We have established that neuroblastoma is composed of two phenotypically divergent types of tumor cells (van Groningen et al., Nat Genet., 2017. PMID 28650485). An undifferentiated, mesenchymal tumor cell-type is resistant to therapy and we hypothesize that these cells are responsible for the outgrowth of relapse tumors. In a KWF-funded project, we aim to rigorously test this model using genetic lineage tracing of the divergent neuroblastoma cell types in relapse models of human neuroblastoma.
You will be responsible for the development and validation of lineage-tracer cell lines, which includes the molecular cloning of targeting vectors and CRISPR/Cas9-mediated targeted integration in neuroblastoma cell lines. These lineage-tracing lines will be used to identify the cellular origin of neuroblastoma relapse in xenograft models. You will analyze lineage-traced cells using single-cell RNA sequencing to study transcriptional plasticity during the development of relapse.
Research in our laboratory is focused on the phenotypic heterogeneity and plasticity of cancer cell types to unravel the fundamental principles of neuroblastoma biology. We aim to identify the cell-of-origin of neuroblastoma relapse and understand the plasticity of cellular states in tumor progression and relapse development. The outcome of these studies will guide the development of new combination therapy to combat neuroblastoma.
Successful candidates have a PhD degree with a strong background in stem cell biology, developmental biology, and/or cancer research. Expertise with molecular cloning, cell culture, CRISPR/Cas9 targeting, and mouse xenograft models is required. Experience with single-cell RNA sequencing is advantageous. We look for an ambitious, independent scientist with a critical and analytical mind-set to develop this research line. Excellent English communication skills, both written and oral, are required.
You will work at the Department of Oncogenomics (Dr. Johan van Nes, Amsterdam UMC – location AMC). We collaborate with the bio-informatic team of Dr Jan Koster (Amsterdam UMC, r2.amc.nl) for genome-wide epigenetic analysis and transcriptional data at single-cell resolution. Live imaging-, cell sorting- and genome-analysis facilities at the Amsterdam UMC provide state-of-the-art technolgy and support for the in-depth analysis of lineage tracing data.
For further information about the position, please contact dr. Johan van Nes by e-mail (firstname.lastname@example.org) or phone (+31 (0)20 5667536).
For more information about the application procedure please contact Tanja Hart, Recruitment Adviser, via T: 06-21603178 or E: email@example.com
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