The laboratory research of Serdar E. Bulun, MD, studies steroid hormone action and production in hormone-dependent human diseases such as endometriosis, uterine fibroids, and skeletal muscle atrophy.
About Our Work
- Yin P, Ono M, Moravek MB, et al. Human uterine leiomyoma stem/progenitor cells expressing CD34 and CD49b initiate tumors in vivo. J Clin Endocrinol Metab. 2015;100(4):E601-606.
- Moy I, Todorovic V, Dubash AD, et al. Estrogen-dependent sushi domain containing 3 regulates cytoskeleton organization and migration in breast cancer cells. Oncogene. 2015;34(3):323-333.
- Dyson MT, Kakinuma T, Pavone ME, et al. Aberrant expression and localization of deoxyribonucleic acid methyltransferase 3B in endometriotic stromal cells. Fertil Steril. 2015;104(4):953-963 e952.
- Navarro A, Yin P, Ono M, et al. 5-Hydroxymethylcytosine promotes proliferation of human uterine leiomyoma: a biological link to a new epigenetic modification in benign tumors. J Clin Endocrinol Metab. 2014;99(11):E2437-2445.
- Monsivais D, Dyson MT, Yin P, et al. ERbeta- and prostaglandin E2-regulated pathways integrate cell proliferation via Ras-like and estrogen-regulated growth inhibitor in endometriosis. Mol Endocrinol. 2014;28(8):1304-1315.
- Dyson MT, Roqueiro D, Monsivais D, et al. Genome-wide DNA methylation analysis predicts an epigenetic switch for GATA factor expression in endometriosis. PLoS Genet. 2014;10(3):e1004158.
- Ono M, Yin P, Navarro A, et al. Paracrine activation of WNT/beta-catenin pathway in uterine leiomyoma stem cells promotes tumor growth. Proc Natl Acad Sci U S A. 2013;110(42):17053-17058.
- Moy I, Lin Z, Rademaker AW, Reierstad S, Khan SA, Bulun SE. Expression of estrogen-related gene markers in breast cancer tissue predicts aromatase inhibitor responsiveness. PLoS One. 2013;8(11):e77543.
- Ma JJ, Monsivais D, Dyson MT, et al. Ligand-activated peroxisome proliferator-activated receptor beta/delta modulates human endometrial cancer cell survival. Hormones & cancer. 2013;4(6):358-370.
- Bulun SE. Uterine fibroids. N Engl J Med. 2013;369(14):1344-1355.
- Zhao H, Pearson EK, Brooks DC, et al. A humanized pattern of aromatase expression is associated with mammary hyperplasia in mice. Endocrinology. 2012;153(6):2701-2713.
- Yin P, Roqueiro D, Huang L, et al. Genome-wide progesterone receptor binding: cell type-specific and shared mechanisms in T47D breast cancer cells and primary leiomyoma cells. PLoS One. 2012;7(1):e29021.
- Ono M, Qiang W, Serna VA, et al. Role of stem cells in human uterine leiomyoma growth. PLoS One. 2012;7(5):e36935.
- Navarro A, Yin P, Monsivais D, et al. Genome-wide DNA methylation indicates silencing of tumor suppressor genes in uterine leiomyoma. PLoS One. 2012;7(3):e33284.
- Pavone ME, Dyson M, Reirstad S, et al. Endometriosis expresses a molecular pattern consistent with decreased retinoid uptake, metabolism and action. Hum Reprod. 2011;26(8):2157-2164.
- Chen D, Reierstad S, Fang F, Bulun SE. JunD and JunB integrate prostaglandin E2 activation of breast cancer-associated proximal aromatase promoters. Mol Endocrinol. 2011;25(5):767-775.
- Yin P, Lin Z, Reierstad S, et al. Transcription factor KLF11 integrates progesterone receptor signaling and proliferation in uterine leiomyoma cells. Cancer Res. 2010;70(4):1722-1730.
- Pavone ME, Reierstad S, Sun H, Milad M, Bulun SE, Cheng YH. Altered retinoid uptake and action contributes to cell survival in endometriosis. J Clin Endocrinol Metab. 2010;95(11):E300-309.
- Lin Z, Yin P, Reierstad S, et al. Adenosine A1 receptor, a target and regulator of estrogen receptoralpha action, mediates the proliferative effects of estradiol in breast cancer. Oncogene. 2010;29(8):1114-1122.
