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07 rencontres biomédicale LIR Bart Staels
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07 rencontres biomédicale LIR Bart Staels

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2ND INTERNATIONAL RESEARCH MEETING

2ND INTERNATIONAL RESEARCH MEETING
4 JUNE 2010- HÔTEL DE MARIGNY PARIS

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  • HD: i have replaced the title by the project title
  • HD: format changes to fit the screen; 05/11/2008: change title (add ‘hypothesis’)
  • HD: front change so that the ‘nuclear receptor’ fit into the circles + 05/11/2008: I have added the nature med reference

07 rencontres biomédicale LIR Bart Staels 07 rencontres biomédicale LIR Bart Staels Presentation Transcript

  • Bart Staels Diabetes: from risk factors to cardiovascular complications Université Lille Nord de France; INSERM U1011; Institut Pasteur de Lille; Lille, France The « European Genomics Institute of Diabetes » (EGID) project in Lille
  • Obesity predisposes to diabetes and cardiovascular disease
  • Nutrition Exercise Signal transduction pathways Transcription factors Genes Insulin resistance Inflammation Hyper- tension Lipid disorders
  • Clock Sleep-wake cycles Body temperature Activation of intestinal system Endocrine systems Liver metabolism Renal activity Cardiovascular system (blood pressure, heart beat, …) Example 1: Circadian dysregulation and Metabolic disorders
  • Clock outputs Physiological response / metabolic adaptation Metabolic signals Molecular pathways? (ex.Rev-erb  and ROR  ) Chronopharmacology
  • Clock transcription factors link circadian oscillators to metabolic pathways Staels B . , Nature Medicine , 2006 Light Peripheral tissues Food availability (glucose) Hormones (insulin) SCN (hypothalamus) Clock Bmal1 Cry Per Rev-erb  ROR 
    • Rev-erb 
    • ROR 
    • PPARs,..
    Target genes Glucose metabolism (PEPCK), Bile acid metabolism (CYP7A1), Lipid metabolism (FAS),… ‘ Metabolic’ transcription factors NRE Nuclear receptor Nuclear receptor
  • Normal state NR interactome A Cistrome A Regulon A Example 2: Molecular analysis of gene regulation in cardiometabolic diseases Pathological state Epigenetic events NR interactome B Regulon B Cistrome B
  • Lean PPAR  interactome A Cistrome A Regulon A GO functional classification: 1) Extracellular signalling 2) Carboxylic acid metabolism 3) Oxido-reduction 4) Development 5) Subcellular transport Role of the proteasome in the response visceral WAT responsiveness to PPAR  Lefebvre et al. J.Clin.Invest. 2009 Hypoxia UCHL1, Proteasome Obese PPAR  interactome B Regulon B Cistrome B GO functional classification: 1) Monocarboxylic acid and lipid metabolism 2) Mitochondrion 3) Metabolic processes 4) Glucose and pyruvate metabolism 5) Citrate cycle
  • European Consortia
      • DIABESITY ( 24 partners, integrated project )
      • HEPADIP (26 partners, integrated project)
      • IAP Stigo (20 partners)
      • X-TRA-NET (5 partners, specific target project)
      • TOBI (10 partners, Collaborative project)
      • OLNORME (4 partners, Era-Net involving Genfit)
      • EVGN (28 partners, Network)
      • COST BM0602 (Network)
  • Diagnostic tools
    • Therapeutic compounds:
    • Innovating compounds / β cell mass restauration
    • Valorisation of research tools
    IT-DIAB (2008-2012)
        • National consortium
        • Industry (4) / academic teams (8)
        • Support A2I / OSEO
    Diabesity DIAGNOSTIC THERAPY MONITORING R & D UMR 8090 U 859 U1011
  • European Genomics Institute of Diabetes : a model of industrie – academia partnership, towards tomorrow’s treatments Basic Research Clinical Research Translational Research Valorisation Platform Pharmaceutical industrie
  • Who …………........ and why EGID?
    • Vamberghe &
    • P. Fontaine
    P. Froguel B. Staels F. Pattou
    • Create high-technology platforms dedicated
    • to diabetes research
    • 2) Develop translational and clinical research
    • activities
    • 3) Host new research teams
    • 4) Create and coordinate collaborative
    • projects (EU)
    • 5) Develop a valorisation platform to collaborate
    • with pharma industry