The German Cancer Research Center offers 2 Ph.D. Student positions at the National Center for Tumor Diseases (NCT Dresden), Department of Translational Medical Oncology.
Deadline for application:
|July 3, 2018.|
The department “Translational Medical Oncology” headed by Prof. Hanno Glimm of the German Cancer Research Center (DKFZ) at the National Center for Tumor Diseases (NCT) Dresden focuses on the functional and molecular characterization of malignant cell regulation and metastasis formation. NCT has established and extensively characterized biobanks of patient-derived in vivo and in vitro cancer models and investigated clonal dynamics and regulation of tumor-initiating cell (TIC) activity in gastrointestinal cancers (e.g. Cell Stem cell 2011; Cancer Letters 2016; EMBO MolMed 2017; IJC 2017; JEM 2017; Nature Genetics 2017).
- In human colorectal cancer (CRC) a hierarchically organized cell compartment drives progression in vivo (Dieter et al., 2011).
- Tumor initiation and long-term tumor formation is driven by multiple genomic subclones and functional heterogeneity of CRC TIC is not based on the genomic architecture (Gießler et al., 2017).
- In striking contrast to such a continuous activity of a limited number of self-renewing TIC within a fixed cellular hierarchy, we showed that in pancreatic cancer a succession of transiently active TIC clones drives tumor growth in serial xenotransplantation (Ball et al., 2017).
- In line with this, recent data from other groups indicate that in CRC a very rare proportion of differentiated tumor cells can de-differentiate and gain TIC activity, thereby driving tumor re-growth after TIC depletion.
- These findings in different gastrointestinal cancer entities emphasize that tumor growth is not exclusively dependent on a fixed stem-cell-like population which drives tumor growth in top-down, but can recruit TIC activity from other cells in the absence of such a cell population.
- Understanding the regulation of tumor-initiating cell (TIC) activity is therefore pivotally important to eradicate cells with TIC activity in human cancer and to develop safe and efficient therapeutic strategies.
For specific targeting of TIC activity, researchers have evaluated the impact of novel therapeutic approaches on primary patient-derived tumor models. Global insertional mutagenesis gene activation and pooled shRNA knockdown screens allowed identification of candidate genes potentially critical for proliferation, tumor and metastasis formation. In addition, the department drives a precision oncology program for genomic analysis of patient cancers as a basis for interventional clinical trials (NCT MASTER). This program has demonstrated that whole-exome/genome and RNA sequencing in a clinical setting provides relevant diagnostic information and creates opportunities for pharmacologic intervention.
- Based on these efforts, successful Ph.D. candidates will utilize state-of-the-art technologies to develop and validate molecular strategies specifically targeting tumor-initiating cell activity in human gastrointestinal cancers and sarcomas.
- Moreover, patient-derived tumor models will be generated from patient tumors, molecularly characterized, and the identification of targetable mutations will trigger the testing of appropriate single-agent or combination therapies in vitro and in vivo.
- Genomics-guided treatment will be recommended for the respective patient within the MASTER program whenever feasible.
- In addition, candidate structures potentially regulating self-renewal, tumor-initiation or metastasis formation and novel substances with TIC inhibitory potential identified will be chosen for the development and validation of molecular strategies targeting TIC activity in human colorectal cancer.
The German Cancer Research Center is looking for 2 highly motivated fellows with a background in cell and molecular biology as well as cancer research. Within their projects, the successful candidates will drive the development and implementation of highly innovative translational approaches for personalized oncology.
- Applicants should hold a Master’s degree or equivalent in biology/life sciences with an excellent background and experience in cellular and molecular biology as well as cancer biology, or closely related fields.
- The applicants should be highly self-motivated and be able to pursue and drive research projects independently as well as in collaborations.
- An excellent written and oral command of English is essential.
- Applications should include a CV, cover letter, certificates, expected availability date, a complete list of publications and 2-3 references.
You will get:
- Interesting, versatile workplace
- International environment
- Opportunities for part-time work
- Flexible working hours
- Good education and training