- Lin BC, Suzawa M, Blind RD, et al. Stimulating the GPR30 estrogen receptor with a novel tamoxifen analogue activates SF-1 and promotes endometrial cell proliferation. Cancer Res. 2009;69(13):5415-5423.
- Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268-279.
- Utsunomiya H, Cheng YH, Lin Z, et al. Upstream stimulatory factor-2 regulates steroidogenic factor-1 expression in endometriosis. Mol Endocrinol. 2008;22(4):904-914.
- Demura M, Bulun SE. CpG dinucleotide methylation of the CYP19 I.3/II promoter modulates cAMP-stimulated aromatase activity. Mol Cell Endocrinol. 2008;283(1-2):127-132.
- Demura M, Martin RM, Shozu M, et al. Regional rearrangements in chromosome 15q21 cause formation of cryptic promoters for the CYP19 (aromatase) gene. Hum Mol Genet. 2007;16(21):2529-2541.
- Chen D, Reierstad S, Lin Z, et al. Prostaglandin E(2) induces breast cancer related aromatase promoters via activation of p38 and c-Jun NH(2)-terminal kinase in adipose fibroblasts. Cancer Res. 2007;67(18):8914-8922.
Treatment of Endometriosis with Aromatase Inhibitors
Treatment with aromatase inhibitors is the most commonly used form of nontoxic treatment in postmenopausal breast cancer. Aromatase is the key enzyme for estrogen formation in human tissues. Our research recently showed large amounts of aromatase thus estrogen formation in endometriosis. Inhibition of this enzyme in animal models and human disease decreased inflammation and growth in endometriosis and significantly reduced pain associated with endometriosis. In postmenopausal women, use of an aromatase inhibitor in combination with a bisphosphonate is the treatment of choice in patients who do not respond to surgical resection.
In premenopausal women, aromatase inhibitors are used in combination with an additional drug that suppresses the ovaries because aromatase inhibitor-only treatments may give rise to ovarian stimulation. This additional drug may be a GnRH agonist (eg, Zoladex), progestin (eg, norethindrone acetate) or a birth control pill (eg, Alesse). Currently, some physicians prescribe these regimens to treat premenopausal endometriosis not responding to currently available treatments or in patients who cannot use existing treatments because of their side effects. The majority of these premenopausal patients respond favorably having decreased pelvic disease and reduced pain. Treatment of endometriosis with aromatase inhibitors is still considered experimental, since there are no current efforts known to the public for obtaining FDA approval for their use in treating endometriosis.
The side effects of aromatase inhibitors include mild hot flashes and decreased libido. If aromatase inhibitors are administered alone to postmenopausal women, they cause osteoporosis and should be combined with a bisphosphonate. In premenopausal women, the combination of an aromatase inhibitor with a progestin or birth control pill does not cause osteoporosis, whereas that combination with a GnRH agonist (eg, Zoladex) causes osteoporosis.
Clinical Trials and Case Reports (Aromatase Inhibitors for Treatment of Endometriosis)
- Takayama, K, Zeitoun, K, Gunby, RT, Sasano, H, Carr, BR and Bulun, SE, Treatment of severe postmenopausal endometriosis with an aromatase inhibitor. Fertil Steril. 1998; 69: 709-713.
- Ailawadi, RK, Jobanputra, S, Kataria, M, Gurates, B and Bulun, SE, Treatment of endometriosis and chronic pelvic pain with letrozole and norethindrone acetate: a pilot study. Fertil Steril 2004; 81: 290-6.
- Amsterdam L, GW, Rubin S, Jobanputra S, Wolf M, Bulun SE, Anasrozole and oral contraceptives: A novel treatment for endometriosis. Fertil Steril. 2005. In Press.
- Soysal, S, Soysal, M, Ozer, S, Gul, N and Gezgin, T, The effects of post-surgical administration of goserelin plus anastrozole compared to goserelin alone in patients with severe endometriosis: a prospective randomized trial. Hum Reprod 2004; 19: 160-167.
- Shippen, ER and West, WJ, Jr., Successful treatment of severe endometriosis in two premenopausal women with an aromatase inhibitor. Fertil Steril 2004; 81: 1395-8.
- Razzi, S, Fava, A, Sartini, A, De Simone, S, Cobellis, L and Petraglia, F, Treatment of severe recurrent endometriosis with an aromatase inhibitor in a young ovariectomised woman. Bjog 2004; 111: 182-4.
