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Monday, October 21 • 12:30pm - 12:50pm
Enabling Technologies- Multiparametric Phenotyping of Compound Effects on Patient Derived Organoids

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Patient derived organoids (PDOs) closely resemble individual tumor biology and allow testing of small molecules ex vivo. To systematically dissect compound effects on 3D organoids, we developed a high-throughput imaging and quantitative analysis approach. We generated PDOs from colorectal cancer patients, treated them with >500 small molecules and captured >3 million images by confocal microscopy. We developed the software framework SCOPE to measure compound induced re-organization of PDOs. We found diverse, but re-occurring phenotypes that clustered by compound mode-of-action. Complex phenotypes were not congruent with PDO viability and many were specific to subsets of PDO lines or were influenced by recurrent mutations. We further analyzed specific phenotypes induced by compound classes and found GSK3 inhibitors to disassemble PDOs via focal adhesion signaling or that MEK inhibition led to bloating of PDOs by enhancing of stemness. Finally, by viability classification, we show heterogeneous susceptibilities of PDOs to clinical anticancer drugs.

Authors:
Johannes Betge, Niklas Rindtorff, Jan Sauer, Benedikt Rauscher, Clara Dingert, Haristi Gaitantzi,
Frank Herweck, Thilo Miersch, Erica Valentini, Veronika Hauber, Tobias Gutting, Larissa Frank, Sebastian Belle,
Timo Gaiser, Inga Buchholz, Ralf Jesenofsky, Nicolai Härtel, Tianzuo Zhan, Bernd Fischer, Katja Breitkopf-Heinlein, Elke Burgermeister, Matthias P. Ebert, Michael Boutros

Speakers
avatar for Niklas Rindtorff

Niklas Rindtorff

MD/Ph.D. Student, German Cancer Research Center (DKFZ)

Chair
avatar for Hazel Screen, Ph.D., MRes, BEng

Hazel Screen, Ph.D., MRes, BEng

Professor of Biomedical Engineering, Queen Mary University of London
Hazel Screen is Professor of Biomedical Engineering and Chair of Bioengineering at Queen Mary University of London.Her research group focuses on multi-scale structure-function behaviour and mechanobiology in tissues. She has particular interest in in vitro models to explore health... Read More →


Monday October 21, 2019 12:30pm - 12:50pm
Wellcome Auditorium