University of Kentucky, 1993
The female sex steroids estrogen and progesterone play critical roles in the normal biology of hormone-responsive tissues such as uterus, breast and bone. Within the uterus, estrogen and progesterone are critical for modulating cellular proliferation, apoptosis and differentiation in well-defined spatio-temporal patterns to assure normal uterine physiology and function. Recently, these steroid actions have been proposed to be "fine-tuned" by microRNAs (miRNAs). Not surprising, improper steroid responsiveness and altered miRNA expression have been associated with uterine diseases such as endometrial cancer, uterine fibroids and endometriosis. Our research focuses on understanding the mechanisms, which lead to miRNA biogenesis, how these miRNAs regulate uterine function, the mechanisms, which lead to their mis-expression and the role that this aberrant expression plays in uterine pathologies. Specifically, we are examining the regulation and role of the miRNA biogenesis components, Dicer and Exportin-5 and how their mis-expression leads to altered uterine development and function. Further, we are exploring the role of miRNA-451 as a regulator of steroid action on the expression of the macrophage migration inhibitory factor and how alterations in this pathway may lead to the development of endometriosis.
Nothnick WB, Healy C. Estrogen induces distinct patterns of microRNA expression within the mouse uterus. Reprod Sci. 2010 Nov;17(11):987-94.
Nothnick WB. (2010) Endometriosis: in search of optimal treatment. Minerva Ginecol. 2010 Feb;62(1):17-31.
Nothnick WB, Healy C, Hong X. Steroidal regulation of uterine miRNAs is associated with modulation of the miRNA biogenesis components Exportin-5 and Dicer1. Endocrine. 2010 Apr;37(2):265-73.
Gerin I, Louis GW, Zhang X, Prestwich TC, Kumar TR, Myers MG Jr, Macdougald OA, Nothnick WB. Hyperphagia and obesity in female mice lacking tissue inhibitor of metalloproteinase-1. Endocrinology. 2009 Apr;150(4):1697-704.
Nothnick WB, Zhang X. Future targets in endometriosis treatment: targeting the endometriotic implant. Mini Rev Med Chem. 2009 Mar;9(3):324-8.
Zhang X, Hoang E, Nothnick WB. Estrogen-induced uterine abnormalities in TIMP-1 deficient mice are associated with elevated plasmin activity and reduced expression of the novel uterine plasmin protease inhibitor serpin b7. Mol Reprod Dev. 2009 Feb;76(2):160-72.