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CRS Members (N-Z) ... CRS Members
(A-M)
Redei, Eva | Scarpulla, R.C.
| Schnaper, H.W. Schwartz,
N.B | Sciarra, J.J. | Shea,
Lonnie | Shulman, Lee P. | Stack,
Sharon M. | Takahashi,J.S. | Tourtellotte,
Warren | Turek, F.W. | Urbanek
| Wang, Xiaobin | Wang, Zhou
| Weiss, J. | Woodruff, T.K.
| Woolley, C.S. | Xu, E.Y. |
Zoloth, Laurie
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Eva Redei, Ph.D.
Departments of Phychology & Behavioral Sciences
and Molecular Pharmacology & Biological Chemistry
Ph.D., Eotvos Lorand University, Budapest, Hungary
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The major focus of our research is to elucidate the
molecular mechanisms of vulnerability to stress and to depression. One focus of our
research is related to the recent characterization of the biological activity of a
hypothalamic neuropeptide, prepro-TRH 178-199. This peptide inhibits ACTH and prolactin
response to stress and shows anxiolytic and antidepressant activity in animal models of
these behaviors. Ongoing work is aimed to clone the receptor for rat prepro-TRH 178-199
and its human analog, human prepro-TRH 158-183.
A second area of research is focused on the characterization of the inbred Wistar Kyoto
(WKY) rat as a genetic animal model of depressive behavior and stress hyper-reactivity.
This strain exhibits depressive-like behavior in numerous behavioral tests and exhibits
hormonal abnormalities that are similar to those associated with depressive disorder in
humans. These behavioral and hormonal differences between WKY and other inbred strains
serve as phenotypes for quantitative trait loci (QTL) analysis, which we have recently
started. Wistar Kyoto rats are also used to identify novel vulnerability genes that are
expressed differentially in the amygdala and frontal cortex, brain regions involved in the
psychopathology of human affective disorders, of “depressed” versus less “depressed”
animals using the differential display RT-PCR technique.
We have been also investigating how environmental challenges in utero, such as fetal
alcohol exposure, can lead to altered, and sexually dimorphic changes in the adult
offspring neuroendocrine and immune functions. In addition to studying the biochemical
mechanisms by which fetal alcohol exposure affects stress-responsiveness of the adult
offspring, we are also studying its behavioral consequences. As early developmental,
environmental insult seems to play a major role in depressed behavior in adulthood, and
fetal alcohol exposure and prenatal stress share a common neuroendocrine “imprinting”
mechanism, this approach could provide important information on where and when the
developing fetus acquires changes in the expression of specific genes that contribute to
this vulnerability later in life.
Recent Publications:
Baum AE, Solberg LC, Kopp P, Ahmadiyeh N, Churchill G, Takahashi JS, Jameson JL, Redei EE. Quantitative Trait Loci Associated with Elevated TSH in the Wistar-Kyoto Rat. Endocrinology. [Epub 2004 Oct 28].
Solberg LC, Baum AE, Ahmadiyeh N, Shimomura K, Li R, Turek FW, Churchill GA, Takahashi JS, Redei EE. Sex- and lineage-specific inheritance of depression-like behavior in the rat. Mamm Genome. 2004 Aug;15(8):648-62.
Redei EE. Old principles in new clothes. Pharmacogenomics J. 2004;4(4):219.
Slone-Wilcoxon J, Redei EE. Maternal-fetal glucocorticoid milieu programs hypothalamic-pituitary-thyroid function of adult offspring. Endocrinology. 2004 Sep;145(9):4068-72.
Ahmadiyeh N, Slone-Wilcoxon JL, Takahashi JS, Redei EE. Maternal behavior modulates X-linked inheritance of behavioral coping in the defensive burying test. Biol Psychiatry. 2004 Jun 1;55(11):1069-74.
Wilcoxon JS, Redei EE. Prenatal programming of adult thyroid function by alcohol and thyroid hormones. Am J Physiol Endocrinol Metab. 2004 Aug;287(2):E318-26. Epub 2004 Apr 27.
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Richard C. Scarpulla, Ph.D.
Department of Cell and Molecular Biology
Ph.D., Albert Einstein College of Medicine
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The capacity for oxidative metabolism is a fundamental property of the differentiated state
that varies widely among animal cells and tissues. Differences in respiratory function in
both normal cells and in a variety of cellular pathologies are reflected in the number,
size, and morphology of mitochondria as well as in the expression of respiratory gene
products. A fundamental issue is how the biosynthetic activities of nuclear and
mitochondrial genetic systems are coordinated to meet cellular energy demands. Because of
the limited coding capacity of the mitochondrial genome, oxidative function relies upon
nuclear genes for the majority of respiratory subunits and all of the gene products
required for the transcription and replication of mitochondrial DNA (mtDNA).
