Dr Eric O'Neill

Rasf1a is a tumour suppressor gene that is epigenetically silenced in a wide variety of sporadic human malignancies. Expression of alternative isoforms fail to substitute for RASSF1A promoted cell cycle arrest and apoptosis. Molecular events that lead activation of RASSF1A signalling are not well understood; however downstream signalling involves the tumour suppressors LATS1 and MST2.  Moreover the signalling pathway emanating from RASSF1A is involved in the efficacy of the p53 family of tumour suppressors. Our research aim is to validate the extent to which RASSF1A/MST2 signalling contributes to an overall DNA damage response, via p53, and if RASSF1A silencing hampers the effectiveness of DNA damaging therapeutics. Moreover, utilising proteomics to identify interacting proteins we are able to highlight important regulatory steps in the pathway that can be manipulated to potentially re-sensitise RASSF1A silenced tumours to therapies such as radiation.