| Michel M. Sanders |
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Research Description
Most eucaryotic genes are controlled by developmental, hormonal, tissue-specific, and/or nutritional cues. Insight into these complex regulatory events is fundamental to our understanding of the processes controlling cellular proliferation and oncogenesis, differentiation, and development. The long-term goal of the research in my laboratory focuses on investigating how estrogen and testosterone regulate gene expression, both physiologically and pathologically. To address this, we are investigating the structure and function of the estrogen- and testosterone-responsive ZEB-1 (delta EF1) transcription factor. ZEB-1 both activates and represses transcription through as yet undetermined mechanisms to regulate target gene activity in reproductive tissues, bone, and T-cells. In addition, over expression of ZEB-1 is associated with numerous types of cancers including breast cancer, myometrial cancer, ovarian cancer, and endometrial cancer. We are examining how ZEB-1 regulates genes, what its target genes are, and what the resultant effects are in bone, the ovary, and the prostate. Thus, much of our research effort in the coming years will focus on the effects of estrogen and testosterone on gene activity in various reproductive cancers. Another area of research is the investigation of the transcriptional regulation of the chick ovalbumin gene. This gene serves as a model to investigate how a secondary or delayed transcriptional response gene is induced by estrogen in a tissue-specific manner. The expectation is that a better understanding of the events in this system will be broadly applicable to other secondary response genes in estrogen-responsive tissues.
Recent Publications
Chamberlain, E. M. and M. M. Sanders (1999). Identification of the novel player d EF1 in estrogen transcriptional cascades. Molecular and Cellular Biology 19: 3600-3606.
Monroe, D. G. and M. M. Sanders (2000). Estrogen opposes the apoptotic effects of bone morphogenetic protein 7 on tissue remodeling. Molecular and Cellular Biology 20: 4626-4634.
Dean, D. M., P. S. Jones, and M. M. Sanders (2001). Alterations in chromatin structure are implicated in the activation of the steroid hormone response unit in the ovalbumin gene. DNA and Cell Biology 20: 27-39.
Monroe, D. G., R. R. Berger, and M. M. Sanders (2002). Tissue-protective effects of estrogen involve regulation of caspase gene expression. Molecular Endocrinology 16: 1322-1331.
Dillner, N.B. and M.M. Sanders (2002). Upstream Stimulatory Factor (USF) is recruited into a steroid hormone-triggered regulatory circuit by the estrogen-inducible transcription factor d EF1. Journal of Biological Chemistry 277: 33890-33894.
Dillner, N. B. and M. M. Sanders. (2004). Transcriptional activation by the zinc finger homeodomain protein d EF1 in estrogen signaling cascades. DNA Cell Biology 23:25-34.
Anose, B.M., M.P. Linnes, and M.M. Sanders (2005). Hormonal regulation of ZEB-1 and implications for progression of human reproductive cancers. Hormonal Carcinogenesis IV. J.J. Li , S.A. Li, and A. Llombart-Bosch (eds). New York: Springer, pp 455-461.
Dougherty, D.C. and M. M. Sanders (2005). Comparison of the responsiveness of the pGL3 and pGL4 luciferase reporter vectors to steroid hormones. BioTechniques 39:203-207
Dougherty, D.C. and M. M. Sanders (2005). Estrogen action: Revitalization of the chick oviduct model. Trends in Endocrinology and Metabolism 16:414-419
Park, H-M, M. M. Sanders, T. Suzuki, and T. Muramatsu (2006). An oviduct-specific and enhancer-like element resides at about -3000 in the chicken ovalbumin gene. Biochimie (in press) |