My research interests include identification and validation of new genes involved in formation and progression of cancers, particularly colorectal cancer, gynaecological cancers, melanomas, as well as other neoplasms. This involves analysis of human cancer samples, cultured cells and in vivo model systems using both comparative pathology, molecular pathology and digital pathology approaches. Carcinogenesis involves cellular transit from normal via precursor lesions to malignant neoplasms. These transitions are usually associated with characteristic genetic and epigenetic changes. In the bowel, these include alterations to APC (>80%), the DNA mismatch repair genes MLH1 & MSH2 (~15%), KRAS (~40%), and TP53 (~60%) amongst others, and these genes also influence the regulation of proliferation, differentiation and apoptosis. In the endometrium, these include alterations to PTEN (80-90%), the DNA mismatch repair genes MLH1 & MSH2 (~30%), and KRAS (~20%), amongst others. High throughput array and DNA sequencing analyses have identified genes that consistently show loss or gain of copy number in colorectal tumours including BRUNOL4, PARK2 and IRS2 as new genes in colorectal cancer development and progression. Sleeping Beauty transposition studies have been used to identify new tumour-related genes, including those that cooperate with mutated APC in intestinal tumour formation, with mutant Nucleophosmin in leukaemogenesis and with mutated BRAF in melanoma development. DNA methylation studies of epigenetic silencing of cancer-related genes demonstrated involvement of MLH1, MGMT, PTEN, DNMT3B and others in the WNT/APC/B-CATENIN signalling pathway in colorectal neoplasia. In vivo models of intestinal tumourigenesis were used to determine contributions to tumour formation by mutant MSH2, KRAS, RASSF1A, GNAS, PARK2, NRBP1, PKHD1 and others. Use of knockout models validated SLX4/FANCP as a new Fanconi Anaemia gene and demonstrated that the Fanconi DNA repair pathway for interstrand DNA crosslinks was shown to be critically important in repairing both acetaldehyde-induced and formaldehyde-induced DNA damage thus protecting against tumour formation. Mutant ALDH gene models confirmed the involvement of ethanol and acetaldehyde as both mutagens and promoters in intestinal and liver tumour formation. Currently, conditional MSH2 knockout models allow investigation of ethanol and acetaldehyde as mutagens and promoters in colonic tumourigenesis.