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Letter from the Directors

Reproductive Science at Northwestern

Administration & Faculty

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CRS Members, Students, Research Staff, and Support Personnel

Grants

Seminars

Minisymposium

Newsletter and Announcements

Training Programs for Undergraduate, Graduate, & Post-Docs

Marcia L. Storch Scholarship Fund for Undergrad Women

CRS Go-to-Meeting Travel Award for Undergraduates

Sites of Interest

Support CRS


Newsletter

A publication of the Center for Reproductive Science
Northwestern University, Evanston and Chicago
Spring 2004 Volume 1 No. 6


From the Director
Seminars
Marcia L. Storch MD Scholarship Fund for Undergraduate Women
Travel Awards for Undergrads
CRS Undergraduate Achievements
Recent Ph.D. Graduates
Faculty & Interest Areas
Research Notes
Minisymposium
Recent Publications
CRS Faculty Honors


From the Director

I am very pleased to inform you that the CRS Executive Committee has approved 7 new faculty for membership in the Center. Serdar Bulun, Sherman Elias, Julie Kim and Lee Shulman join us from Obstetrics & Gynecology; Caroline Bledsoe from Anthropology; Joseph Bass from Medicine/ENH; and Margrit Urbanek from Endocrinology, Metabolism & Molecular Medicine. Please join me in welcoming them all into the Center. To find out more about their research interests, visit the CRS website!

Our October Minisymposium was a great success, and this issue includes information about the event and the various trainee award winners. It is hard to believe that the 2004 Minisymposium is just around the corner- October 18, 2004 to be precise. This will be the 25th annual Minisymposium on Reproductive Biology, a significant event in the history of the Center. Our keynote speaker will be Dr. William Crowley from the Massachusetts General Hospital. Please mark your calendars now!

I am also happy to inform you that two of our long-standing CRS grants were successfully renewed in the last few months. The "Training Program in Reproductive Biology" (Jon Levine, P.I.) was renewed for years 26-30, while the Program Project Grant "Hormonal Signals that Regulate Ovarian Differentiation" (Mary Hunzicker-Dunn, P.I.) was renewed for years 16-20. Congratulations to Jon and Mary!

Finally, remember - with growing concern about an increasing world population and a deteriorating environment:

    Finally, remember - with growing concern about an increasing world population and a deteriorating environment---reproduction matters!
Kelly Mayo, Director   


Seminars 

March 22, 2004 - Art Arnold from UCLA School of Medicine. Seminar Title: "Sex differences in the brain: Are XX and XY brain cells equivalent?" At 3:45 p.m. in Pancoe Auditoriuam, 2000 Campus Drive, Evanston Campus.

March 23, 2004 - Humphrey Yao from University of Illinois, Urbana. Seminar Title: "Emerging evidence of active signaling during mammalian ovary organogenesis." At 4:00 p.m. in Room 2-058, Cook Hall, Evanston Campus.

May 3, 2004 - Evan Simpson from Prince HenryÕs Institute of Medical Research, Clayton, Victoria, Australia. Seminar Title: "Life without estrogens - the gonads of mice and men with deficiency." At 3:00 p.m. in Room 407, Wieboldt Hall, Chicago Campus.

May 10, 2004 - Richard Schultz from the University of Pennsylvania. Seminar Title: "RNAi in mouse oocytes and embryos." At 3:45 p.m. in Room 2-058, Cook Hall, Evanston Campus.

May 24, 2004 - John H. Nilson from Washington State University. Title: "TBA." At 3:45p.m. in Room 2-058, Cook Hall, Evanston Campus.

The 16th Chicago Transduction Symposium will be held on May 20, 2004 at NorthwesternÕs Chicago Campus. For further information and registration forms see: http://www.pharm.northwestern.edu/SignalTransduction/SYMPOSIUMWELCOMPAGE.html


Awards for Undergraduate Research

Marcia L. Storch MD Scholarship Fund for Undergraduate Women
Before her death from ovarian cancer Dr. Marcia Storch expressed the wish that contributions be sent to the Center for Reproduction Science at Northwestern University to establish a fund to encourage undergraduate women to study the basic physiology and biochemistry to the ovary. With contributions we have received the Center invites applications from undergraduate women working in the laboratories of Center faculty. A committee will review the applications, which should include a brief description of projected work and a statement from the advisor, and budget for supplies (not to exceed $400). Please submit supporting documents to Dr. Kelly Mayo, Center for Reproductive Science, Hogan 2-171, 2205 Tech Drive, Evanston campus by June 1st , 2004.

