1) Name – Title of the research project in CCHD
The role of serine protease inhibitors (serpins) in cell signalling
2) Coordinates of the Faculty Member
Center for Physiology and Pharmacology
Department of Vascular Biology and Thrombosis
Research, Medical University of Vienna
Schwarzspanierstrasse 17
1090 Vienna, Austria
phone: +431 4277 62506
fax: +431 4277 9625
eMail: margarethe.geiger@meduniwien.ac.at
3) Keywords
Serpins, serine protease inhibitors, protein C inhibitor, proteases, phospholipids, phospholipid signalling.
4) Research interest of the Faculty Member
Dr. Geiger is interested in the analysis of the physiological role of serpins (Serine protease inhibitors). Serpins are a family of closely related glycoproteins, which includes inhibitors of serine proteases as well as non-inhibitory members with other biological functions such as the hormone precursor angiotensinogen, the hormone-binding proteins CBG and TBG, the tumor suppressor maspin, or the heat shock protein HSP47. Dr. Geiger is especially interested in the serpin protein C inhibitor (PCI, serpinA5). Her focus is the analysis to which extent additional, non-inhibitory functions/properties of PCI and other inhibitory serpins are physiologically relevant. Dr. Geiger’s group has established and analyzed PCI-knockout mice (Uhrin et al. 2000). They have shown that male PCI-deficient mice are infertile due to abnormal spermatogenesis in a testis, in which the blood-testis barrier seemed disrupted. In their work with mice Dr. Geiger and coworkers have also shown that in adult mice – unlike in men – PCI is almost exclusively expressed in the reproductive tract. During embryonic development, however, PCI appears to be expressed in several organs and at specific developmental stages (Wagenaar et al., 2010). Dr. Geiger has also shown that the protease inhibitor PCI can bind retinoids (Jerabek et al. 2001) as well as certain phospholipids (e. g. phosphatidylserine, oxidized phosphatidylethanolamine, different phosphoinositides) (Malleier et al., 2007). They have also demonstrated phospholipid-dependent internalization and nuclear translocation of extracellular PCI. Based on these results Dr. Geiger’s group is currently analyzing the mechanism of PCI-internalization as well as the effect of PCI on phosphoinositide –dependent signaling. Furthermore they are aiming to identify intracellular, nuclear and/or cell membrane associated proteins interacting with PCI.
5) Collaborating research groups where PhD Students can perform their research stay
James A. Huntington, PhD, Department of Haematology, University of Cambridge, UK
Frank C. Church, PhD, Division of Hematology-Oncology, University of North Carolina Medical School, Chapel Hill, USA
Bernd Engelmann, MD, Institut für Klinische Chemie, Ludwig-Maximilians- Universität, Munich, Germany
6) Know-how and infrastructure of the research group
Dr. Geiger’s group was the first to establish a knockout mouse model (PCI knockout) at the Medical University of Vienna (Uhrin et al., 2000). The group has a long-lasting experience in the work with proteases and protease inhibitors. Expertise includes qualitative and quantitative methods in protein biochemistry and molecular biology, cell and tissue culture, transfection of cells, expression and purification of recombinant proteins, subcellular fractionation and analysis of subcellular fractions, flow cytometry, immunocytochemistry, immunohistochemistry, and work with transgenic animals. The group also cooperates closely with Dr. H. Lindner and Dr. B. Sarg, Biocenter, Medical University Innsbruck, to identify proteins interacting with PCI by mass spectrometry.
The Center for Physiology and Pharmacology, which includes the Department of Vascular Biology and Thrombosis Research, where Dr. Geiger’s laboratory is located, utilizes top edge technologies and hosts core facilities for transgene technology and advanced imaging including time laps and laser confocal microscopy. All equipment necessary for experimental work in cell and tissue culture, for morphological/morphometric analysis including access to electron microscopy, for protein and lipid biochemistry, for molecular biology, for work with transgenic animals including the generation of transgenic mice, as well as for work with radioactive isotopes is therefore available at the center.
