1) Name – Title of the research project in CCHD
Oswald Wagner – Protective mechanisms of Heme Oxygenase-1
2) Coordinates of the Faculty Member
Department of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna; Waehringer Guertel 18 – 20, A-1090 Wien, Austria, phone: +431 40400 5356, fax: +431 40400 5389; email: oswald.wagner@meduniwien.ac.at
3) Keywords
Heme Oxygenase-1, adipocyte differentiation, macrophage, inflammation, obesity
4) Research interest of the Faculty Member
Oswald Wagner is interested in the pathophysiology of cardiovascular disease, more specifically in the role of vasoactive peptides, fibrinolysis and coagulation as well as inflammation in the process of atherosclerosis and arteriosclerosis. Due to his involvement in laboratory diagnostics his goal is to identify new prognostic and diagnostic markers of cardiovascular disease including the clinical endpoints myocardial infarction, stroke and peripheral arterial disease. Within that frame he became interested in the role of protective genes in inflammation and vascular medicine. One of those molecules is Heme Oxygenase-1 (HO-1), an enzyme with potent anti-inflammatory properties, through which it plays a role in the development of metabolic diseases. Dr. Wagner investigated anti-inflammatory effects of carbon monoxide in macrophage and is now investigating similar mechanisms in obesity. Furthermore, Dr. Wagner is interested in HO-1 effetcs on trophoblast and adipocyte differentiation.
5) Collaborations within CCHD
We have recently generated a conditional knockout of the Hmox1 gene in C57/BL6 mice, which are now being crossed with conditionally Cre-expressing strains to investigate tissue-specific effects of HO-1 within CCHD. Together with T. Stulnig we will investigate cytoprotective mechanisms of macrophage HO-1 in obesity using mice deficient in macrophage HO-1 (Lyz-Cre x HO-1fl/fl). In cooperation with H. Esterbauer we will study regulatory effects of HO-1 in white adipose tissue using mice lacking HO-1 in adipocytes (aP2-Cre x HO-1fl/fl). With C. Binder the role of HO-1 in B1-cell biology and natural antibody secretion will be studied utilizing the newly available HO-1fl/fl mouse, in addition to transcriptional profiling studies of B1-cells using DNA Microarrays. Together with H. Lassmann we will investigate effects of HO-1 in different MS patterns using various mouse models With G. Superti-Furga we will collaborate on transcriptional profiling using DNA microarrays and on the characterization of HO-1 by interaction proteomics. Together with B. Binder the regulation of HO-1 expression and gene regulation in endothelial cells during inflammation will be studied. With C. Mannhalter we will extend our long standing collaboration with respect to genetic risk factors in vascular diseases, focusing on polymorphisms of HO-1. With S. Knapp we will study the role of HO-1 in acute lung injury. With E. Jensen-Jarolim mimotope experiments are pursued for the identification of mimics for several autoantigens,
6) Collaborating research groups where PhD Students can perform their research stay
Prof. Fritz H Bach, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
Prof. Leo E Otterbein, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
Prof. Miguel P Soares, Gulbenkian Institute for Science, Oeiras, Portugal
7) Know-how and infrastructure of the research group
First description of a role of an HO-1 promoter ploymorphism in restenosis (Schillinger et al., 2004), aortic abdominal aneurysm (Schillinger et al., 2002), stroke (Funk et al., 2004), kidney allograft function (Exner et al., 2004) and others (reviewed in Exner et al., 2005). Description of the anti-inflammatory mechanisms of CO in macrophages via PPARg and ROS (Bilban et al., 2006 and 2008). Protection of CO against endotoxic shock involves reciprocal effects on iNOS in lung and liver (Sarady et al., 2004). First analysis of therapeutic effects of CO in man (Mayer et al., 2005). First description of regulatory effects of HO-1 on trophoblast-invasion via PPAR (Bilban et al., 2008). Cytokine profile of macrophages is measured by real-time PCR, GeneChip analysis as well as ELISA (Bilban et al., 2006). This research group uses mice specifically deficient of HO-1 in WAT (aP2-Cre x HO-1fl/fl) for examination of HO-1 effects on mature adipocyte histology, apoptosis/necrosis as well as endocrine function (secretion of adiponectin, leptin, resistin). HO-1 gain- and loss-of-function 3T3-L1 cell lines are generated via retroviral gene transduction of the HO-1 cDNA or HO-1-specific shRNA, respectively (Bilban et al., 2008), Mature adipocyte formation is evaluated by real-time PCR of typical adipogenic genes PPARg, CEBPa, adiponectin, LPL, GLUT4 and KLF-15 as well as oil-red staining of neutal lipids (REF). Members of this research group have one complete cell culture lab (preparative microscope, 2 sterile hoods, two incubators, fluorescence microscopes), one standard radioactivity lab, one standard biochemistry and molecular biology lab, a fluorscence microscope with monochromator, filter wheels, and CCD camera at their disposal. Furthermore, this reaearch group houses a full Affymetrix GeneChip facility as well as a ABI Prism 7900HT sequence detection system for (genome-wide) gene expression analysis.