CRS Go-to-Meeting Travel Award for Undergraduates
A
number of undergraduates at Northwestern work in the research laboratories of Center faculty. We have started a fund to enable some of them to attend professional meetings with their preceptors and other lab members. We invite applications for travel for the year 2004 meetings. Undergraduates should submit a letter outlining their research project and a description of the meeting to which they wish to go. They should also estimate the travel cost. Faculty advisors should countersign the documents. Please submit supporting documents by June 1
st , 2004 to Dr. Kelly Mayo, Center for Reproductive Science, Hogan 2-171, 2205 Tech Drive, Evanston campus.

Undergraduate Student Achievements
Molly Morgan
, with Jon Levine, was awarded the Constance Campbell Research Award in May 2003 in the Biological Sciences for her research entitled, "Role of neuropeptide Y1 receptors in the regulation of reproductive hormone secretion".
Daniel Balkin, with Teresa Woodruff, received the Erwin Macey Scholarship in the Life Sciences in Summer 2003.
Sudhi Kurup, with Teresa Woodruff, received an Endocrine Society Summer 2003 Fellowship. She graduated December 2003, with an Honor Thesis, "Mutational analysis of activin A at the Activin A:ActRIIB luteface and a putative ALK4-binding site".


wpe3.gif (1380 bytes)Recent Ph.D. Graduates

Jaqueline Jeruss (with Teresa Woodruff) "The role of activin in mammary gland development and breast cancer progression."
Jose Santiago
(with Teresa Woodruff) "TGF-b superfamily signaling systems in ovarian cancer".
Beiyan Zhou (with Dan Linzer) "Two placental hematopoietic cytokines: PLP-E and PLP-F".
Dr. Sarah Leupen, formerly with Jon Levine, has recently accepted a position as Assistant Professor in the Biology Department of the Ohio Weslyan University in Delaware.


CENTER FOR REPRODUCTIVE SCIENCE
FACULTY & INTEREST AREAS

Testis Function
James Bartles, Cell & Molecular Biology
Erwin Goldberg, Bio Chem Mol & Cell Biology
Richard Scarpulla, Cell & Molecular Biology

Pituitary Function
J. Larry Jameson, Medicine
Neena Schwartz, Neurobiology & Physiology
Jeffrey Weiss, Endocrine, Metabolism & Molecular Medicine

Circadian Rhythms
Joseph Takahashi, Neurobiology & Physiology
Fred Turek, Neurobiology & Physiology
Teresa Horton, Neurobiology & Physiology

Neural Control of Sexual Function
Kevin McKenna, Physiology

Prostate Biology
Chung Lee, Urology
Robert E. Brannigan, Urology
Zhou Wang, Urology
Neuroendocrinology
George Flouret, Physiology
Jon Levine, Neurobiology & Physiology
Thomas W. McDade, Anthropology
Eva Redei, Psychiatry & Behavioral Science
Catherine Woolley, Neurobiology & Physiology

Clinical Fertility & Infertility
Serdar Bulun, Obstetrics & Gynecology
Sherman Elias, Obstetrics & Gynecology
Ralph Kazer, Obstetrics & Gynecology
Julie Kim, Obstetrics & Gynecology
John Sciarra, Obstetrics & Gynecology
Lee P. Shulman, Obstetrics & Gynecology
Margrit Urbanek, Endocrine, Metabolism & Molecular Medicine

Growth & Development
Joe Bass, Medicine
Gerhard Baumann, Medicine
Daniel Linzer, Bio Chem Mol & Cell Biology
Kelly Mayo, Bio Chem Mol & Cell Biology
H. William Schnaper, Pediatrics
Warren Tourtellotte, Pathology

Infection & Inflammation
Emmet Hirsch, Obstetrics & Gynecology/ENH

Ovarian Function
 

Reproduction & Society
Caroline Bledsoe, Anthropology

Steroid Hormones & Receptors
Magdy Milad, Obstetrics & Gynecology
V. Craig Jordan, Cancer Center


CRS - RESEARCH NOTES
 

CRS researcher explores the molecular pathology of premature labor
Emmet Hirsch, M.D.
Dr. Hirsch is an Associate Professor at Evanston Northwestern Healthcare Research Institute, Department of Obstetrics & Gynecology, Northwestern University

Premature birth is the major cause of neonatal morbidity and mortality in the developed world, accounting for at least 75% of neonatal deaths that are not due to congenital malformations. An infant weighing less than 3.3 pounds at birth is approximately 200 times more likely to die in the first year of life than an infant weighing more than 5.5 pounds. This immense toll in loss of life is compounded by the suffering endured by survivors of premature birth. Neonates who survive preterm delivery are 10 times more likely than are term babies to be neurologically impaired and are more likely to suffer mental retardation, blindness, deafness, chronic lung disease and cerebral palsy. It was estimated that in 1988 there were 4 million low-birth-weight children aged 0-15 in the US and that the cost to society of caring for them was 5.4 billion dollars. Prematurity affects approximately 10% of all deliveries in the United States, or 390,000 women yearly. By comparison, the American Cancer Society predicted that in 2003 there would be 1.3 million new cases of all types of cancer, and the Centers for Disease Control and Prevention reported 42,745 new cases of AIDS in 2002.

