Characterization of the molecular mechanisms of resistance to radiochemotherapy of head and neck squamous cell carcinoma

As part of a project funded by the German Consortium for Translational Cancer Research (DKTK) the molecular mechanisms of resistance to radiochemotherapy in squamous cell carcinoma of the Head and Neck region will be evaluated. For this purpose DNA from FFPE material from primary and recurrent tumors and plasma samples from a homogeneous cohort of patients, who were treated with radiochemotherapy, will be analyzed using the targeted NGS sequencing technique. By correlating DNA alterations with recurrence-free- and overall survival of patients, a possible influence of genetic changes on the effectiveness of radiochemotherapy will be addressed. The comparative analysis of primary and recurrent tumors will lead to improved understanding of resistance mechanisms and thus improve primary therapy. Additionally target validation by detailed analyses of identified genes in cell line models have to be performed to evaluate suitable biomarkers that can predict the response of head and neck cancer cells to radiochemotherapy. Suitable interventions or combinatorial strategies will be tested with regard to resensitizing tumor cells and improving future therapies. Since the genomic heterogeneity in tumor tissue represents a hurdle for personalized treatment approaches, a comparison of diagnostic biopsies and surgical material, as well as blood plasma of patients will be performed in addition.

Scope of work:
- Sequencing of DNA from FFPE tissue samples and cf DNA from plasma
- Evaluation of the potential correlation between genetic changes and clinical parameters
- Cultivation, characterization and genetic modification of HNSCC cell lines
- Investigation of cell viability and clonogenic survival after radiochemotherapy and treatment with various protein kinase inhibitors
- Statistical Analysis

Methods include:
- DNA isolation and purification from FFPE tissue samples and cf DNA from plasma
- Targeted NGS sequencing
- Bioinformatic analysis of the sequencing data to correlate genetic changes with clinical parameters
- Sterile cell culture techniques
- MTT and clonogenic survival assays
- Molecular biology methods (RNA / DNA isolation, cDNA synthesis, PCR, Real-time PCR, gel electrophoresis, knock-in / down experiments)
- Protein analysis (Western blot and flow cytometry)

Weitere Informationen

Unternehmen

Thesius Inspiration

Bereich/Abteilung

German Consortium for Translational Cancer Research (DKTK) Berlin

Abschlussart

Bachelorarbeit

Branche

Bio- und Gentechnologie

Anforderungen

- Completed master's degree in biology, biotechnology or a related field
- Highly motivated and committed scientist with interest in Radiation Oncology
- Personal organizational skills
- Highly proficient in spoken and written English
- Social- and team skills
- Methodological experience in the following areas is essential: molecular biology, protein analysis, cell culture and statistics

The Translation Centre is located in the premises of the Charité - University Medicine Berlin, Translational Radiobiology and Radiooncology Laboratory.

Zusatzinformationen

PhD Student

Ausschreibung hier: http://www.dkfz.de/de/stellenangebote/index.php?id=150/2014&campaign=hgfjobs

Wir bieten:

Interessanten, vielseitigen Arbeitsplatz
Internationales Umfeld
Vergütung nach TV-L
Möglichkeiten zur Teilzeitarbeit
Flexible Arbeitszeiten
Gute Fort- und Weiterbildung

Beginn: as soon as possible

Befristung: The position is limited for 3 years.

Bewerbungsschluss: October 9, 2014

Weitere Informationen:
PD Dr. Ingeborg Tinhofer-Keilholz
phone 030 450-527 074

Leistungen

Finanzielle Unterstützung

› Vergütung nach TV-L, Möglichkeiten zur Teilzeitarbeit, Flexible Arbeitszeiten