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Division of Theoretical Systems Biology

Prof. Dr. Thomas Höfer

Computational reconstruction of neuroblastoma evolution from genome sequencing data (schematic redrawn from G. Caravagna, Mathematical modeling of neuroblastoma associates evolutionary patterns with outcomes, Nat. Genet. 2023).

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.


Prof. Dr. Thomas Höfer
Theoretical Systems Biology (B086)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 580
69120 Heidelberg
Tel: +49 6221 42-1980

Selected Publications

  • Körber V et al. (2023) Neuroblastoma arises in early fetal development and its evolutionary duration predicts outcome. Nature Genetics 55, 619-630.
  • Pei W., Feyerabend, T.B. et al. (2017) Polylox barcoding reveals haematopoietic stem cell fates realized in vivo. Nature 548, 456-460.
  • Busch K et al. (2015) Fundamental properties of unperturbed hematopoiesis from stem cells in vivo. Nature 518, 542-546.
  • Buchholz VR, Flossdorf M, et al. (2013) Disparate individual fates compose robust CD8+ T cell immunity. Science 340, 630-635.
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