Hugo Snippert Group
Phenotypic heterogeneity in cancer
Cells within a cancer are highly heterogeneous. As a consequence, it is challenging to design treatment therapies that target all cancer cells as effectively. The Snippert group studies heterogeneity of cellular behavior during cancer growth and therapy resistance in human cancer samples. We mainly use patient-derived cancer organoids to study cellular phenomena that have a large impact on human cancer (treatment), such as therapy resistance. Most importantly, cancer organoid cultures can be established from virtually all cancer types, thereby allowing us to study phenomena across many different tumor subtypes, cancer stages and mutational landscapes that are present within the patient population.
In addition, we apply molecular genetics to engineer the cancer organoids to our own interest, which includes CRISPR/Cas9-mediated homologous recombination to introduce or correct cancer mutations at their exact endogenous location. Alternatively, we generate and introduce reporters to monitor and/or manipulate cellular processes in real-time that underlie the plasticity of cellular identities and behavior during tumor growth and therapy resistance. Together, we integrate different sensors and biomarkers as well as develop and utilize state-of-the-art imaging techniques to monitor and quantify cellular identities and signaling activities on a cellular level in real-time.