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NOV 15, 2018 4:00 AM PST

Generation and application of 3D-organoid cell culture models using human induced pluripotent stem cells (iPSCs) for drug discovery

Speaker
  • Associate Director - Stem & Primary Cell Group, AstraZeneca
    Biography
      Ryan Hicks is the Associate Director of the Stem & Primary Cell Group at AstraZeneca. Ryan's group is responsible for the generation, engineering and differentiation of iPS cells, adult stem cells and use of primary cells for assay development, target validation, hit finding, hit-to-lead, lead optimization and phenotypic screening activities. Models are generated in 2D and 3D cultures and part of the model development work includes using precise genome modification techniques to introduce gene knock-outs, knock-in mutations or endogenous reporters into iPS cells. The groups work primarily focuses on AstraZeneca's cardiovascular, metabolic, renal and respiratory disease areas. Ryan Hicks joined AstraZeneca in 2001 and has been based in Sweden for the past 8 years. Prior to working in Sweden, Ryan worked as the Associate Director of the Cell & Protein reagents group at AstraZeneca, Alderley Park, UK, with responsibilities in the cell and protein disciplines. Ryan Hicks received his degree in Medical Biochemistry from the University of Birmingham, UK. Following this Ryan received his Ph.D. in Biochemistry and Molecular Biology from the University of Leeds, UK, in 2001.

    Abstract

    Development of physiologically relevant cellular models, with strong translatability to human pathophysiology, is critical for identification and validation of novel therapeutic targets. Cell types derived from induced pluripotent stem cells (iPSCs) provide an important resource for modelling native biology in human cells and tissues for drug discovery.  Understanding the phenotypic and functional relevance of these iPSC derived cells and tissues and how well they represent human biology is vital and as such we have developed tool iPSC-lines and techniques to optimize and monitor differentiation. Applying CRISPR/Cas9, Next Generation Sequencing (NGS), functional testing and advanced imaging techniques to iPSC model validation, we have established a platform that enables an accurate assessment of their benefits, maturity, gaps and challenges, as well as application in a drug discovery setting. Data presented will be from a key kidney model system we have developed to examplify our platforms.  This will describe the validation and application of our kidney model, using SIX2 and NPHS1 markers non-invasively in real-time, to trace early nephron commitment and podocyte-maturation in the same cell. In adition, we will also describe how we use transcriptomic analysis by NGS, in addition to functional assays, to get the most from our iPS derived 3D cell models.


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