The focus of our group is blood vessels, inflammation, and secondary lymphoid organs, and how the extracellular matrix affects these tissues and processes.
It is well established that the ECM can influence the development, migration and longevity of cells by direct receptor-mediated interactions. However, there is increasing evidence for indirect effects of the ECM resulting from presentation or controlled release of bound factors or bioactive fragments, and mechanical signals resulting from the 3D organization of the ECM. Our aim is to define how both direct and indirect effects of the ECM influence tissue development and homeostasis, and how this is altered in pathological situations.
Several models/ tissues are central to our investigations:
- Murine experimental autoimmune encephalomyelitis (EAE) a model for the human disease, multiple sclerosis. Work on this model focuses on mechanisms employed by different leukocyte types to transmigrate across central nervous system (CNS) blood vessels. Comparisons are made with other inflammation models include type 1 diabetes (NOD mice), skin inflammation (delayed hypersensitivity - DTH), and peritonitis. (see SFB 1009; TR SFB 128 and Marie Curie ITN ENTRAIN).
- Secondary and tertiary lymphoid organs, including lymph nodes, the spleen and the lymph node-like structures that form in chronically inflamed tissues, where the contribution of the ECM to structure and function of the organ is investigated.
- The use of the cre-loxP system to generated mice lacking specific ECM molecules in defined tissues and/ or at define developmental stages. This work focuses on the laminin family of glycoproteins, one of the major components of basement membranes, and conditional elimination of defined laminins in the skin, endothelium, pericytes and smooth muscle. Part of this work is in an EU fund "Inititial Training Network (ITN)" entitled SmArt, which deals with small artery remodelling in vascular disease (see www.smallartery.eu).
- Murine models of stroke and small vessel disease, with focus on the role of the ECM on structural and functional integrity of the neurovascular unit and the role of inflammation these pathologies. This work is carried out within the EU cooperative project SVDs@Target (http://www.svds-at-target.eu).