Hugo Snippert Group
Functional 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 the causes and consequences of cellular heterogeneity during the evolutionary trajectory of cancer, with specific interest at the emergence of malignancy within precancerous lesions and therapy resistance. 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 remove cancer mutations. Alternatively, we generate and introduce genetic knockins to monitor and/or manipulate cell biological processes in real-time, e.g. to understand plasticity of cellular identities and their behavior during malignant transformation or 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 in real-time, e.g. to measure single-cell drug responses in patient organoids.