The ambition of the VIB Center for Cancer Biology (CCB) is to contribute to a better understanding of the biology that underlies cancer initiation, progression and metastatic dissemination with the ultimate goal to develop more effective and specific anti-cancer (combination) therapies.
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Postdoctoral Researcher in Cancer Epigenetics
The Laboratory for Translational Genetics is looking for a highly motivated postdoctoral scientist to join their team. Our laboratory is interested in discovering genetic and epigenetic mechanisms that underlie cancer development and that contribute to therapeutic resistance of human cancers. We aim to gain fundamental insights in these processes, as well as a therapeutic impact. To achieve these goals, we are relying on experimental animal models of cancer, a large biobank of tumor samples and advanced high-throughput sequencing techniques and applied bio-informatics.
Specifically, in this project the applicant will be working on assessing the impact of tumor hypoxia on DNA demethylation. DNA methylation was originally described in the 1970s as an epigenetic mark involved in transcriptional silencing, whereas the existence of DNA demethylation was only recently discovered. In particular, it was established that TET hydroxylases catalyse the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) through a reaction requiring O2 and 2-oxoglutarate (2OG). Interestingly, decreased O2 concentrations (hypoxia) are common in cancer, as is an altered 2OG metabolism. Hypoxia induces the activity of Hypoxia Inducible Factor (HIF) transcription factors, which alter gene expression to counter and cope with hypoxia. It is however poorly characterized how DNA (de)methylation influences HIF binding, and how HIF in turn interfaces with the epigenome. Our objective in this project is to determine the influence of hypoxia on the epigenome and the resulting phenotypic response in cancer. In particular, we postulate that gene promoters become hypermethylated, because DNA demethylation −as initiated by the TET hydroxylases− is impaired under conditions of hypoxia. Since hypoxia is also a key regulator of the cancer stem cell (CSC) niche and within the tumour microenvironment promotes metastasis and tumor angiogenesis, we also seek to establish the relevance of DNA demethylation in these processes. Finally, since these hypoxia-induced DNA methylation changes might also be detected in circulating tumor DNA, we aim to assess whether they might serve as a predictive biomarkers for metastasis and resistance to anti-cancer therapies, such as anti-angiogenic therapies.
As an ideal applicant
- You are passionate and motivated to work on ambitious projects in an open, dynamic and scientifically advanced team
- You have ample experience in mouse genetic, molecular and cellular biology methods and a strong interest in applying next-generation sequencing to epigenetic research
- You have a general interest in pursuing research in a stimulating and competitive field of science
- You have an outstanding publication record in peer-reviewed international journals
- You can work in a team, but also initiate research lines independently
- Excellent communication skills in spoken and written English are required.
- An exciting work environment where quality, professionalism and human contacts are paramount
- The opportunity to be part of a new, young and dynamic team and provide a meaningful contribution to epigenetic cancer research
- The opportunity to work on scientifically exceptional and high impact projects supported by an ERC Consolidator Research grant to Diether Lambrechts
- An attractive salary that will be based on previous experience and skills
Applicants interested are invited to send their CV and a cover letter describing their motivation to firstname.lastname@example.org. Additional information can be obtained via the above email address or telephone number 016/373 199