We are identifying and characterizing targets for potential therapy of sepsis patients using cell culture in vitro, as well as the polymicrobial sepsis model, induced in the mouse by caecum ligation and puncture. With the cell culture systems, we have access to high-throughput screening methods which allow us to screen test compounds at transcriptional and translational levels. An emphasis is laid on methods which permit testing of compounds on intact cells. The data acquired in this way are validated by translation as rapidly as possible to the experimental model in vivo. Conversely, in-vivo findings are studied mechanistically in vitro.

Selected Publications

Brenneis M, Aghajaanpour R, Knape T, Sha LK, Neb H, Meybohm P, Zacharowski K, Hauser IA, Büttner S, Parnham MJ, Brüne B, von Knethen A. (2016) PPARγ expression in T Cells as a prognostic marker of sepsis. Shock Published ahead of printing DOI:10-1097/SHK.0000000000000568.

Knape T, Flesch D, Kuchler L, Sha LK, Giegerich AK, Labocha S, Ferreirós N, Schmid T, Wurglics M, Schubert-Zsilavecz M, Proschak E, Brüne B, Parnham MJ, von Knethen A. (2015) Identification and characterisation of a prototype for a new class of competitive PPARγ antagonists. Eur J Pharmacol 755:16-26.

von Knethen A, Sha LK, Knape T, Kuchler L, Giegerich AK, Schulz M, Hauser IA, Brüne B (2015) Activation of the peroxisome proliferator-activated receptor γ counteracts sepsis-induced T cell cytotoxicity toward alloantigenic target cells. J Mol Med 93:633-644.