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Lienhard Schmitz: Characterization and selective targeting of deregulated NF-κB activation pathways in ovarian cancer cells

Lienhard Schmitz aims to unravel the NF-κB activation status and signaling in ovarian cancer cells and immune cells using drugs specifically targeting (I) defined steps in the different NF-κB activating pathways and (II) the expression of a subset of NF-κB target genes. These highly selective inhibitors will not shut off the entire NF-κB response and we will aim to interfere with NF-κB activity in tumor cells while having no (or at leastless) effects on the associated immune cells. The impact of the NF-κB-dependent components within the altered secretome on tumor- and immune cells will be studied.

The different NF-κB signaling pathways (canonical IκBa, IKKa/b; non-canonical characterized by p100 processing; atypical NF-κB associated with ATM phosphorylation) are analyzed in tumor cells to unravel their impact on the secretome and its biological function. The role of the interaction of NF-κB signaling with CDKs for shaping de novo protein synthesis, shedding and secretion of inflammatory mediators and their impact on plasticity and function of tumor-associated immune cells will be investigated.