Education
- B.S. 1967, National Taiwan University
- M.Ph. 1970, Yale University
- Ph.D. 1972, Yale University
Links
Conferences
Research Summary and Publications
Specific areas of current interest in the lab are:
- Function of polyamines;
- Biochemistry of hypusine formation and eukaryotic initiation factor 5A (eIF5A);
- Mechanism of the action of nutraceuticals;
- Stress and heat shock factor activation.
(1) Hypusine Project:
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Hypusine formation, the spermidine-dependent posttranslational modification of eIF5A, occurs in archaebacteria and all eukaryotes, but not in eubacteria. Both eIF5A and its modifying enzyme, deoxyhypusine synthase, are essential for cell survival and proliferation. We are interested in all aspects of eIF5A research, particularly its function.
Gosslau, A., Jao, D., Liu, A.Y-C. and Chen, K.Y. Thermal killing of human colon cancer cells Is associated with the loss of eukaryotic initiation factor 5A. J. Cell. Physiol., 219, 485-493, 2009
Chatterjee, I., Gross, S.R., Kinzy, T.G. and Chen, K.Y. Rapid depletion of mutant eukaryotic initiation factor 5A at restrictive temperature reveals connections to actin cytoskeleton and cell cycle progression. Mol. Genet. Genomics, 275, 264-276, 2006
Jao DL, Chen KY. Tandem affinity purification revealed the hypusine-dependent binding of eukaryotic initiation factor 5A to the translating 80S ribosomal complex. J Cell Biochem. 97, 583-598, 2006
Xu, A. Jao, D.L. and Chen, K.Y. Identification of messenger RNA species that bind specifically to eukaryotic initiation factor 5A by affinity co-purification and differential display. Biochemical J., 384, 585-590, 2004
Jao, D.L. and Chen, K.Y. Subcellular localization of the hypusine-containing eukaryotic initiation factor 5A by immunofluorescent staining and Green Fluorescent protein tagging. J Cell Biochem, 86, 590-600, 2002
Xu, A. and Chen, K.Y. Hypusine is required for a sequence-specific interaction of eukaryotic initiation factor 5A with post-SELEX RNA. J. Biol. Chem., 276, 2555-2561, 2001
Chen, K.Y. and Jao, D.L Chemistry Hypusine formation on eukaryotic initiation factor 5A,in bilogical systems J. Chinese Chem. Soc., 146, 727-734, 1999
Chen, K.Y. and Liu, A.Y.-C. Hypusine formation on eukaryotic initiation factor 5A, biochemistry and function. Biol. Signals, 6, 105-109, 1997
Yan, Y.P., Tao, Y. and Chen, K.Y. Molecular cloning and functional expression of human deoxyhypusine synthase cDNAs based on expressed sequence tag information. Biochem J., 315, 429-434, 1996
Tao, Y. and Chen, K.Y. Molecular cloning and functional expression of Neurospora deoxyhypusine synthase cDNA and identification of yeast deoxyhypusine synthase cDNA. J. Biol. Chem. 270, 23984-23987, 1995
(2) Nature Products:
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Natural products are rich sources for novel chemical structures with chemopreventive and chemotherapeutic activities. We are screening for compounds that specifically kill cancer cells but not normal cells. We are also searching for compounds that can modulate the life span of human cells. In addition, we are developing novel methods to identify target genes of effective nutraceuticals.
