Most of our knowledge of tissue homeostasis, tumor initiation and tumor progression is derived from techniques that draw a static picture of these highly dynamic processes. To study the dynamic aspects of these processes, our group develops state-of-the-art imaging techniques to visualize and study individual cells in real-time in living animals, referred to as intravital microscopy. We have crossed the latest lineage tracing mouse models and cell type-specific fluorescent mouse models with genetic tumor mouse models and combined these with intravital microscopy to study the migratory properties and fate of cells, with a focus on stem cells, during tissue homeostasis, tumor initiation and progression, and development of therapy resistance.
Filming the dynamic processes of cancer with intravital microscopy requires visual access to tissues over prolonged times. Therefore, group invented the mammary imaging window to intravitally visualize breast tumors, and the abdominal imaging window to intravitally visualize intestines and liver metastases. We were the first to visualize the growth of a liver metastasis from individual colorectal tumor cells in real time, and showed that for the maturation of liver metastasis tumor cells need to retain their migratory properties.
Recently the group has adopted the organoid culture system developed by Hans Clevers to obtain patient derived tumor xenografts (PDTX) in order to study tumor growth, progression and therapy resistance in a human setting. Human (engineered) organoids are transplanted and grown in mice, and used to visualize and study the dynamic properties of human tumor cells.