PhD Student - Targeting phenotype switching as melanoma therapy
Your function within the department
Melanoma cells exist in two fundamentally different cellular states, and display heterogeneity and plasticity with respect to these two phenotypes. The ability to switch between the two phenotypes allows cells to metastasize and contributes to immunotherapy resistance. We have recently shown that both acquired and intrinsic resistance to MAPK pathway inhibitors is associated also with a melanoma phenotype switch. However, the process of phenotype switching is ill-understood, which precludes possibilities to pharmacologically target this process to improve therapeutic responses. The aim of this project is to study melanoma phenotype switching using a multi-angular approach. Various techniques, including single cell transcriptomics, proteomic analysis and CRISPR/Cas9 genetic screens, will be used to this end. Importantly, we have established a patient-derived xenograft (PDX) platform, which allows studying phenotype switching in relevant in vivo models. In close collaboration with an (animal) technician, you will characterize melanoma phenotypes, as well as the transition between them to come to a better description of phenotype switching. Using this knowledge, you will investigate how we can pharmacologically interfere with phenotype switching, with the goal to prevent metastasis and therapy resistance.
We seek an experienced and ambitious molecular/medical biologist with an interest in immunology. Strong commitment, experience in animal studies and a desire to translate your findings to the clinic are recommended.
Your career opportunities and terms of employment
You will be employed for a period of 4 years. The gross salary per month is € 2.567,- to € 3.097,- according to the standard PhD scales. The terms of employment will be in accordance with the CAO Ziekenhuizen (Collective Labour Agreement for Hospitals).
For further information please contact Dr. Thomas Kuilman or prof. Daniel Peeper (Division of Molecular Oncology). E-mail: or email@example.com.
- Kemper et al. (2016). BRAF(V600E) Kinase Domain Duplication Identified in Therapy-Refractory Melanoma Patient-Derived Xenografts. Cell Reports, 16(1), 263–277. http://doi.org/10.1016/j.celrep.2016.05.064
- Müller et al. (2014). Low MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma. Nature Communications, 5, 5712. http://doi.org/10.1038/ncomms6712
Acquisition for this vacancy is not appreciated.