Cell Plasticity and Regeneration
We aim to improve quality of life for cancer survivors, which suffer side effects of radiotherapy including an acute and chronic inflammation of the intestine. In order to achieve this goal, we study the cellular and molecular mechanisms involved in epithelial recovery after radiation injury. Furthermore we study the establishment of the chronic radiation-induced enteritis with a particular attention to the epithelial-immune cell crosstalk.
The primary function of the intestine is the digestion and absorption of nutrients. The small intestine is composed of proliferative crypts and differentiated villus structures. The adult intestine is lined with epithelium, which is maintained by intestinal stem cells. Radiation therapy is a common treatment used in at least 50% of cancer patients and despite its efficiency in eradicating cancer it induces intestinal toxicity. Radiation triggers apoptosis of proliferative cells, this denudes the intestinal mucosa and in turn results in an inflammatory response; the main features are initially an acute atrophy of the mucosa and at later stages fibrosis of the intestinal wall. The number of cancer survivors with post-radiation dysfunction of intestinal epithelium is continuously rising. However this condition to date has no effective treatments. Our primary objective is to understand the mechanisms triggering these processes in order to develop therapeutic options for those patients. In order to achieve this goal we use state of the art technologies and a plethora of groundbreaking approaches such as patient derived intestinal organoids, complemented by mouse models, lineage tracing, single cell transcriptomics and 3-dimensional imaging.