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Clincal Fertility & Infertility
Bulun, S. |
Elias, S. |
Kazer, J. |
Kim, Julie |
Sciarra, R. |
Shulman, Lee P. |
Urbanek, Margrit
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Serdar E. Bulun, M.D.
Department of Obstetrics & Gynecology
and a member of the Breast Cancer and Hormone Action & Signaling Transduction programs
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The laboratory research of Serdar E. Bulun, MD, focuses on studying estrogen biosynthesis and metabolism, in particular aromatase expression, in hormone-dependent human diseases such as breast cancer, endometriosis and uterine fibroids. A team of investigators works on understanding the epithelial-stromal interactions and aromotase overexpression in breast cancer tissue. Since aromatase inhibitors treat breast tumors primarily via suppressing intratumoral estrogen biosynthesis, theseeffortsare important for discovering new targets of treatment. Another teamstudies endometriosis. Basic data from this laboratory led to the introduction of aromatase inhibitors into endometriosis treatment. Human tissues and a primate model are used to elucidate cellular and molecular mechanisms responsible for the development of endometriosis. Regulation of aromatase expression is also studied in uterine fibroids, benign tumors that are dependent on estrogen for growth, by a third team.A fourth teamis investigatingthe link between progesterone action and estrogen inactivation in normal endometrium and endometriosis. Lastly,a fifth team has identified novel mutations that cause familial excessive estrogen formation syndrome. This syndrome is characterized by short stature, gynecomastia and hypogandism in males and early breast development and irregular menses in females. In this syndrome, heterozygous inversions in chromosome 15 q21, which cause the coding region of the aromatase gene to lie adjacent to constitutively active cryptic promoters that normally transcribe other genes, result in estrogen excess owing to the overexpression of aromatase in many tissues.
Recent Publications:
Fang Z, Yang S, Lydon JP, DeMayo F, Tamura M, Gurates B, Bulun SE. Intact progesterone receptors are essential to counteract the proliferative effect of estradiol in a genetically engineered mouse model of endometriosis. Fertil Steril. 2004 Sep;82(3):673-8.
Deb S, Amin S, Imir AG, Yilmaz MB, Suzuki T, Sasano H, Bulun SE. Estrogen regulates expression of tumor necrosis factor receptors in breast adipose fibroblasts. J Clin Endocrinol Metab. 2004 Aug;89(8):4018-24.
Tamura M, Deb S, Sebastian S, Okamura K, Bulun SE. Estrogen up-regulates cyclooxygenase-2 via estrogen receptor in human uterine microvascular endothelial cells. Fertil Steril. 2004 May;81(5):1351-6.
Bulun SE, Fang Z, Imir G, Gurates B, Tamura M, Yilmaz B, Langoi D, Amin S, Yang S, Deb S. Aromatase and endometriosis. Semin Reprod Med. 2004 Feb;22(1):45-50. Review.
Bulun SE, Takayama K, Suzuki T, Sasano H, Yilmaz B, Sebastian S. Organization of the human aromatase p450 (CYP19) gene. Semin Reprod Med. 2004 Feb;22(1):5-9. Review.
Ailawadi RK, Jobanputra S, Kataria M, Gurates B, Bulun SE. Treatment of endometriosis and chronic pelvic pain with letrozole and norethindrone acetate: a pilot study. Fertil Steril. 2004 Feb;81(2):290-6.
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Sherman Elias, M.D.
John J. Sciarra Professor and Chair
Feinberg School of Medicine
M.D., University of Kentucky
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Dr. Sherman Elias is currently the Chair of the Department of Obstetrics and Gynecology, and is a clinical geneticist with over 20 years of experience. Dr. Elias was awarded his medical degree from the University of Kentucky, and completed his residency in Obstetrics and Gynecology at the University of Louisville, followed by fellowships in genetics at Yale University and Northwestern University. Dr. Elias's professional career began at Northwestern in 1978, where he held a faculty appointment until 1986, followed by appointments at Baylor College of Medicine and the University of Tennessee College of Medicine. Most recently Dr. Elias was the Head of the Department of Obstetrics and Gynecology at the University of Illinois at Chicago from 1998-2003.
