University of Kentucky, 19935014 Wahl Hall West
3901 Rainbow Boulevard
Kansas City, KS 66160
Phone: (913) 588-6277
Fax : (913) 588-6271
wnothnic@kumc.edu
My research focuses on the role of tissue remodeling factors in the female reproductive tract. Our major area of interest is the role of the matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) in uterine growth, development and function. Using TIMP-1 deficient mice, we have demonstrated that absence of the TIMP-1 gene product results in alterations in uterine development and reduced reproductive lifespan. Current studies are aimed at determining the mechanisms by which TIMP-1 regulates uterine development and growth and employ a variety of molecular, cellular and biochemical techniques.
A second project in my laboratory focuses on the role of TIMP-1 in corpus luteum physiology. The corpus luteum produces progesterone which is essential for the establishment of pregnancy. We have demonstrated that TIMP-1 deficient mice are subfertile and this subfertility may be due to reduced progesterone production. We are currently examining the mechanisms by which TIMP-1 influences corpus luteum development and progesterone production using both in vivo and in vitro methodologies.
A third research interest of my laboratory involves the study of the female disease endometriosis. Endometriosis occurs in as many as 10% of all women of reproductive age and is defined as the presence of endometrial tissue in ectopic locations. We are currently examining the role of various MMPs, TIMPs, adhesion molecules and cytokines in the pathophysiology of the disease using both animal and human models. By understanding how these factors contribute to the etiology of the disease we hope to develop novel treatments for the disease which would offer benefits over current therapies.
Nothnick WB, Fang F, Iczkowski KA, Thomas P, Ashwell R., Tawfik OW. (2001) CD44s expression is reduced in endometriotic lesions compared to eutopic endometrium in women with endometriosis. Int J Gynecol Pathol 20:140-146.
Nothnick WB. (2001) Treating endometriosis as an autoimmune disease. Fertil Steril 76:223-231.
Nothnick WB. (2001) Disruption of the tissue inhibitor of metalloproteinase-1 (TIMP-1) gene in reproductive-age female mice is associated with estrous cycle stage-specific increases in stromelysin mRNA expression and activity. Biol Reprod 65: 1780-1788.
Nothnick WB. (2001) Reduction of reproductive lifespan in tissue inhibitor of metalloproteinase-1 (TIMP-1) deficient female mice. Reproduction 122:923-927.
Stephens EB, McCormick C, Pacyniak E, Griffin D, Pinson DM, Sun F, Wong SW, Gunderson R, Nothnick WB, Berman NEJ, Singh DK. (2002) Deletion of the vpu Sequences Prior to the env in a Simian-Human Immunodeficiency Virus Results in Enhanced Env Precursor Synthesis but is Less Pathogenic for Pig-Tailed Macaques . Virology 293:252-261.
Nothnick WB. (2003) Tissue inhibitor of metalloproteinase-1 (TIMP-1) deficient mice display reduced serum progesterone levels during corpus luteum development. Endocrinology 144:5-8. (published as a Rapid Communication)
Nothnick WB and D’Hooghe TM (2003) Medical management of endometriosis: novel targets and approaches towards the development of future treatment regimes. Gynecol Obstet Invest 55: 189-198.
Nothnick WB., Zhang X, Zhou H-E. (2004) Steroidal regulation of uterine edema and TIMP-3 mRNA expression is altered in TIMP-1 deficient mice. Biol Reprod 70:500-508.
Zhou H-E, Zhang X, Nothnick WB. (2004) Disruption of the TIMP-1 gene product is associated with accelerated endometrial gland formation during early post-natal uterine development. Biol Reprod 71:534-539.
Hu J, Zhang X, Nothnick WB, Spencer TE. (2004) Characterization of matrix metalloproteases and their tissue inhibitors in neonatal mouse uterus. Biol Reprod (published 7 July 2004; epub ahead of print).
Nothnick WB. (2004) Novel targets for the treatment of endometriosis. Expert Opin Ther Targets (in press).
Zhang X, Nothnick WB. (2004) The role of the metalloproteinase system within the uterus of menstruating and non-menstruating species. Front Biosci (in press).
Zhang X, Nothnick WB. (2004) Disruption of the TIMP-1 gene product indicates functional overlap in regulation of MMP-9 and serine protease activity during steroidal regulation of uterine edema. Biol Reprod (accepted).
Zhou H-E, Nothnick WB. (2004) The Relevancy of the Matrix Metalloproteinase System to the Pathophysiology of Endometriosis. Front Biosci (accepted).
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The University of Kansas Medical Center