Like most types of cancer, leukemia can be caused by mutations in various genes that regulate cell division, differentiation and apoptosis. In hematological cancers, approximately 30-50 genes have been identified that are recurrently mutated. In individual patients 3-10 mutations may be found that together induce full malignant transformation of blood forming cells leading to leukemia. Different combinations of mutations may be found in different patients, which is associated with a heterogeneous response to therapy and different survival probability. Recently, it was found that also within the tumor, genetic heterogeneity can be detected. In an individual patient, distinct leukemic clones may be present at the same time that share mutations, but also harbor clone-specific aberrations. Preliminary studies have shown that these different clones may respond differently to therapy.
In this project we will study clonal evolution in leukemia and MDS before, during and after therapy using next generation sequencing techniquesThe different subclones will be isolated, and studied for stem-cell characteristics in cellular culture systems, as well as molecular characteristics like gene expression (RNA-seq), and epigenetic alterations (histone modifications and DNA-methylation). Better insight in the genes that cause leukemia, and the effect on clonal expansion and response to therapy should lead to better treatment schedules and better survival rates for these patients. This research will be embedded in the RIMLS research institute and the Radboud Research Theme “Cancer Development and immune Defense”.
Tasks and responsibilities
- Designs and performs scientific research, and reports the results in conferences and scientific publications;
- Designs, tests and uses next-generation sequencing panels for high-throughput genetic analyses;
- Develops assays for the detection of mutations in single cells;
- Performs stem cell assays on various normal and leukemic subpopulations of cells;
- Works in a team with clinical and non-clinical researchers.
We are looking for an ambitious Postdoc with a strong background in molecular and cellular biology and interest in the molecular origin and evolutionary processes involved in the development of cancer.
- PhD in a relevant discipline, eg Biology, Biomedical sciences or Molecular life sciences;
- Ample experience in molecular biology as well as cellular techniques;
- Enthusiasm and ambition to succeed in academic and translational research environment;
- Highly motivated to work in an interdisciplinary team at the cutting edge of science;
- Good interpersonal and communicative skills.
Interested in the genetic origin of cancer and the evolutionary processes that underlie disease progression? We are looking for an ambitious Postdoc to bring this research further: Join our team!
- Scale 10: max. € 58838 gross income per year at full employment (incl. vacation bonus and end of year payments);
- This project is financed by a grant of the Dutch Cancer Foundation (KWF). Appointment will be for the duration of the project, with a maximum of 4 years, depending on positive interim evaluations;
- Read more about the Radboudumc employment conditions.
First interview scheduled: week 13
Applications should send a letter of intent outlining their specific interest in the position, overall qualifications, experience and career goals, a curriculum vitae including study grades and names and addresses of professional references.
All additional information about the vacancy can be obtained from Prof. Joop Jansen, Full professor Department of Haematology. Use the Apply button to submit your application.
Relevant publications on this topic from our team:
- Berger G, Kroeze LI, Koorenhof-Scheele TN, de Graaf AO, Yoshida K, Ueno H, Shiraishi Y, Miyano S, van den Berg E, Schepers H, van der Reijden BA, Ogawa S, Vellenga E, Jansen JH. Early detection and evolution of pre-leukemic clones in therapy-related myeloid neoplasms following autologous SCT. Blood. 2018 Jan 8. 2018 PubMed PMID: 29311096.
- P. da Silva-Coelho, L.I. Kroeze, K. Yoshida, T.N. Koorenhof-Scheele, L.T. van de Locht, A.O. de Graaf, M. Massop, M.J. Stevens-Kroef, J. Cermak, T. de Witte, N.M.A. Blijlevens, P. Muus, G. Huls, B.A. van der Reijden, S. Ogawa,J.H. Jansen. Clonal evolution in myelodysplastic syndromes. Nature Communications. 2017 Apr 21;8:15099.
- GN Nikoloski, SMC Langemeijer, RP Kuiper , R Knops, M Massop, A van der Heijden, TN Scheele, P Vandenberghe, T de Witte, BA van der Reijden JH Jansen. Somatic mutations of the histone methyltransferase EZH2 gene in myelodysplastic syndromes. Nature Genetics (2010) Aug;42(8):665-7. PubMed PMID: 20601954.
- SMC Langemeijer, RP Kuiper, M Berends, R Knops, MG Aslanyan, M Massop, E Stevens-Linders, P van Hoogen, A Geurts van Kessel, RAP Raymakers, EJ Kamping,GE Verhoef, , P Vandenberghe, T de Witte, BA van der Reijden, JH Jansen. Acquired mutations in TET2 are common in myelodysplastic syndromes. Nature Genetics (2009) 41(7):838-42.
Upon commencement of employment we require a certificate of conduct (Verklaring Omtrent het Gedrag, VOG) and there will be a screening based on the provided CV. Radboud university medical center’s HR Department will apply for this certificate on your behalf.
Radboudumc strives to be a leading developer of sustainable, innovative and affordable healthcare to improve the health and wellbeing of people and society in the Netherlands and beyond. This is the core of our mission: To have a significant impact on healthcare. To get a better picture of what this entails, check out our strategy film.
Our key strength is medical life-sciences and clinical practice, with an impressive infrastructure comprising state-of-the-art technology platforms and (translational) research facilities. The Radboudumc is therefore uniquely positioned in the emerging Euregio and Dutch healthcare infrastructure to play a leading role in the new healthcare paradigm of prediction, prevention and personalised medicine.
The Radboudumc focuses on scientific health challenges of today, with an eye on emerging diseases of the future.
Read more about what it means to work at Radboudumc and how you can do your part.
The research project will be conducted in the Molecular Hemato-Oncology group of the Laboratory of Hematology, Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands. The laboratory of Hematology employs 60-70 persons who are specialized in research and advanced diagnostics in the field of hemato-oncology and thrombosis-hemostasis.