In the Stam group, focusing on high-risk types of childhood leukemia, we have an open position for a postdoc with experience in molecular/cellular (cancer) biology, and comprehensive mouse experiments.
Background information Stam research group
The main focus of the Stam research group has always been MLL-rearranged acute lymphoblastic leukemia (ALL) in infants (i.e. children <1 year of age), which represents a highly aggressive and difficult to treat type of childhood leukemia. Recently, however, we have expanded our focus by initiating research on high-risk types of pediatric acute myeloid leukemia (AML) characterized by MLL translocations or NUP98 gene fusions. For these specific ALL and AML patient groups we collectively aim to 1. Understand the biology and (epi)genetics underlying a. leukemogenic transformation at pre-leukemic stages, b. leukemia maintenance during full-blown overt leukemia, and c. disease relapse, 2. Unravel the molecular mechanisms underlying drug resistance and therapy failure, and develop therapeutic strategies to circumvent adverse drug responses, and 3. Identify and pre-clinically validate novel therapeutic targets and innovative treatment strategies, using refined in vitro and in vivo model systems.
While our ability to treat pediatric acute myeloid leukemia (AML) has significantly increased in the past decades, leading to current long-term survival rates of approximately 70%, certain subtypes of pediatric AML remain difficult to treat. This particularly involves patients harboring a translocation involving the Mixed-lineage Leukemia (MLL) gene or the Nucleoporin 98 (NUP98) gene, who are burdened with a high-risk of treatment failure and disease relapse, conferring a very poor clinical outcome. Clearly, novel and more adequate treatments are required for these patients, but clinical evaluation of experimental agents is limited due to small patient populations. Therefore, robust pre-clinical models of these high-risk pediatric AML subtypes are urgently needed to evaluate novel treatments that potentially have clinical benefits. Therefore, we aim to establish patient-derived xenografts (PDXs) of MLL-rearranged and NUP98-rearranged pediatric AML. For this, we intend to utilize the ‘humanized’ immune-deficient MISTRG mouse strain in an attempt to achieve robust engraftment, which should be superior over earlier attempts made with the more classical immunodeficient NOD-SCID or NSG mouse strains. Once established, these PDXs will provide a clinically relevant platform for the evaluation of the in vivo efficacy of potentially effective drugs against these specific types of childhood AML, as recently identified in our in vitro drug library screens. Furthermore, we will utilize these PDX models to develop and evaluate an ‘induction therapy-type’ in vivo treatment regimen in mice, designed to mimic the actual clinical induction therapy as received by patients. This will allow further investigation of novel agents of interest by evaluating their efficacy in a clinically relevant setting (i.e. alongside an established treatment protocol). As part of the in vivo induction therapy experiments, we will also harvest leukemia cells from mice at ‘diagnosis’, remission and relapse stages of treatment, and subject these cells from each stage to RNA-sequencing. Doing so will allow us to investigate gene expression changes during and post-relapse, providing insights into mechanisms underlying relapse, potentially revealing therapeutic options to circumvent or target relapsed disease following frontline therapy. Altogether this project aims to create robust preclinical models of high-risk types of pediatric AML, which will enable identification and testing of novel treatment strategies capable of improving clinical outcomes.
Tasks and responsibilities
We are looking for an enthusiastic and driven post-doc who is skillful, independent and creative, as well as able to deepen the provided research project by implementing self-acquired hypotheses and additional research ideas. At the same time we are looking for a team-player who is willing to actively participate in the research of other members of the Stam group, helping young PhD-students, technicians, and students develop and advance in their careers. The research activities will involve a vast amount of in vivo mouse experiments, but also involves various molecular biological techniques and cellular culturing of leukemic cells. Some basic knowledge of bioinformatics analyses is preferable. When your performance is deemed satisfactory, possibilities will be available to submit additional research grants to expand the contract beyond this 2-year research project.
Skills and education
For this research project, the candidate:
- Has a PhD in biomedical science, molecular/cellular biology, or an equivalent thereof, and has a clear interest in pre-clinical cancer research.
- Has experience, legal permission, and interest in in vivo drug testing using mouse models.
- Has an accurate, creative, efficient, and pro-active work ethos.
- Is an enthusiastic team-player with strong communication skills.
- Is able and willing to build bridges between pre-clinical research and clinical applications, and is open to participate and collaborate with many different research groups in a stimulatory scientific environment.
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 an additional year. Salary is based on postdoc salary scales depending on your years of experience. The Princess Máxima Center operates according to the collective labor agreement ‘cao algemene ziekenhuizen’.
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You can apply for this position until the April 30th by pressing the apply button on this screen.
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