Research Focus
Our research group investigates the molecular mechanisms of hematologic and oncologic diseases, with a special focus on genetic and epigenetic factors underlying the differentiation block of leukemic blasts. A central focus is on the role of transcription factors and epigenetic modifications in disease development and progression as well as on the release of the curative potential of all-trans-retinoic acid (ATRA) in acute myeloid leukemia (AML).
We develop innovative biophotonic methods, such as UV laser ChIP-seq and Laser-Flow-Cytometry, to analyze specific DNA-protein interactions and aberrant cell changes. The aim is to better understand fundamental biological processes and to establish new approaches for diagnosis, therapy and personalized medicine.
Publications
Schenk, T., Chen, W. C., Göllner, S., Howell, L., Jin, L., Hebestreit, K., Klein, H. U., Popescu, A. C., Burnett, A., Mills, K., Casero, R. A., Jr, Marton, L., Woster, P., Minden, M. D., Dugas, M., Wang, J. C., Dick, J. E., Müller-Tidow, C., Petrie, K., & Zelent, A. (2012). Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia. Nature medicine, 18(4), 605–611. https://doi.org/10.1038/nm.2661
Schenk, T., Stengel, S., & Zelent, A. (2014). Unlocking the potential of retinoic acid in anticancer therapy. British journal of cancer, 111(11), 2039–2045. https://doi.org/10.1038/bjc.2014.412
Göllner, S., Oellerich, T., Agrawal-Singh, S., Schenk, T., Klein, H. U., Rohde, C., Pabst, C., Sauer, T., Lerdrup, M., Tavor, S., Stölzel, F., Herold, S., Ehninger, G., Köhler, G., Pan, K. T., Urlaub, H., Serve, H., Dugas, M., Spiekermann, K., Vick, B., … Müller-Tidow, C. (2017). Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia. Nature medicine, 23(1), 69–78. https://doi.org/10.1038/nm.4247
Steube, A., Schenk, T., Tretyakov, A., & Saluz, H. P. (2017). High-intensity UV laser ChIP-seq for the study of protein-DNA interactions in living cells. Nature communications, 8(1), 1303. https://doi.org/10.1038/s41467-017-01251-7
Kahl, M., Brioli, A., Bens, M., Perner, F., Kresinsky, A., Schnetzke, U., Hinze, A., Sbirkov, Y., Stengel, S., Simonetti, G., Martinelli, G., Petrie, K., Zelent, A., Böhmer, F. D., Groth, M., Ernst, T., Heidel, F. H., Scholl, S., Hochhaus, A., & Schenk, T. (2019). The acetyltransferase GCN5 maintains ATRA-resistance in non-APL AML. Leukemia, 33(11), 2628–2639. https://doi.org/10.1038/s41375-019-0581-y
Sbirkov, Y., Ivanova, T., Burnusuzov, H., Gercheva, K., Petrie, K., Schenk, T., & Sarafian, V. (2021). The Protozoan Inhibitor Atovaquone Affects Mitochondrial Respiration and Shows In Vitro Efficacy Against Glucocorticoid-Resistant Cells in Childhood B-Cell Acute Lymphoblastic Leukaemia. Frontiers in oncology, 11, 632181. https://doi.org/10.3389/fonc.2021.632181
Stengel, S., Petrie, K. R., Sbirkov, Y., Stanko, C., Ghazvini Zadegan, F., Gil, V., Skopek, R., Kamiński, P., Szymański, Ł., Brioli, A., Zelent, A., & Schenk, T. (2022). Suppression of MYC by PI3K/AKT/mTOR pathway inhibition in combination with all-trans retinoic acid treatment for therapeutic gain in acute myeloid leukaemia. British journal of haematology, 198(2), 338–348. https://doi.org/10.1111/bjh.18187
Sbirkov, Y., Schenk, T., Kwok, C., Stengel, S., Brown, R., Brown, G., Chesler, L., Zelent, A., Fuchter, M. J., & Petrie, K. (2023). Dual inhibition of EZH2 and G9A/GLP histone methyltransferases by HKMTI-1-005 promotes differentiation of acute myeloid leukemia cells. Frontiers in cell and developmental biology, 11, 1076458. https://doi.org/10.3389/fcell.2023.1076458
Funding
Deutsche Forschungsgemeinschaft, JSMM, Landesgraduiertenstipendium (Faezeh Ghazvini Zadegan)