Dr. Elias is distinguished internationally in reproductive endocrinology and genetics. He is a member of many prominent academic societies, including the American Association for Advancement of Science and has held important leadership positions in many professional societies. Principal Investigator on a research program to develop a non-invasive method for prenatal diagnosis using fetal cells and DNA from maternal blood. He has received continuous funding from NIH for this project since 1987.
Recent Publications:
Bischoff FZ, HZhn S, Johnson, Simpson JL, Bianchi DW, Lewis DE, Weber WD, Klinger K, Elias S, Jackson LG, Evans MI, Holzegreve W, de la Cruz F. Intact fetal cells in maternal plasma: are they really there? Lancet 361: 139-140, 2003.
Sharma A, Gussin HE, Marquz-Do D, Martinez D, Horne C, Lewis D, Hoffman R, Elias S, Simpson JL, Bischoff F. Expansion of fetal cells in the maternal circulation occurred using Progenitor RosetteSeptm enrichment procedure with IL-3, SCF and G-CSF. Am J Hum Genet 73:595, 2003.
Johnson KL, Bianchi DW, Elias S, Holzegreve W, Simpson JL, Klinger KW, NICHD Fetal Cell Isolation Study (NIFTY). Inter-laboratory comparison of fetal DNA detection from common maternal plasma samples using real-time PCR. Am J Hum Genet 73:600, 2003.
Simpson, J.L. and Elias, S. Genetics in Obstetrics and Gynecology. W.E. Saunders, Philadelphia (In Press).
Annas GJ, Elias S. Politics, morals and embryos. Nature. 2004 Sep 2;431(7004):19-20.
Elias S. The human gynome. Am J Obstet Gynecol. 2004 Jun;190(6):1528-33.
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Ralph R. Kazer, M.D.
Department of Obstetrics and Gynecology
M.D., Tufts University School of Medicine
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Dr. Kazer maintains an ongoing interest in gynecologic disorders associated with insulin
resistance and enhanced activity of insulin-like growth factor-I (IGF-I). Prior studies
from his unit describing abnormalities of the growth hormone-IGF-I axis in women with
polycystic ovary syndrome were followed by studies indicating that such abnormalities were
not dependent on abnormal serum concentrations of sex steroids. Most recently, in
conjunction with other investigators on the Chicago campus, he has been exploring the
potential role of IGF-I as a mediator of diet-associated breast cancer risk.
Recent Publications:
Kazer RR 1995 Insulin resistance, insulin-like growth factor I and breast cancer: a hypothesis. Int J Cancer 62:403-406.
Kazer RR 1996 Breast cancer and the reproductive endocrinologist. Fertil Steril 65:470-471.
Kazer RR. Endometrial biopsy should be abandoned as a routine component of the infertility evaluation. Fertil Steril. 2004 Nov;82(5):1297-8.
Confino E, Zhang X, Kazer RR. GnRHa flare and IVF pregnancy rates. Int J Gynaecol Obstet. 2004 Apr;85(1):36-9.