Characterization of mammalian genes encoding the respiratory cytochromes has led to the
discovery of nuclear respiratory factors (NRFs). These nuclear transcriptional activators
promote the expression of genes encoding both respiratory subunits and key components of
the mtDNA transcription and replication machinery. These observations have led to the
hypothesis that NRFs may be the targets of extra- and intracellular signaling pathways. As
such, they would relay regulatory signals to the mitochondria via their activation of
nuclear genes and also communicate the oxidative state of the cytoplasm to the nuclear
transcriptional apparatus. In this way NRFs may serve to integrate nuclear and
mitochondrial genetic systems to accommodate cellular demands for respiratory energy. Our
long term objectives are to further define the molecular interactions and physiological
functions of NRFs and related activators.
Recent Publications
Gleyzer N, Vercauteren K, Scarpulla RC. Control of Mitochondrial Transcription Specificity Factors (TFB1M and TFB2M) by Nuclear Respiratory Factors (NRF-1 and NRF-2) and PGC-1 Family Coactivators. Mol Cell Biol. 2005 Feb;25(4):1354-66.
Cam H, Balciunaite E, Blais A, Spektor A, Scarpulla RC, Young R, Kluger Y, Dynlacht BD. A common set of gene regulatory networks links metabolism and growth inhibition. Mol Cell. 2004 Nov 5;16(3):399-411.
Kelly DP, Scarpulla RC. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev. 2004 Feb 15;18(4):357-68.
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H. William Schnaper, M.D.
Department of Pediatrics
M.S., University of Maryland
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The
interests of our laboratory center upon the regulation of endothelial cell angiogenic
activity by estrogen. We have determined that estrogen augments human endothelial cell
migration, proliferation, attachment to extracellular matrix proteins, and differentiation
into capillary-like structures in vitro. In a murine in vivo model, estrogen
augments actual angiogenesis induced by basic fibroblast growth factor (bFGF), a major
participant in angiogenic pathways. These activities may play an important role in growth
of decidual tissue during the menstrual cycle and in placental development during
gestation.
We have identified a
functional estrogen receptor in human endothelial cells that appears to modulate cell
function via a classical steroid hormone receptor mechanism. In one model system, we have
determined that estrogen stimulates delayed induction of mitogen-activated protein kinase
(ERK 1/2) activity, probably via an autocrine loop involving bFGF. A major goal of the
laboratory is to identify upstream and downstream elements of this signaling cascade and
to determine the role each plays in regulating endothelial cell activity.
Recent Publications:
Runyan CE, Schnaper HW, Poncelet AC. The role of internalization in TGF-beta 1-induced Smad2 association with SARA and Smad2-dependent signaling in human mesangial cells. J Biol Chem. 2004 Dec 21; PMID: 15613484
Hayashida T, Schnaper HW. High ambient glucose enhances sensitivity to TGF-beta1 via extracellular signal--regulated kinase and protein kinase Cdelta activities in human mesangial cells. J Am Soc Nephrol. 2004 Aug;15(8):2032-41.
Runyan CE, Schnaper HW, Poncelet AC. The phosphatidylinositol 3-kinase/Akt pathway enhances Smad3-stimulated mesangial cell collagen I expression in response to transforming growth factor-beta1. J Biol Chem. 2004 Jan 23;279(4):2632-9.
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Neena B. Schwartz, Ph.D.
Department of Neurobiology and Physiology
Ph.D., Northwestern University
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We are interested in the factors that regulate the secretion of the
gonadotropic hormones luteinizing hormone (LH) and follicle stimulating hormone (FSH) by
the anterior pituitary gland. Negative and positive feedback hormonal signals from
the testis or ovary are important. Feedforward neuropeptide signals from the brain are
also important, and gonadotropin releasing hormone (GnRH) is a well established and
necessary signal from the hypothalamus. Our laboratory pioneered in demonstrating that
estradiol and progesterone are inadequate negative feedback signals for suppression of
FSH in the female lacking ovaries, and discovered a gonadal peptide inhibin,
necessary for proper suppression of FSH. We have used GnRH antagonists to
demonstrate relative lack of dependence of FSH on endogenous GnRH in males and
females. We are currently investigating sex differences in hypothalamic and pituitary
function, in vivo and in an in vitro perifusion organ culture system.
Another discovery from the laboratory is that glucocorticoid hormones from the adrenal
differentially affect LH and FSH in vivo and in vitro, suppressing LH
secretion and enhancing FSH synthesis and secretion. These steroids are an important tool
in examining the mode by which the gonadotrope cell can separately synthesize and secrete
LH and FSH, and we are studying the effects in pituitaries in vivo and in vitro,
measuring gonadotropin secretion rates and gene transcription levels, as well as direct
glucocorticoid effects on the gene for the rat FSH-beta subunit. We are also investigating the interactions among progesterone receptors, activin and steroids on FSH
synthesis and secretion.
Recent Publications:
Schwartz NB 1995 Follicle stimulating hormone and luteinizing hormone:
a tale of two gonadotropins. Can J Physiol Pharmacol 73(6):675-684.
