Our research is directed at understanding how the immune system regulates itself. This is important because the immune system has to distinguish ‘non-self’ from ‘self’ in order to eradicate infections and tumors on the one hand and avoid causing autoimmune disease on the other. We study how the environment and our genes interact (‘epigenetics’) in early life to alter immune function and cause autoimmune disease. In the case of type 1 diabetes, we have developed ways to identify people at risk and are undertaking clinical vaccine trials to boost protective immunity and prevent this disease.
We investigate immunoregulatory mechanisms to identify biomarkers of immune disease and targets for immunotherapy. Our focus is on type 1 diabetes (T1D) as a paradigm for the pre-clinical diagnosis, prediction and prevention of autoimmune disease; we also study immune-inflammatory mechanisms in type 2 diabetes (T2D).
After demonstrating the primacy of insulin as an autoantigen driving pancreatic beta-cell destruction in T1D, and its application as a therapeutic tool to induce regulatory anti-diabetogenic T cells, we have conducted a series of trials to determine if a nasal insulin vaccine will prevent T1D in humans. To better understand environment-gene interactions in T1D we are undertaking microbiome, metabolome, epigenome and immunome studies of mothers during pregnancy and their T1D at-risk infants though early life.
Recently, we described a novel immunoregulatory mechanism whereby soluble CD52, released from activated T cells, suppresses other T cells and innate immune cells via Siglec receptor pathways. The therapeutic potential of CD52-Fc is being investigated.