Postdoc - Trace the cellular origin of neuroblastoma relapse

Updated: 3 months ago
Job Type: Temporary
Deadline: 23 Nov 2021

A postdoc position is available at the department of Oncogenomics, Amsterdam UMC, to study mechanisms of therapy resistance and development of relapse in the pediatric tumor neuroblastoma.

About your role
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.

The project
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.

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