The Princess Máxima Center 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. The research team led by Frank van Leeuwen (8 fte), studies the molecular mechanisms of tumor development and therapy resistance, with a focus on Acute Lymphoblastic Leukemia (ALL). By genetic modelling of genetic aberrations associated with therapy resistance or relapse, we aim to develop novel therapies for patients with relapsed ALL. Moreover, we employ CRISPR/CAS9-based reverse genetic screens to identify signaling intermediates that can be targeted to enhance response to treatment in distinct genetic ALL subgroups. The current project focuses on the role of TP53 deletions/mutations, a strong predictor of poor therapy response in relapsed ALL.
Tasks and responsibilities
You will work on the project “Defining specific vulnerabilities in relapsed TP53 mutated Acute Lymphoblastic Leukemia”. Although TP53 aberrations in Acute Lymphoblastic Leukemia (ALL) are relatively rare at diagnosis (<3%), the incidence rises to about 12% in relapsed ALL. Particularly at relapse, deletions or mutations affecting TP53 predict a poor response to therapy. To date, little is known about what makes TP53-aberrant leukemias difficult to treat. You will introduce targeted TP53 mutations or deletions in well defined ALL cell line modes, to study how these affect gene expression and response to different treatments. Moreover, you will combine CRISPR/CAS9 based reverse genetic screens with bio-affinity labeling approaches to define specific vulnerabilities in TP53 mutated ALL that can be targeted to overcome therapy resistance.
Using a variety of techniques (including RNAseq, reverse-phase protein array, reverse genetic screening and drug interaction studies) you will select therapeutic targets for further extensive validation, including in vitro and in vivo experiments with patient-derived leukemic cells as well as patient-derived xenografts.
Skills and education
We are looking for an ambitious biologist or biomedical scientist ready to mature into an expert in therapy resistant leukemia, leading to a thesis defense at the University of Utrecht. Medical doctors who, based on previous hands-on experience in the lab are enthusiastic about translational research, are also welcome to apply.
You will spend most of your time in the lab, using molecular techniques like CRISPR/Cas9, building leukemia models and testing these in various cell biological assays, aimed at measuring cell fitness and sensitivity to commonly used and new drugs. Hands on experience with molecular and cell biology is a prerequisite. Using molecular biology tools, you will help develop novel treatment strategies that will be validated in vivo in animal experiments using primary patient cells. Possession of a license to work with laboratory animals (article 9) is considered an advantage. Finally, you will work closely together with the other group members on this topic, which requires well developed social skills.
We offer a 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, and your performance will be evaluated by a training and supervision plan.
Salary according to FWG 45 increment 6 (for the 1st year, increased to FWG 45 increment 10 in case of renewal). The Princess Máxima Center operates according to the collective labor agreement ‘cao algemene ziekenhuizen’.
Contact and application:
You can apply for this position until April 30th 2019 by pressing the apply button on this screen.
We welcome you to contact Dr. F. van Leeuwen, F.N.vanLeeuwen@prinsesmaximacentrum.nl for additional information about the vacancy.
Detailed information about the Princess Máxima Center for Pediatric Oncology can also be found at www.prinsesmaximacentrum.nl.
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