Nuclear Receptors, Metabolic and Cardiovascular Diseases

RNMMC | U 1011
Biology and health Research unit Precision health

Our laboratory 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 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 identified 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 therapies or under development. We are open to all academic and industrial collaborations and propose services in line with our expertise.

Informations

Director: Bart Staels

https://u1011.pasteur-lille.fr/accueil/

1 rue du Professeur Calmette
Institut Pasteur de Lille, BP 245
59019 LILLE

Mots-clés

Nuclear receptors, Diabetes, Metabolic diseases, Cardiovascular diseases, Obesity, Liver diseases

Localisation

  • Implication of nuclear receptors in perturbations of metabolism and energy homeostasis
  • Hallmark of Type 2 Diabetes
  • Regulatory role of nuclear receptors in the inflammatory process in adipose tissue, the liver and vascular wall
  • Molecular mechanisms by which nuclear receptors may modulate the progression to Type 2 Diabetes
  • Pathophysiology of early (metabolic syndrome) and late stages of Type 2 Diabetes, obesity and cardiovascular diseases
  • Contribution of nuclear receptors to the pathophysiology of Type 2 Diabetes and cardiovascular diseases
  • Metabolic regulators (FXR, Reverba, RORa and orphan receptors)
  • Therapeutic potential of selective ligands

Examples of projects:

  • ERC Immunobile - Bile acid, immunometabolism, lipid and glucose homeostasis
  • ANR-NASHILCCD8 – Contribution of ILCs and CD8 T cells to non-alcoholic fatty liver disease and its progression to hepatocarcinoma (2019-2022)
  • ANR-CALMOS – Mitochondrial calcium homeostasis and cardiac arrhytmias in the metabolic syndrome (2019-2022)
  • ANR-MET Intestin – Acute effect of metformin on intestinal sodium-glucose co-transport (2019-2022)

Biochemistry
Measurement of circulating biochemical parameters (glucose, insulin, transaminases, free fatty acids, etc.)
Measurement of lipid and lipoprotein concentrations
Determination of lipid distribution profiles
Determination of bile acid profiles (21 species) in biological environments (plasma, feces, bile)

Histology (Ultra-microtomy, Immunohistochemistry, Microscopy, Laser capture microdissection)

Immunophenotyping  (Flow cytometry)

Cellular Biology
Cell lines (Human and murine hepatic cells, murine preadipocyte cells, murine  fibroblastic  cells, human leukocyte cells, murine beta-pancreatic cells, human kydney cells, murine enteroendocrine cells…)
Primary cell cultures (Murine and human hepatocytes, murine and human monocytes and macrophages)
Human and murine intestinal organoids

Molecular Biology (Microarray, Proteomic analysis, Real time PCR)

In Vivo
Animal imaging (scanner/MRI small animal)
Bone marrow transplantation
Measures of animal metabolic function
Plethysmography (lung function)
Measures of animal cardiovascular function
Genetically modified animal models
Allergy models

We possess a wide range of equipment regrouped within 6 platforms:

  • Biochemistry platform (Konelab 20 system to measure classical biochemical parameters (glucose, lipids, transaminases...), HPLC, ultracentrifuge
  • Immunophenotyping platform (FORTESSA X20 analyzer, cell sorter INFLUX, mass cytometry system CyTOF 2)
  • Histology platform (device for tissue preparation STP 120 Spin, paraffin embedding device Leica EG1160, microtome Leica RM2145, cryostats Leica CM3050S and Microm HM560, staining devices Leica Autostainer XL and Lab Vision 360-2D, microscopes Leitz DMRB, Leica MZ6 et Nikon Ti, microdissector Arcturus XT, bioanalyzer Agilent 2100)
  • Epigenetics platform (Affymetrix GeneChip(R) device)
  • Animal phenotyping platform (system for measuring exercise endurance, metabolic cages)
  • Oxygraphy platform (oxygraph OROBOROS)

Biological materials
Cell lines 
Human and murine hepatic cells, murine preadipocyte cells, murine  fibroblastic  cells, human leukocyte cells, murine beta-pancreatic cells, human kydney cells, murine enteroendocrine cells…

Primary cell cultures
Murine and human hepatocytes, murine and human monocytes and macrophages

Human and murine intestinal organoids

Private
The unit collaborates or has collaborated with many companies (Genfit, Servier, Tiger, Sanofi, Oseo-Anvar, Galderma, Pfizer, LFB, Corwave, Carmat, Stago, Sebia, Siemens,…)

Academic
Pasteur Institute of Paris, University of Paris, Sorbonne University, University of Montpellier
University of Antwerp (Belgium), University of Liege (Belgium), Maastricht University (Germany)

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