Molecular/cellular biologist ALL (post-doc)

Group Stam

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.

The project

As the 5-year event free survival chances for infants (<1 year of age) diagnosed with MLL-rearranged acute lymphoblastic leukemia (ALL) still remain <40%, current therapeutic regimens are clearly not sufficient for these patients, emphasizing the urgent need for more adequate treatment options for these very young children. In order to identify novel and more effective therapeutics against MLL-rearranged infant ALL, we recently conducted elaborate in vitro drug library screens on MLL-rearranged ALL cell line models, as well as on primary MLL-rearranged infant ALL patient samples. These screens and subsequent validation experiments revealed various types of novel drugs that appeared highly effective against MLL-rearranged infant ALL. Moreover, in additional research that is currently being finalized, the underlying mechanism(s) of the sensitivity of MLL-rearranged ALL cells towards these agents are clearly starting to emerge. In order to render these agents suitable for clinical application, the work at hand now is to pre-clinically validate the efficacy of these therapeutics against MLL-rearranged infant ALL in vivo, using comprehensive mouse models. Therefore the current 4-year research project aims to determine the in vivo efficacy of these agents as mono-therapy, or in combination with additional drugs with which these novel agents have shown strong synergy in recent in vitro experiments. Agents that show promising results in the mono-therapeutic setting will then be tested in mice in the background of the combination chemotherapeutic treatment as currently used in the treatment of MLL-rearranged infant ALL. For this, mice will be treated for 3-4 weeks with a derivative of the actual induction therapy for MLL-rearranged infant ALL patients, either in the absence or presence of the novel therapeutic agents. This approach in which mice receive a 3-4 week window of induction therapy will also be used to deliberately provoke leukemia relapses in mice after induction therapy has been stopped. This will allow us to test the in vivo efficacy of selected agents and/or drug combinations against relapsed leukemia (which is notoriously chemo-resistant). Furthermore this strategy will also allows us to more efficiently study substantial numbers of relapsed MLL-rearranged ALL samples (that, given the rarity of this malignancy, are difficult to obtain), provided that the mouse equivalent of relapsed disease resembles that of actual relapsed MLL-rearranged infant ALL samples. Therefore, another aim of the project will be to compare relapsed leukemia samples obtained from mice with relapsed samples from actual MLL-rearranged infant ALL patients, in order to determine whether or not our mouse model produces genuine leukemia relapses. If so, we will adopt this mouse model to explore the possibilities of therapeutically eliminating disease relapses in a very early, still pre-leukemic stages, preferably using limited numbers of drugs at low dosages. Obviously, the entire project aims to provide sufficient amounts of pre-clinical evidence on various therapeutic strategies that pave the way for clinical application.   

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 4-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 3 years. 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 February 15th by pressing the apply button on this screen.

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