Research Interests
          Currently, our laboratory is interested in three areas. First, we are working to define the genetic pathways underlying hematopoiesis and vasculargenesis. We are especially interested in identifying those factors that mediate the initial determination of hemangioblast and its subsequent differentiation into blood and vascular lineage-specific progenitor cells. Genetic, transgenic and microarray approaches have been used to identify and characterize these key factors. Secondly, we are studying the genetic basis underlying organ formation. The main focus of this research is to understand the genes and cells that direct pancreatic organogenesis. To this end, a number of zebrafish mutations affecting development of pancreas and endocrine beta cells have been isolated. There is a great need to be able to grow and develop pancreatic beta cells for treating diabetes by cell transplantation. This need challenges us to understand how a precursor cell gives rise to the pancreas and to characterize the gene products that specify cell fates during organogenesis. Thirdly, we are developing zebrafish as a pre-clinic drug discovery animal model. Using specific zebrafish models created in our laboratory, we are collaborating closely with chemists to generate and identify small molecules that have therapeutic potential for treating cancer and neurological degeneration diseases.
         In addition to pursuing biological studies of our own interest, we are developing new technologies, such as high-throughput genetic mutagenesis and transgenesis for zebrafish so that this organism can be better used to address fundamental questions raised by the whole research community. We have already developed a streamlined procedure to carry out genome-wide mutagenesis by retroviral insertions. We plan to knockout 50% of genes contained in the zebrafish genome within the next five years. We have also developed an efficient method that allows direct selection of multiple bacterial artificial chromosome (BAC) clones based on public sequence database followed by rapid modification with GFP or RFP. BAC constructs offer greater fidelity in directing desirable expression of transgenes. Application of this technology in the transparent zebrafish embryos with the fluorescent protein reporter genes enables unparalleled visual analysis of gene expression in a living organism. To further cover tissue-specific gene expression patterns by transgenic GFP or RFP reporter gene we carried out a large-scale enhancer trap screen, in collaboration with Peking University. As a result, hundreds of transgenic lines have been produced. These genetic resources will be highly valuable for biomedical research of the whole community.
Research Projects
Hematopoiesis and
Vasculargenesis 		Organogenesis and
Pancreas
 		Chemical Genetics and
Drug Discovery
 		Mutagenesis and
Transgenesis