Bart Staels Diabetes: from risk factors to cardiovascular complications Université Lille Nord de France; INSERM U1011; Ins...
Obesity predisposes to diabetes and cardiovascular disease
Nutrition  Exercise Signal transduction pathways Transcription factors Genes Insulin resistance Inflammation Hyper- tensio...
Clock Sleep-wake cycles Body temperature Activation of intestinal system Endocrine systems Liver metabolism Renal activity...
Clock outputs Physiological response / metabolic adaptation   Metabolic signals Molecular pathways? (ex.Rev-erb   and ROR...
Clock transcription factors link circadian oscillators to metabolic pathways  Staels B . ,  Nature Medicine , 2006 Light P...
Normal state NR interactome A Cistrome A Regulon A Example 2:  Molecular analysis of gene regulation in cardiometabolic di...
Lean PPAR   interactome A Cistrome A Regulon A GO functional classification: 1) Extracellular signalling 2) Carboxylic ac...
European Consortia <ul><ul><li>DIABESITY  ( 24 partners, integrated project ) </li></ul></ul><ul><ul><li>HEPADIP  (26 part...
Diagnostic tools <ul><li>Therapeutic compounds: </li></ul><ul><li>Innovating compounds /  β  cell mass restauration </li><...
European Genomics Institute of Diabetes :  a model of industrie – academia partnership, towards tomorrow’s treatments Basi...
Who …………........ and why EGID? <ul><li>Vamberghe & </li></ul><ul><li>P. Fontaine </li></ul>P. Froguel B. Staels F. Pattou ...
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07 rencontres biomédicale LIR Bart Staels

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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

    1. 1.
    2. 2. 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
    3. 3. Obesity predisposes to diabetes and cardiovascular disease
    4. 4. Nutrition Exercise Signal transduction pathways Transcription factors Genes Insulin resistance Inflammation Hyper- tension Lipid disorders
    5. 5. 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
    6. 6. Clock outputs Physiological response / metabolic adaptation Metabolic signals Molecular pathways? (ex.Rev-erb  and ROR  ) Chronopharmacology
    7. 7. 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  <ul><li>Rev-erb  </li></ul><ul><li>ROR  </li></ul><ul><li>PPARs,.. </li></ul>Target genes Glucose metabolism (PEPCK), Bile acid metabolism (CYP7A1), Lipid metabolism (FAS),… ‘ Metabolic’ transcription factors NRE Nuclear receptor Nuclear receptor
    8. 8. 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
    9. 9. 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
    10. 10. European Consortia <ul><ul><li>DIABESITY ( 24 partners, integrated project ) </li></ul></ul><ul><ul><li>HEPADIP (26 partners, integrated project) </li></ul></ul><ul><ul><li>IAP Stigo (20 partners) </li></ul></ul><ul><ul><li>X-TRA-NET (5 partners, specific target project) </li></ul></ul><ul><ul><li>TOBI (10 partners, Collaborative project) </li></ul></ul><ul><ul><li>OLNORME (4 partners, Era-Net involving Genfit) </li></ul></ul><ul><ul><li>EVGN (28 partners, Network) </li></ul></ul><ul><ul><li>COST BM0602 (Network) </li></ul></ul>
    11. 11. Diagnostic tools <ul><li>Therapeutic compounds: </li></ul><ul><li>Innovating compounds / β cell mass restauration </li></ul><ul><li>Valorisation of research tools </li></ul>IT-DIAB (2008-2012) <ul><ul><ul><li>National consortium </li></ul></ul></ul><ul><ul><ul><li>Industry (4) / academic teams (8) </li></ul></ul></ul><ul><ul><ul><li>Support A2I / OSEO </li></ul></ul></ul>Diabesity DIAGNOSTIC THERAPY MONITORING R & D UMR 8090 U 859 U1011
    12. 12. 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
    13. 13. Who …………........ and why EGID? <ul><li>Vamberghe & </li></ul><ul><li>P. Fontaine </li></ul>P. Froguel B. Staels F. Pattou <ul><li>Create high-technology platforms dedicated </li></ul><ul><li>to diabetes research </li></ul><ul><li>2) Develop translational and clinical research </li></ul><ul><li>activities </li></ul><ul><li>3) Host new research teams </li></ul><ul><li>4) Create and coordinate collaborative </li></ul><ul><li>projects (EU) </li></ul><ul><li>5) Develop a valorisation platform to collaborate </li></ul><ul><li>with pharma industry </li></ul>

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