Given the magnitude of this problem, it is remarkable that the rate of prematurity in the United States has not fallen over the last five decades and in fact has been rising in recent years. In part this is due to our lack of understanding of the complex interactions of fetal and maternal systems required for both normal and abnormal labor. This knowledge deficit in turn has contributed to the paucity of effective interventions to either prevent preterm labor or to treat it once it has occurred.

Preterm birth is the major cause of neonatal morbidity and mortality in developed countries!

The main thrust of Dr. HirschÕs research is to advance the state of knowledge of the mechanisms underlying preterm labor, with a focus on bacterial infection (the cause of up to 30-40% of cases). Using mouse models and data and tissue samples obtained from pregnant women, members of his lab are investigating the roles of the uterus, fetus and placenta in this process. Ongoing work includes the use of mutant animals with altered expression of candidate critical factors (knockout and transgenic mice). A DNA microarray chip experiment is being used to characterize on a global scale the maternal and fetal signals important for preterm labor. This technology will help generate large and unique gene expression databases of laboring human and mouse pregnancy tissues.

Recent studies in Dr. HirschÕs lab have focused on the roles of inflammatory mediators such as interleukin 1, tumor necrosis factor (TNF), prostaglandins and members of the innate immune systemÕs recognition pathway for bacterial pathogens (toll-like receptors and their downstream mediators). Data from the lab were the first to demonstrate that interleukin 1 is not an essential mediator of bacterially induced preterm labor, although it plays a critical role together with TNF. Important distinctions between fetal and maternal gene expression have led to novel insights regarding the relative roles of the fetus and mother in initiating labor. Other studies have shown that the expression of prostaglandins (long considered the central downstream player in generating uterine contractions) is regulated via altered degradation rather than altered production.

The goal of these studies is to improve our understanding of the physiology and pathophysiology of parturition. Once the critical fetal and maternal signals responsible for labor have been defined, those factors can be used to develop therapeutic targets.


A cDNA microarray comparing gene expression in the uteruses of mice in preterm labor to normal controls


MINISYMPOSIUM Ð 2003

The 24th Annual Minisymposium on Reproductive Biology took place on October 20, 2003, at the Omni Orrington Hotel in Evanston. 35 trainees presented their work in oral platform presentations and in the poster session. In addition to presenters from the Chicago and Evanston campuses of Northwestern, papers were given by trainees from the University of Illinois (Chicago and Urbana campuses), the University of Chicago ChildrenÕs Hospital, Rush Medical College, the University of Wisconsin-Madison, and the Chicago Medical School. The day ended with the keynote address by Dr. Louis J. Guillette, Jr., Distinguished Professor of Zoology and Associate Dean of Research at the University of Florida. Dr. GuilletteÕs research focuses on the mechanism by which environmental factors influence the evolution, development and functioning of the reproductive systems in vertebrates.  His talk was titled, "New Lessons from an Old Beast: Alligators, Contaminants and Reproductive Biology".

Six Constance Campbell Memorial Awards are presented at the end of the meeting: 1st, 2nd and 3rd place prizes in both the oral presentation and poster categories. This yearÕs winners were:

Oral Presentations
First Place:
Anna D. Burkart (Northwestern University). The title of her talk was, "Multiple mechanisms of repression of the inhibin a subunit gene by the transcription factor C/EBPb".
Second Place: Denise Holsberger (University of Illinois at Urbana-Champaign).  The title of her talk was, "Cell cycle inhibitors p27kip1 and p21Cip1 regulate Sertoli cell proliferation".
Third Place: Pamela K. Kreeger (Northwestern University). The title of her talk was, "Collagen type I improves survival and stimulates granulose-oocyte complex growth in vitro".

