FEB 22, 2018 9:00 AM PST

Investigating colorectal cancer using epithelial organoid cultures

Speaker
  • Postdoctoral researcher, Hubrecht Institute
    Biography
      Kai Kretzschmar received his PhD from the University of Cambridge (UK) in 2014. During his doctoral training under the supervision of Fiona Watt, he studied the role of canonical Wnt signalling in the plasticity of adult murine skin and epidermal stem cell heterogeneity. Subsequently, Kai joined the laboratory of Hans Clevers at the Hubrecht Institute in Utrecht (The Netherlands) to investigate the heterogeneity of the tumour microenvironment in colorectal cancer.

    Abstract

    DATE: February 22, 2018
    TIME: 09:00am PST, 12:00pm EST, 06:00pm CEST(Europe)

    Colorectal cancer (CRC) develops during a multi-step process from small lesions of the intestinal epithelium. Genetic mutations in the canonical Wnt signalling pathway are considered to be the initial step of tumour formation. Using 3D organoid technology, tumour organoid cultures from CRC patients can be established. CRC organoids closely recapitulate key properties of the original tumour epithelium, including histological appearance, general gene and protein expression pattern and mutational load. Tumour organoids are amenable to radiation treatment, gene-drug association studies and high-throughput drug screens. Organoid cultures from adjacent healthy colon mucosa that retain the identity of the healthy intestinal epithelium in vitro can also be generated. Sequential introduction of the most commonly mutated CRC genes (APC, P53, KRAS and SMAD4) into healthy colon organoids using CRISPR/Cas9 genome editing technology allows for the modelling of tumorigenesis in vitro. Xenotransplantation of mutated organoids into mice recapitulates critical features of CRC progression and metastasis. In sum, (cancer) organoid technology can be used as experimental tool for basic research as well as diagnostic and therapeutic tool for (personalised) medicine.

    Learning Objectives:

    • Understand the advantages of epithelial organoids cultures for (colorectal) cancer modelling.
    • Learn about applications of (colorectal) cancer organoids for experimental, diagnostic and therapeutic use

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