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G. Stanley Cox
- Associate Professor, Biochemistry and Molecular Biology and Eppley Institute
Ph.D., 1973, University of Iowa
Phone: (402) 559-6651
Fax: (402) 559-6650
Email: gscox@unmc.edu
Click here for biographical sketch and publications.
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.
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