(421e) Area 15D/E Life Sciences Plenary Award: “Physiome on a Chip”: How Integration of Systems Biology with “Organs-on-Chips” May Humanize Therapeutic Development

“Mice are not little people” – a refrain becoming louder as the strengths and weaknesses of animal models of human disease become more apparent. At the same time, three emerging approaches are headed toward integration: powerful systems biology analysis of cell-cell and intracellular signaling networks in patient-derived samples; 3D tissue engineered models of human organ systems, often made from stem cells; and micro-fluidic and meso-fluidic devices that enable living systems to be sustained, perturbed and analyzed for weeks in culture. This talk will highlight the integration of these rapidly moving fields to understand difficult clinical problems, with an emphasis on translating academic discoveries into practical use. Applications in cancer and chronic inflammatory diseases are highlighted. In particular, technical challenges in modeling complex diseases with “organs on chips” approaches include the need for relatively large tissue masses and organ-organ cross talk to capture systemic effects, as well as new ways of thinking about scaling to capture multiple different functionalities from drug clearance to cytokine signaling crosstalk. An example of how gut-liver interactions can be parsed at these levels will be featured, along with new approaches for culturing complex 3D tissues with synthetic extracellular matrix.