Head of laboratory
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This laboratory seeks to decipher the fine interactions between microvascular endothelial cells and circulating blood cells, by studying the biology and pathophysiology of microvascular endothelial cells. Diseases such as cerebral malaria, multiple sclerosis and viral encephalitis are being modelled using brain-derived endothelium, while lung-derived cell-lines are being used to study adult respiratory distress syndrome, asthma, and other pulmonary illnesses. In addition to functional studies, the latest imaging technology is being used to visualise the diverse players involved in inflammation. Using these integrated approaches, the cellular, molecular and genetic features of microvascular biology will be explored.
Improved understanding of pathophysiological mechanisms will lead not only to significant advances in fundamental knowledge of biology, but also will identify new targets for the development of drugs intended to treat the many diseases caused by inflammatory processes.
We recently demonstrated that microparticles (MP), which we found to be present in greatly increased concentrations in the peripheral blood of Malawian children with CM (JAMA 2004) are crucial elements of pathogenesis in experimental murine CM (Am J Pathol 2005). Based on these findings, we now aim, in vitro and in vivo, to demonstrate that by modulating the process of vesiculation (i.e. by reducing the production or release of MPs, or by blocking their toxic effects) we can reduce the pathological processes characteristic of CM. The ultimate aim is to reach a novel intervention for preventing the progression of severe malaria towards a fatal outcome and for hastening recovery from severe malarial disease.
In our current projects, we therefore intend to unravel the mechanisms of MP production and action, to delineate pharmacological ways to interfere with these mechanisms, and to define the pathophysiological consequences of excessive MP production.