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.
Abali, E.E., N. Osheroff, E. Buxbaum, E. C, Niederhoffer, K. Symes, and M.M. Sanders (2014) Evolving role of the basic science course director in an evolving curriculum. Medical Science Education. doi:10.1007/s40670-014-0047-9
Broege, A. M., B. M. Anose, and M. M. Sanders (2011). Regulating the expression of the ZEB1 transcription factor in health and disease. Current Trends in Endocrinology 5:75-91
Anose, B.M. and M. M. Sanders (2011). Signal transduction by androgen involves the zinc finger E-box binding protein-1 (ZEB-1). International Journal of Endocrinology 2011: Article ID 903918 doi:10.1155/2011/903918
Saykally, J. N., Dogan, S., Cleary, M. P. and Sanders, M. M. (2009). The ZEB1 transcription factor is a novel repressor of adiposity in female mice. PLoS One 4(12):e8460 (doi:10.1371/journal.pone.0008460), PMID: 20041147. [PubMed]
Dougherty, D. C. and Sanders, M. M. (2009). IRF family members repress transcription of the ovalbumin gene in chick oviduct. Gene 439:63-70 (doi:10.1016/j.gene.2009.03.016), PMID: 19341784.
Hurt, E. C., Saykally, J. N., Kalli, K. R., Anose, B. and Sanders, M. M. (2008). Expression of the ZEB1 (deltaEF1) transcription factor in the human: additional insights. Molecular and Cellular Biochemistry 318:89-99 (doi: 1007/s11010-008-9860-z), PMID: 1862289. [PubMed]
Dougherty, D. C. and Sanders, M. M. (2008). High efficiency transfection of primary oviduct cells by nucleofection. Trends in Reproductive Biology 3:9-14.
Park, H-M, Sanders, M. M., Suzuki, T. and Muramatsu, T. (2006). An oviduct-specific and enhancer-like element resides at about -3000 in the chicken ovalbumin gene. Biochimie. [PubMed]
Dougherty, D.C. and Sanders, M. M. (2005). Estrogen action: Revitalization of the chick oviduct model. Trends in Endocrinology and Metabolism 16:414-419. [PubMed]
Dougherty, D.C. and Sanders, M. M. (2005). Comparison of the responsiveness of the pGL3 and pGL4 luciferase reporter vectors to steroid hormones. BioTechniques 39:203-207. [PubMed]
Anose, B.M., Linnes, M. P. and Sanders, M. M. (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.
Dillner, N. B. and Sanders M. M. (2004). Transcriptional activation by the zinc finger homeodomain protein d EF1 in estrogen signaling cascades. DNA Cell Biology 23:25-34. [PubMed]