Position: PhD Student
Department: Pediatric Neurooncology
Code number: 2018-0311
The German Cancer Research Center is the largest biomedical research institution in Germany. With approximately 3,000 employees, we operate an extensive scientific program in the field of cancer research.
Project: Targeting MYC-driven pediatric brain tumors
MYC family members are among the most deregulated proto-oncogenes in pediatric brain tumors, giving rise to different brain tumor entities, including medulloblastoma (MB) and glioblastoma (GBM). The central role of MYC, the highly aggressive nature of these MYC-deregulated brain tumors, the extremely poor outcome of the patients, and the low direct druggability of MYC creates a huge clinical challenge and urgent need to develop better strategies for targeting these MYC-driven brain tumors. The aim of this project, which is part of a larger DKTK- and DKH-funded program with other groups in and outside the DKFZ targeting MYC-driven cancers, is to develop new treatment strategies for these MYC-driven pediatric brain tumors. We will use sophisticated pre-clinical models including orthotopically transplanted patient-derived xenografts (PDX) and organoid cultures. Many PDX models from MYC-driven MB and GBM have already been established and molecularly characterized, but many more are needed to fully represent the patient population. Organoid cultures are being established in collaboration with Hans Clevers in the Netherlands. We will use these models (a) for hypothesis-driven targeted treatment approaches in vitro and in vivo, and (b) for large scale synthetic lethal screens using CRISPR/shRNA or drug libraries (collaboration with Claudia Scholl and Michael Boutros at the DKFZ) to identify novel drug targets in these MYC-driven brain tumors.
For more info:
- Johann PD, Erkek S, Zapatka M, et al. Atypical teratoid / rhabdoid tumors (ATRT) are comprised of three epigenetic subgroups with distinct enhancer landscapes. Cancer Cell 2016;29:379-93.
- Pajtler KW, Witt H, Sill M, et al. Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups. Cancer Cell 2015;27:728-43.
- Kool M, Jones DT, Jager N, et al. Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. Cancer Cell 2014;25:393-405.
- Sturm D, Orr BA, Toprak UH, et al. New brain tumour entities emerge from molecular classification of CNS-PNETs. Cell 2016;164:1060-72.
- Northcott PA, Lee C, Zichner T, et al. Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature 2014;511:428-34.
- Mack SC, Pajtler KW, Chavez L, et al. Therapeutic targeting of ependymoma as informed by oncogenic enhancer profiling. Nature 2018;553:101-105.
- Brabetz, S., Leary, S.E.S., Gröbner, S.N., et al. A biobank of patient-derived pediatric brain tumor models. Nature Medicine 2018, in press.
Applicants should be highly motivated, hard-working individuals who enjoy working in an international team and are passionate about making a difference through cancer research. They should hold a university degree in biology or a related field, have expertise in working with animals, a strong interest in cancer biology, are highly self-motivated, and able to pursue research projects independently. Excellent communication skills and proficiency in English are mandatory.
- Interesting, versatile workplace
- International, attractive working environment
- Campus with modern state-of-the-art infrastructure
- Access to international research networks
- Doctoral student payment including social benefits
- Flexible working hours
- Comprehensive training and mentoring program through the Helmholtz International Graduate School
Earliest Possible Start Date: as soon as possible
Duration: The position is limited to 3 years.
Application Deadline: 24.01.2019
Dr. Marcel Kool
Phone +49 (0)6221/42-4636
Please note that we do not accept applications submitted via email.