Szabo M, Knox KL, Ringstrom SJ, Perlyn CA, Sutandi P, Schwartz NB 1996
Mechanism of the inhibitory action of RU486 on the secondary follicle-stimulating
hormone surge. Endocrinology 137:85-89.
Kilen SM, Szabo M, Strasser GA, McAndrews JM, Ringstrom SJ, Schwartz NB
1996 Corticosterone selectivity increases FSH subunit primary anterior pituitary cell
culture without affecting its halflife. Endocrinology 137:3802-3807.
Ringstrom SJ, Szabo M, Kilen SM, Saberi S, Knox KL, Schwartz NB 1997
The antiprogestins RU486 and ZK98299 affect follicle-stimulating hormone secretion
differently on estrus, but not on proestrus. Endocrinology 138:2286-2290.
Schwartz, Neena B. 1999 Neuroendocrine
regulation of reproductive cyclicity,. In: Neuroendocrinology in Physiology and
Medicine P.M. Conn and M.E. Freeman, Eds.), Humana Press Inc., Totowa, NJ, pp
135-145.
Szabo, M., Kilen, S.M., Nho, J. and
Schwartz, N.B. 2000 Progesterone receptor A and B messenger ribonucleic acid levels in the
anterior pituitary of rats are regulated by estrogen. Biol. Reprod.,
62:95-102.
Bohnsack, B.L., Kilen, S.M., Tam, D.H.Y. and Schwartz, N.B. 2000 Follistatin suppresses steroid-enhanced follicle-stimulating
hormone release in vitro. Biol. Reprod., 62:636-641.
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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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Lonnie Shea, PhD
Department of Chemical and Biological Engineering
PhD, University of Michigan
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My laboratory develops and employs biomaterials and controlled delivery (protein, DNA) systems to create synthetic environments for directing and analyzing cellular functions, which have applications to tissue regeneration and development, and diagnostics assays. Biomaterial scaffolds can create three-dimensional culture environments that regulate cell-cell and cell-matrix interactions, and to provide a controlled release of protein and DNA. In a highly collaborative project with Teresa Woodruff, we are developing scaffolds for the in vitro maturation of ovarian follicles. Follicles from several stages of development are encapsulated within designer hydrogels, cultured, and the resulting oocyte are isolated and examined for meiotic competence and fertilization. This system is being applied to examine the basic biology underlying follicle development, and may provide a critical technology that will enable the preservation of fertility for chemotherapy-induced sterility or other reproductive disorders.
Recent Publications:
P.K. Kreeger, J. Deck, T.K. Woodruff, and L.D. Shea. ÒReconstructed Basement Membrane Regulation of Murine Follicle Maturation in a Three-Dimensional Culture System.Ó Society for the Study of Reproduction. Vancouver, Canada. August 2004. USDA Merit Award
P.K. Kreeger, C.B. Berkholtz, N.N. Fernandes, T.K. Woodruff, and L.D. Shea,. ÒGonadotrophin Supplementation Enhances Development for Murine Preantral Follicles Cultured in a Three-Dimensional System.Ó Society for the Study of Reproduction. Vancouver, Canada. August 2004.
Berkholtz, C.B., T.K. Woodruff, and L.D. Shea ÒNGF enhances survival in 3D primary follicle cultures in vitro.Ó Society for the Study of Reproduction. Vancouver, Canada. August 2004
Kreeger, P.K., "Alginate Scaffolds for the Culture of Ovarian Follicles in a Stage Specific Manner" 2004 Annual AIChE meeting, Austin, TX, November 2004, Meet the Faculty Candidates
Whittlesey, K.J., C. Rives, L. De Laporte, and L.D. Shea, ÒDegradable Multilumen Scaffolds To Potentiate Regeneration By Gene DeliveryÓ Society for Neuroscience, November 2004.
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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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M. Sharon Stack, Ph.D.
Cell & Molecular Biology
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Recent Publications:
Graves LE, Ariztia EV, Navari JR, Matzel HJ, Stack MS, Fishman DA. Proinvasive properties of ovarian cancer ascites-derived membrane vesicles. Cancer Res. 2004 Oct 1;64(19):7045-9.
Munshi HG, Wu YI, Mukhopadhyay S, Ottaviano AJ, Sassano A, Koblinski JE, Platanias LC,
Stack MS. Differential regulation of membrane type 1-matrix metalloproteinase activity by ERK 1/2- and p38 MAPK-modulated tissue inhibitor of metalloproteinases 2 expression controls transforming growth factor-beta1-induced pericellular collagenolysis. J Biol Chem. 2004 Sep 10;279(37):39042-50.
Lorch JH, Klessner J, Park JK, Getsios S, Wu YL, Stack MS, Green KJ. Epidermal growth factor receptor inhibition promotes desmosome assembly and strengthens intercellular adhesion in squamous cell carcinoma cells. J Biol Chem. 2004 Aug 27;279(35):37191-200.
