Project 8

IDENTIFICATION OF THE MOLECULAR MECHANISMS BEHIND THE INCREASED CELLULAR RADIOSENSITIVITY OF PAPILLOMAVIRUS-INDUCED HEAD AND NECK TUMOR CELLS USING CRISPR/CAS ACTIVATOR AND REPRESSOR LIBRARIES

An important form of cancer treatment for many tumor types, including head and neck tumors, is radiation therapy. Head and neck tumors caused by human papillomaviruses are particularly sensitive to radiation because HPV-positive tumor cells cannot effectively repair radiation-induced DNA damage. However, the exact molecular mechanisms behind this are not yet fully understood and are controversially discussed. With my project, I would like to decipher these mechanisms in order to identify new possibilities for specific, targeted treatments. The long-term goal behind the project is a less intensive but safer therapy for patients with these tumors.

Specifically, gene expression will be modulated genome-wide in HPV-positive head and neck tumor cell lines using CRISPR/Cas effector libraries. In this procedure, the DNA sequence is not altered, but the expression of the targeted genes is enhanced or reduced. Repeated irradiation is used to select those modifications that counteract the repair defect of the cells and thus induce radiation resistance. In further steps, the candidates found are then validated and their significance for radiosensitivity or radioresistance is investigated in more detail.