Project Details
Projekt
Reversible histone acetylation and its inhibitors in myeloid neoplasia
Applicant
Professor Dr. Manfred Jung
Subject Area
Hematology, Oncology
Pharmacy
Pharmacy
Term
from 2010 to 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 171267211
Reversible acetylation of histones is a key element in epigenetic regulation and has been shown to be involved in the pathogenesis of myeloid disease on a molecular level for both histone acetylation and deacetylation. In a combination of medicinal chemistry, in-vitro biochemistry, cellular studies and translational studies on patient blood samples we want to further develop the insight on the role of reversible histone acetylation in myeloid diseases. We plan to synthesize potent and selective inhibitors of histone acetyltransferases (HATs) and test their activity on isolated enzymes, leukemic cells in culture and on patient blasts cultured ex-vivo. Selected optimized inhibitors will be tested in animal models of myeloid disease. This will also be realized for optimized histone deacetylases (HDACs) inhibitors and prodrugs that we have developed in the first phase of the programme. We will use assays to measure cellular HDAC and HAT activity to correlate those with diseases states and especially for samples from clinical HDAC inhibitor trials with inhibitor response. This research program covers a wide range of aspects of reversible histone acetylation and its inhibitors and will bring further knowlege on its inhibitors as tools for signalling studies and potential drugs and on the use of enzymatic assay in translational studies. In interaction with the biomedical and clinical groups from the consortium a high level of synergy can be expected.
DFG Programme
Priority Programmes
