Aberrant differentiation in cancer
Cancer is a consequence of gene mutations often leading to an aberrant over-proliferative cell state. In many cases, mutations cause a block in a differentiation pathway inducing a massive expansion of a proliferative progenitor stage, frequently at the expense of other cell types. In this proliferative state, secondary mutations can be acquired and give rise to an oligoclonal tumor composition. In some cancers, the proliferative state itself may have stem cell characteristics and reside at the apex of an aberrant tumor-internal differentiation hierarchy. It is also known that the tumor microenvironment and interactions between tumor cells and infiltrating immune cells can have a strong impact on the tumor growth and composition.
We are applying single-cell RNA-seq and spatial transcriptomics, as well as single-molecule fluorescence in situ hybridization (smFISH) methods in addition to genome sequencing in order to characterize cellular tumor heterogeneity. In collaborations with clinicians we are investigating human solid tumors to elucidate mechanisms underlying tumor emergence and progression. We have a particular interest in characterizing interactions between tumor cells and immune cells. Apart from a basic understanding of the disease transformation we are trying to establish a better stratification of tumor risk by the underlying genetic aberrations on the basis high-resolution tumor maps obtained with our approach.
In addition, we are utilizing mouse models to investigate clonal dynamics within tumors. To achieve this, we are combining single-cell RNA-seq with lineage tracing techniques.