Primary AppointmentAssociate Professor, Pharmacology
- PhD, University of Vienna
Role of lipid oxidation products in inflammation and vascular immunology in atherosclerosis and diabetes
1. Resolution of acute and propagation of chronic inflammation.
2. Mechanisms of endothelial-monocyte interaction in chronic inflammation.
3. Intracellular signaling induced by oxidized lipids.
4. Pattern recognition in innate immunity (Toll like receptors).
5. Antiinflammatory activities of PPARs.
6. Regulation of heme oxygenase-1.
Techniques in Use: Quantitative RT-PCR, Promoter-reporter assays, Gel shift, siRNA, Transfection,
HPLC and ESI-MS, TLC, Cell culture, Immunohistochemistry, Flow cytometry, SDS-PAGE,
Western blotting, Mouse models of inflammation.
Current Summary: Inflammation is generally accompanied by tissue damage associated with oxidation
of host macromolecules by inflammation-derived free radicals. Recent evidence
suggests that phospholipid oxidation products (OxPL), which are generated by
oxidation of cellular membranes, lipoproteins and during apoptosis, represent
danger signals that modulate inflammation and the activation of the innate immune
response. My laboratory has recently demonstrated that certain OxPL are potent
negative feedback regulators of innate immune responses via blocking the interaction
of endotoxin with its Toll-like receptor-4 (TLR-4). Ongoing projects aim to
1) identify mechanisms by which OxPL modulate a specific immune response and
delineate pathways that determine the signal differentiation between OxPL (altered
self) and pathogen-associated molecular patterns (PAMPs) such as LPS (non-self),
2) investigate how acute inflammation is resolved or driven into a chronic state
by OxPL, and 3) examine how monocyte specificity is brought about in chronic
inflammation. The long-term goals of this research are to understand how oxidative
modification of lipids during tissue damage leads to an inadequate immune response
during infection, causes disruption of the tightly controlled balance of immune
tolerance, and ultimately provokes chronic inflammation.
Peroxisomal proliferator activated receptors (PPARs) are ligand-activated transcription
factors belonging to the superfamily of nuclear hormone receptors. In addition
to regulating the fatty acid and glucose metabolism in liver, myocardium and
adipose tissue, they have been shown to exert direct anti-inflammatory effects
in the vascular wall, although the underlying mechanisms are poorly understood.
Consequently PPAR ligands are able to slow down the progression of inflammatory
vascular diseases like atherosclerosis and restenosis. Currently, we investigate
the hypothesis that the induction of the potent anti-inflammatory gene heme
oxygenase-1 (HO-1) by PPARs in the vascular wall significantly contributes to
their anti-inflammatory effects.