
Research Focus: The uterus is a vital organ for the successful propagation of all higher species. Understanding the molecular mechanisms that contribute to the development and subsequent function of the uterus are absolutely essential for successful reproduction as well as adequate treatment of uterine disorders that impede the reproductive process. It is well established that numerous biological mediators dictate the normal pattern of uterine development and that disruption of these factors plays a causative role in uterine abnormalities, disease and infertility. Our research focuses on the role of the matrix metalloproteinase system in the development and function of the uterus and examines how unopposed protease activity may lead to uterine diseases. We are most interested in examining the regulation of these proteases at the post-transcriptional and post-translational level. Post-translational projects focus on the role of specific matrix metalloproteinase inhibitors including TIMP-1, TIMP-3 and RECK using a variety of approaches including genetically modified mouse models. Research examining post-transcriptional regulation of MMP activity focuses on the role of microRNAs in modulating uterine MMP translation during uterine development and disease. Further emphasis is placed upon examining the overall function of microRNAs in the development of the reproductive organs and how alterations in miRNA biogenesis may lead to disease within these tissues. Collectively, the research in my laboratory focuses on examining the mechanisms which regulate uterine development and function, identifying factors which contribute to these mechanisms and understanding how alterations in these mechanisms lead to uterine diseases such as endometriosis and endometrial cancer.
Zhang X, Nothnick WB. (2005) The role of the metalloproteinase system within the uterus of menstruating and non-menstruating species. Front Biosci 10:353-366.
Zhou H-E, Nothnick WB. (2005) The Relevancy of the Matrix Metalloproteinase System to the Pathophysiology of Endometriosis. Front Biosci 10:569-575.
Zhou H-E, Zhang X, Nothnick WB. Disruption of the TIMP-1 gene product is associated with accelerated endometrial gland formation during early post-natal uterine development. Biol Reprod 2004; 71:534-539.
Nothnick WB. Novel targets for the treatment of endometriosis. Expert Opin Ther Targets 2004; 5:459-471.
Zhang X, Nothnick WB. The role of the metalloproteinase system within the uterus of menstruating and non-menstruating species. Front Biosci 2005; 10:353-366.
Zhou H-E, Nothnick WB. The relevancy of the matrix metalloproteinase system to the pathophysiology of endometriosis. Front Biosci 2005; 10:569-575.
Zhang X, Christenson LK, Nothnick WB. Regulation of matrix metalloprotein-9 (MMP-9) expression and activity in the mouse uterus by estrogen. Mol Reprod Dev 2006; In press.
