G. Stanley Cox

Associate Professor, Biochemistry and Molecular Biology and Eppley Institute

G. Stanley Cox, PhDPhone: 402-559-6651
Fax: 402-559-6650
Email: gscox@unmc.edu

Education/Training:
Ph.D., University of Iowa, 1973

Research: 

Dr. Cox's research interests are focused in the areas of molecular biology, recombinant DNA technology, and biochemical oncology, with an emphasis on mechanisms of gene expression. 

A model system, comprising of both trophoblastic and nontrophoblastic tumor cell lines that produce chorionic gonadotropin (CG) or its isolated alpha- and beta-subunits, is being used to define those parameters responsible for tissue-specific CG gene expression. Several avenues of investigation are currently being pursued to further understand how the CG genes are regulated and to clarify the role of CG in cancer. 

  1. DNA-mediated transfection of chimeric genes is being used to define the DNA elements and protein factors that control expression of the CG alpha-subunit gene. Preliminary experiments have identified multiple cis-acting elements in the CG gene that behave as tissue-restricted silencers and enhancers. Immediate goals are to determine the nucleotide sequence of their respective core elements and identify regulatory proteins through which their action is manifest. Two nuclear DNA-binding proteins have been identified with properties expected of transcriptional repressors, and a third functions as a trans-activator. Future objectives are to purify, characterize, and clone the cDNA encoding these factors. 
  2. Previous studies have shown that expression of the alpha-subunit gene is higher in tumor cell lines where the gene is extensively methylated and lower (or negligible) in cell lines where the gene is hypomethylated. The effect of DNA methylation on transcription factor binding to their cognate recognition sites is under investigation. 
  3. Signal transduction pathways terminating with enhancer binding proteins that mediate CG induction by glucose, replication inhibitors, and short chain fatty acids are under investigation.   
  4. A cDNA for the human CG receptor has been cloned in this laboratory, and experiments are in progress to characterize receptor synthesis in ovarian carcinoma cells. 

Publications:

Cox, G.S., Cosgrove, D.E., Sullivan, T.T. and Haas, M.J. Induction by Cycloheximide of the Glycoprotein Hormone Alpha-Subunit Gene in Human Tumor Cell Lines and Identification of a Possible Negative Regulatory Factor. J. Biol. Chem., 265:13190-13197, 1990.

Campain, J.A. and Cox, G.S. Deoxyribonuclease Hypersensitive Sites in the Glycoprotein Hormone Alpha-Subunit Gene in Trophoblastic and Nontrophoblastic Tumor Cell Lines: Correlation with Expression and Effect of Chemical Inducers. Mol. Endo., 6:677-693, 1992.

Campain, J.A., Gutkin, D.W. and Cox, G.S. Differential DNA Methylation in the Choriogonadotropin Beta-Subunit Multigene Family. Mol. Endo., 7:1331-1346, 1993.

Campain, J.A., Eudy, J.D. and Cox, G.S. Permissive Effect of Cyclic-AMP and Cycloheximide for Induction by Sodium Butyrate of the Glycoprotein Hormone Alpha-Subunit in Choriocarcinoma Cells. Cell Growth Diff., 5:827-838, 1994.

Cox, G.S. Correlation in HeLa cells of Anchorage-Independent Growth and Synthesis of the Glycoprotein Hormone Alpha-Subunit. Biochem. Biophys. Res. Commun. 233:452-431, 1997.

Cox, G.S., Cosgrove, D.E., Haas, M.J., Stiles, W., and McIntosh, D.G. Msp I Restriction Fragment Length Polymorphism at the Glycoprotein Hormone Alpha-Subunit Locus: Association of Certain Genotypes with Neoplasia. Biochim. Biophys. Acta, 1354: 83-96, 1997.

Cox, G.S., Gutkin, D.W., Haas, M.J., and Cosgrove, D.E. Isolation of an Alu Repetitive DNA Binding Protein and Effect of CpG Methylation on Binding to its Recognition Sequence. Biochim. Biophys. Acta, 1396: 67-87, 1998.

Haas, M. J., Xiong, W., Cosgrove, D. E., and Cox, G.S. Sodium Butyrate-Mediated Induction of the Glycoprotein Hormone -Subunit Gene: Requirement for Continued Protein Synthesis, Identification of a Butyrate-Responsive Element, and Inhibition of Promoter Activity by 2-Deoxyglucose. J. Cell. Biochem. 74: 242-263, 1999.

Cox, G.S. and Xiong, W. Influence of a Cap Site Element on Tissue-Restricted Expression of the Glycoprotein Hormone -Subunit Gene. Biochem. Biophys. Res. Commun., 260: 752-759, 1999.

Scofield, M.A., Xiong, W., Haas, M.J., Zeng, Y., and Cox, G.S. Sequence analysis of the human glycoprotein hormone a-subunit gene 5’-flanking DNA and identification of a potential regulatory element as an Alu repetitive sequence. Biochim. Biophys. Acta (Gene Structure and Function), 143:302-318, 2000.

Cox, G.S. Cellular responses to sodium butyrate exhibit the dominance of one parental phenotype in somatic cell hybrids.  Mol. Cell Biol. Res. Commun., 3:329-337, 2000.

Xiong, W. Tapprich, W.E., and Cox, G.S. Mechanism of Gonadotropin Gene Expression:  Identification of a Novel Negative Regulatory Element at the Transcription Start Site of the Glycoprotein Hormone a-Subunit Gene. J. Biol.Chem. 227: 40235-4246, 2002.

 

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