Lu, J., Gosslau, A., Liu, A.Y.-C. and Chen, K.Y. PCR differential display-based dentification of regulator of G protein signaling 10 as the target gene in human colon cancer cells induced by black tea polyphenol theaflavin monogallate. European J Pharmacology, 601, 66-72, 2008
Gosslau, A., Pabbaraja, S., Knapp, S. and Chen, K.Y. Trans- and cis-stilbene polyphenols induced rapid perinuclear mitochondrial clustering and p53-independent apoptosis in cancer cells but not normal cells. European J. Pharmacology, 587, 25-34, 2008
Gosslau, A., Chen, M., Ho, C.-T. and Chen, K.Y. A methoxy derivative of resveratrol analog exhibits potent and striking differential growth inhibitory effect against human cancer cells. British J. Cancer, 92, 513-521, 2005
Fang, F., Sang, S., Chen, K.Y., Gosslau, A., Ho, C.-T., and Rosen, R.T. Isolation and identification of cytotoxic compounds from bay leaf (Laurus nobilis). Food Chem., 93, 497-501, 2005
Gosslau, A. and Chen, K.Y. Nutraceuticals, apoptosis and disease prevention. Nutrition, 20, 95-102, 2004
Lu, J.B., Ho, C.-T., Ghai, G. and Chen, K.Y. Resveratrol analog, 3,4,4,5- etrahydroxystilbene, differentially induces pro-apoptotic p53/BAX gene expression and inhibits the growth of transformed cells but not their normal counterparts. Carcinogenesis, 22, 321-328, 2001
Lu, J.B., Ho, C.-T., Ghai, G. and Chen, K.Y. Differential effects of theaflavin monogallates on cell growth, apoptosis and Cox-2 gene expression in cancerous versus normal cells. Cancer Research, 60, 6465-6471, 2000
Chen, Z.P., Schell, J.B., Ho, C-T. and Chen, K.Y. Green tea epigallocatechin gallate shows pronounced growth inhibitory effect on cancerous cells but not on their normal counterparts. Cancer Letters, 129, 173-179, 1998
(3) Stress Response Project:
Hypo- and hyper-osmotic stresses represent two opposing physical forces in nature. Surprisingly, both stresses activate heat shock factor 1, a universal stress transcription factor present in all eukaryotes. What is the mechanism of activation? What is the physiological significance of this stress response?
Lee, Y.K., Liu, D.J., Lu, J., Chen, K.Y. and Liu, A.Y. Aberrant regulation and modification of heat shock factor 1 in senescent human diploid fibroblasts. J. Cell Biochem. 106, 267-278, 2009
Yang, J., Oza, J., Bridges, K., Chen, K.Y. and Liu, A. Y.-C. Neural differentiation and the attenuated heat shock response. Brain Res. 1203, 39-50, 2008
Oza J., Yang J., Chen K.Y., Liu A.Y. Changes in the regulation of heat shock gene expression in neuronal cell differentiation. Cell Stress Chaperones. 13, 73-84, 2008
Yang, J., Bridges, K., Chen, K.Y., Liu, A.Y. Riluzole increases the amount of latent HSF1 for an amplified heat shock response and cytoprotection. PLoS ONE. 3, e2864, 2008
Chen, K.Y., Lu, J. and Liu, A.Y.-C. The activation of trans-acting factors in response to hypo-and hyper-osmotic stress in mammalian cells. in " Environmental Stressors and Gene Responses." (eds. Storey, K. and Storey, J), JAI Press, CT, pp141-155, 2000
Lu, J., Park, J., Liu, A.Y-C. and Chen, K.Y. Osmotic stress-induced activation of HSF1 DNA binding activity is dramatically attenuated in senescent human cells. J. Cell. Physiol., 184, 183-190, 2000.
Caruccio, L., Bae, S., Liu, A.Y-C. and Chen, K.Y. Rapid activation of the heat shock factor, HSF1, by hyper- and hypo-osmotic stress in mammalian cells. Biochem. J. 327, 341-347, 1997.
Huang, L, E, Caruccio, L., Liu, A.Y., Chen, K.Y. Rapid activation of the heat shock transcription factor, HSF1, by hypo-osmotic stress in mammalian cells. Biochem J. 307, 347-352, 1995
(4) Cell Aging Project:
Lee, Y.K., Liu, D.J., Lu, J., Chen, K.Y. and Liu, A.Y. Aberrant regulation and modification of heat shock factor 1 in senescent human diploid fibroblasts. J. Cell Biochem. 106, 267-278, 2009
Matuoka, K., Chen, K.Y. and Takenawa, T. A positive role of phosphatidylinositol 3-kinase in aging phenotype expression in cultured human diploid fibroblasts. Archives Gerontology and Geriatrics, 36, 203-219, 2003
Matuoka, K. and Chen, K.Y. Telomerase positive human diploid fibroblasts are resistant to replicative senescence but not premature senescence induced by chemical reagents. Biogerontology, 3, 365-372, 2002
Matuoka, K. and Chen, K.Y. Transcriptional regulation of cellular senescence by the CCAAT box-binding proteins CBF/NF-Y. Aging Research Reviews, 1, 639-651, 2002
Matuoka, K. and Chen, K.Y. Possible role of subunit A of nuclear factor Y (NF-Y) in normal human diploid fibroblasts during senescence. Biogerontology, 1, 261-271, 2000
Matuoka, K. and Chen, K.Y. Nuclear factor Y (NF-Y) and cellular senescence. Exp. Cell Res., 253, 365-371, 1999
Liu, A.Y.-C., Chen, K.Y. and Denhardt, D.T. Transcription Factors and Cell Aging. Biol. Signals, 5, 127-129, 1996
Good, L.F., Dimri, G.P., Campisi, J. and Chen, K.Y. Regulation of dihydrofolate reductase gene expression and E2F components in IMR-90 human diploid fibroblasts during growth and senescence. J. Cell. Physiol.,168, 580-588, 1996
Pang, J.H and Chen, K.Y. A "CCAAT" binding protein, CBP/tk, may be involved in the regulation of thymidine kinase gene expression in human IMR-90 diploid fibroblasts during senescence. J. Biol. Chem., 268, 2909-2916, 1993
(5) Tumor Differentiation Project:
Manipulation of polyamine content in neuroblastoma, melanoma, and other tumors could lead to tumor reversion (differentiation). Based on this information, we are designing and synthesizing compounds that can cause tumor differentiation and investigating the underlying mechanism.
