EGFR-mediated tumor cell dissemination in HNSCC (Gires)

Department / Institute
Department of Head and Neck Research, Clinic and Policlinic of Otorhinolaryngology
Subject area
Tumor cell dissemination
Project title
EGFR-mediated tumor cell dissemination in HNSCC
Name of supervisor
Prof. Dr. rer. Nat. Olivier Gires
Number of open positions
Language requirements
Fluent in English
Academic requirements
Applicants should hold a master in Biological Sciences such as Molecular Biology, Biochemistry, Cell Biology, Molecular Biotechnology or similar or Master in Medicine.

Women are especially encouraged to apply. Applicants with disabilities and equalqualifications will be given preferential treatment.

Project description

We are looking for a highly motivated doctoral student who will dissect molecular andfunctional aspects of tumor cell dissemination in HNSCC with our group. The Epidermal Growth Factor Receptor EGFR is a signaling active receptor that is highlyexpressed in HNSCC and that serves as a therapeutic target for adjuvant therapy. Ourgroup reported that EGFR has dual function in HNSCC in that it can induce eitherproliferation or EMT depending on the strength and duration of activation (Pan et al. PLoS Biology 2018). Further, we defined the EMT transcription factor SLUG as a potential regulator of EMT in HNSCC that is activated by EGFR signaling (Pan et al. PLoS Biology 2018; Schinke et al. Molecular Oncology 2021). In the proposedproject, the candidate will study molecular aspects of EGFR-mediated invasion andmigration in 3D models of HNSCC cell lines and organoids. Photoconvertiblefluorescence-tagged HNSCC cell lines have been established that allowed us tospecifically isolate and (RNA-)sequence invasive and sessile cells. RNAseq datasetsare currently analyzed to identify molecular differences between invasive and sessilecells following EGF treatment. The resulting molecular targets will be at the dispositionof the candidate for further studies of their role in HNSCC dissemination in vitro and inprimary samples.

Our Group

We address central aspects of tumor cell dissemination and epigeneticreprogramming in head and neck squamous cell carcinomas (HNSCC) with a focuson EGFR-governed epithelial-to-mesenchymal transition (EMT). We use 3D-modelsof HNSCC dissemination in combination with live cell imaging, photo-conversionmethods, RNA sequencing, bioinformatic approaches, and functional assays toidentify molecular determinants of HNSCC dissemination. Results from cellularmodels are validated and further expanded in in-house HNSCC patient cohorts andpublicly available cohorts with the aim to develop prognostic and predictive genesignature and to identify potential therapeutic targets.

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