Mukhopadhyay S, Munshi HG, Kambhampati S, Sassano A, Platanias LC, Stack MS. Calcium-induced matrix metalloproteinase 9 gene expression is differentially regulated by ERK1/2 and p38 MAPK in oral keratinocytes and oral squamous cell carcinoma. J Biol Chem. 2004 Aug 6;279(32):33139-46.
Tam EM, Morrison CJ, Wu YI, Stack MS, Overall CM. Membrane protease proteomics: Isotope-coded affinity tag MS identification of undescribed MT1-matrix metalloproteinase substrates. Proc Natl Acad Sci U S A. 2004 May 4;101(18):6917-22.
DeClerck YA, Mercurio AM, Stack MS, Chapman HA, Zutter MM, Muschel RJ, Raz A, Matrisian LM, Sloane BF, Noel A, Hendrix MJ, Coussens L, Padarathsingh M. Proteases, extracellular matrix, and cancer: a workshop of the path B study section. Am J Pathol. 2004 Apr;164(4):1131-9.
Wu YI, Munshi HG, Sen R, Snipas SJ, Salvesen GS, Fridman R, Stack MS. Glycosylation broadens the substrate profile of membrane type 1 matrix metalloproteinase. J Biol Chem. 2004 Feb 27;279(9):8278-89.
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Joseph S. Takahashi, Ph.D.
Department of Neurobiology and Physiology
Ph.D., University of Oregon
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The long-term objective of the research in the Takahashi laboratory is to understand the
cellular and molecular mechanisms that regulate circadian rhythms. Our approach to
studying the mechanisms of circadian clocks has been threefold. First, we have developed
cellular model systems that express oscillations in vitro. Second, we have analyzed
the role of gene expression in the control of circadian rhythms. Finally, we have isolated
and identified clock mutants in mammals using classical and molecular genetics. At
present, our group is analyzing a number of vertebrate systems that fall into four areas
of research: (1) mechanisms of circadian oscillations in chick pineal cells; (2) circadian
and photic regulation of photoreceptor gene expression; (3) regulation of cellular
immediate early genes in the suprachiasmatic nucleus; and (4) molecular genetics of
circadian clock mutants in the mouse and hamster.
In future work, we seek to
identify the set of genes and gene products involved in the clock mechanism. Among
vertebrates this will require the use of model systems that are amenable to molecular
genetic approaches. The isolation of clock mutants, the molecular genetic analysis of
clock genes, and the creation of immortalized cell lines that express circadian
oscillations will ultimately be required to identify elements of the clock system. Once
fundamental elements are identified, we will be in a position to analyze the dynamics of
the oscillator in order to describe its mechanism.
Recent Publications:
Takahashi JS. Finding new clock components: past and future. J Biol Rhythms. 2004 Oct;19(5):339-47.
Lowrey PL, Takahashi JS. Mammalian circadian biology: elucidating genome-wide levels of temporal organization. Annu Rev Genomics Hum Genet. 2004;5:407-41.
Solberg LC, Baum AE, Ahmadiyeh N, Shimomura K, Li R, Turek FW, Churchill GA, Takahashi JS, Redei EE. Sex- and lineage-specific inheritance of depression-like behavior in the rat. Mamm Genome. 2004 Aug;15(8):648-62.
Miller BH, Olson SL, Turek FW, Levine JE, Horton TH, Takahashi JS. Circadian clock mutation disrupts estrous cyclicity and maintenance of pregnancy. Curr Biol. 2004 Aug 10;14(15):1367-73.
Ahmadiyeh N, Slone-Wilcoxon JL, Takahashi JS, Redei EE. Maternal behavior modulates X-linked inheritance of behavioral coping in the defensive burying test. Biol Psychiatry. 2004 Jun 1;55(11):1069-74.
Bult C, Kibbe WA, Snoddy J, Vitaterna M, Swanson D, Pretel S, Li Y, Hohman MM, Rinchik E, Takahashi JS, Frankel WN, Goldowitz D. A genome end-game: understanding gene function in the nervous system. Nat Neurosci. 2004 May;7(5):484-5.
Kolker DE, Vitaterna MH, Fruechte EM, Takahashi JS, Turek FW. Effects of age on circadian rhythms are similar in wild-type and heterozygous Clock mutant mice. Neurobiol Aging. 2004 Apr;25(4):517-23.
Yoo SH, Yamazaki S, Lowrey PL, Shimomura K, Ko CH, Buhr ED, Siepka SM, Hong HK, Oh WJ, Yoo OJ, Menaker M, Takahashi JS. PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues.Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5339-46.
Hong HK, Chakravarti A, Takahashi JS. The gene for soluble N-ethylmaleimide sensitive factor attachment protein alpha is mutated in hydrocephaly with hop gait (hyh) mice. Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1748-53.
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Warren G. Tourtellotte, M.D., Ph.D.