Poster Presentations
First Place (jointly):
Jingjing Liu Kipp and Sarah Bristol (Northwestern University). The title of their poster was, "Neonatal genistein exposure induces multi-oocytic follicles and alters activin subunit gene expression in wild type and inhibin a transgenic mouse ovaries".
Second Place Veronica Ledoux (Northwestern University). The title of her poster was, "Ultrastructural correlates of estrogen-induced disinhibition of CAI pyramidal cells".
Third Place:  Vimal Selvaraj (University of Illinois). The title of his poster was, "Gene expression profiling of 17b-estradiol and genistein effects on the mouse thymus".

The Symposium was organized by a committee of CRS trainees: Sumit Bhattacharyya, Jingjing Kipp (Chair), Christine Lauay, Brooke Miller and Susan Park, under the supervision of Muhkthar Rafiqi and Susan-Hall Perdomo.
The general consensus after every Minisymposium has been that the papers and posters presented by our trainees equal or exceed in quality those presented at national professional meetings, and that the meeting serves as an excellent training ground for our students. Thanks you all for your support of the 24
th Minisymposium, and put on your calendar the date for the 25th , October 18, 2004!

 


RECENT PUBLICATIONS

Loomis PA, Zheng L, Sekerkova G, Changyaleket B, Mugnaini E, Bartles JR. Espin cross-links cause the elongation of microvillus-type parallel actin bundles in vivo. J Cell Biol. 2003 Dec 8;163(5):1045-55.
Quing-xin, H, Wilken, J, Nakagawa, S, Ramos, MR, Jia, W, Bass J, and Weiss MA. A divergent invertebrate protein structurally resembles human insulin and activates the human insulin receptor. 2003. Genes and Development 17:826-831 (Perspective p813-818).
Jang TL, Yap RL, Batler RA, Brannigan RE. Intraperitoneal bladder rupture and bowel injury from perirectal impalement. J Urol. 2003 Dec;170(6 Pt 1):2383-4.
Maheshwari, H.G., Bouillon, R., Nijs, J., Oganov, V.S., Bakulin, A.V., Baumann, G. The Impact of Congenital, Severe, Untreated Growth Hormone (GH) Deficiency on Bone Size and Density in Young Adults: Insights from Genetic GH-Releasing Hormone Receptor Deficiency. J. Clin. Endocrinol. Metab. 88:2614-2618, 2003.
Bulun SE. Ovulation induction in women with infertility: a new indication for aromatase inhibitors. Fertil Steril. 2003 Dec; 80(6): 1338; discussion 1339.
Chatterton, R.T., Jr., Geiger, A.S., Gann, P.H., and Khan, S.A. Formation of estrone and estradiol from estrone sulfate by normal breast parenchymal tissue. J. Steroid Biochem. Mol. Biol. 86:159-166, 2003.
Sam S, Dunaif A. Polycystic ovary syndrome: syndrome XX? Trends Endocrinol Metab. 2003 Oct;14(8):365-70.
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.
Flouret G, Chaloin O, Slaninova J. Analogues of a potent oxytocin antagonist with truncated C-terminus or shorter amino acid side chain of the basic amino acid at position 8. J Pept Sci. 2003 Jun;9(6):393-401.
Kroft TL, Li S, Doglio L, Goldberg E. A transgenic analysis of mouse lactate dehydrogenase C promoter activity in the testis. J Androl. 2003 Nov-Dec;24(6):843-52
Wang H and Hirsch E. Bacterially induced preterm labor and regulation of prostaglandin metabolizing enzyme expression in mice: the role of toll-like receptor 4. Biol Reprod published 6 August 2003; 10.1095/biolreprod.103.019620 .
Anand S, Turek FW, Horton TH. Chemosensory Stimulation of Luteinizing Hormone Secretion in Male Siberian Hamsters (Phodopus sungorus). Biol Reprod. 2003 Nov 26.
Cottom J, Salvador L, Maizels ET, Reierstad S, Park Y, Carr D, Davare MA, Hell J, Dent P, Palmer S, Kawakatsu H, Ogata M, and Hunzicker-Dunn M (2003) Follicle Stimulating Hormone Stimulates Activation of Extracellular Regulated Kinases via Protein Kinase A-Dependent Phosphorylation of a 100 kDa Phosphotyrosine Phosphatase , J Biol Chem 278, 7167-7179.
Weiss J, Meeks JJ, Hurley L, Raverot G, Frassetto A, Jameson JL. Sox3 is required for gonadal function, but not sex determination, in males and females. Mol Cell Biol. 2003 Nov; 23(22):8084-91.
Bentrem D, Fox JE, Pearce ST, Liu H, Pappas S, Kupfer D, Zapf JW, Jordan VC. Distinct molecular conformations of the estrogen receptor alpha complex exploited by environmental estrogens. Cancer Res. 2003 Nov 1;63(21):7490-6.
Zhang X, Barnes R, Confino E, Milad M, Puscheck E, Kazer RR. Delay of embryo transfer to day 5 results in decreased initial serum beta-human chorionic gonadotropin levels. Fertil Steril. 2003 Dec;80(6):1359-63.
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.
Zhou W, Park I, Pins M, Kozlowski JM, Jovanovic B, Zhang J, Lee C, Ilio K. Dual regulation of proliferation and growth arrest in prostatic stromal cells by transforming growth factor-beta1. Endocrinology. 2003 Oct.144(10):4280-4.
Schneider JS, Stone MK, Wynne-Edwards KE, Horton TH, Lydon J, OÕMalley B, Levine JE. Progesterone receptors mediate male aggression toward infants. Proc Natl Acad Sci U S A. 2003 Mar 4.100(5):2951-6.
McDade TW. Life history theory and the immune system: Steps toward a human ecological immunology. Am J Phys Anthropol. 2003;Suppl 37:100-25.
Podlasek CA, Zelner DJ, Harris JD, Meroz CL, Tang Y, McKenna KE, McVary KT. Altered Sonic hedgehog signaling is associated with morphological abnormalities in the penis of the BB/WOR diabetic rat. Biol Reprod. 2003 Sep;69(3):816-27.
Runyan CE, Schnaper HW, Poncelet AC. The PI3K-Akt pathway enhances Smad3-stimulated mesangial cell collagen I expression in response to TGF-beta 1. J Biol Chem. 2003 Nov 10.
Sciarra JJ, Valle RF. Endometriosis: treatment strategies. Ann N Y Acad Sci. 2003 Nov. 997:229-39.
Shulman LP, Goldzieher JW. The truth about oral contraceptives and venous thromboembolism. J Reprod Med. 2003 Nov;48(11 Suppl):930-8.
Kolker DE, Fukuyama H, Huang DS, Takahashi JS, Horton TH, Turek FW. Aging alters circadian and light-induced expression of clock genes in golden hamsters. J Biol Rhythms. 2003 Apr;18(2):159-69.
Feng Jiang and Zhou Wang: Identification of androgen-response genes in the rat ventral prostate using cDNA subtraction and microarray. Endocrinology, 144:1257-65, 2003.
Chapman SC, Woodruff TK 2003. Betaglycan localization in the female rat pituitary: Implications for the regulation of FSH by inhibin. Endocrinology. 2003 Dec;144(12):5640-9.
Rudick CN, Woolley CS. Selective estrogen receptor modulators regulate phasic activation of hippocampal CA1 pyramidal cells by estrogen. Endocrinology. 2003 Jan;144(1):179-87.


