- Department / Institute:
- Department of Head and Neck Research, Clinic and Policlinic of Otorhinolaryngology
- Subject area
- Tumor cell dissemination
- Project title
- Receptor-mediated tumor cell dissemination in HNSCC
- Name of the supervisor
- Prof. Dr. rer. Nat. Olivier Gires
- 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 equal qualifications will be given preferential treatment.
Knowledge in computational, bioinformatic analyses methods are highly welcome. - Our group
- We address central aspects of tumor cell dissemination and epigenetic reprogramming in head and neck squamous cell carcinomas (HNSCC) with a focus on EGFR-governed epithelial-to-mesenchymal transition (EMT). We use 3D-models of HNSCC dissemination in combination with live cell imaging, photo-conversion methods, RNA sequencing, bioinformatic approaches, and functional assays to identify molecular determinants of HNSCC dissemination. Results from cellular models are validated and further expanded in in-house HNSCC patient cohorts and publicly available cohorts with the aim to develop prognostic and predictive gene signature and to identify potential therapeutic targets.
Project Description
We are looking for a highly motivated doctoral student who will dissect molecular and functional aspects of tumor cell dissemination in HNSCC with our group. The Epidermal Growth Factor Receptor EGFR is a signaling active receptor that is highly expressed in HNSCC and that serves as a therapeutic target for the treatment of recurrent-metastatic HNSCC (R/M-HNSCC). However, response rates are low and predictive markers for the stratification of patients prior to treatment are not available. Our group reported that EGFR induces EMT depending on the strength and duration of the activation of the MAP kinase pathway 1. Upon RNA-sequencing of HNSCC cells in EGFR-mediated EMT, we have defined a transcriptomic signature that comprise prognostic and potential therapeutic factors 2,3. Using 3D-models of HNSCC local invasion in extracellular matrix, we identified an EGFR-dependent gene regulatory network of invasive cells (invGRN) controlled by major gene hubs such as INHBA, SLUG, and effectors of local invasion (ITGB4, Laminin 332, SPHK1). Gene members of the invGRN are controlled by the availability of EGFR ligands AREG and EREG, and selected invGRN members predicted response to Cetuximab in retrospective human HNSCC cohorts (manuscript submitted).
In the proposed project, the candidate will carry on the study of molecular aspects of EGFR-mediated invasion and migration in 3D models of HNSCC cell lines and organoids. Photoconvertible fluorescence-tagged HNSCC cell lines have been established that allowed us to specifically isolate and (RNA-)sequence invasive and sessile cells with genetic disturbances of interest. Identified molecular targets are at the disposition of the candidate for further studies of their role in HNSCC dissemination in vitro and in primary samples using CRISPR-cas9-mediated knockouts, antagonizing antibodies, and small molecule inhibitors. A prime focus will reside on genetic hubs of the invGRN such as INHBA and SLUG.
To applicants: Please send following initial application documents to LMU-CSCOffice before 15th December:
- Resume and Research Motivation Letter
- Certificate of Proficiency in English, equivalent to IELTS Test Academic 6.5 (no module below 6) or TOEFL IBT 95, is required
- Two letters of recommendation directly sent from your current Supervisors/Professors to LMU-CSC Office
Contact LMU-CSC Office: csc.international@lmu.de