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Ji-Yong Julie Kim
Department of Obstetrics and Gynecology
Ph.D.,
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Our laboratory is interested in better understanding the dynamic interaction that occurs between the conceptus and the mother that allow for the establishment and maintenance of pregnancy. The major focus of our research is on the molecular events that occur in the endometrium in response to early embryonic signals and the invading trophoblast. Aberrant expression of genes in the endometrium during this time is detrimental to the maintenance of pregnancy and could lead to miscarriages, spontaneous abortions and infertility. In response to pregnancy hormones and conceptus factors, the endometrium undergoes a major transformation, termed decidualization. During this process, the stromal cells of the endometrium express important genes. We're focusing on the regulation of a major secretory product of the decidualizing stromal cells, insulin-like growth factor binding protein-1 (IGFBP-1). IGFBP-1 modulates the actions of insulin-like growth factors (IGFs) which are critical during early pregnancy and can act independently of IGFs to regulate trophoblast invasion. Recently, we demonstrated that two transcription factors, FKHR and HOXA10, which have been demonstrated to be important in reproductive processes, interact with one another and upregulate the IGFBP-1 promoter in a cooperative manner in endometrial stromal cells. Based on this novel data, studies have been designed to further delineate the mechanisms involved in the cooperative upregulation of the IGFBP-1 promoter by FKHR and HOXA10. With the use of a powerful new technique, chromatin immunoprecipitation (ChIP), the binding sites for endogenous FKHR and HOXA10 proteins on the endogenous IGFBP-1 gene within the chromatin in the decidualized stromal cells are determined. This technique allows one to study interaction of transcription factors with the chromatin as they occur in situ. Using this technique we will also look at FKHR and HOXA10 proteins in non-pregnant and pregnant endometrium in order to demonstrate the influence of the conceptus on FKHR and HOXA10 expression and their activation of the IGFBP-1 gene. Finally, we have found in the eutopic endometrium of cases of endometriosis that FKHR and HOXA10 do not significantly activate the IGFBP-1 promoter. It is apparent that stromal cells from the endometrium of endometriosis are obviously different from that of a normal endometrium. These studies will give a better understanding of the molecular events that may be associated with increased implantation failure in women with endometriosis. These results from these studies will provide valuable insights into the molecular dynamics of the endometrium in response to pregnancy.
Recent Publications:
Kim, J.J., Taylor, H.S., Akbas, G.E., Foucher, I., Trembleau, A., Jaffe, R.C., Fazleabas, A.T., Unterman, T.G. (2003) Regulation of insulin-like growth factor binding protein-1promoter activity by FKHR and HOXA10 in primate endometrial cells. Biology of Reproduction 68(1):24-30.
Arosh, J.A., Banu, S.K., Chapdelaine, P., Emond, V., Kim, J.J., MacLaren, L.A., Fortier MA. (2003) Molecular Cloning and Characterization of Bovine Prostaglandin E(2) Receptors EP2 and EP4: Expression and Regulation in Endometrium and Myometrium during the Estrous Cycle and Early Pregnancy. Endocrinology 144(7):3076-3091.
Fazleabas, A.T., Kim, J.J. (2003) What makes an embryo stick?. Science 299:355-356.
Fazleabas, A.T., Kim, J.J. and Strakova, Z. (2004) Implantation: Embryonic signals and the modulation of the uterine environment. Placenta. 25 Suppl:S26-31.
Jasinska, A., Han, V., Fazleabas, A.T., Kim, J.J. (2004) Induction of Insulin-like growth factor-binding protein-1 in baboon endometrial stromal cells by cells of embryonic origin. J Soc Gyn Investig 11(6):399-405.
Kim J.J., Fazleabas, A.T. (2004) Uterine receptivity and implantation: The regulation and action of insulin-like growth factor binding protein-1 (IGFBP-1), HOXA10 and forkhead transcription factor-1 (FOXO-1) in the baboon endometrium. Reprod Biol Endocrinol. 2:34-39.
Fazleabas AT, Strakova Z, Kim JJ. Implantation in the baboon. Gynecol Obstet Invest. 2004;57(1):30-1.
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John J. Sciarra, M.D., Ph.D.
Department of Obstetrics and Gynecology
MD/PhD, Columbia University
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The interest of Dr. Sciarra and his colleagues in the Department of Obstetrics and Gynecology
at Northwestern University Medical School and Northwestern Memorial Hospital are in the
field of contraceptive research and development, fertility regulation and human
infertility including reproductive surgery.
