Functional metabololipidomics
The enzymatic conversion of polyunsaturated fatty acids leads to the formation of numerous oxygenated lipid mediators. These include pro-inflammatory prostaglandins and leukotrienes, but also specialized pro-resolving mediators (SPM), such as: B. lipoxins, protectins maresins and resolvins. Lipid mediators control numerous physiological and pathophysiological processes, especially the initiation and resolution of inflammation. We combine state-of-the-art mass spectrometry-based lipid mediator analysis with biochemical, cell biological, and molecular biological methods to investigate the influence of lipid mediators on immunological and inflammation-relevant cellular processes. The aims are to 1) identify new bioactive lipid mediators, 2) elucidate their biosynthetic pathway, 3) decipher their signal transduction, 4) clarify their biological functions, and 5) explore their pharmacological potential. We preferentially examine the lipid mediator spectrum in human or animal immune cells, but also in algae, bacteria, fungi, and amoebae. Furthermore, we characterize the role of lipid mediators in diseases with inflammatory pathogenesis (peritonitis, colitis, fibrosis, Alzheimer's, Parkinson's, etc.) and we identify new approaches for pharmacological, inflammation-resolving interventions. In addition, we focus on pathogen-host interactions and characterize pathogen-induced lipid mediator biosynthesis in innate immune cells. Cutting edge of this project is the discovery of the differential bacteria-induced formation of pro-inflammatory and anti-inflammatory lipid mediators through bacterial infection in macrophages, monocytes and neutrophils.
Key publications:
Werz O., Gerstmeier J., Libreros S., De la Rosa X., Werner M., Norris PC., Chiang N., Serhan CN (2018) Human macrophages differentially produce specific resolvin or leukotriene signals that depend on bacterial pathogenicity. Nat. Commun., 9, 59
Jordan P.M., Gerstmeier J., Pace S., Bilancia R., Rao Z., Börner F., Miek L., Gutiérrez-Gutiérrez O., Arakandy V., Rossi A., Ialenti A., González-Estévez C., Löffler B., Tuchscherr L., Serhan C.N., Werz O. (2020) Staphylococcus aureus-derived α-hemolysin evokes generation of specialized pro-resolving mediators promoting inflammation resolution. Cell Rep, 33, 108247
Jagusch H., Werner M., Werz O.*, Pohnert G.* (2019) 15‐Hydroperoxy‐PGE2 – A Novel Intermediate in Mammalian and Algal Prostaglandin Biosynthesis. Angew. Chem. Int Ed Engl., 58, 17641-17645
Collaborative Research Centers:
DFG SFB1127 „ChemBioSys“
DFG TR-SFB124 „FungiNet“