Modelling Cancer

Cancer is the scourge of modern society, and our lab is involved in various translational research efforts to better understand how aberrant cell-cell communication leads to this disease. One focus is colorectal cancer (CRC), which is the third most common cancer worldwide. Alarmingly, the incidence of CRC is increasing in adults younger than 50.

More than half of the patients diagnosed with colorectal cancer (CRC) either harbor metastases or will develop metastatic disease, which is the primary cause of death for CRC patients. Unfortunately, the molecular mechanisms driving CRC metastasis are still poorly understood and thus effective treatment modalities are currently missing. A reason for this has been the challenge to experimentally model the entire metastatic cascade (invasion, intravasation, circulation, extravasation, and colonisation) in vivo in a fully immunocompetent background.
In the lab, we established a murine orthotopic model of metastatic CRC, based on the colonoscopy-guided injection of organoids that harbor tumorigenic mutations. We use state-of-the-art methods (e.g., single cell transcriptomic analysis, CRISPR/Cas9 based lineage tracing etc.) to study the primary tumor, circulating tumor cells and metastases from the same animal. By creating integrated single-cell transcriptomic atlases of the entire metastatic cascade in different contexts we aim to build a foundation of knowledge to guide future therapy development.

Various Drosophila tumor models have been developed that mimic key hallmarks of human cancers, including metastasis. An emerging experimental paradigm is the induction of tumors in the adult Drosophila midgut. We are using this system to identify potential regulators of cell invasion, a key initiating step in metastasis. Our tumor model is based on hyperactivation of Wnt and Ras signaling, the most common mutations in colorectal cancer. This project is part of a 3RCC initiative that aims to reduce harmful animal experiments.
https://swiss3rcc.org/funded-projects/2020-call-identifying-new-regulators-of-cell-invasion-in-colorectal-cancer-using-the-drosophila-adult-intestine  
In addition, we are using different Drosophila tumor models to probe the role of the Toll pathway in tumorigenesis. The role of TLR signaling (homologous to the Drosophila Toll pathway) in tumorigenesis is controversial. Depending on the context, pathway activation has been reported to be either pro- or anti-tumorigenic. By examining the effect of perturbing the Toll pathway in different Drosophila tumor models, including in the midgut, we hope to shed light on the mechanisms underlying this context dependency.