CRS Faculty Honors

CRS member G. Baumann was listed in "WhoÕs Who in America" and also listed in "AmericaÕs Top Physicians".

CRS member Mary Hunzicker-Dunn was elected President of the Society for the Study of Reproduction. Mary is also an Associate Editor of Molecular Endocrinology. She is on the editorial board of Endocrine Reviews.

CRS member V. Craig Jordan was given the NAMS/Eli Lilly award which recognizes research in any area including osteoporosis, raloxifene and SERM action. Dr. JordanÕs work on tamoxifen, raloxifene and selective estrogen receptor modulators (SERMs) was also honored with the Third George and Christine Sosnovsky Award from the Royal Society of Chemistry (UK) which recognizes land mark achievements in the medicinal chemistry of cancer diseases. In addition, Dr. Jordan received the Charles F. Kettering Prize. It is the highest cancer prize in the world and is given by the General Motors Cancer Research Foundation. The award recognizes Dr. JordanÕs role in the development of tamoxifen that has resulted in the survival of thousands of women with breast cancer.

CRS member Chung Lee was presented with the 2003 Distinguished Preceptor Award by the American Foundation in Urological Disease/American Urological Association.

The Medical School established the John J. Sciarra Professorship after CRS member John Sciarra. He also received the Honorary Fellowship from the Ghana College of Physicians and Surgeons.

CRS member Zhou Wang was named the OÕConnor Family Research Professor of Urology.

CRS member Kelly Mayo was the recipient of the Beacon Award in Reproductive Science.

CRS member Joseph Takahashi was elected Member of the National Academy of Sciences and also received the W. Alden Spencer Award from the Columbia University.

CRS member Catherine S. Woolley was the recipient of the Distinguished Young Scholar in Medical Research Award from the W.M. Keck Foundation.

CRS member J. Larry Jameson was elected Member of the American Clinical and Climatological Association.
 

CRS congratulates each of these individuals for this recognition of their outstanding achievements!




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