Cardiovascular Diseases; Cardiovascular Physiological Processes; Cell Membrane Permeability; Intracellular Signaling Peptides and Proteins; Physiology; Serpins
My research focus are non-inhibitory functions of serine protease inhibitors (serpins), especially functions in cell signaling. We are focusing on serpinA5 (protein C inhibitor, PCI), a secreted protease inhibitor with wide tissue distribution and broad protease reactivity. SerpinA5 can be internalized by cells in a phospholipid-mediated process and then translocate to the nucleus. Based on these results we are currently investigating the mechanism of serpinA5-internalization. We are also working on the identification of intracellular/nuclear interaction partners and on the analysis of the biological relevance of these interactions.
Techniques, methods & infrastructure
Diverse basic molecular and cellular biology techniques, immunological and functional assays, subcellular fractionation, 2D-electrophoresis, flow cytometry, immunohistochemistry, confocal microscopy, analysis of protein-phospholipid interactions, phagocytosis assays, expression and purification of recombinant proteins, transgenic animals.
- Einfinger K, Badrnya S, Furtmüller M, Handschuh D, Lindner H, Geiger M. Phospholipid Binding Protein C Inhibitor (PCI) Is Present on Microparticles Generated In Vitro and In Vivo. PLoS One. 2015 Nov 18;10(11):e0143137. doi: 10.1371/journal.pone.0143137. eCollection 2015. PMID: 26580551
- Yang H, Wahlmüller FC, Sarg B, Furtmüller M, Geiger M. A+-helix of protein C inhibitor (PCI) is a cell-penetrating peptide that mediates cell membrane permeation of PCI. J Biol Chem. 2015 Jan 30;290(5):3081-91. doi: 10.1074/jbc.M114.581736. Epub 2014 Dec 8. PMID: 25488662 Free PMC Article
- Wahlmüller FC, Sokolikova B, Rieger D, Geiger M. New lipid interaction partners stimulate the inhibition of activated protein C by cell-penetrating protein C inhibitor. Thromb Haemost. 2014 Jan;111(1):41-52. doi: 10.1160/TH13-06-0478. Epub 2013 Oct 17. PMID: 24136361
- Malleier JM, Oskolkova O, Bochkov V, Jerabek I, Sokolikova B, Perkmann T, Breuss J, Binder BR, Geiger M. Regulation of protein C inhibitor (PCI) activity by specific oxidized and negatively charged phospholipids. Blood. 2007 Jun 1;109(11):4769-76. Epub 2007 Mar 1. PMID: 17332248 Free Article
- Uhrin P, Dewerchin M, Hilpert M, Chrenek P, Schöfer C, Zechmeister-Machhart M, Krönke G, Vales A, Carmeliet P, Binder BR, Geiger M. Disruption of the protein C inhibitor gene results in impaired spermatogenesis and male infertility. J Clin Invest. 2000 Dec;106(12):1531-9. PMID: 11120760, Free PMC Article