Molecular and Cellular Immunology Laboratory
The main focus of the laboratory is on understanding of the molecular and cellular mechanisms that lead to pathological inflammation and to translate these findings to the clinical setting. Our main interests are: |
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Signalling by Immunoglobulin receptors: targeting key signalling molecules in autoimmune diseases and allergies
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On leukocytes, aggregation of receptors for Immunoglobulins (FcRs), lead to a number of cellular responses including proinflammatory mediator release, oxidative burst and antigen presentation. FcRs have been implicated in the pathogenesis of several diseases, in particular in inflammatory autoimmune diseases such as, lupus, rheumatoid arthritis, and allergies. We are investigating the intracellular signalling molecules that lead to FcR-mediated inflammation, and have identified several key molecules involved in inflammatory responses. We have started to validate some of these molecules including PLD1 and sphingosine kinase as potential novel target for therapeutic intervention. |
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Molecular mechanism of immune-cell activation during sepsis: identification and validation of novel therapeutic targets
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Sepsis is one of the most common causes for admission to intensive care units worldwide. Despite all the efforts made in the ICU, the fatality rate for sepsis patients remains 30% to 50%. Lipopolysaccharide (LPS)-mediated septic shock (endotoxemia), is a major problem in sepsis. Despite many efforts to understand the intracellular signalling pathways triggered by LPS in immune-cells, responsible for the inflammatory effects, many questions remain to be answered. Our aim is to gain a better understanding of endotoxin signalling in human leukocytes in order to identify key mediators of endotoxic shock and sepsis, and to validate key signalling molecules in vivo, potentially leading to the development of novel therapeutics to treat sepsis. |
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Understanding anaphylatoxin (C5a) signalling in vitro and in vivo
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When tissue is injured or becomes locally infected, an inflammatory reaction ensues. Inflammatory responses are characterized by the accumulation of neutrophils and macrophages at an inflammatory site. Where local inflammation is triggered by infection, trauma, or immune complex deposition, the anaphylatoxin C5a is likely to be an important mediator. The stimulation of leukocytes withbyC5a, leads to the production and release of various pro-inflammatory mediators. We investigate the intracellular signalling pathways triggered by C5a in Neutrophils, Macrophages and Mast cells, and have recently identified several key signalling molecules involved in the inflammatory responses. We are now utilising in vivo siRNA silencing to validate these molecules as potential therapeutic targets in inflammation. |
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Targeting Sphingosine kinase in tumour cells
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There is no treatment for several cancers because we do not understand the specific breakdown in normal cell control. Our group have specialist knowledge of cell biology and we have pioneered the discovery of a cell system controlled by a molecule called sphingosine kinase1 (SphK1). It is known that that SphK1 is grossly elevated in various tumour cells, and that molecules that counteract SphK1 can restore normal function to tumour cells. This strongly suggests a new treatment option for cancers that merits further investigation. Using cutting-edge research technology, we aim to systematically study the biology of SphK1 in tumour cells. The whole purpose is to provide sound evidence to better understand the SphK1 cell control system in cancer, and to test whether drugs that target SphK1, including our own compounds, can successfully treat tumours. |
