YU Wei-Ping 
PhD
Head & Principal Investigator
Gene Regulation Laboratory
NNI Research Laboratories
National Neuroscience Institute
11 Jalan Tan Tock Seng
Singapore 308433
Tel: (65) 6357-7547 (office)
(65) 6357-7523 (lab)
Fax: (65) 6256-9178
Email : weiping_yu@nni.com.sg

       
PROJECTS

1. Protocadherins in neural circuitry formation

The clustered protocadherins are a subfamily of cell adhesion molecules that are predominantly expressed in neurons and highly enriched in the synaptic membrane. In mammals, genes encoding for this subset of protocadherins are closely associated on the chromosome that arrange in tandem into three clusters, namely alpha, beta and gamma. Each gene cluster, which contains about 15-22 genes, is further divided into variable and constant regions (except the beta cluster, which lacks the constant region). This type of gene organization in many ways resembles the immunoglobulin and T-cell receptor gene loci in the immune system, which are widely known for their ability to give rise to a remarkably diverse repertoire of antigen recognizing molecules. The unique genomic organization and expression pattern have led to an intriguing speculation that protocadherins may provide a profound molecular code for specifying neuron-neuron connection in the nervous system. Specifically, we are interested in studying the following questions:

• The genomic organization and transcriptional regulation of protocadherin gene locus

• Biological and cellular functions of protocadherins in the developing nervous system

2. Animal models for human neurological diseases

We have developed an ES cell-based method for generating transgenic mice. In contrast to the traditional pronuclear injection approach, this approach allows for the integration and expression of the transgene in a totally controllable and predictable manner. Thus, phenotypes between different transgenic lines that express distinct but related transgenes can be directly compared. This approach provides an ideal platform for generating animal models for human diseases. Currently, we are using this approach for following studies.

• LRRK2-expressing mouse model for Parkinson’s disease.

• Biological function of NRSF/REST in the developing nervous system and its potential implication in neurological disorders 
   
  

SELECTED PUBLICATONS

• Wei-Ping Yu*, Viknesawari Rajasegaran, Kenneth Yew, Wailin Loh, Boon-Hui Tay, Chris T. Amemiya, Sydney Brenner* and Byrappa Venkatesh* Elephant shark sequence reveals unique insights into the evolutionary history of vertebrate genes: A comparative analysis of the protocadherin cluster. Proc. Natl. Acad. Sci. U.S.A. 105: 3819-3824 (2008) (*correspondence)
  
  

• Wei-Ping Yu*, Kenneth Yew, Vikneswari Rajasegaran, Byrappa Venkatesh*. Sequencing and comparative analysis of fugu protocadherin clusters reveal diversity of protocadherin genes among teleosts. BMC Evol. Biol. 7:49 (2007) (*correspondence)

• Wei-Ping Yu, Jeanne M.M. Tan, Katherine C.M. Chew, Tania Oh, Prasanna Kolatkar, Byrappa Venkatesh, Ted M. Dawson, Kah Leong Lim. The 350-fold compacted Fugu parkin gene is structurally and functionally similar to human Parkin. Gene 346:97-104 (2005)

• Wei-Ping Yu, Sydney Brenner and Byrappa Venkatesh. Duplication, degeneration and complementation of the nested synapsin-Timp genes in Fugu rubripes. Trends in Genetics 19:180-183 (2003)

• Nigel P. Pringle, Wei-Ping Yu, Marisa Howell, Jennifer S. Colvin, David M. Ornitz and William D. Richardson. Fgfr3 expression by astrocytes and their precursors: evidence that astrocytes and oligodendrocytes originate in distinct neuroepithelial domains. Development 130:93-102 (2003)

• Wei-Ping Yu, Catherine J. Pallen, Alice Tay, Frank R. Jirik, Sydney Brenner, Y.H. Tan, and Byrappa Venkatesh. Conserved synteny between the Fugu and human PTEN locus and the evolutionary conservation of vertebrate PTEN function. Oncogene 20:5554-5561 (2001)

• Andy Calver, Anita Hall, Wei-Ping Yu, Frank Walsh, John Heath, Christer Betsholtz and William D Richardson. Oligodendrocyte population dynamics and the role of PDGF in vivo. Neuron 20:869-882 (1998)

• Lin Cui*, Wei-Ping Yu*, Henry J. DeAizpuruz, Robert S. Schmidli and Catherine J. Pallen. Cloning and characterization of islet cell antigen-related protein-tyrosine phosphatase (PTP), a novel receptor-like PTP and autoantigen in Insulin-dependent diabetes. Journal of Biological Chemistry 271:24817-24823 (1996). (*co-first authorship)

• Nigel P. Pringle*, Wei-Ping Yu*, Sarah Guthrie, Henk Roelink, Andrew Lumsden, Alan C. Peterson, and William D. Richardson. Determination of neuroepithelial cell fate: induction of the oligodendrocyte lineage by ventral midline cells and sonic hedgehog. Developmental Biology 177:30-42 (1996). (*co-first authorship)

• Wei-Ping Yu, Ellen J. Collarini, Nigel P. Pringle, and William D. Richardson. Embryonic expression of myelin genes: evidence for a focal source of oligodendrocyte precursors in the ventricular zone of the neural tube. Neuron 12:1353-1362 (1994)

RESEARCH TEAM MEMBERS

Yu Wei-Ping, PhD	Research Scientist (Principal Investigator)
Li Shaobing, PhD	Postdoctoral Research Fellow
J.A. Christopher John, PhD	Postdoctoral Research Fellow
Loh Wai Lin	Senior Research Assistant (Lab Manager)
Wang Fulu	Senior Research Assistant
Lew Qiao Jing	Senior Research Assistant

  

COLLABORATORS

• Dr Byrappa Venkatesh, Molecular Genetics Lab, Institute of Molecular and Cell Biology, SIngapore
• Dr Sathivel Ponniah, Biological Resource Centre, Biopolis, Singapore
• Dr Fu Jian Lin, Institute of Molecular and Cell Biology, Singapore