Aspirin and related non-steroidal anti-inflammatory drugs (NSAIDs) have anti-tumour activity and the potential for cancer prevention. However, their side effect profile precludes their use as chemopreventative agents. My laboratory is focussed on understanding the mechanisms by which NSAIDs act against cancer cells, in order to identify biomarkers of response and targets for novel, safer and more effective agents. A theme that has emerged from these studies is regulation of cell proliferation and apoptosis by nucleolar compartmentalisation of the RelA subunit of NF-kappaB.
The primary objectives of our research are to understand how NSAIDs stimulate the NF-kappaB pathway, identify the signals that regulate the nuclear distribution of RelA and reveal the pathways by which nucleolar RelA induces apoptosis. We are also interested in nucleolar stress and how this regulates cell growth and death. We employ a variety of strategies and model systems. These include the use of SILAC-based proteomics to understand global effects of aspirin on the abundance and cellular distribution of proteins and organ cultures of human colorectal cancers to establish the in vivo relevance of in vitro findings.