Head: Prof. Hubert Serve, MD
In our lab, we focus on interactions of hematopoietic cells with their microenvironment. We are very interested in the question, how changes in the metabolic wiring make leukemic cells more or less responsive to environmental stimuli, such as cytokine stimulation, cell-cell interactions or to toxic agents like cytotoxic drugs that are used in the clinics to fight hematological malignancies. We concentrate on two diseases: Acute Myeloid Leukemia (AML) and Multiple Myeloma (MM).
In both diseases, we started to very thoroughly define, whether metabolic conditions like the availability of nutrients, biomolecules or oxygen change the way how the malignant cells grow, proliferate, differentiate and die. We decipher the molecular pathways that are responsible for these changes. Given the exquisite dependency of AML and MM cells from the bone marrow microenvironment (both diseases only rarely can survive in patients without their “home base”, the bone marrow), we are convinced that this dependency will be therapeutically exploitable - and that it largely depends on seemingly subtle metabolic changes.
However, the experiments are challenging, they require state-of-the-art technology for cell manipulation as well as for measurements, which we are happy to have available and which we constantly optimize - in close collaboration with many groups from Frankfurt, several consortia in Germany and Europe, and from all around the world. Technologies that we have developed or that we have immediate access to entail quantitative peptide mass spectrometry to characterize protein expression and posttranslational modifications, forward genetic screening technology utilizing RNA interference and CRISPR/CAS9-mediated DNA recombination, generation of disease models using newly emerging gene editing techniques, and mass spectrometry and nuclear magnetic resonance to analyze metabolic changes. The combination of these tools with the classical tools of protein chemistry, molecular biology, and experimental hematology allows us to study the consequences of metabolic changes on leukemia and myeloma cells, and on their stromal interaction partners in great detail. By comparison of our findings between physiological conditions on one hand, and leukemia and myeloma on the other hand, we aim to identify molecular determinants of therapy response, be it to targeted drugs or to cytotoxic agents.