The University of Sydney
- Immunopathology of microvascular lesions, particularly of cerebral and pulmonary complications of infectious and auto-immune diseases. Principal interest is cerebral malaria, since 1985; other interests include septic shock and multiple sclerosis.
- Analysis of the cellular and molecular mechanisms of the interactions between microvascular endothelial cells and cells of the immune system.
- Experience in various in vivo (mouse models) and in vitro experimental systems as well as in clinical studies.
- More recently, focus on the neurovascular lesion of human cerebral malaria, using co-culture model systems involving brain endothelium, P. falciparum-infected erythrocytes, as well as circulating cells, particularly platelets and monocytes.
- Phenotypic and functional analysis of extracellular vesicles released in these co-cultures
Working experience and current research areas:
Professor Georges Grau obtained a MD from the University of Liège and a Privat-Docent from the University of Genève. He has been the Chair of Vascular Immunology at the University of Sydney since 2006. Since 1979, his research has focused on immunopathological mechanisms of infectious diseases, notably in cerebral malaria, multiple sclerosis and septic shock, with particular emphasis on cytokines and the microvascular endothelium.
His in vivo intervention studies in murine models contributed to the elucidation of cytokine interactions leading to tissue injury, with particular attention to tumour necrosis factor (TNF), which had important implications for cell adhesion molecules in various models of pathology. In multi-compartment co-culture systems involving human endothelial cells, his group found that platelets can act as effectors of cytokine-induced microvascular damage. His team also demonstrated that membrane microparticles, released by several cell types, profoundly alter endothelial integrity and thereby can be crucial elements in immunopathology.
Recently, with his team at the Vascular Immunology Unit, he has:
- shown that microvesicles (MV, previously called microparticles) are nanometer-range elements that behave as crucial effectors in the mechanisms of cytokine-mediated pathology, using in vivo and in vitro models;
- developed a brain endothelium co-culture system, to study blood-brain barrier changes in cerebral malaria, sepsis, multiple sclerosis, viral encephalitides and cryptococcal meningitis.
- established that MV can dramatically activate monocytes and stimulate T cell proliferation
- deciphered critical cellular and molecular mechanisms of MV release in inflammatory conditions
- shown that inhibition of MV release can prevent pathology
His 366 papers (271 peer-reviewed) have been cited over 29,000 times and his h-index is 87.
Current projects at the Vascular Immunology Unit deal with pathophysiological events at the level of brain microvascular endothelium. They aim at defining novel pathogenic mechanisms, in order to propose new therapeutic avenues in inflammation.