Diese Präsentation wurde erfolgreich gemeldet.
Wir verwenden Ihre LinkedIn Profilangaben und Informationen zu Ihren Aktivitäten, um Anzeigen zu personalisieren und Ihnen relevantere Inhalte anzuzeigen. Sie können Ihre Anzeigeneinstellungen jederzeit ändern.

2019 01-19 Retina symposium 2019, Amsterdam, Alain van Gool

82 Aufrufe

Veröffentlicht am

Lecture outlining innovations in molecular biomarkers to drive personalized health(care) for an enthusiastic audience of 200 Netherlands eye doctors.

Veröffentlicht in: Gesundheit & Medizin
  • DOWNLOAD THIS BOOKS INTO AVAILABLE FORMAT (Unlimited) ......................................................................................................................... ......................................................................................................................... Download Full PDF EBOOK here { https://tinyurl.com/y6a5rkg5 } ......................................................................................................................... Download Full EPUB Ebook here { https://tinyurl.com/y6a5rkg5 } ......................................................................................................................... ACCESS WEBSITE for All Ebooks ......................................................................................................................... Download Full PDF EBOOK here { https://tinyurl.com/y6a5rkg5 } ......................................................................................................................... Download EPUB Ebook here { https://tinyurl.com/y6a5rkg5 } ......................................................................................................................... Download doc Ebook here { https://tinyurl.com/y6a5rkg5 } ......................................................................................................................... ......................................................................................................................... ......................................................................................................................... .............. Browse by Genre Available eBooks ......................................................................................................................... Art, Biography, Business, Chick Lit, Children's, Christian, Classics, Comics, Contemporary, Cookbooks, Crime, Ebooks, Fantasy, Fiction, Graphic Novels, Historical Fiction, History, Horror, Humor And Comedy, Manga, Memoir, Music, Mystery, Non Fiction, Paranormal, Philosophy, Poetry, Psychology, Religion, Romance, Science, Science Fiction, Self Help, Suspense, Spirituality, Sports, Thriller, Travel, Young Adult,
       Antworten 
    Sind Sie sicher, dass Sie …  Ja  Nein
    Ihre Nachricht erscheint hier

