Grant: Foundation Grant

Twenty-three years ago, my research group discovered a novel family of mammalian genes, which we called the inhibitors of apoptosis (or IAPs) due to their similarity with viral genes that regulate a process of cell death known as apoptosis. The IAPs not only control how cells die under stress but also have critical roles in cell division and in cell signalling. Moreover, they are especially important for the function of the immune system. The dysregulation of the IAPs are associated with a range of diseases, from cancer to neurodegeneration to infection. Indeed, drugs that target key IAPs, known as Smac mimetics (SMCs) are in clinical trials for the treatment of various cancers and infectious diseases. The inactivation of the IAPs by SMCs renders cancer cells quite sensitive to death triggers produced by the immune system. Remarkably, normal cells do not die when treated with SMCs. We have recently shown that SMCs can complement a new class of revolutionary anti-cancer drugs, called cancer immunotherapy. The combination of SMCs and cancer immunotherapy cures mice of cancer and this research has now led to the initiation of human clinical trials for cancer in 2017-18. My research program studies how the IAPs control life and death decisions at the cellular level and how the IAPs modulate immunity to enhance the activity of immunotherapies. In the span of two decades, we have gone from gene discovery and the creation of a whole new field of study, to the clinical investigation of novel drug classes and approaches that are expected to yield insights into disease and therapy.