Junior Research Group "Developmental Origins"

The DKFZ Junior Research Group “Developmental Origins of Pediatric Cancer” headed by Lena M. Kutscher, PhD, is part of the DKFZ research program "Functional and Structural Genome Research" and closely associated with Prof. Stefan Pfister’s department “Pediatric Neurooncology”. Our group is focused on understanding how aberrations in normal neurodevelopment can lead to pediatric brain cancer. We are particularly interested in investigating and modeling the cell-of-origin and driver mutations for pediatric medulloblastoma and glioma. Because no single model completely recapitulates normal human brain development, our group uses a combination of mouse models, human cerebellar organoids and induced pluripotent stem cells, and patient-derived xenograft (PDX) models to investigate the interplay between neurodevelopment and tumorigenesis.


Main research aspects

Because pediatric tumors may arise from a block in development, understanding normal progenitor cell differentiation is a crucial first step to understanding tumor formation. To study normal development, however, we need appropriate experimental tools and models. Using single cell sequencing data derived from Stefan Pfister’s ERC-funded “BRAIN-MATCH” project, we will differentiate granule neuron progenitors (GNP), the cell-of-origin for SHH-medulloblastoma, in vitro from induced pluripotent stem cells. After establishing GNP differentiation in vitro, we can use this model to create tumor-prone GNPs and study their transformation to malignancy. We will also create a framework to differentiate other cells-of-origin in vitro based on our human single-cell sequencing data sets.

To complement our in vitro studies, we use genetically engineered mouse models and in utero electroporation to understand how mutations in precursor cells after neural development and tumorigenesis in mice. We focus on genes that are recurrently mutated in human tumors to understand the mechanistic underpinnings of these mutations. The models and mechanisms uncovered will be further investigated preclinically in collaboration with other groups at the KiTZ.

Team

  • Lena Kutscher, PhD (DKFZ Junior Group Leader)
  • Laura Sieber (Technician)
  • Patricia Benites, PhD (Postdoc)
  • Piyush Joshi, PhD (Postdoc)
  • Daniel Haag, PhD (consultant)

Lena M. Kutscher, PhD

Group leader "Developmental Origins"

Postal address:
Hopp Children's Cancer Center Heidelberg
Im Neuenheimer Feld 580
D-69120 Heidelberg
Germany