SP4: Exploring ER stress-induced metabolic adaptation in the treatment of pancreatic cancer
SP4 investigates the influence of distinct metabolic phenotypes occurring in defined PDAC subtypes on therapy responses. The team postulates that therapy-induced, subtype-specific ER stress responses affect cell compartment interactions, e.g. the ER-mitochondria-nucleus network, thereby defining the cellular and molecular consequences of PDAC therapy. To this end, the PhD-candidate of the first cohort (Bogeski group) will apply advanced biosensor technologies, life cell imaging, mRNA-sequencing and HPLC/MS methods to examine chemotherapy-induced inter-organelle communication and transcriptional reprogramming. These studies, conducted in patient-derived PDAC models, will be accomplished by the MD-candidate of the first cohort (Ellenrieder lab) who will study how ER-stress responses affect the chromatin landscape, the metabolic state and the functional capacities of the tumor cell. The PhD-candidate of the second cohort (Ellenrieder group) will employ translational PDAC models to investigate the consequences of key ER stress response manipulation on cell metabolism, gene expression and compartment-communications. Finally, the MD-candidate of the second cohort (Bogeski group) will characterize the composition of the inflammatory tumor microenvironment in vitro, in patient samples and translational tumor models with respect to the given treatment approach. Together, the interdisciplinary SP4 team combining expertise in clinical and pre-clinical PDAC research and ER-signaling (Ellenrieder group) and organelle and immune biology, Ca2+ and redox signaling (Bogeski lab) seeks to establish the foundation for novel combination therapies designed to overcome adaptation and resistance to conventional treatment in PDAC.
