Caltech 216-76
Pasadena, CA 91125
Tel: 626-395-3197 Fax: 626-584-6088
Home Tel: 626-577-0970
M. S., Biology,
_
California Institute of Technology, 1993-1996
M. S., Biomedical Engineering and Instrumentation, _ GPA 4.0/4.0, Univ. of Sci. & Tech. of China 1989-1992
B. S., Biophysics, _ Magna Cum Laude, GPA 3.9/4.0, Univ. of Sci. & Tech. of China, 1984-1989
A primary research on the role of cadherin family of cell adhesion molecules in synaptic plasticity of adult hippocampus. Details in section "SUMMARY OF MY PH.D. THESIS".
Programmer of human genome project, Caltech Genome Research Center, with Dr. Ung-Jin Kim, 9/97 - 12/98
Created interactive human genome database manager - front-end GUI (C++, SQL)
connecting SQL server.
Coordinated projects: OOA/D, meetings, presentations,
software integration, upgrading, user support.
Graduate Research Assistant, Caltech, with Dr. Kai Zinn, 4/94 - 8/94
Identification of a grasshopper receptor-linked PTPase homologous to Drosophila PTPase by RT-PCR from total RNA of grasshopper and sequencing PCR clones.
Graduate Research Assistant, Caltech, with Drs. Henry A. Lester 1/94-4/94
A study of the structure-function of nAChRs by heterologous expression after
site-directed mutagenesis in the conserved leucine residue in the M2
transmembrane of nACh receptor and dual electrode voltage clamping recording in Xenopus Oocytes.
Discovered the symmetrically altered gating properties of
nAChRs with mutation in different subunits.
Master's Thesis Research, University of Science and Technology of China, 9/89 - 8/92
A primary research on oxidant damages of developing nervous system after chronic exposure to environmental lead and protection by zinc and selenium.
Created a large program doing data acquistion and analysis of single units from different cell types, reengineered A/D D/A board for samping of nerver signals.
Research Assistant, University of Science and Technology of China, 9/88 - 8/89
A primary research on the potential therapeutic effect of magnetic fields with different intensities on the biological system using enzyme kinetics analysis.
WORK EXPERIENCE:
TEACHING EXPERIENCE:
Teaching Assistant, University of Science and Technology of China, 1989 - 1992
COMPUTER SKILLS:
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"A computer software tool for graphic management of physical mapping data", L. Tang, J. Boulton, B. Liau, H. Zhang, W. Qin, S. H. Huh, R. X. Xu, Y. Cao, G. A. George and U.-J. Kim, Biotechnique, submitted.
"Determinants of BDNF-induced Hippocampal Synaptic Plasticity: role of the Trk B receptor and the kinetics of neurotrophin delivery", H. Kang, L. Z. Jia, K.-Y. Suh, L. Tang and E. M. Schuman, Learning and memory , 3:188-196, 1996.
"Channel Gating Governed Symmetrically By Conserved Leucine Residues in the M2 Domain of Nicotinic Receptors", C. Labarca, M. W. Nowak, H. Zhang, L. Tang, P. Deshpande & H. A. Lester, Nature, 376:514-516, 1995.
"Effects of Lead on Temporal Response Properties of Retinal Ganglion Cells in Developing Rats", D.-Y. Ruan, L. Tang, C. Zhao, and Y.-J. Guo, Science in China, 37(5):538-546, 1994.
"Effects of Low Level Lead on Retinal Ganglion Sustained and Transient Cells in Developing Rats", D.-Y. Ruan, L. Tang, C. Zhao, and Y.-J. Guo, Neurotoxicology and Teratology, 16:47-53, 1994.
"Effects of Rare Earth Element Yttrium on VEP and ERG of Developing Rats", D.-Y. Ruan, Y.-F. Hu, L. Tang, and F.-Q. Li, Journal of China University of Science and Technology, 23:229-233, 1993.
"Lead-induced Oxidant Damage in Developing Rats", L. Tang and D.-Y. Ruan, Journal of Advances in Free Radical Biology and Medicine, Beijing , 1:315-320, 1991.