Department of Pathology
M.D., Ph.D., The University of Iowa College of Medicine
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Complex cellular processes such as growth and
differentiation are influenced by epigenetic factors such as cytokines, trophic factors
and cell-cell contact. These factors exert their control by activating cellular signal
transduction pathways that alter gene expression via transcriptional regulators. We are
studying a family of immediate early genes that behave as transcriptional regulators known
as Egr1, Egr2, Egr3 and Egr4. Our research focuses on their function during development of
the mammalian nervous system. We and others have discovered that these transcription
factors regulate a variety of developmental processes including hindbrain organization,
peripheral nerve myelination, male and female fertility, and muscle mechanoreceptor
development involved in limb position perception (proprioception).
We are particularly interested in understanding the signal transduction processes involved
in the activation of Egr genes, the specific target genes and developmental pathways that
they regulate, and identifying biological processes where Egr transcription factors have
redundant functions with one another. We use a variety of contemporary approaches to
functional genomics that are guided by phenotypes revealed in our engineered (mutant
transgenic) mice. Some of the techniques utilized in the laboratory include mouse
transgenics (knockout, knockin and transgenic), recombinant virus (adenovirus and
retrovirus) production for use as in vivo and in vitro transgenic vectors, gene expression
analysis including real-time PCR (Taqman) and microarray technologies. There are many
opportunities in the laboratory to pursue molecular neurobiology research related to gene
regulation in the mammalian nervous system.
Recent Publications:
Tourtellotte WG, Nagarajan R, Bartke A,
Milbrandt J: Functional compensation by Egr4 in Egr1-dependent luteinizing hormone
regulation and Leydig cell steroidogenesis. Mol. Cell. Biol., 20, 5261-5268 (2000).
W.G. Tourtellotte, R. Nagarajan, A. Auyeung,
C. Mueller and J. Milbrandt (1999) Infertility associated with incomplete spermatogenic
arrest and oligozoospermia in Egr4 deficient mice. Devel. 126: 5061-5071.
Whitehead J, Keller-Peck C, Kucera J, Tourtellotte WG. Glial cell-line derived neurotrophic factor-dependent fusimotor neuron survival during development. Mech Dev. 2005 Jan;122(1):27-41.
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Fred W. Turek, Ph.D.
Department of Neurobiology and Physiology
Ph.D., Stanford University
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My research program is focused on the study of circadian and seasonal rhythms in mammals,
primarily in rodents. Ongoing work on circadian rhythms includes an investigation of:
- the neurochemical molecular and cellular events involved in the entrainment, generation suprachiasmatic nucleus (SCN) of the hypothalamus,
- the role of melatonin in modulating circadian rhythms and pulsatile hormone release,
- the interaction between ultradian and circadian rhythm generating centers in the regulation of endocrine and behavioral events,
- the genetics of the circadian clock system,
- the feedback effects of the sleep-wake cycle on the circadian clock regulating the timing of that cycle, and
- the effects of advanced age on the expression of behavioral and endocrine rhythms.
Of particular interest
is the role of the circadian system in measuring the annual change in daylength;
information which is used in the photoperiodic regulation of the seasonal reproductive
cycle. Other studies on the photic regulation of reproductive cycles involve:
- examining hypothalamic GnRH secretion under different photoperiodic conditions,
- determining the role of the pineal gland and melatonin in the regulation of hypothalamic-pituitary-gonadal activity,
- identifying the neural events which mediate the effects of light on neuroendocrine-gonadal activity,
- identifying early gene products in the brain, pituitary gland and gonads that are induced in response to a change in the length of the day.
A variety of neurobiological and endocrinological approaches are
being utilized to address these problems. In addition, to our work on rodents, we have
established extensive collaborations with clinical researchers. Studies in humans are
aimed at shifting the human clock in an attempt to alleviate mental and physical problems
that are associated with disorders in circadian time-keeping, particularly in the elderly
and in shift-workers. In addition, we are using both pharmacological and
non-pharmacological approaches to determine if we can reverse the effects of aging on the
circadian clock system of both rodents and humans.
Recent Publications:
Turek FW. Circadian rhythms: from the bench to the bedside and falling asleep. Sleep. 2004 Dec 15;27(8):1600-2.
Easton A, Meerlo P, Bergmann B, Turek FW. The suprachiasmatic nucleus regulates sleep timing and amount in mice. Sleep. 2004 Nov 1;27(7):1307-18.
Turek FW, Gillette MU. Melatonin, sleep, and circadian rhythms: rationale for development of specific melatonin agonists. Sleep Med. 2004 Nov;5(6):523-32.
Solberg LC, Baum AE, Ahmadiyeh N, Shimomura K, Li R, Turek FW, Churchill GA, Takahashi JS, Redei EE. Sex- and lineage-specific inheritance of depression-like behavior in the rat. Mamm Genome. 2004 Aug;15(8):648-62.
Meerlo P, Westerveld P, Turek FW, Koehl M. Effects of gamma-hydroxybutyrate (GHB) on vigilance states and EEG in mice. Sleep. 2004 Aug 1;27(5):899-904.
