Project Details
Projekt
Development of integrative methods for the analysis of epigenetic data on myeloid neoplasia
Applicant
Professor Dr. Benedikt Brors
Subject Area
Hematology, Oncology
Term
from 2010 to 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 171437153
Regulatory mechanisms based on epigenetic marks can only be understood if we are able to bring together, and analyze in an integrative fashion, the following data: (i) information on epigenetic marks and their systematic changes, e.g. DNA methylation patterns or modifications of histone proteins; (ii) transcript concentrations; (iii) genetic aberrations that occur in cancer cells or their precursors. In this project, we will develop integrative bioinformatic methods that mine this data simlutaneously and will reveal the most relevant epigenetic factors for cancer initiation or cancer progression in the context of myeloid leukemias or pre-leukemias. Within this Research Priority Program, we will then use these methods in three prototypic collaborations:1. To identify mechanisms that lead to a particularly poor prognosis and to therapy failure in patients with acute myeloid leukemia (AML) with loss of chromosome 7, or of the long arm of this chromosome (collaboration with Christoph Plass, DKFZ).2. To study demethylation of DNA that occurs in leukemic cells from AML patients in clinical trials that receive a treatment with the drug decitabine. We want to study whether this demethylation is global or restricted to certain places in the genome, and whether the patterns are random or consistent between different patients and cell types. We will combine this information with gene expression data to identify those changes that are coupled to significant differences in the expression of genes nearby and thus have a high likelihood to be of functional relevance (collaboration with Michael Lübbert, University Hospital Freiburg).3. To understand how epigenetic regulation of genes involved in pluripotency triggers differentiation of mouse embryoinc stem cells and formation of blood cells. Here, we have already identified patterns of histone methylation in chromatin regions of pluripotency-associated genes. We will integrate this with gene expression measurements that have been derived from wild-type mice as well as from a mutant that cannot fully methylate a particular amino acid in the histone 3 protein (H3K27). (Collaboration with Albrecht Müller, University of Würzburg)
DFG Programme
Priority Programmes
