Grant: Foundation Grant

Autoimmune diseases are chronic inflammatory diseases whereby the immune system attacks tissues of the body. However, these therapies are not a cure and they come with risks such as susceptibility to infection. Moreover, they don't always work in all patients. For example, 30% of patients who have inflammatory bowel disease and receive anti-TNF (Tumour Necrosis Factor) do not respond to the drug. Thus, we need to design better therapies that are less risky and more effective. Genetics are very important in determining ones possible risk of developing an Autoimmune Disease, and mutations in genes of the TNF superfamily (TNFSF) have been implicated in several autoimmune diseases. However, genetics are not the only determinant accounting for Autoimmune Disease - we know that environmental risk factors such as diet, smoking, microbial exposure, drugs/antibiotics etc also play an important role in increasing ones risk of getting an autoimmune disease. However, we know far less about environmental risks of disease compared to genetics. Our team is interested in the "black box" of environmental risk in the context of autoimmune disease. In particular, we would like to know how the TNFSF cooperates with a particular dietary factor - Vitamin A, as well as the microbiome (the microbes that co-exist with us in/on our bodies), to mediate effects on the immune system. As we define how specific environmental risk factors that cooperate with TNFSF, we can then re-visit the design of TNFSF-directed therapies to include potential co-therapies. This will likely improve existing therapies, making them more effective in larger groups of patients. It will also provide invaluable insights into how autoimmune diseases develop in humans.