Warren B. Nothnick, PhD
Professor and Vice Chair
Director, Center for Reproductive Sciences
Molecular and Integrative Physiology
PhD, University of Kentucky, 1993
Postdoctoral Fellowship, University of Kentucky, 1993-1997
The research in the Nothnick Laboratory focuses on the physiology and pathophysiologies of the uterus/endometrium with the primary focusing being endometriosis. Endometriosis is a chronic disease in which endometrial tissue grows ectopically, is characterized by pelvic pain and infertility and affects over 70 million women world-wide. One of the reasons for its high prevalence is that the disease is usually diagnosed only after it has established. An additional clinical shortcoming is that the majority of treatments for the disease rely on the induction of a hypo-estrogenic state which is associated with unwanted side effects and negative impacts on bone health. Clearly, both better diagnostic tools and treatment options are warranted.
microRNAs have emerged as critical post-transcriptional regulators of gene expression that are fundamental for development and function of many organ systems. Recent reports have suggested that miRNAs are mis-expressed in endometriosis. While these reports have laid the initial groundwork to examine the potential role of miRNAs in the pathophysiology of the disease, they have provided no functional evidence demonstrating a role for miRNAs in the development of endometriosis. To fill this gap in our knowledge, we are currently examining the mechanisms by which miR-451 contributes to the pathology of the disease using in vitro and in vivo models. Secondary interests focus on the regulation and function of microRNAs in the decidualization process and endometrial infertility.
As discussed above, there is a clear need for the development of more effective and better tolerated compounds which spare the induction of a hypo-estrogenic state for endometriosis treatment. A second major focus area of our laboratory is the identification of novel targets which are over-expressed in endometriotic tissue (compared to eutopic endometrium) which may play a role in the events conducive to endometriosis development and/or growth. We are currently examining the potential of these molecules as targets for development of novel, estrogen-sparing treatments for endometriosis and the symptoms associated with this disease. The outcomes from this research have significant potential to provide novel insights into the role of these molecules in pathogenesis of endometriosis and potentially modify the way in which this debilitating disease is treated.
Nothnick WB, Graham A, Holbert J, Weiss MJ. (2014) miR-451 deficiency is associated with altered endometrial fibrinogen alpha chain expression and reduced endometriotic implant establishment in an experimental mouse model. PLoS ONE 9(6): e100336. doi:10.1371/journal.pone.0100336.
Tawfik O, Rao DS, Nothnick W, Graham A, Mau, B, Fan F. (2014) Transgelin, a novel marker that effectively distinguishes endometrial stromal tumors from uterine smooth muscle tumors. IJGORMR 1:26 - 31.
Nothnick WB. (2015) Endometriosis: Bright future for a cloudy past? Sci Transl Med. 7:271fs.
Graham A, Falcone T, Nothnick WB. (2015) The expression of microRNA-451 in human endometriotic lesions is inversely related to that of macrophage migration inhibitory factor (MIF) and regulates MIF expression and modulation of epithelial cell survival. Hum Reprod 30:642 - 52.
Nothnick WB, Al-Hendy A, Lue J. (2015) Circulating microRNAs as diagnostic biomarkers for endometriosis: privation and promise. J Minim Invasive Gynecol. 22:719 - 26.
Rao D, Kimler BF, Nothnick WB, Davis M, Fan F, Tawfik O. (2015) Transgelin: A potentially useful diagnostic marker differentially expressed in triple-negative and non-triple negative breast cancers. Hum Pathol 46:876 - 83.
Nothnick, WB. (2016) Non-coding RNAs in uterine development, function and disease. Adv Exp Med Biol. 886:171-186.