Background information
The research group of Prof. Monique den Boer (~13fte) focusses on identifying features of leukemic cells that can be used to improve the clinical outcome for children with acute lymphoblastic leukemia (ALL). Our 30-year track record in preclinical/translational research has resulted in knowledge being implemented in new treatment protocols, and our journey continues to further improve the specificity of anti-leukemia treatment. We have expertise in so-called pathobiological studies addressing which (combination of) genetic lesions characterize the patients’ leukemia, how these lesions functionally contribute to chemotherapy, targeted inhibitors and immunotherapy response and how these lesions affect the behavior of leukemic cells in the bone marrow microenvironment.
The Den Boer group routinely uses many molecular techniques including a.o. (single cell) sequencing, lentivirus-mediated gene silencing, conventional and spectral flow cytometry, cell sorting, confocal imaging and cell migration assays.
Project summary
Among high-risk BCP-ALL in need of improved treatment are tyrosine kinase-altered subtypes including BCR::ABL1. The addition of tyrosine kinase inhibitors to multi-agent chemotherapy has greatly improved outcome but does not reach that of good-risk subtypes. An important poor prognostic factor in BCR::ABL1 BCP-ALL is deletion of the IKZF1 gene, encoding a B-cell transcription factor. IKZF1 deletion is associated with poor response to chemotherapy and may also affect immunotherapy. We discovered that IKZF1 deletions were associated with reduced response to tyrosine kinase inhibitors. In the current project, we plan to generate (single cell) sequencing of patients’ samples and model the deletion in cell lines to find vulnerabilities related to IKZF1 deletion. Our aim is to understand the underlying mechanisms and find modulators of tyrosine kinase inhibitor resistance and immunotherapy to improve outcome of pediatric patients with IKZF1-deleted BCR::ABL1 ALL.
Tasks and responsibilities
The PhD candidate will generate and analyze multi-omics (single cell) sequencing data of ALL patient samples, generate knock-out and overexpression cell line models to investigate the effect of IKZF1 alteration, and test candidate drugs in cell lines and patient samples for synergistic targeting to improve the response to tyrosine kinase inhibitors and immunotherapy.
Your profile
- Master’s degree in biomedical sciences or an equivalent thereof, and a clear interest in pre-clinical cancer research
- Excellent problem-solving attitude and eagerness to learn
- Preferably experience in cell biological and molecular technologies
- Preferably experience in working with data analyses software like R or interest in learning
- Team player with excellent communication and presentation skills in English
We offer
We offer a challenging PhD project in an inspiring and inter-disciplinary research environment. The total duration of the project is 4 years (full-time). You will initially be appointed for a period of 1 year, during which your performance will be evaluated. Your gross monthly salary will be in scale FWG 45-6 and will include 8,33% holiday allowance and 8,33% end-of-year bonus. The Princess Máxima Center operates according to the collective labor agreement ‘CAO ziekenhuizen’.
Contact and application
You can apply for this position until June 30 by pressing the “apply” button on this screen. The selection process will start in the meantime and may end before this deadline if a good candidate is hired.
We require a current resume, a short cover letter (maximum one A4) and the contact information of 2-3 references.
For more information, please contact Dr. Judith Boer.
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