The major goal of this laboratory is to elucidate the molecular mechanisms
of cellular and molecular response in stressed mammalian cells. Cells
in culture respond to suboptimal conditions by reprogramming a series of
metabolic processes including reorganization of cytoskeletal systems, alteration
of protein phosphorylation, and induction of stress (heat shock) proteins,
etc. We are particular interested in knowing the roles of various
cell signaling systems leading to the initiation of stress response and/or
apoptotic cell death. We use heat-shock as well as a number of cytotoxic
compounds as stressors and the metabolic responses are monitored in cells
during and recovering from the stress treatment. Currently, several
related research projects are being undertaken in this laboratory.
1. Stress response in mammalian cells - Transactivation of Stress Seventies
by Protein Phosphatase Inhibitors in 9L Rat Brain Tumor Cells; 2. Molecular
Mechanisms of Taxol-Induced Apoptosis in Human Leukemic HL-60 cells; and
3. Molecular Mechanism of Taxol Cytotoxicity in Human Non-Small Cell Lung
Cancer H460 cells.
Yiu-Kay Lai (¾¤Ä£°ò)
B.Sc. in Botany, National Taiwan University, 1974
Ph.D. in Genetics, North Carolina State University, 1980
Postdoctor, Yale University, 1980~1984
Associate Professor, 1984~1991
Whei-meih Chang (±i¼zª´)
B.Sc. in Medical Technology, National Taiwan University, 1986
Ph.D. in Developmental Genetics, University of Texas at Austin, 1998
Jao-Jia Chu (¦¶¥ü¹Å)
B.Sc. in Botany, Chinese Culture University, 1985
M.Sc. in Biology, Tung-Hai University, 1989
Chih-Chung Chao (»¯P©¾)
B.Sc. in Bioengineering, Tatung Institute of Technology, 1996
M.Sc. in Marine Technology, National Taiwan Ocean University, 1998
Jun-Hung Cho (¨ô«T§»)
B.Sc. in Marine Resource, National Sun Yat-sen University, 1998
Chi-Hung Richard Weng (¯Î§ÓÂE)
B.Arg. in Animal Science, Tung Hai University, 1998
Yun Lai (¿à ªå)
B.Sc. in Medical Technology, Kaohsiung Medical University, 1997
Yu-Fang Tseng (´¿§¤è)
B.Sc. in Biology, National Cheng Kung University, 1998
Nai-Lin Cheng (¾G¤DµY)
B.Sc. in Medical Technology, Tzu-Chi Medical College, 1998
Hsin-I Hung (¬xªY©É)
B.Sc. in Food Science, National Taiwan Ocean University, 1998
Shou Wei (ÃQºÓ)
B.Sc. in Chemistry, National Sun Yat-sen University, 1998
Huei-Chung Dai (À¹¼z¤¤)
Senior in Chemistry, National Tsing Hua University
Kai-Ling Huang (¶À³Í¬Â)
Junior in Biology, National Changhua Normal University
Jason Sih-Yu Lai (¾¤«ä¦t)
Freshman in Biology, National Taiwan Normal University
Recent Publications (1993~):
Hou, M.-C., C.-H. Shen, W.-C. Lee and Y.-K. Lai (1993) Okadaic Acid as
an Inducer of the 78-kDa Glucose-Regulated Protein in 9L Rat Brain Tumor
Cells. J. Cell. Biochem. 51: 91-101.
Lai, Y.-K., C.-H. Shen, T.-J. Cheng, M.-C. Hou and W.-C. Lee (1993) Enhanced
Phosphorylation of a 65 kDa Protein is Associated with Induction of Stress
Protein in 9L Rat Brain Tumor Cells. J. Cell Biochem. 51: 369-379.
Lee, W.-C., Y.-C. Lee, M.-D. Perng and Y.-K. Lai (1993) Induction of Vimentin
Modification and Vimentin-HSP72 Association by Withangulatin A in 9L Rat
Brain Tumor Cells. J. Cell. Biochem. 52: 253-265.
Lai, Y.-K., W.-C. Lee and K.-D. Chen (1993) Vimentin Serves as a Phosphate
Sink During the Apparent Activation of Protein Kinases by Okadaic Acid
in Mammalian Cells. J. Cell. Biochem. 53: 161-168.
Hsu, C.-M., W.-P. Yang, C.-C. Chen, Y.-K. Lai and T.-Y. Lin (1993) A Point
Mutation in the Chloroplast rps12 Gene from Nicotiana plumbaginifolia Confers
Streptomycin Resistance. Plant Mol. Biol. 23:179-183.
Hung, C.-Y., Y.-K. Lai, T.-Y. Feng and C.-C. Chen (1993) Chloroplast Segregation
in Somatic Hybrids of Nicotiana plumbaginifolia and N. sylvestris having
Different Ratios of Parental Nuclear Genomes. Plant Cell Rep. 113: 83-86.
Cheng, T.-J. and Y.-K. Lai (1994) Transient Increase in Vimentin Phosphorylation
and Vimentin-HSC70 Association in 9L Rat Brain Tumor Cells Experiencing
Heat-Shock. J. Cell. Biochem. 54: 100-109.
Huang, T.-J., T.-T. Lee, W.-C. Lee, Y.-K. Lai, J.-S. Yu and S.-D. Yang
(1994) Autophosphorylation-Dependent Protein Kinase Phosphorylates Ser25,
Ser38, Ser65, Ser71, and Ser411 in Vimentin and Thereby Inhibits Cytoskeletal
Intermediate Filament Assembly. J. Prot. Chem. 13: 517-525.
