Epigenetic Regulation of normal hematopoiesis and its dysregulation in myeloid neoplasia

Histone deacetylase activity and its inhibitors in myeloid neoplasia

Epigenetics deals with heritable changes in gene expression that occur without changes in the genome. Inhibitors of histone deacetylases (HDACs) have shown great promise in the development as new epigenetic anticancer agents. New lead HDAC inhibitors from our group have shown antiproliferative activity against leukemia cells.
Starting from this leads, we want to establish potent optimized analogues with a defined HDAC subtype inhibition profile as potential antileukemic drugs.

Furthermore, we have discovered a potential new prodrug principle for HDAC inhibitors that leads to optimized cellular activity and we want to apply this principle to established and new HDAC inhibitors in order to investigate its general validity. The assays that are used to measure the inhibition of HDACs in-vitro can also be applied to the measurement of cellular HDAC activity, also from blood samples from patients in clinical trials with HDAC inhibitors. We want to use this methodology in collaboration with clinical groups from the SPP to investigate whether this might be used as a novel biomarker for optimized drug dosage and patient treatment.

  • Kaufmann K. B., Gründer A., Hadlich T., Wehrle J., Gothwal M., Bogeska R., Wagner J. M., Jung M., Günther T., Schüle R., Rambaldi A., Pahl H. L. (2012). A novel murine model of myeloproliferative disorders generated by overexpression of the transcription factor NF-E2. J. Exp. Med. PMID:22231305

  • Wagner J. M., Hackanson B., Lübbert M., Jung M. (2010). Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy. Clin. Epigenetics 1:117-136. PMID:21258646

  • Schlimme S., Hauser A.T., Carafa V., Heinke R., Stolfa D. A., Cellamare S., Carotti A., Altucci L., Jung M., Sippl W. (2011). Carbamate prodrug concept for hydroxamate HDAC inhibitors. ChemMedChem. 6:1193-1198. PMID:21416613

  • D. A. Stolfa, A. Stefanachi, J. M. Gajer (née Wagner), A. Nebbioso, L. Altucci, S. Cellamare, M. Jung, A. Carotti. (2012). Design, synthesis and biological evaluation of 2-aminobenzanilide derivatives as potent and selective HDAC inhibitors. ChemMedChem. (in press)

  • Manfred Jung

    University of Freiburg
    Albertstr 25
    D-79104 Freiburg, Germany
    Phone +49-761-2034896
    Fax +49-761-2036321




    Kristina Keller
    Julia M. Gajer (geb. Wagner)