Prof. Dr. Steffen Koschmieder

 

Oncology, Molecular Biology, Cell Biology, Animal Models, Primary Patient Samples

We focus on the elucidation of critical mechanisms in the pathogenesis of myeloid leukemias (CML, AML, Myeloproliferative Neoplasms [MPN]). This involves in vitro and in vivo assays at the cellular and molecular level. In particular, we are currently studying novel oncogenic kinase mutants, the effects of interferon on chromatin, and critical pathways in malignant stem cells. Clinically, we can provide samples and expertise to study cancer in humans and mice.

 

Expertise

Hematology, Oncology, and Hemostaseology (clinical diagnostics and management, clinical trials phase I-IV, morphology, coagulation disorders), molecular biology (ChIPseq, qPCR, Western blotting, luciferase assays, next-generation sequencing), cell biology (proliferation, viability, apoptosis, hematopoietic differentiation, clonogenic assays, stem and progenitor cell flow cytometry and FAC sorting), animal models (transgenic inducible Bcr-Abl positive mouse model, transplantation assays), primary patient samples (from a large national MPN registry and biobank).

 

Needs

Support to predict the conformation and binding proteins of our novel tyrosine kinase mutants (molecular dynamics, organic chemistry), large-scale drug screens and targeted design of novel inhibitors binding partners for these mutants (chemistry, computer simulations), logistics for translational research and treatment unit (stem cell factory, GMP facility).

 

References

1. Koschmieder, S., Göttgens, B., Zhang, P., Iwasaki-Arai, J., Akashi, K., Kutok, J. L., ... &Huettner, C. S. (2005). Inducible chronic phase of myeloid leukemia with expansion of hematopoietic stem cells in a transgenic model of BCR-ABL leukemogenesis. Blood, 105(1), 324-334.
2. Huang, G., Zhang, P., Hirai, H., Elf, S., Yan, X., Chen, Z., ... &Tenen, D. G. (2008). PU. 1 is a major downstream target of AML1 (RUNX1) in adult mouse hematopoiesis. Nature Genetics, 40(1), 51-60.
3. Schemionek, M., Elling, C., Steidl, U., Bäumer, N., Hamilton, A., Spieker, T., ... & Koschmieder, S. (2010). BCR-ABL enhances differentiation of long-term repopulating hematopoietic stem cells. Blood, 115(16), 3185-3195.
4. Elling, C., Erben, P., Walz, C., Frickenhaus, M., Schemionek, M., Stehling, M., ... & Koschmieder, S. (2011). Novel imatinib-sensitive PDGFRA-activating point mutations in hypereosinophilic syndrome induce growth factor independence and leukemia-like disease. Blood, 117(10), 2935-2943.
5. Hamilton, A., Helgason, G. V., Schemionek, M., Zhang, B., Myssina, S., Allan, E. K., …, Koschmieder, S. & Holyoake, T. L. (2012). Chronic myeloid leukemia stem cells are not dependent on Bcr-Abl kinase activity for their survival. Blood, 119(6), 1501-1510.