Testis-specific transcription factors and gene expression, Sperm-specific antigens in prostate cancer

The Reddi laboratory studies the transcriptional regulatory mechanisms underlying the terminal differentiation of male germ cells utilizing the mouse as a model system. The terminal differentiation genes of the spermatogenic lineage are not expressed elsewhere in the body except in certain types of cancer. There is now a growing list of cancer-testis-antigens. The current focus of the lab is to understand how the terminal differentiation genes of the male germ cells are repressed under normal conditions. To this end, the lab has identified transcriptional repressors TDP43 and PURalpha as regulators of gene expression during spermatogenesis. Interestingly, TDP43 and PURalpha are aberrantly expressed in cancerous cells suggesting a possible link to the production of cancer-testis-antigens. The lab recently discovered a novel chromatin insulator in the promoter of a testis-specific gene, which protects genes form position effects. Currently, the concept that a heterologous (potentially therapeutic) gene flanked by this insulator will be protected from position effects in vivo is being tested. If successful, the insulator will be used to design novel gene therapy vectors. This research made extensive use of the Mouse Transgenic Core and the Biomolecular Research Facility. Collaborative studies with Dr. John. C. Herr, a member of the Cancer Center , involving functional studies of several testis-specific genes has resulted in several joint publications. In collaboration with Dr. Henry Frierson, the lab will investigate the expression of TDP43 and PURalpha in various types of cancer including germ cell tumors.