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J. Julie Kim, PhDAssistant Professor
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Progesterone is essential for the regulation of normal female reproductive function. Its mode of action is diverse and dependent on the target tissues. In my lab we are interested in delineating the molecular mechanisms of progesterone action through its receptor, PR in the uterus. This is done in the context of normal endometrial differentiation, specifically, decidualization, as well as in uterine pathologies, such as endometriosis, endometrial cancer and uterine fibroids. Interestingly, in these three diseases, progesterone responsiveness is aberrant.
Specifically, we are interested in studying PR function in relation to other signaling pathways and transcription factors. We have demonstrated that the forkhead transcription factor FOXO1 is an important regulator of decidualization and that it synergistically regulates genes with PR. In endometrial cancer, the expression of FOXO1 is significantly downregulated and we hypothesize that this decrease contributes to the suboptimal response of the endometrium to progesterone. In uterine fibroids, progesterone promotes growth and we are studying potential mechanisms by which progesterone does this. Specifically the activation of the AKT pathway by progesterone is under investigation. Thus, we are studying diverse modes of action of PR both at the genomic and non-genomic levels in different uterine diseases. We hope to use the information generated from these studies towards the development of better therapies for endometriosis, endometrial cancer and uterine fibroids.
Kim, J.J., Buzzio OL, Li S, Lu Z. (2005) Regulation of IGFBP-1 by FOXO1 and progesterone receptor in human endometrial cells. Biol Reprod 73(4):833-839.
Buzzio OL, Lu Z, Miller CD, Unterman TG, Kim JJ. (2006) FOXO1A differentially regulates genes of decidualization. Endocrinology 147: 3870 – 3876
Kim JJ, Taylor HS, Lu Z, Ladhani M, Wu Y, Guo SW, Fazleabas AT. (2007) Altered expression of HOXA10 in endometriosis: potential role in decidualization. Mol Hum Reprod. 13(5):323-32.
Jackson KS, Brudney A, Hastings JM, Mavorganis PA, Kim JJ, Fazleabas AT. (2007) The altered distribution of the steroid hormone receptors and the chaperone immunophilin FKBP52 in a baboon model of endometriosis is associated with progesterone resistance during the window of uterine receptivity. Reproductive Sciences 14: 137-150
Takano M, Lu Z, Goto T, Fusi L, Higham J, Francis J, Withey A, Hardt J, Stavropoulou A, Ishihara O, Lam EWF, Unterman TG, Brosens JJ, Kim JJ. (2007) Transcriptional cross-talk between the forkhead transcription factor FOXO1 and the progesterone receptor coordinates cell cycle regulation and differentiation in human endometrial stromal cells. Mol Endo 21:2334-2349
Yin P, Lin Z, Cheng Y, Marsh EE, Utsunomiya H, Ishikawa H, Xue Q, Reierstad S, Innes J, Thung S, Kim JJ, Xu E, Bulun SE (2007). Progesterone receptor regulates bcl-2 gene expression through direct binding to its promoter region in uterine leiomyoma cells. J Clin Endocrinol Metab 11:4459-66.
Hoekstra AV, Kim JJ, Keh P, Schink JC. (2007) Absence of progesterone receptors in a failed case of fertility-sparing treatment in early endometrial cancer: A case report. Journal of Reproductive Medicine (in press).
Hoekstra AV, Ward EC, Hardt JL, Lurain JR, Singh DK,. Buttin BM, Schink JC, Kim JJ. (2007) Chemosensitization of Endometrial Cancer Cells through AKT Inhibition involves FOXO1A. Gynecol Oncol 2008 Jan 28; [Epub ahead of print]
Ward EC, Hoekstra AV, Blok LJ, Hanifi-Moghaddam P, Lurain JR, Singh DK, Buttin BM, Schink JC, Kim JJ. (2007) The regulation and function of the forkhead transcription factor, FOXO1, is dependent on the progesterone receptor in endometrial carcinoma. Endocrinology Dec 20; [Epub ahead of print]
Utsunomiya H, Cheng YH, Lin Z, Reierstad S, Yin P, Attar E, Xue Q, Imir G, Thung S, Suzuki T, Sasano H, Kim JJ, Yaegashi, N, and Bulun SE. (2007) Upstream stimulatory factors regulate steroidogenic factor-1 expression in endometriosis. Mol Endocrinol. Dec 28; [Epub ahead of print]
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View Publications by Julie Kim listed in the National Library of Medicine (PubMed). |
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