Targeted therapy in high-risk childhood acute leukemia
This working group is dedicated to advancing the understanding and treatment of pediatric leukemia by focusing on three primary research domains: i) elucidating the molecular mechanisms of drug resistance, ii) targeting epigenetic modifications, and iii) addressing stress signaling pathways to overcome therapy resistance. In collaboration with our partners, we are actively developing novel HDAC and HSP90 inhibitors. Additionally, we employ a drug repurposing approach by performing high-throughput drug sensitivity screening on initial and relapsed leukemia samples. We also propagate primary leukemia samples in xenograft NSG mouse models for downstream analysis and testing potent therapeutic candidates.
We welcome applications from highly motivated candidates.
Selected Publications:
- Vogt M, Dienstbier N, Schliehe-Diecks J, Scharov K, Tu JW, Gebing P, Hogenkamp J, Bilen BS, Furlan S, Picard D, Remke M, Yasin L, Bickel D, Kalia M, Iacoangeli A, Lenz T, Stühler K, Pandyra AA, Hauer J, Fischer U, Wagener R, Borkhardt A, Bhatia S. Co-targeting HSP90 alpha and CDK7 overcomes resistance against HSP90 inhibitors in BCR-ABL1+ leukemia cells. Cell Death Dis. 2023 Dec 6;14(12):799. doi: 10.1038/s41419-023-06337-3. PubMed PMID: 38057328
- Reßing N, Schliehe-Diecks J, Watson PR, Sönnichsen M, Cragin AD, Schöler A, Yang J, Schäker-Hübner L, Borkhardt A, Christianson DW, Bhatia S*, Hansen FK*. Development of Fluorinated Peptoid-Based Histone Deacetylase (HDAC) Inhibitors for Therapy-Resistant Acute Leukemia. J Med Chem. 2022 Nov 9;. doi: 10.1021/acs.jmedchem.2c01418. PubMed PMID: 36351184.
- Bhatia S, Diedrich D, Frieg B, Ahlert H, Stein S, Bopp B, Lang F, Zang T, Kröger T, Ernst T, Kögler G, Krieg A, Lüdeke S, Kunkel H, Rodrigues Moita AJ, Kassack MU, Marquardt V, Opitz FV, Oldenburg M, Remke M, Babor F, Grez M, Hochhaus A, Borkhardt A, Groth G, Nagel-Steger L, Jose J, Kurz T, Gohlke H, Hansen FK, Hauer J. Targeting HSP90 dimerization via the C terminus is effective in imatinib-resistant CML and lacks the heat shock response. Blood. 2018 Jul 19;132(3):307-320. doi: 10.1182/blood-2017-10-810986. PubMed PMID: 29724897
Further Publications: PubMed
External Support:
- Deutsche Forschungsgemeinschaft (DFG)
- Elterninitiative Kinderkrebsklinik e.V.
- Löwenstern e.V.