Lu, J., Chen, Z.P., Yan, Y.P., Knapp, S., Schugar, H. and Chen, K.Y. Aminohexanoic hydroxamate is a potent inducer of the differentiation of mouse neuroblastoma cells. Cancer Letters, 160, 59-66, 2000
Chen, Z.P., Yan, Y.P., Ding, Q., Potenza, J.A., Knapp, S., Schugar, H.J. Chen, K.Y. Effects of inhibitors of deoxyhypusinesynthase on the differentiation of mouse neuroblastoma and ertthroleukemia cells. Cancer Letters, 105, 233-239, 1996
Mehta, S., Hsu, L., Jeng, A. and Chen, K.Y. Neurite outgrowth and protein phosphorylation in chick embryonic sensory ganglia induced by a brief exposure to 12-O-tetradecanoylphorbol-13-acetate.J. Neurochem., 60, 972-981, 1993
Chen, Z.P. and Chen, K.Y. Differentiation of a mouse neuroblastoma variant cell line whose ornithine decarboxylase gene has been amplified. Biochim. Biophys. Acta, 1133, 1-8, 1991
(6) Intact Cell Spectroscopy Project:
Chen, K.Y. Study of polyphosphate metabolism by 31P nuclear magnetic resonance spectroscopy. in "Progesss in Molecular and Subcellular Biology" (ed. Schroder, H.C.), Springer Verlag, Germany, 1999
Tiku, M., Yan, Y.P., Liesch, J.B., Tiku, K. and Chen, K.Y. Electron Spin resonance/spin trapping evidence for hydroxyl radicalformation by chondrocytes and cartilage. Free Radical Research, 29, 177-187, 1998
Yang, Y.C., Bastos, M. and Chen, K.Y. Effects of osmotic stress and growth stage on cellular pH and polyphosphate metabolism in Neurospora crassa as studied by 31P nuclear magnetic resonance spectroscopy. Biochim. Biophys. Acta. 1179, 141-147, 1993
(7) Paleography Project:
Early China, particularly oracle bone inscriptions and Shang Civilization, comparison of of original writings.
Chen, K.Y. Ershi Jiapu zhi zi yu huadong zhi zi. (Chinese) 2009
Chen, K.Y. Analysis of Zixia's role in developing Confucianism and in bridging Confucianism and Legalism. International Conference on East Asian Confucianism: Interactions and Innovations, Rutgers University, 2009
Chen, K.Y. The four original writings: time and space of their genesis. Journal of Paleography (Chinese) 27, 1-15, 2008
Chen, K.Y. Dating of the origin of Chinese writing and a comparison with other original writings. Wenbo Journal 4, 26-34, 2008
Chen, K.Y. A new interpretation of Shang titles that contain the character duo, in "Huayuan Zhuang Dongdi Jiagu Luncong" 209-222, 2006
Chen, K.Y. "Origin and Development of Chinese Writing: Oracle Bone Inscription and other Ancient Writings" Lecture Notes, Rutgers University, 2006
Chen, K.Y. The Book of Odes: A Case Study of the 2600 Years Chinese Hermeneutic Tradition. in "Interpretation and Intellectual Change" , p.47 - 62, 2005
Chen, K.Y. New interpretation of the temple name of Shang King Pan-Keng. Journal of Chinese Linguistics, 29, 340-350, 2001
Chen, K.Y. Zhui-Wang in Oracle Bone Language: Possible relationship to the bird totem of Shang Dynasty (1700-1100 BC). Journal of Chinese Linguistics, 22, 101-113, 1994