Research at FAST

44 Representative Publications • Conboy et al., ( 2019 ) Hepatology Comm. 3, 1496-1509 • Zhang et al., ( 2019 ) Biochem. Biophys. Res. Comm. 515, 50-56 • Chiu et al., ( 2019 ) Mol. Cancer Res. 17, 1582-1593 • Li et al., ( 2019 ) Biomed. Pharmacother. 111, 68-75 • Li et al., ( 2019 ) G3 (Bethesda) 9, 297-303 • Li et al., ( 2018 ) Cancer Med. 7, 4791-4800 Dr KENG Wee Keong Vincent Associate Professor Research Overview The development of human cancer is a complex process involving the acquisition of multiple genetic changes that confer a selective advantage on a tumor clone. Transposon-tagged mutagenesis using the Sleeping Beauty (SB) system has proven invaluable for functional genomic screens. SB is a two-component system, composed of the transposase and a transposon vector, flanked by special inverted terminal repeats (IRs). When the transposon vector is present in a cell expressing the transposase, the “cut-and-paste” transposition reaction occurs. The SB transposase enzyme recognizes specific binding sites within the IRs, excises and then integrates the transposon elsewhere at a TA-dinucleotide. In order to elucidate novel cancer- associated genes in solid tumors, a conditional SB expression system together with a tissue-specific Cre transgene were used. When these two components are combined with a transposon mutagenic vector capable of either disrupting tumor suppressor genes or misexpressing oncogenes, we have a powerful conditional SB somatic mutagenesis forward genetics screen for cancer gene identification involved with hepatocellular carcinoma (Keng et al., Nat. Biotech. 2009). Qualification MSc (UWA) PhD (Fukui Medical U) ORCID ID 0000-0003-3473-0653 Based on the genetic information obtained from forward genetic screens, we can compare with existing human mutation data to identify strong candidate cancer genes. Subsequently, we can establish valuable reverse genetic mouse models for liver cancer gene validation and importantly, testing novel therapeutic drugs (Keng et al., Hepatology 2011 & 2013). Figure 1 Figure 2 Figure 3 • Riordan et al., ( 2018 ) Hepatology. 67, 924-939 • Tschida et al., ( 2017 ) Cancer Res. 77, 6576-6588 • Wu et al., ( 2016 ) Cell Rep. 14, 1979-1990 • Chiu et al., ( 2015 ) World J. Gastroenterol. 21, 12157-12170 Department of Applied Biology & Chemical Technology Department of Applied Biology & Chemical Technology