TRANSGENIC FISH:
In the past few years, our laboratory has employed the transgenic technology in two small model aquarium fish, the zebrafish (Danio rerio) and medaka (Oryzias latipes), for various applications including generation of fluorescent ornamental fish, biomonitoring fish, bioreactor fish and oncofish. So far we have successfully generated many lines of fluorescent transgenic zebrafish and medaka with several different colors and some of the transgenic fish are being marketed in USA as the first transgenic pet. We also developed transgenic lines in response to estrogenic compounds and/or other toxical chemicals. As our transgenic system allows us to express foreign proteins up to 17% of total muscle proteins, currently we are testing the concept using transgenic fish as a bioreactor to produce useful proteins. Other transgenic applications include generation of tissue-specific living color transgenic lines for developmental analysis, conditional transgenesis, germline excision of transgene, transgenic oncofish, etc.

ZEBRAFISH LIVER DEVELOPMENT AND CARCINOGENESIS:
In 2002, several zebrafish laboratories in National University of Singapore, Genome Institute of Singapore and Institute of Cell and Molecular Biology have initiated a Zebrafish Liver Program funded by Biomedical Research Council of Singapore. In this program, we are using the zebrafish model to investigate molecular mechanisms of liver development and carcinogenesis. There are three major areas in this program: 1) Zebrafish liver genomics:  we are developing zebrafish genomic tools including large scale of full length cDNA sequencing and microarray technology, and using these tools to analyze global expression profile during zebrafish liver development and carcinogenesis; we are also developing zebrafish DNA chips for environmental monitoring. 2) Zebrafish models for human liver cancers: we are generating zebrafish tumors both by carcinogen treatment and by transgenic approach using some well characterized candidate oncogenes such as c-myc, ras, etc.; microarray technology is also used to compare the set of genes in response to carcinogenesis between zebrafish and human and thus providing insight into the molecular mechanism of carcinogenesis. 3) Zebrafish liver development: zebrafish liver development will be examined by several different approaches, including characterization of liver development in both wild type and mutant embryos, establishment of a liver-GFP transgenic model, identification of growth factors and transcription factors important in liver development, and screening of small molecules capable of modulation of liver development. As a leading laboratory in this program, we are actively involved in essentially all of the proposed projects in the Zebrafish Liver Program.