- Bulun, SE, Imir G, Utsunomiya H, Thung S, Gurates B, Tamura M, Lin Z. Aromatase in endometriosis and uterine leiomyomata. J Steroid Biochem Mol Biol. 2005. In Press.
Reviews and Original Articles on the Role of Aromatase in Endometriosis
- Zeitoun, KM and Bulun, SE, Aromatase: a key molecule in the pathophysiology of endometriosis and a therapeutic target. Fertil Steril 1999; 72: 961-9.
- Bulun, SE, Zeitoun, K, Takayama, K, Noble, L, Michael, D, Simpson, E, Johns, A, Putman, M and Sasano, H, Estrogen production in endometriosis and use of aromatase inhibitors to treat endometriosis. Endocr Relat Cancer 1999; 6: 293-301.
- Noble, LS, Takayama, K, Putman, JM, Johns, DA, Hinshelwood, MM, Agarwal, VR, Zhao, Y, Carr, BR and Bulun, SE, Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells. J Clin Endocrinol Metab 1997; 82: 600-606.
- Zeitoun, K, Takayama, K, Michael, MD and Bulun, SE, Stimulation of aromatase P450 promoter (II) activity in endometriosis and its inhibition in endometrium are regulated by competitive binding of SF-1 and COUP-TF to the same cis-acting element. Molec Endocrinol 1999; 13: 239-253.
- Noble, LS, Simpson, ER, Johns, A and Bulun, SE, Aromatase expression in endometriosis. J Clin Endocrinol Metab 1996; 81: 174-179.
- Bulun, SE, Yang, S, Fang, Z, Gurates, B, Tamura, M, Zhou, J and Sebastian, S, Role of aromatase in endometrial disease. J Steroid Biochem Mol Biol. 2001; 79: 19-25.
- Tsai, SJ, Wu, MH, Lin, CC, Sun, HS and Chan, HM, Regulation of steroidogenic acute regulatory protein expression and progesterone production in endometriotic stromal cells. Journal of Clinical Endocrinology & Metabolism 2001; 86: 5765-5773.
- SE Bulun, Imir AG, Utsunomiya H, Thung S, Gurates B, Tamura M, Lin Z. Aromatase in Endometriosis and Uterine Leiomyomata. J Steriod Biochem Mol Bio. 95:57-62 (2005).
- Attar E and Bulun SE, Aromatase and Other Steroidogenic Genes in Endometriosis: Translational Aspects. Human Reproduction. In Press.
Articles on the Use of Aromatase Inhibitors in Breast Cancer
- Goss, PE and Strasser, K, Aromatase inhibitors in the treatment and prevention of breast cancer. J Clin Oncol 2001; 19: 881-94.
- Buzdar, A and Howell, A, Advances in aromatase inhibition: clinical efficacy and tolerability in the treatment of breast cancer. Clin Cancer Res 2001; 7: 2620-35.
- Buzdar, AU, Robertson, JF, Eiermann, W and Nabholtz, JM, An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane. Cancer 2002; 95: 2006-16.
- Haynes, BP, Dowsett, M, Miller, WR, Dixon, JM and Bhatnagar, AS, The pharmacology of letrozole. J Steroid Biochem Mol Biol 2003; 87: 35-45.
- Goss, PE, Qi, S, Cheung, AM, Hu, H, Mendes, M and Pritzker, KP, Effects of the steroidal aromatase inhibitor exemestane and the nonsteroidal aromatase inhibitor letrozole on bone and lipid metabolism in ovariectomized rats. Clin Cancer Res 2004; 10: 5717-23.
- Coleman, RE, Hormone- and chemotherapy-induced bone loss in breast cancer. Oncology (Huntingt) 2004; 18: 16-20.
- Buzdar, AU, The ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial: an update. Clin Breast Cancer 2004; 5 Suppl 1: S6-S12.
Articles on the Use of Aromatase Inhibitors for Ovulation Induction
- Mitwally, MF and Casper, RF, Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril 2001; 75: 305-9.
- Kafali, H, Iriadam, M, Ozardali, I and Demir, N, Letrozole-induced polycystic ovaries in the rat: a new model for cystic ovarian disease. Arch Med Res 2004; 35: 103-8.
- Kilic-Okman, T, Kucuk, M and Altaner, S, Comparison of the effects of letrozole and clomiphene citrate on ovarian follicles, endometrium, and hormone levels in the rat. Fertil Steril 2003; 80: 1330-2.
