High-throughput biology of cancer and immunity
We use multi-omics profiling and CRISPR technology to discover exciting new biology in cancer and immunity, and we take the most interesting results forward, together with our clinical partners to make them useful for precision medicine.
The biological concept of cellular identity connects a cell’s past with its future potential. Our research is based on the hypothesis that epigenetic cell states and the “epigenetic landscape” constitute a highly informative intermediate layer of information processing – one that captures a cell’s regulatory identity and retains the flexibility to respond swiftly to a broad range of perturbations. This definition of the “epigenetic landscape” is not restricted to specific epigenetic marks such as DNA methylation and histone modifications. Rather, it reflects the full range of transcription regulation by which cells translate various inputs into sustainable changes in their cell state. In particular, the epigenetic landscape not only defines a cell’s current state, but also details its developmental past (e.g., cell-of-origin in cancer) and future trajectories (e.g., plasticity in response to drug treatment).
To study the fundamental role of epigenetic and transcription-regulatory programs in cancer and immunity, we have established high-throughput pipelines to profile gene expression (i.e., bulk and single-cell RNA-seq) and transcriptional regulation (e.g., ATAC-seq, RRBS, ChIPmentation) to dissect the epigenetic landscape in patient cohorts and in disease-relevant mouse models. For example, we have established genome-scale maps of tumor heterogeneity in cancers of children (Ewing sarcoma, Langerhans histiocytosis) and elderly patients (glioblastoma, chronic lymphocytic leukemia). Our work also focuses on immune gene regulation – the first single-cell DNA methylation maps of hematopoietic stem cell differentiation and the first systematic map of immune regulation in non-immune cells (“structural immunity”).
Publications
* shared first or shared senior authorship