Regulation Of Autoimmunity By Non-apoptotic Caspases
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Excessive cell death can lead to chronic inflammation and autoimmunity. Cells can die by different mechanisms including necroptosis which causes inflammation, and apoptosis which does not. Recent studies show that caspases, a component of the apoptosis pathway which accelerate cell death, also prevent immune activation by dying cells. I will investigate whether caspases contribute to autoimmune disease and whether caspases can dampen the inflammation that occurs during necroptotic cell death.
Src Family Kinases: Regulation Of Phosphoinositol-3 Kinase Signaling And Autoimmune Disease Development.
Funder
National Health and Medical Research Council
Funding Amount
$526,683.00
Summary
The immune system has to be capable of responding to an unlimited array of pathogens, but at the same time remain unresponsive to, or tolerant of, self-antigens. A breakdown in the tolerance to self-antigens results in autoimmunity. Autoimmune disease includes more than 70 chronic disorders that affect about 1 in 20 people in the Western population. Improving our understanding of the mechanisms that underlie autoimmune disease is essential for the design of more successful treatments. The Lyn ty ....The immune system has to be capable of responding to an unlimited array of pathogens, but at the same time remain unresponsive to, or tolerant of, self-antigens. A breakdown in the tolerance to self-antigens results in autoimmunity. Autoimmune disease includes more than 70 chronic disorders that affect about 1 in 20 people in the Western population. Improving our understanding of the mechanisms that underlie autoimmune disease is essential for the design of more successful treatments. The Lyn tyrosine kinase is an enzyme that is found within blood cells. It participates in transmitting information across the cell membrane to turn off cellular responses. Studies in mutant mice have shown that Lyn is critically important for maintaining stability in the immune system. Mice that are unable to make Lyn protein (Lyn-deficient mice) as well as mice that express an activated form of the Lyn enzyme (Lyn-up mice) develop autoimmune disease with characteristics similar to the human autoimmune disease systemic erythematosus (SLE). These studies suggest that Lyn is an important severity gene in autoimmunity. The aim of this grant will be to identify Lyn-dependent signaling pathways that lead to autoimmune disease, with a major focus being on the lipid kinase pathway. We will use a combination of genetic and biochemical approaches to reveal critical genes and pathways. Cataloging the molecular changes related to alterations in Lyn activity will, we believe, provide insight into the genetic defects or signal perturbations underlying human autoimmune diseases. In this way, our study will aid in the diagnosis of human autoimmune diseases and uncover useful targets for more specific and effective treatments.Read moreRead less
I am the leading scientist studying a factor named BAFF and discovered its role in autoimmunity. BAFF inhibitors are effective in late stage clinical trials treating lupus patients. Our new work shows that BAFF has other fascinating roles, in particular the ability to control effects from some microbes capable of activating autoimmune and inflammatory reactions. This new work is leading us to the development of an entirely new generation of therapeutics treating autoimmunity and inflammation.