Apoptosis; Calcium Signaling; Chemotherapy resistance; Melanoma, Experimental; Neuroblastoma; Ryanodine Receptor Calcium Release Channel; Signalling by G protein-coupled receptors (GPCRs)
- Hohenegger Lab
My current research focus covers pharmacological strategies to impair melanoma and neuroblastoma survival. We try to understand the importantance of signalling pathways as a prerequisit for elucidation of key nodes as novel drug targets. Beside, we try to describe drug side effects on molecular level in order to contribute to enhanced drug safety.
Although the nucleotide NAADP is the most potent Ca2+ releaser little is known about it´s synthesis and binding targets. We are interested in NAADP signalling in skeletal and cardiac muscle.
Techniques, methods & infrastructure
A broad spectrum of biochemical, cell biological, and imaging techniques are used to perform pathway delineation. We are familiar with enzyme kinetics, ligand binding studies and chemical modification of proteins. As a source for these analyses we use material from cell lines, primary cells and tissue from in vivo model organisms.
- Wasinger, C. et al., 2014. Autocrine secretion of 15d-PGJ 2 mediates simvastatin-induced apoptotic burst in human metastatic melanoma cells . Br J Pharmacol, 171(24), pp.5708-5727. Available at: http://dx.doi.org/10.1111/bph.12871.
- Sieczkowski, E. et al., 2009. Double impact on p-glycoprotein by statins enhances doxorubicin cytotoxicity in human neuroblastoma cells. Int. J. Cancer, p.NA-NA. Available at: http://dx.doi.org/10.1002/ijc.24885.
- Dammermann, W. et al., 2009. NAADP-mediated Ca2+ signaling via type 1 ryanodine receptor in T cells revealed by a synthetic NAADP antagonist. Proceedings of the National Academy of Sciences, 106(26), pp.10678-10683. Available at: http://dx.doi.org/10.1073/pnas.0809997106.
- Sacher J, Weigl L, Werner M, Szegedi C, Hohenegger M. Delineation of myotoxicity induced by 3-hydroxy-3-methylglutaryl CoA reductase inhibitors in human skeletal muscle cells. J Pharmacol Exp Ther. 2005 Sep;314(3):1032-41.
- Hohenegger M, Suko J, Gscheidlinger R, Drobny H, Zidar A. Nicotinic acid-adenine dinucleotide phosphate activates the skeletal muscle ryanodine receptor. Biochem J. 2002 Oct 15;367(Pt 2):423-31.