Perng, M.-D., T.-J. Cheng, C.-M. Chen and Y.-K. Lai (1994) Induction of
Aggregation and Augmentation of Protein Kinase-Mediated Phosphorylation
of Purified Vimentin Intermediate Filaments by Withangulatin A. Mol. Pharmacol.
Lee, Y.-C. and Y.-K. Lai (1995) The Integrity of Intermediate Filaments
is Associated with the Development of Acquired Thermotolerance in 9L Rat
Brain Tumor Cells. J. Cell. Biochem. 57: 150- 160.
Chen, K.-D., J.-J. Chu and Y.-K. Lai (1996) Modulation of Protein Phosphorylation
and Stress Protein Expression by Okadaic Acid on Heat-Shock Cells. J. Cell.
Biochem. 61: 255-265.
Lai, Y.-K., W.-C. Lee, C.-H. Hu and G. L. Hammond (1996) The Mitochondria
are Sensory Organelles for Cell Stress Recognition. J. Surgical Res. 62:
Lieu, C.-H., Y.-N. Chang and Y.-K. Lai (1997) Dual Cytotoxic Mechanisms
of Submicromolar Taxol on Human Leukemia HL-60 Cells. Biochem. Pharmacol.
Hwu, J. R., G. H. Hakimelahi, T. Sambaiah, H. V. Patel, S.-C. Tsay, Y.-K.
Lai and C.-H. Lieu (1997) Design and Synthesis of New Taxol-Containing
Aminophosphates as Protaxols. Bioorg. Med. Chem. Lett. 7: 545-548.
Chen, K.-D., J.-J. Hung, H.-L. Huang, D.-T. Chang, and Y.-K. Lai (1997)
Rapid Induction of Grp78 Gene by Cooperative Actions of Okadaic Acid and
Heat-Shock in 9L Rat Brain Tumor Cells: Involvement of a cAMP Responsive
Element-Like Promoter Sequence and a Protein Kinase A Signaling Pathway.
Eur. J. Biochem. 248: 120-129.
Chen, K.-D., L.-Y. Chen, H.-L. Huang, C.-H. Lieu, Y.-N. Chang, M. D.-T.
Chang, and Y.-K. Lai (1998) Involvement of p38 Mitogen-Activated Protein
Kinase Signaling Pathway in the Rapid Induction of the 78 kDa Glucose-Regulated
Protein in 9L Rat Brain Tumor Cells. J. Biol. Chem. 273: 749-755.
Chu, J.-J., K.-D. Chen, Y.-L. Lin, C.-Y. Fei, A.-S. Chiang, C.-D. Chiang,
Y.-K. Lai (1998) Taxol Induces Concomitant Hyperphosphorylation and Reorganization
of Vimentin Intermediate Filaments in 9L Rat Brain Tumor Cells. J. Cell.
Biochem. 68: 472-483.
Cheng, T.-J., T.-M. Chen, C.-H. Chen and Y.-K. Lai (1998) Induction of
Stress Response and Differential Expression of 70 kDa Stress Proteins by
Sodium Fluoride in HeLa and Rat Brain Tumor 9L Cells. J. Cell. Biochem.
Wang, T.-T., A.-S. Chiang, J.-J. Chu, T.-J. Cheng, T.-M. Chen, and Y.-K.
Lai (1998) Concomitant Alterations in Distribution of 70 kDa Heat Shock
Proteins, Cytoskeleton, and Organelles in Heat Shocked 9L Cells. Intl.
J. Biochem. Cell Biol. 30: 745-759.
Hung, J.-J., T.-J. Cheng, M. D.-T. Chang, K.-D. Chen, H.-L. Huang, and
Y.-K. Lai (1998) Involvement of Heat-Shock Elements and Basal Transcription
Elements in the Differential Induction of the 70 kDa Heat-Shock Protein
and Its Cognate by Cadmium Chloride in 9L Rat Brain Tumor Cells. J. Cell.
Biochem. 71: 21-35.
Lieu, C.-H., C.-C. Liu, T.-H. Yu, K.-D. Chen, Y.-N. Chang and Y.-K. Lai
(1998) Role of Mitogen Activated Protein Kinase in Taxol-Induced Apoptosis
on Human Leukemic U937 Cells. Cell Growth Differ. 9: 767-776.
Cheng, T.-J. and Y.-K. Lai (1998) Identification of Mitogen-Activated Protein
Kinase Activated Protein Kinase-2 as a Vimentin Kinase Activated by Okadaic
Acid in 9L Rat Brain Tumor Cells. J. Cell. Biochem. 71:169-181.
Hung, J.-J., T.-J. Cheng, Y.-K. Lai and M. D.-T. Chang (1998) Differentiation
Activation of p38 Mitogen-Activated Protein Kinase and Extracellular-Regulated
Protein Kinases Confers the Cadmium-Induced HSP70 Expression in 9L Rat
Brain Tumor Cells. J. Biol. Chem. 273:31924-31931.
Rao, C.S., J.-J. Chu, R.-S. Liu and Y.-K. Lai (1998) Synthesis and Evaluation
of [14C]-Labeled and Fluorescent-Tagged Taxol Derivatives as New Biological
Probes. Bioorg. Med. Chem. 6:2193-2204.
Chen, K.-D., M.-T. Lai, J.-J. Hung, L.-Y. Chen and Y.-K. Lai (2000) Activation
of p38 Mitogen-Activated Protein Kinase and Mitochondrial Ca2+-Mediated
Oxidative Stress Are Essential for the Enhanced Expression of grp78 Induced
by the Protein Phosphatase Inhibitors Okadaic Acid and Calyculin A. J.
Cell. Biochem., in press.