Miller BH, Olson SL, Turek FW, Levine JE, Horton TH, Takahashi JS. Circadian clock mutation disrupts estrous cyclicity and maintenance of pregnancy. Curr Biol. 2004 Aug 10;14(15):1367-73.
Kolker DE, Vitaterna MH, Fruechte EM, Takahashi JS, Turek FW. Effects of age on circadian rhythms are similar in wild-type and heterozygous Clock mutant mice. Neurobiol Aging. 2004 Apr;25(4):517-23.
Challet E, Malan A, Turek FW, Van Reeth O. Daily variations of blood glucose, acid-base state and PCO2 in rats: effect of light exposure. Neurosci Lett. 2004 Jan 23;355(1-2):131-5.
Anand S, Turek FW, Horton TH. Chemosensory stimulation of luteinizing hormone secretion in male Siberian hamsters (Phodopus sungorus). Biol Reprod. 2004 Apr;70(4):1033-40.
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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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Xiaobin Wang, M.D., M.P.H., Sc.D.
Department of Pediatrics
M.D., Beijing Medical University, Beijing, China
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Dr. Wang is a molecular epidemiologist whose work unites molecular biology, genetics, clinical medicine, and epidemiology and brings together laboratory science and child health professionals from multiple disciplines. Her research has covered a broad scope of child health issues ranging from adverse reproductive outcomes, child growth and development, respiratory health, and childhood precursors of adult diseases.
At present, Dr. Wang is the principal investigator of four molecular epidemiological studies on preterm birth, low birth weight, and fetal growth restriction, particularly the interaction between genes and the environment. Her work is supported by grants from the National Institutes of Health and the March of Dimes Birth Defect Foundation.
Recent Publications:
Wang L, Wang X, Wang W, Chen C, Ronnennberg AG, Guang W, Huang A, Fang Z, Zang T, Wang L, Xu X. Stress and dysmenorrhoea: a population based prospective study. Occup Environ Med. 2004 Dec;61(12):1021-6.
Ronnenberg AG, Wood RJ, Wang X, Xing H, Chen C, Chen D, Guang W, Huang A, Wang L, Xu X. Preconception hemoglobin and ferritin concentrations are associated with pregnancy outcome in a prospective cohort of Chinese women. J Nutr. 2004 Oct;134(10):2586-91.
Wang X, Mensinga TT, Schouten JP, Rijcken B, Weiss ST. Determinants of maximally attained level of pulmonary function. Am J Respir Crit Care Med. 2004 Apr 15;169(8):941-9.
Li J, Wang X, Huo Y, Niu T, Chen C, Zhu G, Huang Y, Chen D, Xu X. PON1 polymorphism, diabetes mellitus, obesity, and risk of myocardial infarction: Modifying effect of diabetes mellitus and obesity on the association between PON1 polymorphism and myocardial infarction. Genet Med. 2005 Jan;7(1):58-63.
Hao K, Xu X, Laird N, Wang X, Xu X (2004). Power estimation of multiple SNP association test of case-control study and application. Genetic Epidemiology. 26: 22-30.
Hao K, Wang X, Niu T, Xu X, Li A, Chang W, Wang L, Li G, Xu X (2004). A candidate gene study of preterm delivery: Application of high-throughput genotyping technology and advanced statistical methods. Human Molecular Genetics. 13: 683-691.
Venners SA, Wang X, Chen C, Wang L, Chen D, Guang W, Huang A, Ryan L, OÕConnor J, Lasley B, Overstreet J, Wilcox A, Xu X (2004). Paternal smoking and early pregnancy loss: A prospective study using biomarker. American Journal of Epidemiology. 159(10): 993-1001.
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Jeffrey Weiss, Ph.D.
Center for Endocrinology,
Metabolism, and Molecular Medicine
Ph.D., University of Virginia
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The long-term goal of the laboratory is to understand the hormonal signals and cellular
pathways through which the gonadotropin hormones, LH and FSH, are synthesized and
secreted. In addition to the classic neuroendocrine and steroid signals, we have
undertaken a detailed analysis of the autocrine and paracrine signals that specifically
modulate pituitary FSH. These signals include activin, the potent and specific FSH
stimulatory protein and follistatin, the activin binding protein. Recent work from the
laboratory has confirmed the presence of activin and follistatin in the anterior pituitary
and characterized an activin/follistatin paracrine loop that mediates the hypothalamic
GnRH signal in a frequency-dependent manner. Studies are ongoing to identify the role of
the GnRH/activin/follistatin interaction in the regulation of FSH required for follicular
recruitment and maturation. Other projects in the laboratory include an analysis of the
GnRH-and steroid-responsive regions of the follistatin promoter and studies to explore the
regulation of the intracellular calcium channels during GnRH signalling. Previous studies
in the laboratory identified the first known genetic mutation in a gonadotropin gene. This
defect in the LHb gene formed the basis for hypergonadotropic hypogonadism in a family
with a history of impaired fertility.
