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Winding back the tape of tumors
时间:2025年07月08日 09:51 点击数:

报告人:Kasper Karlsson

报告地点:数学与统计学院105教室

报告时间:2025年07月11日星期五09:00-10:00

邀请人:数学与统计学院

报告摘要:

Stephen J Gould once famously asked: "Should the tape of life be replayed, would it produce similar living beings?". This question may never get fully resolved, but recent technological developments allowed us to ask a similar question transposed to the context of cancer: "If we initiate tumor evolution in multiple similar cells, will the same phenotype emerge?". To tackle this problem, we made use of organoid cell culture models that recapitulates native tumors with increasing fidelity, and expressed cellular barcodes that make it possible to study evolutionary processes with high resolution, to establish an experimental ex vivo platform to study tumorigenesis. Specifically, TP53-deficiency was engineered into primary human gastric organoids from healthy donors and several clonally derived replicate cultures were evolved for over two years. The cultures were extensively interrogated by DNA and single cell RNA sequencing, and cell barcoding was introduced to examine subclonal dynamics. We observed that several features of gastric tumor evolution could be replicated by prolonged ex vivo culturing, that selection was similar across replicates from the same culture and that cultures from different donors evolved similar malignant phenotypes. This suggests that tumor evolution is partly intrinsic to the tumor cells, without the influence of a complex microenvironment, and moreover that this process to some extent is predictable. By "restarting the tape of cancer" under different conditions, we may find a path forward that thwart malignant transformation.

主讲人简介:

Dr. Karlsson started his research career in 2011 as a graduate student at Karolinska Institutet in Stockholm, Sweden. In 2016 he moved to Stanford, USA, for his postdoctoral studies, where he developed in vitro model systems of tumor evolution. Kasper is a senior research specialist at Karolinska Institutet, where he develops new therapies and drug combinations for pediatric cancer, including the concept "Precision Lethality" where cell barcoding is used to identify and target cell populations that are resistant to standard of care with new drugs. Dr. Karlsson's pioneering work has been featured in top-tier scientific publications, most notably in Nature and its specialized sister journal Nature Methods.

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