The Princess Máxima Centre for Pediatric Oncology is a new research hospital concentrating healthcare, research and education with regard to cancer in children in a single location. The institute aims to provide the highest level of care for children with cancer and has the ambition to cure all children of cancer and significantly reduce unwanted side effects. The center brings together the best possible care and scientific research, creating a unique interdisciplinary institute for pediatric oncology in Europe.
Both microenvironment-mediated dependence of the leukemic cells and microenvironment-mediated resistance to anti-cancer therapy (chemotherapy, targeted therapy and immunotherapy) are key challenges in the treatment of B-lineage acute lymphoblastic leukemia (ALL). Leukemic cells actively reprogram their microenvironment to create both a supportive and protective niche. The mechanisms by which the leukemic cells enforce this change in the microenvironment are poorly understood. Insight into these processes will provide novel ways to treat ALL by disrupting their communication with neighbouring cells.
In order to investigate the communication of the leukemic cells with the microenvironment we have adapted and further refined the co-culture system of patient-derived ALL cells grown in direct contact with primary human MSC [Pal et al. Leukemia. 2016 Aug;30(8):1691-700]. In a next step, we have generated iPSC lines from primary human MSC. This provides us with a reproducible and consistent source of MSC (iMSC). Most importantly, iMSC provide a source of MSC that can be genetically modified, e.g. with CRISPR (and RNAi) technology, to probe pathways relevant for the interaction of the MSC with the leukemic blasts [bioRxiv: https://doi.org/10.1101/2021.06.18.448490].
We will investigate how the molecular programme of the ALL blasts drives the reprogramming of the microenvironment using bulk and single cell RNA/Multiome sequencing from co-cultures between ALL blasts and MSC. Based on transcriptome patterns we will perform functional enrichment analyses to identify complementary communication pathways upregulated in both ALL cells and MSC. The focus will be on therapeutically targetable pathways, e.g. adhesion molecules and their partners, cytokine/receptor pairs, key regulatory kinases against which there are drugs available or in clinical development that could be repurposed to treat ALL.
Tasks and responsibilities
We are looking for an enthusiastic candidate enjoying intellectual challenge and out-of-the-box thinking. You have substantial skills in molecular biology and cell biology. Bioinformatics skills and experience in single cell sequencing are a strong plus. You will join an established research team at the Princess Máxima Center. The team is jointly led by Olaf Heidenreich as group leader and Josef Vormoor (Clinical Director of Hemato-oncology) as associated group leader. Josef Vormoor is the lead for the ALL niche project within the group.
PhD or equivalent doctoral degree in a relevant scientific area
Experience in contemporary cell biology/molecular biology techniques
Experience in the bio-informatical analysis of sequencing data (including single cell RNA sequencing)
Experience in the ex vivo culture of primary cells
Excellent publication record in peer-reviewed journals
Excellent analytical and problem-solving skills
Team membership skills within multidisciplinary research teams
Excellent communication and presentation skills
Ability to demonstrate commitment to a research career and evidence of development towards group leadership
Working at the Princess Maxima Center for pediatric Oncology
We offer a full-time position based on 36 hours per week. You will start on a temporary position for the duration of one year that—when satisfactory—will be extended for a total of 3 years. Salary is based on postdoc salary scales depending on years of experience. The Princess Máxima Center operates according to the collective labor agreement ‘cao algemene ziekenhuizen’.
For more information about this project please contact Professor dr Josef Vormoor via email: firstname.lastname@example.org
Apply for this position?
You can apply for this position until the 21st januari 2022 by pressing the orange apply button “” on this screen.
Acquisitie naar aanleiding van deze vacature wordt niet op prijs gesteld.
36 hours a week
1 year, with the intention to extend (for a total of 3 years)