Recent Publications
Woodruff, TK, LM Besecke, N Groome, LB Draper, NB Schwartz, J Weiss. 1996. Inhibin A
and inhibin B are inversely correlated to FSH yet are discordant during the follicular
phase of the rat estrous cycle and inhibin A is expressed in a sexually dimorphic manner.
Endocrinology 137:5463-5467.
Sundaresan, S, J Weiss, AC Bauer-Dantoin, JL Jameson. 1997. Expression of ryanodine
receptors in the pituitary gland: Evidence for a role in GnRH signaling. Endocrinology
138:2056-2065.
Besecke, LM, MJ Guendner, PA Sluss, AG Polak, TK Woodruff, JL Jameson, AC
Bauer-Dantoin, J Weiss. 1997. Pituitary follistatin regulates activin-mediated production
of FSH during the rat estrous cycle. Endocrinology 138:2841-2848.
Draper, LB, MM Matzuk, VJ Roberts, E Cox, J Weiss, JP Mather, TK Woodruff. 1998.
Identification of an inhibin receptor in gonadal tumors from inhibin a
-subunit knockout mice. Journal of Biological Chemistry 273:398-403.
Wang, EY, LB Draper, E Lee, A Polak, P Sluss, J Weiss, TK Woodruff. 1999.
Identification of Naturally Occurring Follistatin Complexes in Human Biological Fluids.
Biology of Reproduction 60:8-13.
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Teresa K. Woodruff, Ph.D.
Center for Medical Endocrinology,
Metabolism and Nutrition Center/NBP
Ph.D., Northwestern University
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An understanding of the
biological, cellular, and molecular mechanisms that regulate the reproductive axis is the
goal of the laboratory. Hormones and locally produced growth factors of the gonads,
pituitary, and hypothalamus interact to maintain reproductive cyclicity in the female and
tonic sperm production in the male. The integration of endocrine, paracrine, and autocrine
mechanisms provides the precision demanded by nature to maintain the germ line of the
species.
The study of normal reproduction function requires measurement of fluctuating hormone
levels, identification of local factors involved in reproductive management, and an
understanding of the signaling mechanisms that cue cellular action. Diseases involving
reproductive systems include infertility (male and female), polycystic ovarian disease,
endometriosis, premature ovarian failure, preterm labor and delivery, and ovarian, breast,
testicular, and prostate cancer.
The specific focus of the laboratory at this time is the female reproductive axis. Our
approach requires an integrated view of the axis as a whole, however, emphasis is placed
on ovarian-regulated events. We seek to understand the hormonal signals produced by the
ovaries, the mechanics of follicular growth, the hormonal and neuronal effectors of
follicle selection and maturation, the factors involved in the development of oocytes, the
events surrounding follicle wall rupture and wound healing, and the interplay between
oocyte and somatic cells. Our scientific approach toward an understanding of
ovarian-directed reproductive events is to identify and study factors produced by the
ovary which regulate local and distal events.
The protein molecules that we are currently evaluating are inhibin and activin. While
our aims are broad, the utility of the inhibin and activin hormone family is that they
provide specific investigative tools. These hormones are integral factors in normal
ovarian function and may be inappropriately regulated in disease states.
We will extend our scope of inquiry to other areas of reproductive function with time.
For example, we are keenly interested in the regulation of the reproductive axis by cues
emanating from the brain, adrenal, and uterus. Signals involved in oocyte implantation,
maintenance of pregnancy, and onset of labor and delivery will be studied. Additionally,
male-specific normative and aberrant reproductive function will be studied. Further, our
work, can be extended to the preservation of the germ line of endangered species. We
anticipate that as we uncover new mechanisms of hormone action and effector function, we
will be more able to understand the biological, cellular, and molecular controls that
regulate the reproductive axis.
Recent Publications:
Park Y, Maizels ET, Feiger ZJ, Alam H, Peters CA, Woodruff TK, Unterman TG, Lee EJ, Jameson JL, Hunzicker-Dunn M. Induction of cyclin D2 in rat granulosa cells requires FSH-dependent relief from FOXO1 repression coupled with positive signals from Smad. J Biol Chem. 2004 Dec 21; PMID: 15613482
Bernard DJ, Woodruff TK, Plant TM. Cloning of a novel inhibin alpha cDNA from rhesus monkey testis. Reprod Biol Endocrinol. 2004 Oct 07;2(1):71.
Thompson TB, Cook RW, Chapman SC, Jardetzky TS, Woodruff TK. Beta A versus beta B: is it merely a matter of expression? Mol Cell Endocrinol. 2004 Oct 15;225(1-2):9-17.
Cook RW, Thompson TB, Jardetzky TS, Woodruff TK. Molecular biology of inhibin action. Semin Reprod Med. 2004 Aug;22(3):269-76.
Tomic D, Miller KP, Kenny HA, Woodruff TK, Hoyer P, Flaws JA. Ovarian follicle development requires Smad3. Mol Endocrinol. 2004 Sep;18(9):2224-40.
