Shuo Lin
email: shuolin@ucla.edu
phone: 310-267-4970
fax: 310-267-4971
office: 490B BSRB
homepage: http://www.mcdb.ucla.edu/Research/ShuoLin
Research Interests
We use zebrafish to investigate the molecular mechanisms by which diverse and specialized cell types are developed during the vertebrate embryogenesis. Currently, our laboratory is particularly 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. Finally, we are developing new technologies, such as genetic knockout and high throughput transgenesis, for zebrafish in order to better address fundamental questions raised in our biological studies. We have already developed a streamlined procedure of directly selecting 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. A large-scale analysis of gene regulation using BAC transgenesis and comparative genomics approaches is currently ongoing in the laboratory. We plan to analyze hundreds of highly conserved developmental and disease genes from human, mouse, rat and zebrafish to reveal their common regulatory cis-acting elements and validate them in transgenic zebrafish. Given that developmental programs are well conserved among vertebrate animals, our studies in zebrafish should ultimately lead to a better understanding of the molecular and genetic basis underlying human development.
Selected Publications
Song, J., Kim, H.J., Gong, Z., Liu, N.A., and Lin, S.. 2007. Vhnf1 acts downstream of Bmp, Fgf, and RA signals to regulate endocrine beta cell development in zebrafish Dev Biol 303: 561-575 .
Wang, D., Jao, L.E., Zheng, N., Dolan, K., Ivey, J., Zonies, S., Wu, X., Wu, K., Yang, H., Meng, Q., Zhu, Z., Zhang, B., Lin, S., and Burgess, S.M.. 2007. Efficient genome-wide mutagenesis of zebrafish genes by retroviral insertions Proc Natl Acad Sci U S A 104: 12428-12433 .
Yang, Z., Jiang, H., Zhao, F., Shankar, D.B., Sakamoto, K.M., Zhang, M.Q., and Lin, S.. 2007. A highly conserved regulatory element controls hematopoietic expression of GATA-2 in zebrafish BMC Dev Biol 7: 1-13 .
Kim, H.J., Sumanas, S., Palencia-Desai, S., Dong, Y., Chen, J.N., and Lin, S.. 2006. Genetic analysis of early endocrine pancreas formation in zebrafish Mol Endocrinol 20: 194-203 .
Sumanas, S., and Lin, S.. 2006. Ets1-related protein is a key regulator of vasculogenesis in zebrafish PLoS Biol 4: 60-69 .
Zhong, H., Wu, X., Huang, H., Fan, Q., Zhu, Z., and Lin, S.. 2006. Vertebrate MAX-1 is required for vascular patterning in zebrafish Proc Natl Acad Sci U S A 103: 16800-16805 .
Magason, S., Amsterdam, A., Hopkins, N. and Lin, S.. 2005. Use of GFP in transgenic vertebrates Green Fluorescent Protein: Properties, Applications and Protocols, Second Edition : 285-304 .
Penberthy WT, Zhao C, Zhang Y, Jessen JR, Yang Z, Bricaud O, Collazo A, Meng A and Lin S. 2004. Pur alpha and Sp8 as Opposing Regulators of Neural GATA-2 Expression Dev Biol 275: 225-234 .
Lee, K.Y., Huang, H., Ju, B.S., Yang, Z. and Lin, S.. 2002. Cloned zebrafish by nuclear transfer from long-term cultured cells Nature Biotechnology 20: 795-799 .
Long, Q., Huang, H.G., Shafizadeh, E., Liu, N. and Lin, S. 2000. Stimulation of erythropoiesis by inhibiting a new hematopoietic death receptor in transgenic zebrafish Nature Cell Biology 2: 549-552 .