Kay-Uwe Wagner, Ph.D.

Professor, Eppley Institute

Education

B.S. - University of Leipzig, Germany, Agriculture
Ph.D. - University of Halle, Germany, Animal Genetics

Research Summary:

My research objectives are to elucidate the mechanisms regulating the normal development of the mammary gland and to identify genetic pathways that control the development of breast cancer. Mammary development is a fascinating process that is unique in several aspects: First, proliferation and differentiation of mammary epithelial cells occur primarily postnatally. Second, mammary development is dependent upon the synergistic action of systemic hormones and local growth factors. Third, a full-functionally differentiated mammary gland requires a complex 3-D structure of epithelial and stromal compartments. Fourth, the mammary gland can serve as an excellent in vivo model for cell proliferation, differentiation, genome stability, and programmed cell death as it develops in defined steps during reproductive cycles.

Numerous genes have been identified that are crucial for normal mammary development and breast cancer. Their role is being studied in my research group through their deregulated expression in mammary tissue of transgenic animals or gene transfer using adenoviral vectors, and through their deletion from the mouse genome by homologous recombination. Specifically, my laboratory has the expertise to delete genes in a tissue-specific and temporally controlled fashion using the Cre-loxP recombination system. Current projects include the analysis of prolactin signaling through the Jak-Stat pathway, and the role of the bcl-x gene as a survival factor for defined cells types. Recently, my research group established in a collaborative effort with researchers at the National Institutes of Health in Bethesda (MD) the first mouse model for a hereditary form of human breast cancer. This mouse model was generated by inactivating the mouse homologue of the human BRCA1 gene (Breast and Ovarian Cancer Gene 1, early onset) specifically in mammary epithelial cells. We have shown that the loss of the BRCA1 protein promotes genomic instability, and triggers tumorigenic events in a subset of cells in the mammary gland. Current studies on this model are focused on steriod hormone action and neoplastic transformation. My laboratory has identified a new gene that is suggested to be involved in genome instability and tumorigenesis. Its function in vivo is currently analyzed by using conventional and conditional knockout approaches.

Recent Publications

Wagner Laboratory Web Site