Professor John Silke completed a law degree in King’s College, London (1989), a Biochemistry degree at Churchill College, Cambridge (1992), a PhD in Zürich, Switzerland, with Prof Walter Schaffner (1997).
Inflammation, which is an essential part of immune and homeostatic repair responses to infection and damage, is nevertheless, one of the scourges of mankind and chronic inflammation and Inflammatory diseases account for a significant proportion of human morbidities and misery. This is in part due to the fact that it must be rapid and intense in order to mount a defence against infection and therefore must be tightly regulated and turned off when no longer needed, in order to prevent collateral damage. One of the, ongoing, breakthroughs in the clinic has been the success of inhibitors targeting cytokines, such as TNF, in chronic inflammatory diseases such as rheumatoid arthritis, IBD and psoriasis. These cytokines were presumed to work by driving a transcriptional inflammatory response Ironically, this clinical breakthrough has in turn led to a broader breakthrough in our understanding of mechanisms driving inflammation including cell death and an explosion in "novel" modes of cell death that can drive inflammation including apoptosis, necroptosis, pyroptosis and panoptosis. A big bottleneck, on the other hand is the redundancy and cross regulation of these inflammatory pathways, and this is another aspect of inflammation explored in this seminar.
John’s own research has marched in step with these developments in the field with post-doc research (Prof David Vaux in the WEHI, 1997-2005), centred around cell death mechanisms and in particular the role of Inhibitor of APoptosis proteins (IAPs) in regulating cell death. His lab in La Trobe University (2006-2011) and WEHI (2011-) has focused on exploring the functions of IAPs and the transcriptional and programmed cell death pathways (e.g., TNF) that they regulate in both cancer and inflammation. Highlights of his research include senior author papers in Cell and Nature showing how IAP antagonist drugs work to kill cancer cells, that cell death can cause inflammation and most recently defining a new cell death inflammatory syndrome that we designated CRIA.