Division of Theoretical Systems Biology

We probe the dynamics of cellular processes in stem cell systems, cancer and immunity. On a quantitative basis, we elucidate how tissue stem and progenitor cell dynamics are regulated in vivo in development, homeostasis and response to stress, how mutation accumulation and clonal selection shape somatic mosaicism, and how cancer evolves in somatic mosaics. Clonal dynamics and somatic evolution in the immune system have been a long-standing focus of our research.

To quantify the underlying processes of cell proliferation, differentiation, migration and cell death and dissect their regulation by feedback and external stimuli, we develop data-driven mathematical models. These models are rooted in population dynamics and population genetics, and are used for model selection and inference from experimental data. Key findings include the inference of differentiation pathways of T cells from clone size distributions measured in acute and chronic immune responses in vivo, the quantification of the differentiation rates of hematopoietic stem and progenitor cells in the intact bone marrow, and the reconstruction of the fetal origin and evolution of the embryonal tumor, neuroblastoma.

To elucidate molecular processes underlying cell-fate dynamics, we integrate single-cell omics (RNAseq and ATACseq) with cell lineage tracing in vivo. Moreover, we develop information-theoretic approaches for the functional characterization of molecular pathways. A hallmark of our research is the close interplay of theory with experiment, with original data directly driving mathematical modeling and theoretical predictions being tested experimentally.