Detail

Keywords

Chemotherapy resistance; Head and Neck Neoplasms; Leukemia, Myeloid, Acute; leukemic stem cells

Research group(s)

• AG Wieser
  Head: Rotraud Wieser
  Research Area: The group focusses on two types of malignant disease, acute myeloid leukemia (AML) and head and neck squamous cell carcinoma (HNSCC). In both tumor entities, therapy resistance is frequent, outcome is unsatisfactory, and novel targets for molecularly directed drugs are urgently needed. Research activities of the group aim at the identification of mechanisms of therapy resistance as well as of potential drug targets.
  Members:
  Rotraud Wieser

Research interests

Acute myeloid leukemia (AML) is the epitome of a stem cell driven malignancy. Despite recent approvals of several targeted drugs, chemotherapy is still a mainstay of treatment. However, both primary and secondary resistance are frequent, and survival outcome is unsatisfactory. A research project recently funded by the Austrian Science Fund deals with the role of the G-protein coupled receptor CALCRL in stemness and chemotherapy resistance of AML. Due to its key role in migraines, inhibitors of CALCRL have already been approved for clinical use. Their potential utility in the treatment of AML is explored in the context of this project.

More recently, collaborating with Assoc. Prof. Thorsten Füreder, Clinic of Medicine I, the group has expanded its research focus to include head and neck squamous cell carcinoma (HNSCC), which is one of the most common malignancies worldwide. Treatment follows a multimodal approach, but is often disfiguring and debilitating, and the only approved targeted drug is the EGFR-inhibitor Cetuximab. Using a bioinformatics approach, we identified a number of genes potentially involved in the emergence and therapy responsiveness of HNSCC. These genes are subjected to functional characterization, with the goal to characterize HNSCC driver mechanisms and to pinpoint novel drug targets.

Grants

• Role of the CGRP-CALCRL axis in stemness and chemotherapy resistance of acute myeloid leukemia (2021)
  Source of Funding: FWF (Austrian Science Fund), Stand alone project
  Principal Investigator
• Functional characterization of a receptor protein associated with poor therapy response and relapse of acute myeloid leukemia (2015)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator
• Functional interactions between EVI1 and atRA in LSCs (2015)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator
• Modulation of ATRA regulated transcription by EVI1 (2009)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator
• Target genes of the MDS-associated transcription factor EVI 1 (Responsible) (2008)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator
• Functions of the oncogene EVI1 in primary human CD34+ cells (2007)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator
• Regulation of the EVI1 gene through 5´-end variability (2004)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator
• The leukemogenic transcription factor EVI1 and its putative antagonist, MDSu/EVI1: Expression patterns, biological properties and search for target genes (2002)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator
• Investigations on the molecular consequences of chromosome 3q aberrations in myeloid Leukemia (Responsible) (2000)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Project
  Principal Investigator

Selected publications

1. Grandits, A.M. et al., 2021. Downregulation of MTSS1 in acute myeloid leukemia is associated with a poor prognosis, chemotherapy resistance, and disease aggressiveness. Leukemia, 35(10), pp.2827–2839. Available at: http://dx.doi.org/10.1038/s41375-021-01224-2.
2. Nguyen, C.H. et al., 2020. All-trans retinoic acid in non-promyelocytic acute myeloid leukemia: driver lesion dependent effects on leukemic stem cells. Cell Cycle, 19(20), pp.2573–2588. Available at: http://dx.doi.org/10.1080/15384101.2020.1810402.
3. Nguyen, C.H. et al., 2020. IL2RA Promotes Aggressiveness and Stem Cell–Related Properties of Acute Myeloid Leukemia. Cancer Research, 80(20), pp.4527–4539. Available at: http://dx.doi.org/10.1158/0008-5472.CAN-20-0531.
4. Nguyen, C.H. et al., 2019. All-trans retinoic acid enhances, and a pan-RAR antagonist counteracts, the stem cell promoting activity of EVI1 in acute myeloid leukemia. Cell Death & Disease, 10(12). Available at: http://dx.doi.org/10.1038/s41419-019-2172-2.
5. Gluexam, T. et al., 2019. CGRP Signaling via CALCRL Increases Chemotherapy Resistance and Stem Cell Properties in Acute Myeloid Leukemia. International Journal of Molecular Sciences, 20(23), p.5826. Available at: http://dx.doi.org/10.3390/ijms20235826.