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Chemistry & Chemical Biology / New Brunswick |
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Kuang-Yu Chen Professor B.S. 1967, National Taiwan University M.Ph. 1970, Yale University Ph.D. 1972, Yale University |
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Research and Publications
Summary
The underlying theme of our research focus is to understand how chemicals interact with biological systems. Specific areas of interest are: Function of polyamines, Hypusine and ,eukaryotic initiation factor 5A , Cell aging and G1/S regulation, Stress and heat shock factor activation, and Nutraceuticals-Genomic interactions.(2002-2006)
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
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. 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., 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
Gosslau, A. and Chen, K.Y. Nutraceuticals, apoptosis, and disease prevention. Nutrition, 20, 95 102, 2004.
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 Journal, 384, 585-590, 2004
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.
Chatterjee I, Gross SR, Kinzy TG, Chen KY. 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
(1) Hypusine Project:
Hypusine is a spermidine-dependent posttranslational modification of eukaryotic initiation factor 5A (eIF-5A) that is conserved from archaebacteria, yeast to human. It is, however, not present in eubacteria. We wish to know the function of eIF-5A and why this protein and its modification are essential for cell survival and proliferation.
Tao, Y. and Chen, K.Y. Molecular cloning and functional expression deoxyhypusine synthase cDNA and identification of yeast ,deoxyhypusine synthase cDNA. J. Biol. Chem. 270, 23984-23987, 1995.
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.
Chen, K.Y. and Liu, A.Y.-C. Hypusine formation on eukaryotic initiation factor 5A, biochemistry and function. Biol. Signals, 6, 105-109, 1997.
Chen, K.Y. and Jao, D.L Chemistry Hypusine formation on eukaryotic initiation factor 5A,in bilogical systems J. Chinese Chemical Society, 146, 727-734, 1999.
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.
(2) Cell Aging Project:
Aging manifests at many levels, from single cell to whole animal . Normal human somatic cells lose their dividing potential and become senescent after about 50 to 60 divisions. Questions that are of interest are: Why normal cells age whereas cancer cells are immortal? What is the clocking mechanism that causes the senescent cells lose dividing potential?
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.
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.
Liu, A.Y.-C., Chen, K.Y. and Denhardt, D.T. Transcription Factors and Cell Aging. Biol. Signals, 5, 127-129, 1996.
Matuoka, K. and Chen, K.Y. Nuclear factor Y (NF-Y) and cellular senescence. Exp. Cell Res., 253, 365-371, 1999.
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
(3) Nutraceuticals and Gene Expression:
Natural products are rich sources for novel chemical structures that possess potent 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.
Chen, Z.P. and Chen, K.Y. Mechanism of regulation of ornithine decarboxylase gene expression in a variant mouse neuroblastoma cell line. J. Biol. Chem. 267, 6946-6951, 1992.
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.
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.
Lu, J.B., Ho, C.-T., Ghai, G. and Chen, K.Y. Resveratrol analog, 3,4,4,5-tetrahydroxystilbene, 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.
(4) 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?
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. Biochemical J. 327, 341-347, 1997.
Lu, J.B., 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.
Chen, K.Y., Lu, Jiebo 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.
(5) Tumor Differentiation Project: Tumor differentiation is a rational alternative to cancer chemotherapy in fighting cancer diseases. 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.
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.
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., 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.
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.
(6) Intact Cell Spectroscopy Project Magnetic spectroscopy can be used to examine biochemistry of living cells on a real time basis. We are particularly interested in the use of nmr and epr to study free radicals and polyphosphate in the intact cells.
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.
Tiku, M., Yan, Y.P., Liesch, J.B., Tiku, K. and Chen, K.Y. Electron Spin resonance/spin trapping evidence for hydroxyl radical formation by chondrocytes and cartilage. Free Radical Research, 29, 177-187, 1998.
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.
(7) Ancient writings and civilizations
Chen, K.Y. Zhui Wang in oracle bone Language: possible relationship to the bird totem of of Shang Dynasty (1700-1100 BC). J. Chinese Linguistics, 22, 101-113, 1994
Chen, K.Y. Origin and Development of Chinese Writing, A Study of oracle bone inscriptions and other ancient writings. Rutgers University, course material.1999
Chen, K.Y. New interpretation of the temple name of Shang King Pan Keng. J. Chinese Linguistics 29, 340-350, 2001
Chen, K.Y. The Book of Odes: A case study of the 2600 years Chinese hermeneutic tradition. Interpretation and Intellectual Change, An International Conference on the History of Hermeneutics, Oct 4-6, Rutgers University.