Recent Publications:
Sciarra JJ. Specialist life-prof. John j. Sciarra. Eur J Obstet Gynecol Reprod Biol. 2004 Nov 10;117(1):121-2.
Sciarra JJ, Kaminetsky H, Keith LG, Williams CK. History of the International Journal of Gynecology & Obstetrics. Int J Gynaecol Obstet. 2004 Aug;86(2):236-63.
Sciarra JJ, Keith LG. FIGO and the IJGO 2003 and 2004. Int J Gynaecol Obstet. 2004 Jan;84(1):1-3.
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Lee Shulman, MD, FACOG, FACMG
Department of Obstetrics and Gynecology
M.D., Cornell University Medical College
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Lee P. Shulman MD is Professor and Head of the Section of Reproductive Genetics in the Department of Obstetrics and Gynecology at the Feinberg School of Medicine at Northwestern University in Chicago, Illinois. He received his bachelors degree from Cornell University and his medical degree from Cornell University Medical College. Dr. Shulman then completed his internship and residency in Obstetrics and Gynecology at North Shore University Hospital in New York, where he served as Chief resident during his final year. From there he completed a fellowship in Reproductive Genetics at the University of Tennessee, Memphis under the guidance of Drs. Joe Leigh Simpson and Sherman Elias. In 1989 he joined the Ob/Gyn faculty of the University of Tennessee, Memphis and became the Director of Reproductive Genetics in 1994. In 1999 he relocated to the University of Illinois at Chicago where he served as Deputy Head of the Department of Obstetrics and Gynecology, Director of the Divisions of Reproductive Genetics and Ambulatory Care Services and Practices and as Medical Director of the Center of Excellence in Women's Health.
Dr. Shulman is a diplomate of the American Board of Obstetrics and Gynecology and the American Board of Medical Genetics and a Fellow of the American College of Obstetricians and Gynecologists and a Founding Fellow of the American College of Medical Genetics. Among his current appointments are Senior Lecturer in the Departments of Obstetrics and Gynecology at Rush-Presbyterian-St.Luke's Hopsital/Rush University Medical School and the University of Illinois at Chicago.
Dr. Shulman is a member of numerous regional, national and international organizations that pertain to the health and care of women. He is the Editor-in-Chief of the emedicine.com textbook and the Yearbook of Obstetrics and Gynecology and is the Associate Editor of The Female Patient. He also serves on the editorial board of three other journals and as a peer-reviewer for 21 journals. A frequent contributor to the peer-reviewed and informational literature with over 100 peer-reviewed articles and over 40 book chapters, Dr. Shulman serves on governmental, foundation and pharmaceutical advisory boards and is currently on the Medical Advisory Board for the Chicago Center for Jewish Genetic Diseases. His major research focus is in reproductive genetics, contraception and medical education.
Recent Publications:
Booth NL, Nikolic D, van Breemen RB, Geller SE, Banuvar S, Shulman LP, Farnsworth NR. Confusion regarding anticoagulant coumarins in dietary supplements. Clin Pharmacol Ther. 2004 Dec;76(6):511-6. PMID: 15592321
Shulman LP. 17 beta-estradiol/levonorgestrel transdermal system. A viewpoint by Lee P. Shulman. Treat Endocrinol. 2004;3(5):325-6.
Shulman LP. The menopausal transition: how does route of delivery affect the risk/benefit ratio of hormone therapy? J Fam Pract. 2004 Jul;Suppl:S13-7.
Piersen CE, Booth NL, Sun Y, Liang W, Burdette JE, van Breemen RB, Geller SE, Gu C, Banuvar S, Shulman LP, Bolton JL, Farnsworth NR. Chemical and biological characterization and clinical evaluation of botanical dietary supplements: a phase I red clover extract as a model. Curr Med Chem. 2004 Jun;11(11):1361-74.
