Georges Grau

The University of Sydney

In February 2006, I took up my appointment as Professor of Vascular Immunology at the University of Sydney, after 26 years of research in Europe. My field of research can be defined as pathophysiology and immunopathology, with particular emphasis on cytokines and microvascular endothelium. I have wide-ranging experience and skills in the investigation of mechanisms of inflammation. Emerging technologies have been applied to the fine analysis of the complex interactions of cells and molecules that are responsible for tissular malfunction. I also have set up multi-compartment cell culture systems in order to model basic pathophysiological processes relevant to diseases such as cerebral malaria, septic shock, and acute respiratory distress syndrome. One of my main assets is to combine experience of in vivo models with transgenic / knock-out / knock-in mice to decipher fine mechanisms of tissue lesions. Research achievements include in vivo intervention studies in murine models, with which I contributed to the elucidation of cytokine interactions leading to tissue injury, with particular attention to tumour necrosis factor, as well as the implication of certain cell adhesion molecules. Selective gene knock-out mice were employed to further dissect fine mechanisms of tissue injury. A major part of my experience is in imaging technology. I have applied fluorescence, confocal and electron microscopy to human post-mortem brain and lung samples. Recently, I have developed in vitro modelling of inflammatory lesions. I set up co-cultures of human microvascular endothelium with circulating cells, i.e., reconstituting the lesion seen in vivo. Using these systems, we are capable of defining the roles of various molecules released because of the cellular interactions, such as cytokines, chemokines, growth factors and proteases. My team has demonstrated that one of the potentially major effector mechanisms of TNF and other cytokines is the release of microparticles. These membrane elements, via their pro-inflammatory and procoagulant properties, might be crucial in immunopathology, and not only in cerebral malaria. Our current project will deal with pathophysiological events at the level of brain endothelium, implying notably interactions with circulating host cells and their consequences.