A major focus of our group is to define the role of nuclear receptors (NRs), in particular liver X receptors (LXRs), as lipid sensors and regulators at distinct endothelial barriers. It is well established that LXRs are key regulators of high-density lipoprotein (HDL) metabolism. Increasing evidence suggests that HDL and HDL-associated (apolipo)proteins protect against cardiovascular and neurodegenerative diseases by modulating cholesterol flux. Low HDL levels might also contribute to the pathophysiology of type 2 diabetes. On the other hand, LXRs beneficially affect glucose homeostasis. Remarkably, diabetes is also a significant risk factor for Alzheimer’s disease (AD). In addition to their beneficial effects on HDL metabolism, LXR agonists decrease the production of amyloid β peptide (Aβ), suggesting a link between HDL metabolism and neurodegeneration.

The entrance of plasma lipoproteins into the brain is restricted due to the presence of tight junctions at the blood-brain barrier (BBB). At the same time, cerebrovascular endothelial cells express several lipoprotein receptors, lipid transporters, and apolipoproteins required for cholesterol turnover. Our group has characterized LXR-regulated cellular cholesterol efflux pathways in brain capillary endothelial cells (BCEC). Recent research projects have established functions of several HDL-associated proteins and/or LXR targets in cholesterol transport and metabolism at the BBB. Currently, the group investigates the interaction of these pathways with the production and processing of amyloid precursor protein (APP)/Aβ at the cerebrovascular interface between the brain and the circulation. Recent data indicated that nuclear receptor ligands (and simvastatin) may modulate the processing of APP and Aβ production and clearance into a more beneficial, non-amyloidogenic direction. In addition, de-regulated insulin signaling in brains and BCEC of AD-mice is possibly mediated by Aβ. While HDL itself also exerts anti-inflammatory actions on endothelial cells, LXRs control immune regulatory functions and can reduce inflammatory cellular reactions, including cytokine release at the BBB. Our DK-MCD students aim to investigate aspects of the relationship in nuclear receptor and insulin signaling between Aβ, cholesterol homeostasis, and immune-metabolic functions in BBB endothelial cells.

 

Curriculum vitae

	1988 - 1994	Studies of Biology (Zoology and Biochemistry), University of Graz, Austria
	1992 - 1994	Master thesis at the Institute of Zoology, Department of Physiology, University of Graz, Austria, graduation "Master of Science" (Mag. rer. nat.)
	1995 - 1997	PhD Thesis at the Institute of Medical Biochemistry, University of Graz, Austria, graduation to Dr. rer. nat. (with distinction)
	1998 - 2000	PostDoc at the Heart Research Institute, Sydney, Australia
	2000 - 2004	PostDoc at the Institute of Molecular Biology and Biochemistry, Medical University of Graz
	2004 - 2005	Research Assistant at the Institute of Molecular Biology and Biochemistry, Medical University of Graz, Austria
	2006 - 2010	University Assistant at the Institute of Pathophysiology, Medical University of Graz, Austria
	2008	Habilitation in Pathophysiology and Immunology
	2010 - 2011	Assistant Professor, Institute of Pathophysiology and Immunology, Medical University of Graz, Austria
	2011 - 2020	Associate Professor, Institute of Pathophysiology and Immunology, Medical University of Graz, Austria
	2012 - 2020	Speaker of the Curricular Committee of the PhD program Molecular Medicine at the Medical University of Graz
	2013 - 2015	Board member of the Research Promotion Committee of the Medical University of Graz
	2016 - 2020	2nd Deputy Chair Immunology and Pathophysiology, Medical University of Graz, Austria

Publications

Grants