Philip J, Silver RK, Wilson RD, Thom EA, Zachary JM, Mohide P, Mahoney MJ, Simpson JL, Platt LD, Pergament E, Hershey D, Filkins K, Johnson A, Shulman LP, Bang J, MacGregor S, Smith JR, Shaw D, Wapner RJ, Jackson LG; NICHD EATA Trial Group. Late first-trimester invasive prenatal diagnosis: results of an international randomized trial. Obstet Gynecol. 2004 Jun;103(6):1164-73.
Shulman LP, Nelson AL, Darney PD. Recent developments in hormone delivery systems. Am J Obstet Gynecol. 2004 Apr;190(4 Suppl):S39-48.
Shulman LP, Harari D. Low-dose transdermal estradiol for symptomatic perimenopause. Menopause. 2004 Jan-Feb;11(1):34-9.
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Margrit Urbanek, Ph.D.
Endocrinology, Metabolism, and Molecular Medicine
Northwestern University Medical School
Ph.D., University of Pennsylvania
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Dr. Urbanek's research focuses on the identification of susceptibility genes for complex diseases. Her approach to this research is to use family based gene-mapping techniques in conjunction with molecular techniques to identify and verify genes and pathways contributing to the pathogenesis of genetically complex diseases. Specifically she is carrying out studies to identify susceptibility genes for polycystic ovary syndrome (PCOS) that map to Chr19p3.13. She has previously shown that this region shows linkage and association with PCOS in a large set of families. A second project focuses on identifying candidate genes for glycemic control during pregnancy and for gestational diabetes.
Research topics:
Identification of sequence variants in PCOS candidate genes.
Identification of candidate genes for impacting glycemic control during pregnancy and for gestational diabetes.
Linkage and family-based association studies.
Haplotype analysis.
Recent Publications:
Urbanek M, Du Y, Silander K, Collins FS, Steppan CM, Strauss JF, 3rd, Dunaif A, Spielman RS, Legro RS (2002) Variation in resistin gene promoter not associated with polycystic ovary syndrome (PCOS). Diabetes in press
Legro RS, Urbanek M, Kunselman AR, Leiby BE, Dunaif A (2002) Self-selected women with polycystic ovary yyndrome are reproductively and metabolically abnormal and under-treated. Fertil & Steril 78:51-7
Fujimoto T, Parry S, Urbanek M, Sammel M, Macones G, Kuivaniemi H, Romero R, Strauss, JF, 3rd, (2002) A single nucleotide polymorphism n the matrix metalloproteinase-1 (MMP-1) promoter influences amnion cell MMP-1 expression and risk for preterm premature rupture of the fetal membranes. J Biol Chem 277:6296-302
Weiss MJ, Guo C, Shusterman S, Hii G, Mirensky TL, White PS, Hogarty MD, Rebbeck TR, Teare D, Urbanek M, Brodeur GM, Maris JM. (2000) Localization of a hereditary neuroblastoma predisposition gene to 16p12-p13. Med Pediatr Oncol 35:526-30
Urbanek, M, Legro, RS, Driscoll, DA, Strauss, JF, 3rd, Dunaif, A, Spielman, RS (2000) Searching for the Polycystic Ovary Syndrome Genes. J Ped Endocrinol & Metab 13:1311-1313.
Urbanek, M, Wu, X, Vickery, KR, Kao, LC, Christenson, LK, Schneyer, A, Legro, RS, Driscoll, DA, Strauss, JF, 3rd, Dunaif, A, Spielman, RS (2000) Allelic variants of the follistatin gene in polycystic ovary syndrome. J Clin Metab & Endocrinology. 85(12):4455-61.
Feldman, G, Li, M, Martin, S, Urbanek, M, Urtizberea, JA, Fardeau, M, LeMerrer, M, Connor, JM, Triffitt, J, Smith, R, Muenke, M, Kaplan, FS, Shore, EM (2000) Fibrodysplasia ossificans progressiva, a heritable disorder of severe heterotopic ossification, maps to human chromosome 4q27-31. Am J Hum Genet. 66(1):128-135
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