Dr. Sidney R. Grimes' Research Focus

Research interests:
Regulation of tissue-specific gene expression is an important problem in molecular biology. We conduct research designed to reveal mechanisms involved in regulating tissue-specific expression of testis and prostate genes. The testis-specific histone H1t gene is expressed only in primary spermatocytes. The H1t promoter sequence is unique when compared to the other mammalian H1 promoters, and data from electrophoretic mobility shift assays and protein- DNA crosslinking experiments reveal binding of testis-specific nuclear proteins to the promoter. The binding proteins are present only in primary spermatocytes where the gene is transcribed. Furthermore, the rat H1t gene is expressed only in testis of mice bearing the rat transgene. An examination of enriched germinal cells from transgenic mice reveal that the pattern of expression is identical to the pattern in normal animals with expression limited to primary spermatocytes. When a region of the promoter is replaced with heterologous stuffer DNA, the rat H1t gene is no longer expressed in transgenic mice, confirming the essential nature of this element. Therefore, the promoter of the H1t gene is being examined to determine how regulatory elements that bind testis nuclear proteins lead to tissue-specific transcription. The binding proteins will be purified and genes encoding the proteins will be identified.

In addition we are involved in a study of the human prostate specific membrane antigen (PSMA) gene also known as the folate hydrolase (FOLH1)gene. Expression of this gene is enhanced in prostate cancer cells as well as in endothelial cells of neovasculature associated with most solid tumors but not in normal vasculature. Our research is involed in analysis of the PSMA promoter and enhancer and we conduct research designed to reveal mechanisms involved in regulating tissue-specific or tissue-enhanced expression of the gene. Prostate cancer is the leading type of cancer in men. We hope to use this promoter and enhancer in future gene therapy studies designed to deliver therapeutic genes to treat male patients that have prostate cancer or to treat both male and female patients that have solid tumors.