2019 01-19 Retina symposium 2019, Amsterdam, Alain van Gool

  1. 1. Innovations towards Personalized Health(care) Prof Alain van Gool Professor Personalized Healthcare Head Translational Metabolic Laboratory Strategic advisor of the executive board Coordinator Radboudumc Technology Centers Retina symposium Amsterdam, 19 Jan 2019
  2. 2. www.radboudumc.nl
  3. 3. 3 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  4. 4. 4 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019 Exponential developments – lab technology 500 1000 1500 2000 m/z 5 10 15 20 25 30 35 40 Time [min]
  5. 5. Exponential developments - data 5 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  6. 6. Consider individual differences in life science research 6 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  7. 7. Source: Chakma, Journal of Young Investigators, 16, 2009 Principle of Personalized Medicine • The right drug for right patient at right dose at right time • Molecular biomarkers as key drivers of patient selection • = Precision medicine or Targeted medicine 7 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  8. 8. Crash course in molecular biology DNA, protein, cell, tissue, system biology 8 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  9. 9. Example: Personalized medicine in melanoma B-RAFV600E mutation Strong growth of cell Growth of tumor • B-RAFV600E cells always grow and become cancer cells • RAF inhibitors will block pathway, block cell growth and inhibit cancers that have a B-RAFV600E mutation • 60% of melanoma patients have B-RAFV600E mutation • Basis for a personalized medicine ! 9 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  10. 10. Personalized medicine in melanoma Treat patients with B-RAFV600E mutation Inhibit growth of cell Patients live longerTumors disappearCells stop growing B-RAFinhibitor 10 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  11. 11. Role of molecular biomarkers in Personalized Healthcare Personalized diagnosis Personalized therapy = Personalized healthcare +Patient participation X-Omics Therapy monitoring 11 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  12. 12. Genomic impact in Personalized Health(care) Personalized medicine: B-RAFV600E drugs for melanoma Personalized health: BRCA-driven preventive surgery 12 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  13. 13. The power of omics 13 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019 single omics Option 1 Option 2
  14. 14. Diagnostic progress by Whole Exome Sequencing Human Genetics Nijmegen (Lisenka Vissers, Marcel Nelen, Han Brunner et al) Retrospective analysis of Intellectual Disability cohort (n=150) Sanger sequencing Gene-by-gene 5.4 tests / patient (1-28) Whole Exome Sequencing All genes at once 1 test / patient 14 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  15. 15. Next: Whole Genome Sequencing Circus plots of Whole Genome Sequences of two metastatic cancer patients Source: Edwin Cuppen, Hartwig Medical Foundation 15 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  16. 16. The DNA-RNA-protein-metabolite dogma Text book DNA RNA Protein Metabolite Reality {Karr, Cell 2012}Environment 16 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  17. 17. ‘DNA’ variants: changes in code • Benign: 370 mL → 371 mL • Pathogenic, easy to notice: 370 mL → 971 mL • Pathogenic, hard to notice: sugar → salt RNA variants: translation and communication Protein variants: interpretation and execution
  18. 18. Complexity in protein biology 21.000 genes 1.000.000 -2.000.000 protein forms N-Glycosylation Truncation Phosphorylation Acetylation Ubiquitination … 18 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  19. 19. Functional Omics platforms Research Biomarkers Diagnostics Translational Metabolic Laboratory (www.youtube.com/watch?v=yhLbuX0H7rg) Glycoproteomics 500 1000 1500 2000 m/z 5 10 15 20 25 30 35 40 Time [min] Metabolomics 400 600 800 1000 1200 1400 m/z 10 20 30 40 50 60 Time [min] Bottom-up proteomics Glycomics Top-down proteomics Functional genomics 19 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  20. 20. Example: Complement system Classical pathway Lectin pathway Alternative pathway C3 C5 C6 C7 C8 C9 C1 factor D factor B Terminal pathway: Lysis Inflammation Opsonization C3bC3a C2 C4 MBL MASP Mannoses, fucoses and N-acetylated sugars on cell surface Spontaneous and foreign substances CRP, IgG, IgM Apoptotic cells {Esther Willems TML/LMI, unpubl} 20 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  21. 21. 40 soluble complement proteins CRP Classical pathway Ag-Ab complex apoptotic cellsβ-amyloid C1q-a C1q-b C1q-c C1r C1s Lectin pathway MBL ficolinscollectin-11 MASP-1 MASP-2 MASP-3 C2 C4 cleavage C2bC4a + C1(C1qr2s2) C4b2a (C3 convertase) Mannoses, fucoses and N-acetylated sugars on cell surface Alternative pathway + MBL-MASP complex (bound to cell surface) C3a C3 C3a Spontaneous and foreign substances (e.g. LPS) C3 C3a C3b factor B C3bB factor D Ba C3bBb(C3 convertase) cleavage cleavagecleavage C3bC3b C4b2a3b C3bBb3b (C5 convertase) (C5 convertase) C5 C5a C6 C7 C8 TCC or MAC factor H (bound to cell surface) cleavage + H2O P P P cleavage C9 n C5bC6C7C8(C9)n C5b C5bC6C7 C5bC6C7C8(C9)n Vitronectin Clusterin Extrinsic pathway Tissue factors thrombin plasmin kallikrein factorXIIa (soluble form2) C1-inh C3a-desR C5a-desR CPN C4a-desR CPN cleavage Factor I Factor I C4BP CD59 CR1 MCP DAF CR1 MCP DAF factor H-like 1 factor H-like 2 factor H-like 3 factor H-like 4 factor H-like 5 Amplification loop C1-inh CPN OpsonizationTerminal pathway Inflammation MBL = Mannose-Binding Lectin MASP = MBL-Associated Serine Proteases CPN = Carboxypeptidase N TCC = Terminal Complement Complex MAC = Membrane Attack Complex C4BP = C4 Binding Protein CR1/CD35 = Complement Receptor 1 MCP/CD46 = Membrane Cofactor Protein DAF/CD55 = Decay Accelerating Factor P = Properdin LPS = Lipopolysaccharide Figure adapted from several sources1,2,3
  22. 22. A B C Targeted proteomics: one multiplex complement assay 22 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  23. 23. Complement in disease: bacterial vs viral infection Controls Healthy vs Patients 23 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  24. 24. Precision medicine in genetic-metabolic disease – current Personalized diagnosis Genomics (WES) Metabolomics (IEM panel) New disease mechanisms Personalized therapies Nature Genetics 2018 NEJM 2014 Nature 2016 NEJM 2014 Genet Med 2017 24 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  25. 25. Precision medicine in genetic-metabolic disease - future Personalized diagnosis Genomics (WGS) Metabolomics (more panels) New personalized therapies Glycomics Glycoproteomics Deep Learning Artificial Intelligence System biology Nature Genetics 2016 Pilot 2017 New disease mechanisms 25 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  26. 26. Moving to personalized health(care) {Source: Barabási 2007 NEJM 357; 4} • People are more than linear pathways • Different systems and networks • Different risk factors • Different preferences 26 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  27. 27. 27 “It’s far more important to know what person the disease has than what disease the person has.” Hippocrates, 400 B.C 27 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  28. 28. Personalized health(care) in a systems view 28 28 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  29. 29. 3 key aspects of personalized health(care) ‘I want to stay healthy. If not, how do I get healthy?’ 1. What to measure? 2. How much can it change? 3. What should be the follow-up for me? 29 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  30. 30. We need a personalized data-driven GPS for health • Monitor on background • Alert when you are at risk • Advice what to do • Doctor as coach? 30 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  31. 31. 31 Exponential developments - digital biomarkers 31 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  32. 32. Do realize there is no single one reflection of health • Funhouse mirror effect • Multiple sources of your data • Omics • EPD • Diagnostics • Wearables • Health apps • Commercial health tests • Social media • Surrounding • Each give an (incomplete) image of you • How to deal with this for personal health? {Mira Vegter, Hub Zwart, Alain van Gool, in prep} 32 Alain van Gool, Retina symposium, Amsterdam, 19 Jan 2019
  33. 33. Acknowledgements Translational Metabolic Laboratory Hans Wessels Dirk Lefeber Karlien Coene Leo Kluijtmans Richard Rodenburg Jolein Gloerich Anouk Suppers Purva Kulkarni Roel Tans Esther Willems Ron Wevers and others Edwin Cuppen Albert Heck Thomas Hankemeier Peter Bram ‘t Hoen Daniella Kasteel and others Collaborators/funders Human Genetics Nijmegen Marcel Nelen Alexander Hoischen Lisenka Vissers Christian Gillisen Han Brunner and others alain.vangool@radboudumc.nl www.radboudumc.nl/en/people/alain-van-gool www.slideshare.net/alainvangool CarTarDis Irene Keularts Hans Scheffer and others Rainer Bischoff Theo Luider and others

×