How are epigenetic marks established and what is their role in myelopoiesis?

On one hand, our lab has a long-standing interest in the biology and differentiation of mononuclear phagocytes. These cells fulfill important roles in development, tissue homeostasis, inflammation and wound healing and are a major cell population in most of the tissues in the body. We are particularly interested in blood monocytes, because they are extremely plastic and are able to mature into various types of macrophages, antigen-presenting dendritic cells or even multinucleated bone-resorbing osteoclasts. Monocytes are non-dividing and their proliferation-independent differentiation represents an excellent model to study active epigenetic processes. In this system, we are studying DNA methylation turnover, the function of particular transcription factors in epigenetic processes, as well as the influence of environmental cues on transcription networks and enhancer usage.

Apart from their role in normal development and differentiation, epigenetic processes and machineries also play important roles in tumorigenesis. In particular leukemia represents a paradigm example for "epigenetic" disease origins with roughly 50% of patients harbouring mutations in genes involved in DNA-methylation turnover. Here, we are trying to understand how aberrant DNA methylation patterns arise during the development of acute myeloid leukemias. Since chromatin landscapes are altered in general, we are also interested in the role of aberrant enhancer usage in leukemic cells. Using a wide array of modern genome-wide approaches, this project aims at defining disease-associated epigenetic changes that may ultimately lead to novel therapeutic approaches.