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 the availability of targeted drugs, chemotherapy is still a mainstay of treatment. However, both primary and secondary resistance are frequent, and survival outcome is unsatisfactory. An FWF-funded research project 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.

In close collaboration with clinicial oncologist Thorsten Füreder, the group has established another research focus on head and neck squamous cell carcinoma (HNSCC). Treatment of HNSCC follows a multimodal approach, but is often disfiguring and debilitating. The effectiveness of immunotherapy and of the only approved targeted drug, the EGFR-inhibitor Cetuximab, is limited. Using a bioinformatics approach, we identified a number of potential HNSCC driver genes. These are subjected to functional characterization, with the goal to pinpoint novel drug targets. Moreover, novel therapeutic approaches are sought through spatial transcriptomics in combination with single cell RNA sequencing analyses.

Grants

• Polo-like kinase 1 in Oral Squamous Cell Carcinoma: Exploration of Novel Biological Functions and Innovative Therapeutic Approaches (2025)
  Source of Funding: FWF (Austrian Science Fund), Bilateral grants
  Principal Investigator
• 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. Grandits, A.M. et al. (2024) ‘<scp>SKA1</scp> promotes oncogenic properties in oral dysplasia and oral squamous cell carcinoma, and augments resistance to radiotherapy’, Molecular Oncology [Preprint]. Available at: https://doi.org/10.1002/1878-0261.13780.
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. HELLER, G. et al. (2024) ‘New perspectives on biology, disease progression, and therapy response of head and neck cancer gained from single cell RNA sequencing and spatial transcriptomics’, Oncology Research, 32(1), pp. 1–17. Available at: https://doi.org/10.32604/or.2023.044774.