Pathology & Laboratory Medicine

Brett Spear,  Ph.D.

Associate Professor

E-mail: bspear@uky.edu
Telephone:   (859) 323-5089
Campus Address:  Microbiology & Immunology, MS433A Wm R Willard Medical Ed Bld, 0298

The mouse alpha-fetoprotein (AFP) gene provides a unique model for liver-specific gene regulation as it is expressed at high levels in the fetal liver; repressed at birth, and reactivated during liver regeneration and in hepatic tumors. Our lab is interested in two aspects of AFP regulation; the activation of AFP transcription during hepatogenesis and the postnatal repression of AFP transcription. Most of our experiments require developmental analysis and are thus performed in transgenic mice. These studies are complemented by transfections in culture cells and in vitro assays to identify and further characterize proteins which bind AFP control elements. A second project is focused on understanding how environmental toxins act as hepatic tumor promoters. We observed that some of these agents can activate the transcription factor NF-kB by a hydrogen peroxide-mediated mechanism. We are studying the biochemical and tumorigenic consequences of NF-kB activation. We have generated transgenic mice that overexpress catalase, the major hydrogen peroxide-detoxifying enzyme, for use in these studies.