"Involvement of Cadherin Molecules in Synaptic Plasticity in the Adult Hippocampus", L. Tang and E. M. Schuman, Society for Neuroscience Abstract, Vol. 23, 47.17, 1997.
"Role of Cadherin Molecules in Synaptic Plasticity in Adult Rat Hippocampus", L. Tang, C. P. Hung and E. M. Schuman, Society for Neuroscience Abstract, Vol. 22, 136.3, 1996.
"Lead-induced Oxidant Damage and Role of Zinc in Antioxidant Defense System of Developing Rats", L. Tang and D.-Y. Ruan, International Symposium on Toxicology, 139-140, 1990.
"Effects of Lead on Development of Visual Nervous System of Albino Rats", D.-Y. Ruan and L. Tang, Biophysics Symposium in China, 6:110, 1990.
"Effects of Lead on Visual System of Rats - Development and Electrophysiology", D.-Y. Ruan and L. Tang, Biophysics Symposium on Environment and Radiation in China, 3:234-235, 1989.
SUMMARY OF MY PH.D. THESIS:
Cell adhesion molecules have been suggested by our and other groups to modulate synaptic function. Cadherins, one of the major classes of cell adhesion molecules, are a family of single-pass integral membrane glycoproteins spanning many different intercellular junctions by forming Ca2+-dependent homophilic bonds. The morphogenetic role of cadherins in developing tissues has been extensively investigated. In contrast, their expression in adult brain has less been studied. Their functional role in synaptic plasticity in adult hippocampus has never been documented.
In the first part of my thesis I examined the expression of cadherins in adult hippocampus. In situ hybridization experiments were performed and mRNAs for both Neural (N-) and Epithelial (E-) cadherins, two well-studied subtypes of cadherins, were found to be present in adult hippocampus even at very high hybridization stringency conditions. Our Western blot analysis of different hippocampal preparations indicated the presence of cadherin in hippocampal homogenate, membranous fraction, and synaptosomes, but not in cytosolic fraction. Immunofluorescent labeling combined with confocal microscopy further revealed that these cadherins and their intracellular signaling partners, the catenins, are present in adult hippocampus. In order to resolve the expression of these proteins at synaptic sites, additional staining in dissociated cultured hippocampal cells was conducted and punctate immuno-positive staining for cadherins and catenins was evident, suggesting synaptic localization. Dual immunofluorescent labeling in cultured cells confirmed that these cadherins and catenins are largely co-localized to staining for the synaptic marker, synapsin I.
The synaptic expression of cadherin implies a functional role in synaptic function in adult hippocampus. In the second part of my thesis, accordingly, I examined whether these cadherins participate in hippocampal synaptic transmission and long-term potentiation using function-blocking antibodies and peptides. Pretreatment of hippocampal slices with adhesion-blocking antibodies raised against the extracellular domain of either N- or E-cadherin had no effect on basal synaptic properties but significantly reduced LTP in adult hippocampal slices. My immunostaining data confirmed that 2-3 hour incubations were sufficient for these antibodies to penetrate fully the interior of the slices. Moreover, infusion of antagonistic peptides containing the His-Ala-Val (HAV) consensus sequence for cadherin dimerization attenuated LTP induction without affecting previously established LTP. Pretreatment of slices with longer HAV peptides also resulted in reduced LTP without affecting basal synaptic parameters. These data suggest that the cadherin signaling is required during the initial triggering of synaptic enhancement. The inhibitory effect of these antibodies and peptides on adhesion was confirmed by our cell adhesion assay performed on mouse fibroblast cell lines expressing transfected E-cadherin.
Currently I am studying the mechanism underlying the involvement of cadherin in hippocampal LTP. One approach is to increase [Ca2+]o and examine if the inhibitory effect on hippocampal LTP by HAV peptides is affected. Meanwhile, a recombinant adenovirus vector containing GFP and a dominant-negative mutant N-cadherin cDNA which lacks most of the extracellular domain has been made. I am currently infecting hippocampus with this recombinant adenovirus and examining whether LTP is similarly affected.