiology of type 2 diabetes, and then to evaluate the therapeutic potential of selective ligands for these receptors in the prevention and treatment of type 2 diabetes and its cardiovascular complications. More specifically, the research objectives are :

    to better understand the functions of new nuclear receptors emerging as important metabolic regulators (FXR, Reverbα, RORα and orphan receptors);
    to define precisely the molecular regulation by nuclear receptors of the differentiation of monocytes into macrophages, and the functions of these macrophages in the context of obesity, diabetes and cardiovascular disease;
    study the contribution of immune system cells to the pathophysiology of diabetes and cardiovascular disease;
    to identify and validate nuclear receptors and their associated cofactors as possible innovative therapeutic targets.

UMR 1011 is organised into 5 themes:

    Theme 1 (Nuclear Receptors in the Metabolic Syndrome) studies the metabolic functions of NRs (FXR, Rev-erbα, RORα) and their implication as potential therapeutic targets in humans.
    Theme 2 (Cardiac pathologies, blood flow anomalies and haemostasis) focuses on the characterisation of macrophages in different pathologies (i.e. metabolic or cardiovascular disorders) in order to modulate their functions by pharmacological means. The relative contribution of macrophage sub-fractions, as well as that of vascular interstitial cells (VICs) in tissue remodelling and the response to vascular calcification will be studied.
    Theme 3 (Immuno-metabolic dialogue in obesity and its comorbidities) studies the contribution and regulation by NRs of other cells of the immune system (mast cells, B lymphocytes) in the pathophysiology of atherosclerosis with a particular interest in PPARγ.
    Theme 4 (Integrated Transcriptional Analysis of Liver Diseases) identifies the molecular mechanisms of RN-mediated regulation, in order to discover new regulatory pathways and better define molecules for therapeutic purposes.
    Theme 5 (Nuclear Receptors and Circadian Rhythms in Physiopathology) has developed a new line of research dedicated to the circadian regulation of metabolism and inflammation, focusing on the components of the clock and the nuclear receptors targeted by drugs, the Rev-erbs and ROR.


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