Neil Perkins - Overview

Over the last decade, a large number of transcriptional regulatory factors have been identified that participate in a complex network of protein:protein interactions that combine to give the pattern of gene expression unique to each cell type or cellular stimulation. Specific control of gene expression has been demonstrated to require a balance between positive and negative acting pathways that must be correctly integrated for normal cellular function. It has also become apparent that many diseases ultimately result from the disruption of gene expression through the inappropriate activation or inhibition of specific transcription factors. This is particularly true of the mechanisms leading to cancer where many of the processes underlying tumorigenesis have been found to result from mutation or constitutive activation/repression of the transcription factors that regulate cellular proliferation and programmed cell death.

My laboratory is investigating mechanisms of transcriptional regulation involving the NF-kappaB transcription factor and the proteins that regulate its function such as the coactivators p300 and CBP. We are interested in how changes to the cellular environment, such as exposure to cytokines, growth factors or DNA damage are integrated with NF-kappaB activity to determine cell fate. We have identified a number of novel transcriptional regulatory mechanisms involving the RelA(p65) NF-kappaB subunit, the tumour suppressor p53, Egr-1, c-Myc and the p300 and CBP coactivator proteins. We aim to characterise these regulatory mechanisms both functionally and biochemically as well as develop reagents that will allow us to assess their significance at the cellular level and determine their potential as targets for the treatment of cancer.