Taking apart pediatric cancer bit by bit

Goals

It is our goal to understand developmental processes in cancer biology. We track development in selected model cancers and characterize (epi)genomic changes that occur in time and space. With these data, we aim to decipher the syntax and semantics of development by formal abstraction into intelligible models, and by reconstruction in tractable experimental systems. To this end, we combine developmental and cancer biology with functional genomics, data analytics, and mathematics. There are three aspects of development that are currently at the heart of our interest: Intra-tumor plasticity, the formation of metastases, and the influence of non-tumor cells on these processes.

+ + = !

Significance

Cancer is a disruption of orderly developmental processes – cancerous cells either fail to reach the destination of their developmental circuit or they revert after they had seemingly completed the track. By achieving a thorough understanding in individual cases and abstracting the findings in quantitative models, we help to elucidate new avenues for detecting (diagnosis), projecting (prognosis), and interfering (therapy) with aberrant development in pediatric cancers.



Recent projects:

Intra-tumor plasticity

Langerhans cell histiocytosis (LCH) is an enigmatic neoplasm with highly variable clinical presentation and severity. Our new study together with CeMM charts molecular heterogeneity in LCH at single-cell resolution and unravels an unexpected hierarchy.

Read the paper Get the data

Finding enhancers

Enhancers are genetic elements that regulate gene expression. Our recent study in collaboration with researchers from Edinburgh and Rotterdam used a genome-wide assay to explore enhancer activity in human ESCs.

Read the paper Get the data

Kinases & blood

Cellular development is shaped by the enzymatic activity of kinases. Two of our recent contributions implicate MAPK in blood stem cell activation, and JAK and Aurora kinases in mutant immune cells -- with impacts on the transcriptome and epigenome.

MEKi & HSCs STAT5 Neoplasia

Epigenetics of hematopoiesis

The hierarchical development of the human blood system is a highly intricate and fascinating process. Within the Blueprint consortium, we charted a map of the epigenetic changes occurring during hematopoiesis using DNA methylation profiling.

Read the paper Get the data

Macrophage development

Tissue-resident macrophages are key elements of the immune system and important for organismal development and homeostasis. We teamed up with researchers from New York and Bonn to trace back the specification of these cells to embryonic progenitors.

Read the paper Get the data

Biomarker benchmark

DNA methylation is a stable epigenetic mark that lends itself for use in biomarker assays. We conducted a large benchmark study -- involving 16 research labs worldwide -- to compare candidate technology platforms for clinical translation.

Read the paper Get the code

Regulation of pluripotency

We have investigated the regulators of mammalian pluripotency to discover what makes ESCs tick.

Esrrb Oct4/Nanog Sox2/Oct Sox2/Nanog Sox Esrrb-loss

Streamlined NGS analysis

To ease access and reuse of functional genomics data, we developed a web-based software suite and database that streamlines NGS data analysis.

Read the paper Read the other paper

Publications: