NOV 16, 2017 09:00 AM PST
WEBINAR: Breaking Bad with 3D: The development of high throughput screening platforms to interrogate physiologically relevant models
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  • Lead, Trans-NIH RNAi Facility Division of Pre-Clinical Innovation National Center for Advancing Translational Sciences National Institutes of Health
      Madhu Lal-Nag currently serves as the head of the Trans NIH RNAi Facility at the National Center for Advancing Translational Sciences (NCATS) which is responsible for developing and conducting genome wide physiologically relevant phenotypic assays for Intramural researchers. Madhu joined NCATS in 2013, where she worked as a research scientist primarily to develop an assay platform of 3 Dimensional physiologically relevant, multi-cell-type disease models that are amenable to high-throughput screening. Prior to joining NCATS, she completed her postdoctoral fellowship at the National Institute on Aging. Her PhD is from the George Washington University in Molecular and Cellular Oncology. She has extensive experience in the miniaturization and optimization of physiologically relevant cell-based 2D and 3D assays to make them amenable for the screening of high-impact small molecule and functional genomics libraries with the goal of identifying unique receptor/ligand interaction and efficacy in various disease pathologies especially as they relate to the epigenetic modulation of cancer and stem cell biology.


    DATE: November 16, 2017
    TIME: 9:00AM PT, 12:00PM ET

    The wide use of 2D monolayer cultures for cancer drug discovery reflects the technical ease of implementation for drug screening, and the view that oncogenes or tumor suppressor genes are the key genetic drivers of cancer cell proliferation, and therefore, inhibiting these tumor driver genes with drugs should prevent tumor growth.   However, there is now ample evidence that the cellular and physiological context in which these oncogenic events occur play a key role in how they drive tumor growth in vivo, and therefore, in how a tumor responds to drug treatments. In vitro three dimensional (3D) spheroid cell culture tumor models are being developed to potentially enhance the predictability and efficiency of drug discovery in cancer.  Furthermore, the insight that primary tumors are vastly different from their metastatic counterparts has necessitated a paradigm shift in the development of HTS screening models to efficiently recapitulate key components of primary and metastatic disease. The ability to increase the throughout for a 3D spheroid assays will enable the generation of pharmacological profiles of chemotherapeutic agents and will hopefully illustrate more effective therapies that might have been missed in 2D, and deprioritize treatments options that might have looked very potent in 2D but have not efficacy in 3D.  This approach to cell biology has the potential to improve the physiological relevance of cell-based assays and advance the quantitative modeling of biological systems from cells to organisms.

     Learning Objecives:

    • Application of 3D models within oncology research and therapeutic strategies
    • Why scaling 3D models to a higher throughput format is important for higher throughput screening of drug candidates
    • Comparison of mechanism of action data from 3D models to that generated from 2D systems


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