Keywords

Cardiovascular Diseases; Cardiovascular Physiological Processes; Cell Membrane Permeability; Intracellular Signaling Peptides and Proteins; Physiology; Serpins

Research group(s)

• Serpins
  Members:
  Margarethe Geiger
  Ulrike Resch

Research interests

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.

Grants

• Nuclear cathepsin L and SERPINA5 (2018)
  Source of Funding: FWF (Austrian Science Fund), Stand-alone projects
  Principal Investigator
• Protein C inhibitor in prostate cancer cells: analysis of the different molecular forms and their subcellular localization (2017)
  Source of Funding: Medical Scientific Fund of the Mayor of the City of Vienna, Medical Research
  Principal Investigator

Selected publications

1. 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
2. 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
3. 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
4. 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
5. 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