Dr. Ning-Hsing Yeh, Professor

Phone: 886-2-2826-7113
E-mail: yphcsl@ym.edu.tw
Education@Research@Publications


Education

1970, B.S.@ Department of Plant Pathology
@@@@@@ National Chung-Hsing University, Taiwan

1978, M.S.@ Department of Bacteriology
@@@@@@ University of Arkansas

1981, Ph.D.@Department of Microbiology and Immunology
@@@@@@ University of Arkansas for Medical Sciences

1981 - 1982@Assistant Research Scientist
@@@@@@ Department of Pharmacology, New York University Medical Center

1982 - 1985@Instructor
@@@@@@ Department of Pharmacology, New York University Medical Center


Research

1. Structural and functional dynamics of nucleolus

@@Nucleolus is originated from the sites on chromatin where the rRNA genes (rDNA) reside and carries out reactions for ribosome biogenesis. Nucleolar structural changes have been observed in a variety of neoplasms and during cellular aging. We have previously identified a novel, cell-proliferation related, nucleolar phosphoprotein p130 (hNopp140), whose dispersion into the cytoplasm during mitosis coincides with the well-known mitotic cease of rDNA transcription. Interestingly, p130 can be triggered to undergo polymerization and depolymerization in vitro. Further experiments have shown that p130 is associated with the largest subunit of RNA polymerase I in vivo. Overexpression of p130, or of its N-terminus containing the RNA polymerase I-interacting domain, leads to a profound disordering of the nucleolus accompanied by an inhibition of rRNA synthesis. We hypothesize that p130 is a building block with self-assembly potential to form a nucleolar fundamental structure. We will test whether the central ten acidic-basic repeats of p130 is responsible for the formation of a spherical structure and whether the N- and C-terminal domains of p130 contribute to place these spheres more effectively in nucleolus. Broad search of the p130-associated proteins and RNAs will be pursued. We will also examine the subcellular localizations of nucleolar proteins in contrast to the spatial rearrangement of rDNA elements in normal cells, tumor cells, and aging cells.


2. Nuclear structural reorganization during mitosis and apoptosis

@@NuMA (220-kDa) is a nuclear matrix-associated protein in interphase but is translocated to the spindle poles during mitosis. We have demonstrated that cleavage of NuMA takes place at the onset of apoptosis and is correlated with events of DNA fragmentation and micronucleation in interphase nuclei. The same truncated NuMA (180-kDa) is normally formed at the late stages of mitosis but fated to be degraded completely before the mitotic exit. Cascades of kinase and protease activation and the subsequent nuclear structural reorganization will be examined during mitosis and apoptosis. We will test the cooperative roles of NuMA with other nuclear proteins for the dynamic redistribution of chromatin between interphase and mitotic phase and mechanisms of chromatin fragmentation in relation to the nuclear matrix reorganization during apoptosis.



Publications

1. Yeh, N.-H., C.-M. Chen, and S.-L. Hsieh. 1988. Rapid identification of monoclonal antibodies to differential antigens by dot immunobinding assay. Chinese J. Microbiol. Immunol. 21: 210-223.

2. Chen, C.-M., S.-Y. Chiang, and N.-H. Yeh. 1991. Increased stability of nucleolin in proliferating cells by inhibition of its self-cleaving activity. J. Biol. Chem. 266: 7754-7758.

3. Li, L.-L., N.-H. Yeh. 1992. Cell cycle-dependent migration of the DNA-binding protein Ku80 into nucleoli. Exp. Cell Res. 199: 262-268.

4. Fang, S.-H., and N.-H. Yeh. 1993. The Self-cleaving activity of nucleolin determines its molecular dynamics in relation to cell proliferation. Exp. Cell Res. 208: 48-53.

5. Yang, T.-H., W-H. Tsai, Y.-M. Lee, H.-Y. Lei, M.-Y. Lai, D.-S. Chen, N.-H. Yeh. and S.-C. Lee. 1994. Purification and characterization of nucleolin and its identification as a transcription repressor. Mol. Cell. Biol. 14: 6068-6074.

6. Pai, C.-Y., H.-K. Chen, H.-L. Hsu, and N.-H. Yeh. 1995. Cell cycle-dependent alterations of a highly phosphorylated nucleolar protein p130 are associated with nucleologenesis. J. Cell Sci. 108: 1911-1920.

7. Hsu, H.-L., and N.-H. Yeh. 1996. Dynamic changes of NuMA during cell cycle and possible apearance of a truncated form of NuMA during apoptosis. J. Cell Sci. 109: 221:581-587.

8. Pai, C.-Y., and N.-H. Yeh. 1996. Cell proliferation-dependent expression of two isoforms of the nucleolar phosphoprotein p130. Biochem. Biophys. Res. Commun. 221: 581-587.

9. Chen, H.-K., and N.-H. Yeh. 1997. The nucleolar phosphoprotein p130 is a GTPase/ATPase with intrinsic property to form large complexes triggered by F- and Mg2+. Biochem. Biophys. Res. Commun. 230: 370-375.

10.Chen, H.-K., Pai, C.-Y., Huang, J.-Y. and Yeh, N.-H. 1999. Human Nopp140, which interacts with RNA polymerase I: implications for rRNA gene transcription and nucleolar structure organization. Mol. Cell. Biol. 19: 8536-8546.


Members of Laboratory