• Kuang Yu Chen
  • Distinguished Professor Emeritus
  • Research Synopsis: 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.

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:

  1. Function of polyamines;
  2. Biochemistry of hypusine formation and eukaryotic initiation factor 5A (eIF5A);
  3. Mechanism of the action of nutraceuticals;
  4. 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

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