Cholesterol; Endoplasmic Reticulum Stress; Lipids; Lymphatic Metastasis; Melanoma; Metabolic Diseases; Unfolded Protein Response
- Lipid metabolism in metabolic disorders
Cholesterol is an essential lipid for mammalian cells as it controls membrane function and rigidity, modulates cell signaling and is a precursor for steroid hormone synthesis. In the circulation, cholesterol is transported by lipoproteins, which distribute lipids between the liver and peripheral tissues. At the cellular level, cholesterol metabolism is tightly regulated by uptake from lipoproteins, endogenous synthesis and efflux to extracellular acceptors.
Deregulation of lipid metabolism is causally involved in the etiology of metabolic disorders and metabolic disorders in turn alter lipoprotein and cholesterol trafficking. Diseases associated with altered lipid metabolism include atherosclerosis, cancer, obesity, diabetes and fatty liver disease. The excessive metabolic demand associated with these diseases can disturb the homeostasis of cell organelles, especially of the endoplasmic reticulum (ER). This leads to ER stress and an adaptive process called the unfolded protein response (UPR). In our research, we particularly focus on the question, how ER stress and the UPR in metabolic disorders overrule the regulatory mechanisms controlling cellular cholesterol homeostasis.
Techniques, methods & infrastructure
We are experienced in the analysis of cellular lipid metabolism and trafficking. Research methods include gas chromatography, techniques on the investigation of lipid uptake and synthesis as well as imaging techniques (CLEM - correlative light and electron microscopy).
- ER stress in hepatic cholesterol uptake and trafficking (2015)
Source of Funding: Herzfelder'sche Familienstiftung,
- Impact of endosomal cholesterol trafficking on melanoma metastasis (2013)
Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
- Eigner, K. et al., 2017. The unfolded protein response impacts melanoma progression by enhancing FGF expression and can be antagonized by a chemical chaperone. Scientific Reports, 7(1). Available at: http://dx.doi.org/10.1038/s41598-017-17888-9.
- Eberhart, T. et al., 2016. The unfolded protein response is a negative regulator of scavenger receptor class B, type I (SR-BI) expression. Biochemical and Biophysical Research Communications, 479(3), pp.557-562. Available at: http://dx.doi.org/10.1016/j.bbrc.2016.09.110.
- Röhrl, C. et al., 2014. Endoplasmic reticulum stress impairs cholesterol efflux and synthesis in hepatic cells. Journal of Lipid Research, 55(1), pp.94-103. Available at: http://dx.doi.org/10.1194/jlr.M043299.
- Röhrl, C. et al., 2014. Bile Acids Reduce Endocytosis of High-Density Lipoprotein (HDL) in HepG2 Cells M. Kanzaki, ed. PLoS ONE, 9(7), p.e102026. Available at: http://dx.doi.org/10.1371/journal.pone.0102026.
- Röhrl, C. & Stangl, H., 2013. HDL endocytosis and resecretion. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1831(11), pp.1626-1633. Available at: http://dx.doi.org/10.1016/j.bbalip.2013.07.014.