- Cortinez, A, De Carvalho, I, Vantman, D, Gabler, F, Iniguez, G and Vega, M, Hormonal profile and endometrial morphology in letrozole-controlled ovarian hyperstimulation in ovulatory infertile patients. Fertil Steril 2005; 83: 110-5.
- Fisher, SA, Reid, RL, Van Vugt, DA and Casper, RF, A randomized double-blind comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on ovulatory function in normal women. Fertil Steril 2002; 78: 280-5.
- Sebastian, S and Bulun, SE, A highly complex organization of the regulatory region of the human CYP19 (aromatase) gene revealed by the human genome project. J Clin Endocrinol Metab 2001; 86: 4600-4602.
- Moudgal, NR, Shetty, G, Selvaraj, N and Bhatnagar, AS, Use of a specific aromatase inhibitor for determining whether there is a role for oestrogen in follicle/oocyte maturation, ovulation and preimplantation embryo development. J Reprod Fertil Suppl 1996; 50: 69-81.
For more information, contact Elena Babineau at 312-472-3980.
Serdar E. Bulun, MD
Chair, Department of Obstetrics & Gynecology
John J. Sciarra Professor of Obstetrics & Gynecology
John Coon V, MS
Coon is the Lab Manager and Senior Research Technologist for the Bulun lab. He graduated with honors in biochemistry from Knox College and received his Master of Science degree in biotechnology from Penn State University. After graduating from Penn State, he joined GlaxoSmithKline as a research scientist, helping to develop novel antibiotics. Upon returning to Chicago, he joined the Bulun Lab in the early spring of 2009. Coon has worked in many areas of research, but particularly enjoys the varied and challenging research of the Bulun Lab.
Hong Zhao, MD, PhD
Research Associate Professor
Zhao received her MD in China and her PhD in molecular endocrinology at the Nanjing Medical University in China and the Utrecht University in the Netherlands. After completing the postdoctoral training in the NIH, she moved to Chicago and began working for Northwestern University. Her current research interests are in defining how aromatase and estrogen cause abdominal muscle fibrosis and hernia formation, pelvic floor disorders, and Alzheimer’s diseases using the humanized aromatase transgenic mouse model and the tissue-specific aromatase knockout mouse models.
Ping Yin, MD, PhD
Research Associate ProfessorYin joined Northwestern as a senior research associate in November 2004. She is investigating mechanisms underlying the formation of uterine leiomyoma and exploring therapeutic strategies for its treatment.
Azna Zuberi, PhD
Post-Doctoral Research ScholarZuberi is currently working as a Post-doctoral research scholar in Dr. Bulun's lab, joining in June 2020. She completed her PhD from AMU, INDIA, where she worked on mechanism to inhibit bacterial biofilms through CRISPRi gene editing technology and now she is working with fibroid group in exploring underlying the formation of uterine fibroids by targeting different involved pathways.
Stacy Ann Kujawa
Research Technician 2
Stacy received her BS degree in Animal Sciences from the University of Illinois in Champaign-Urbana in 2005. In 2011, she was a research technician at Northwestern University for Dr. Takeshi Kurita where she consented patients for Dr. Bulun’s reproductive tissue registry and provided assistance in experiments involving fibroids and xenografting. After Dr. Kurita left NU, she has been working in the Bulun laboratory as a research technician with her main responsibilities being consenting and maintaining the reproductive tissue registry and assisting in the laboratory in genotyping, mouse colony maintenance, mouse xenografting, and other experiments.
Ariel is a 5th year Driskill Graduate Program in Life Sciences (DGP) graduate student and is a recent inductee in the Edward A. Bouchet Graduate Honor Society "recognizing outstanding scholarly achievement and promote diversity and excellence in doctoral education and the professoriate." She joined the group in 2016 after finishing her master’s degree in molecular, cellular and developmental biology at University of Michigan – Ann Arbor. She is currently working on understanding the involvement of progesterone receptor and estrogen receptor in the mechanism underlying labor initiation in the human myometrium.
Tanvi Potluri is a PhD student in the Driskill Graduate Program. She researches the role of estrogens in abdominal muscle fibrosis and inguinal hernias. Previously, Tanvi completed her master’s degree from Johns Hopkins Bloomberg School of Public Health in microbiology & immunology.
Research Technologist 3