The Vollum Institute

VOLLUM INSTITUTE

Wenbiao Chen

Wenbiao Chen has moved to the Department of Molecular Physiology and Biophysics at Vanderbilt University Medical Center. He may be contacted at wenbiao.chen@vanderbilt.edu.

Wenbiao Chen received his Ph.D. degree from the Department of Cell and Developmental Biology at OHSU in 1997. He holds a B.S. from Hunan Normal University and a M.S. from Washington State University. He did four years of postdoctoral research in the Massachusetts Institute of Technology Center for Cancer Research and was appointed as an assistant scientist in the Vollum Institute in 2001.

Research Interests

The interest of the Chen lab is in understanding development and diseases of the central nervous system. The overall approach of the lab is first to use genetic screens in zebrafish to identify genes important for neuronal development and survival and subsequently to employ a variety of modern techniques to elucidate how those genes function at a biochemical, cellular, and systems level. The lab also uses transgenic zebrafish models of human neurodegenerative diseases to understand the underlying pathogenic mechanisms.

For large-scale genetic screens, the lab uses retroviruses as mutagens to look for genes important for the development, function, and survival of retinal cells. The retina consists of seven major cell types that are derived from a common population of progenitors during early development. These retinal cells can easily be identified by their morphology and location; defects in the retina can be easily identified both morphologically and by simple behavioral assays. The lab is a part of an ongoing large-scale screen that aims to identify genes essential for the survival of retinal neurons. In addition, they are developing two new types of viral mutagens that will allow for gene identification based on their tissue-specific mis-expression phenotypes and their expression pattern, respectively. As both types of screens are done in F1, a small team can screen a large number of mutations.

The lab is also studying a previously identified insertional mutant, mind bomb, which displays profound retinal defects. Chen and associates have demonstrated that Mind bomb protein is an E3 ubiquitin ligase that acts on Delta and promotes its endocytosis. They are using a variety of techniques to determine how Mind bomb regulates Notch signaling and to identify other proteins involved in Mind bomb-mediated Delta endocytosis. Additionally, they are characterizing the retinal defects and the underlying mechanisms in the mind bomb mutants.

The Chen lab is also developing zebrafish models of human neurodegenerative diseases. Currently, Chen and associates are interested in understanding how mutations in ELOVL4 cause an early onset autosomal dominant form of macular degeneration in humans. They have generated transgenic zebrafish that express the mutant Elovl4 in the photoreceptors in order to determine whether the transgenic fish model the human condition. In addition, they have demonstrated that “knock-down” of Elovl4 in zebrafish alters fatty acid profiles and induces an unexpected ocular abnormality. The lab is planning to establish transgenic models of other neurodegenerative diseases and will then perform genetic screens to search for genes that, when mutated, enhance or suppress the progression of the diseases in zebrafish.

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Selected Publications

Wan, L., Almers, W., and Chen, W. (2005) Two ribeye genes in teleosts: the role of Ribeye in ribbon formation and bipolar cell development. J Neurosci. 25:941-949.

Chen, W. and Corliss, D.C. (2004) Three modules of zebrafish Mind bomb work cooperatively to promote Delta ubiquitination and endocytosis. Dev. Biol. 267:361-373.

Golling, G., Amsterdam, A., Sun, Z., Antonelli, M., Maldonado, E., Chen, W., Burgess, S., Haldi, M., Artzt, K., Farrington, S., Lin., S.Y., Nissen, R.M., and Hopkins, N. (2002). Insertional mutagenesis in zebrafish rapidly identifies genes essential for early vertebrate development. Nature Genetics 31:135-140.

Chen, W., Burgess, S., Golling, G., Amsterdam, A., and Hopkins, N. (2002) High-throughput selection of retrovirus producer cell lines leads to markedly improved efficiency of germ line-transmissible insertions in zebrafish. J. Virology 76:2192-2198.

Chen, W., Burgess, S., and Hopkins, N. (2001) Analysis of the zebrafish smoothened mutant reveals conserved and divergent functions of hedgehog activity. Development 128:2385-2396.

Amsterdam, A., Burgess, S., Golling, G., Chen, W., Sun, Z., Townsend, K., Farrington, S., Haldi, M., and Hopkins, N. (1999) A large-scale insertional mutagenesis screen in zebrafish. Genes and Development 13:2713-2724.

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