Colorectal cancer (CRC) remains a difficult to treat disease especially at later stages. The main challenge is the enormous patient to patient variation in response as well as the so-called intra tumor heterogeneity.
In our search for novel therapeutic avenues we have focused on the mitochondria as a potential Achilles' heel in CRC. We uncovered that multiple novel combination therapies modulate the mitochondrial integrity and allow for tumor-selective targeting by unleashing the intrinsic cell death machinery.
Your project aims to unravel the mechanism underlying this tumor selectivity and addresses how mitochondrial homeostasis is changed in CRC. The ultimate aim is to identify selective targets for therapy that use mitochondrial dependency of CRC.
About your role
- You will be primarily responsible for the execution of this project. You will combine therapeutic targeting of CRC cell lines and primary normal colon and CRC cultures.
- Mitochondrial metabolism, fission and fusion as well as release of cytochrome c and subsequent cell death will be studied.
- Mechanistic aspects will be studied using CRISPR screens and validated with drugs targeting crucial players.
- Finally you will translate findings to in vivo models.