In the field of “Dissecting mechanisms of tumorigenic chromosome translocations” the research group of Dr Vassilis Roukos offers the following PhD project:
Elucidating Mechanisms of Oncogenic Therapy-Related Translocations
A major problem in chemotherapy today is the occurrence of second primary cancers which arise as response to treatment for a primary tumor. Therapy-induced acute myeloid leukemias (t-AML) develop after treatment of primary cancers with topoisomerase-inhibitors and are often characterized by only one chromosome abnormality involving a translocation of the mixed lineage leukemia locus (MLL). Recurrent MLL translocation hot spots fuse with several different genes and patients carrying these translocations develop acute myeloid leukemia (AML) with very short latency and poor prognosis.
Due to difficulties in modeling the formation of these translocations in vivo very little is known about the molecular mechanisms governing the formation of these cancerous translocations. We have recently established in the lab an imaging-based approach to probe and quantify the formation of these rare events in response to treatment with topoisomerase inhibitors. We are currently using this methodology in combination with high-throughput sequencing techniques to shed light to the molecular pathways that contribute to the formation of these translocations in vivo. We would like to understand (1) what determines the localization of the recurrent breakpoints found in patients with t-AML, (2) which is the molecular basis of the different localization compared to de novo, non-therapy related MLL translocations, (3) which is the role of the various topoisomerase isoforms as well as the potential role of transcription & replication in MLL susceptibility to breakage and translocation formation and (4) which DNA repair pathways are involved in the formation of these translocations. Understanding the molecular mechanisms that facilitate the formation of these specific translocations has a great potential for identification of drugs that minimize their occurrence.
- The possibility to work on a cutting-edge project using state-of-the-art technology in a highly motivated research team
- A stimulating, diverse and international research environment
- Advanced training opportunities in scientific, technical and transferrable skills
- A fully funded PhD position
- Master or Diploma
- Motivation to solve complex biological problems
- Excellent communication skills
Duration of stipend/salary: 3 years, with the possibility of extension
Starting date: 1 October 2018 or later
Deadline for registration (exclusively online via web form): 15 May 2018
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