Vascular Biology – PI: Jürgen Bernhagen
We have discovered the cytokine MIF in inflammatory and vascular disease and have characterized it as a protagonistic member of the class of ‘atypical chemokines’. Relying on biochemical and vascular biology methodologies in combination with transgenic mouse models and clinical approaches, we broadly study the MIF protein family (i.e. MIF, MIF-2/D-DT, CXCR2, CXCR4, CXCR7, CD74, sCD74) and related classical chemokines in atherosclerosis, ischemic stroke, and myocardial infarction. This involves deciphering the receptor complexes and pathways driving atherogenic recruitment of leukocyte sub-populations, but we also focus on site- and disease-specific oxidized iso-forms as encountered under ischemic/oxidative stress as well as on chemokine-like alarmins such as HMGB1.
Another focus is on atheroprotective signaling pathways maintained by the COP9 signalosome (CSN) in atherogenic endothelium. The CSN is a multi-functional protein complex that regulates SCF cullin-RING E3-ligase (CRL) NEDDylation status, controlling ubiquitin/26S-proteasome-mediated degradation of cell-regulatory proteins. Based on our discovery of a link between CSN5/JAB1 and inflammation, we currently study atheroprotective effects of CSN5 via NFκB signaling.
We are also interested in cardioprotective mechanisms of some of these mediators and how they compare with corresponding effects in ischemic stroke and cerebral-/(micro)vascular pathogenesis but also other inflammatory diseases. Lastly, capitalizing on various collaborations, we increasingly pursue links between inflammation and neurodegeneration, i.e. inflammasome and amyloid/chaperone-type mechanisms.
Prof. Dr. rer. nat. Jürgen Bernhagen
Secretary: Sabrina Lukanovic