【第65回がん研先端研究セミナー(1月22日)のお知らせ 「Unraveling non-genetic heterogeneity, cellular plasticity, and drug resistance in patient-derived colorectal cancer organoids」Dr. Roberto Coppo(京都大学大学院医学研究科 クリニカルバイオリソース研究開発講座 JSPS外国人特別研究員)】
2024年01月04日
第65回がん研先端研究セミナー(1月22日)のお知らせ
演題:Unraveling non-genetic heterogeneity, cellular plasticity, and drug resistance in patient-derived colorectal cancer organoids
演者:Dr. Roberto Coppo(京都大学大学院医学研究科 クリニカルバイオリソース研究開発講座 JSPS外国人特別研究員)
抄録:This comprehensive seminar delves into the intricate dynamics of colorectal cancer (CRC) by addressing three pivotal aspects. Firstly, a detailed protocol for patient-derived tumor organoids is presented, enabling the study of heterogeneity and plasticity through single-cell tracking and the isolation of slow-growing cells. Secondly, non-genetic cellular plasticity contributing to intratumor heterogeneity is explored. Through clonogenic growth assays in patient-derived CRC organoids, distinct subpopulations with different growth patterns and drug sensitivity are identified, highlighting the role of extrinsic triggers, Notch signaling, and Musashi-1 in modulating the transition from a slow- to a fast-growing phenotype. Lastly, the non-genetic mechanisms of drug resistance, with a focus on investigating drug-tolerant persister (DTP) cells in CRC, are examined. By applying patient-derived CRC organoids, clinically used chemotherapeutic drugs, and CRISPR dropout screens, the research aims to unveil the molecular mechanisms governing the transition of DTP cells from a senescence-like drug-resistant state to a regrowth phenotype, identifying new genetic vulnerabilities and therapeutic targets. This integrated approach provides valuable insights into CRC dynamics, offering potential strategies against treatment resistance and recurrence.
日時:2024年1月22日(月)16:00 〜 17:00
場所:吉田記念講堂
演題:Unraveling non-genetic heterogeneity, cellular plasticity, and drug resistance in patient-derived colorectal cancer organoids
演者:Dr. Roberto Coppo(京都大学大学院医学研究科 クリニカルバイオリソース研究開発講座 JSPS外国人特別研究員)
抄録:This comprehensive seminar delves into the intricate dynamics of colorectal cancer (CRC) by addressing three pivotal aspects. Firstly, a detailed protocol for patient-derived tumor organoids is presented, enabling the study of heterogeneity and plasticity through single-cell tracking and the isolation of slow-growing cells. Secondly, non-genetic cellular plasticity contributing to intratumor heterogeneity is explored. Through clonogenic growth assays in patient-derived CRC organoids, distinct subpopulations with different growth patterns and drug sensitivity are identified, highlighting the role of extrinsic triggers, Notch signaling, and Musashi-1 in modulating the transition from a slow- to a fast-growing phenotype. Lastly, the non-genetic mechanisms of drug resistance, with a focus on investigating drug-tolerant persister (DTP) cells in CRC, are examined. By applying patient-derived CRC organoids, clinically used chemotherapeutic drugs, and CRISPR dropout screens, the research aims to unveil the molecular mechanisms governing the transition of DTP cells from a senescence-like drug-resistant state to a regrowth phenotype, identifying new genetic vulnerabilities and therapeutic targets. This integrated approach provides valuable insights into CRC dynamics, offering potential strategies against treatment resistance and recurrence.
日時:2024年1月22日(月)16:00 〜 17:00
場所:吉田記念講堂