1) Name – Title of the research project in CCHD
Hans Lassmann – Pathogenesis of multiple sclerosis lesions
2) Coordinates of the Faculty Member
Center for Brain Research, Divsion of Neuroimmunology, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna; Tel.: +43 1 4277 62811; Fax: +431 4277 9628;
eMail.: hans.lassmann@meduniwien.ac.at
3) Keywords
multiple sclerosis, inflammation, demyelination, neuronal injury, remyelination, innate and adaptive immunity
4) Research interest of the Faculty Member
Dr. Hans Lassmann is working on the pathology and pathogenesis of multiple sclerosis. He was the first to define structural and immunological heterogeneity of multiple sclerosis lesions and has contributed highly cited publications on inflammation, patterns and mechanisms of demyelination, axonal injury and remyelination in this disease. Another focus of his research is to analyse mechanisms of brain inflammation and inflammation induced tissue injury in experimental models. In international collaboration he was the first to delineate the role of myelin specific autoantibodies in experimental models of inflammatory demyelination, a mechanisms, which is now recognized to be of key importance in a subset of multipe sclerosis patients and in neuromyelitis optica. Recently he has defined another mechanism of tissue injury, which apparently plays a kex role in the development of multiple sclerosis lesions, the induction of mitochondrial injury in the inflammatory process. A major development in the laboratory during the last years was the adaptation of microarray technology to be applied on formalin fixed and paraffin embedded archival material from multiple sclerosis autopsy tissue. This opens new avenues for molecular research on multiple sclerosis pathogenesis.
5) Collaborations within CCHD
Direct cooperation within the CCHD relates to aspects of innate immunity in the pathogenesis of inflammatory lesions in the central nervous system. This involves the analysis of the coagulation pathway in triggering microglia activation and tissue injury (B. Binder) and the involvement of radical damage within such lesions (G. Superti Furga). Together with O. Wagner and H. Esterbauer we will study the role of heme oxygenase in experimental autoimmune encephalomyelitis. Aspects of innate immunity in MS lesions will be analysed together with B. Binder and G. Superti Furga. Possible kidney pathology in experimental neuromyelitis optica is analysed in cooperation with D. Kerjaschki. The role of CXCL-12 and CXCR-4 in peripheral neurons is investigated together with S. Boehm.
6) Collaborating research groups where PhD Students can perform their research stay
In addition our laboratory provides support in technical issues of immunocytochemistry, immune electron microscopy and in situ hybridisation.
Outside the CCHD program we have intense collaboration within the framework of the EU-Project “Neuropromise” on cytotoxic T-cells (Roland Liblau, INSERM, Toulouse), innate immunity (Ken Smith, Institute of Neurology, Queen Square, London) and on genetic regulation of brain inflammation and tissue injury (Tomas Olsson, Karolinska Institute, Sweden) and with the Max Planck Institute for Neurobiology (Martinsried, FRG) on experimental models of multiple sclerosis.
7) Industrial partners (if applicable)
We are currently involved in cooperative projects with industry dealing with the role of arachidonic acid metabolites in inflammatory demyelinating diseases, including multiple sclerosis (Bayer / Schering) and on a new T-cell activation antigen, which plays a role in downregulating inflammation (GenPath, Germany).
8) Know-how and infrastructure of the research group
The Division of Neuroimmunology at the Center for Brain Research of the MUW is one of the internationally leading centers on the topic of immunopathology of inflammatory brain diseases, with a specific focus of the pathology and pathogenesis of multiple sclerosis. Key publication deal with the immunopathological characterization of multiple sclerosis lesions (Lucchinetti et al 2000; Lucchinetti et al 2002, Stadelmann et al 2005), the definition of pathology of the chronic progressive stage of multiple sclerosis (Kutzelnigg et al 2005, Dal Bianco et al 2008), of the extent of endogenous repair within MS lesions (Patrikios et al 2006) and of molecular mechanisms involved in the formation of MS lesions (Marik et al 2007, Mahad et al 2008, 2009). Mechanistic studies on brain inflammation and inflammatory tissue injury is also performed in respective experimental models (Marik et al 2007, Hochmeister et al 2008, Odoardi et al 2007, Adams et al 2007, Krishnamoothy et al 2006).
On a technical basis we are familiar with all techniques of immunocytochemistry (including confocal microscopy and immune electron microscopy), in situ hybridisation, T-cell and B-cell immunology as well as molecular techniques. Recently we were able to adapt genome wide microarray technology for the use in archival formalin fixed and paraffin embedded human autopsy tissue.
