IAC 2024 - IA Fast Track to Search Focused AI Solutions
Diabetes Systems Biology And Genetics V6
1. Systems Biology and Genetics in Drug Discovery for Diabetes Preston Hensley Senior Director Pfizer Biotherapeutics and Bioinnovation Center
2. SCIENCE VOL 322 3 OCTOBER 2008 Despite the tools and technologies of modern medical science, we are still in the Dark Ages of understanding our own biology and discovering agents that can provide cures
3. Human Genetics and Drug Discovery Molecular Targets Clinical Outcome Human Genetics Traditional Discovery David Cox Historically Difficult Now more Feasible
6. Utilize New Academic-Industrial Partnerships Drug development Knowledge and tool implementation IP Knowledge and tool development Public domain Academia Industry
17. Diabetes – Historic Drug Discovery Failure 50 years of research have produced three new classes of diabetes medicines - > 60% of patients have unmet need Pierre de Meyts
24. Insulin Signaling Recapitulated Forest White, et al., DIABETES 2006, 55 , 2171-2179 20% of pY phosphoproteomic data recapitulates current pY signaling knowledge What is the remaining 80% reporting?
25. Ernest Fraenkel, MIT ChIP-Seq Genome-Wide Chromatin Immunoprecipitation E2F4 ~1500 Transcription sites
31. Confirm and Extend Topologies with Chemical Genetics Chemical genetics: Substrate ID Kevan Shokat, UCSF Norman Kennedy, UMass … Kinase 1 Kinase 2 Many substrates
32. Transform Topologies to Mathematical Models – incorporate time course data SEDAGHAT, et al ., Am J Physiol Endocrinol Metab 283: E1084–E1101, 2002 . Rate Constants Model based in ordinary differential equations, ODEs Frank Doyle - UCSB
38. Use Assays to Deconvolute Phenotype Network Screening Tools
39. Goal: More Successful Progression To and Through Development Robust targets, potential biomarkers and defined patho- and toxico-biology should speed progression and increase success at later stages
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42. Thanks to many WEST: P Hensley S Kennedy E Kuja S Hansen S Faraci CVMED: B Garofalo W Soeller J Hadcock D Flynn RTC & Comp Bio: C Cho D Nathan J Miret R Herrera A Seymour W Loging MIT: D Lauffenburger F White E Frankel Entelos: J Trimmer UMASS: R Davis N Kennedy Drug Safety: A Ryan R Chapin Clinical Research: R Calle A Taylor UCSB: F Doyle L Petzold Cal Tech: John Doyle PFE, Other: O Basavapathruni J McNeish J Treadway
67. Diabetes is a Multi-organ Disease Initial focus on adipocytes Kahn NATURE | VOL 414 | 13 DECEMBER 2001 |
68. Visceral Adipose Tissue as an Endocrine Organ SHOELSON, et al., GASTROENTEROLOGY 2007;132:2169–2180 From Kershaw and Flier, J Clin Endocrinol Metab, June 2004, 89(6):2548–2556