Studies of novel pathogenetic mechanisms and therapeutic approaches in renal disease

This project focuses on the molecular pathogenesis of infectious and inflammatory renal diseases in order to define novel mechanisms of renal injury and thereby develop new therapeutic approaches.

The disease models investigated are hemolytic uremic syndrome, mediated by infection with enterohemorrhagic E. coli (EHEC) or by complement activation, C3 glomerulopathy and vasculitis.

The project derives hypotheses from the applicant’s clinical practice in pediatric nephrology, utilizing patient samples and laboratory models in order to evaluate new treatment options.

Specifically, the project will attempt to develop novel therapies to block EHEC infection, as well as the toxicity of Shiga toxin.

The role of extracellular vesicles in the propagation of renal infection and inflammation, and pathways of vesicle-mediated pathogenesis that can be blocked, will be studied.

Furthermore, we will investigate the role of the kallikrein-kinin and complement systems and attempt to inhibit complement-mediated renal disease using novel approaches, including renin inhibition.

The laboratory receives DNA samples from Nordic patients with complement-mediated renal diseases, which will be sequenced for novel complement mutations followed by phenotypic correlations allowing targeted individualized treatment.

Ultimately, we aim to develop treatments to prevent the spread of bacterial virulence factors and neutralize complement and kinin system activation in acute and chronic renal diseases.