Klein NA, Houmard BS, Hansen KR, Woodruff TK, Sluss PM, Bremner WJ, Soules MR. Age-related analysis of inhibin A, inhibin B, and activin a relative to the intercycle monotropic follicle-stimulating hormone rise in normal ovulatory women. J Clin Endocrinol Metab. 2004 Jun;89(6):2977-81.
Phillips DJ, Woodruff TK. Inhibin: actions and signalling. Growth Factors. 2004 Mar;22(1):13-8.
Bristol SK, Woodruff TK. Follicle-restricted compartmentalization of transforming growth factor beta superfamily ligands in the feline ovary. Biol Reprod. 2004 Mar;70(3):846-59.
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Catherine S. Woolley, Ph.D.
Department of Neurobiology and Physiology
Ph.D., Rockefeller University
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Research in my lab is directed toward understanding the
interaction(s) between endocrine rhythms and the limbic system of the mammalian brain.
Specifically, we study how fluctuating levels of the ovarian steroid hormones, estradiol
and progesterone, regulate structure and function of hippocampal circuitry. The
hippocampus is a brain region that normally plays an important role in cognitive and
sensory information processing and, under pathological conditions, is a circuit that can
generate and propagate seizure activity. Our research uses a multi-disciplinary approach
that combines light and electron microscopy, electrophysiological recording from
hippocampal slices and behavioral testing to understand the "hows" and
"whys" of steroid hormone regulation of synaptic connectivity within the
hippocampus.
We have found that concerted action of estradiol and progesterone regulates excitatory
input to a major group of hippocampal output cells, the CA1 pyramidal cells.
Hormone-induced changes in the density and number excitatory synaptic contacts on CA1
pyramidal cells are associated with increased sensitivity to excitatory synaptic input,
enhanced synaptic plasticity, and greater susceptibility to seizure activity.
Thus, by regulating the physical substrates of information flow in the brain:
dendrites, axons and the synapses that connect them, steroid hormones such as estradiol
and progesterone may predispose neural circuitry to function differently in different
hormonal states. Our aim is to understand how hormone-induced structural and functional
plasticity regulates both normal an pathological brain function.
Recent Publications:
Smith SS, Woolley CS. Cellular and molecular effects of steroid hormones on CNS excitability. Cleve Clin J Med. 2004 Feb;71 Suppl 2:S4-10.
Telgkamp P, Padgett DE, Ledoux VA, Woolley CS, Raman IM. Maintenance of high-frequency transmission at purkinje to cerebellar nuclear synapses by spillover from boutons with multiple release sites. Neuron. 2004 Jan 8;41(1):113-26.
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Eugene Xu, Ph.D.
Department of Obstetrics and Gynecology
Ph.D., University of Chicago
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Germ cells are unique in that they are the only cell type in our bodies that is both totipotent and immortal. How germ cells in early embryos are formed and further developed into sperm and eggs remain one of the central questions in biology and a better understanding of this question could impact directly on our strategy in developing the diagnostic methods and treatment of diseases such as cancer, infertility and many other reproductive syndromes affecting men and women's health. The overall goal of my research program is to understand the genetic and developmental mechanisms of mammalian germline development, in particular how key events such as maintenance/differentiation of germline stem cells and entry into meiosis are regulated in mammals. The pathways that develop germ cells appear to be conserved broadly, at least in outline, in organisms as diverse as insects and mammals. We proposed that there exists conserved core machinery that regulates the germ cell development and we wish to define the components of this underlying machinery through a combined evolutionary, genomic and genetic approach.
Currently we are focusing on
- Dissection of meiotic regulatory machinery involving highly conserved meiotic regulator BOULE (meiosis, mouse genetics)
- Comparative genomic analysis of expression profile of germ cell development between fly and mouse (bioinformatics, genomics)
- Functional genomics approach to male and female contraception : Generation of mouse mutations disrupting conserved reproductive regulators from mouse ES genetrap lines (mouse genetics, development)
- Role of conserved germline stem cell factors Pumilio 1 and Pumilio 2. (stem cell, development)
- Use of mouse and human ES cells as an invitro system for applications in reproductive biology research (cell biology and cancer)
Recent Publications:
Xu, E. Y., D. Lee, A. Klebes, P. J. Turek, T. Kornberg and R. Reijo Pera (2003) Human BOULE rescues the meiotic defects in infertile flies Human Molecular Genetics. Vol 12(2):169-175.
Wu, C.-I. and Xu, E. Y. (2003) Sexual antagonism and X inactivation- the SAXI hypothesis. Trends in Genetics 19(5): 243-7
Xu, E. Y., F. Moore, R. Reijo Pera (2001) A gene family required for human germ cell development evolved from an ancient meiotic gene conserved in metazoans. PNAS Vol 98:7414-7419
C. Marc Luetjens, Xu, E. Y., Renee A. Reijo Pera, Axel Kamischke, Eberhard Nieschlag, Jšrg Gromoll (2004) Association of meiotic arrest in infertile men and lack of BOULE protein expression. J. Clinical Endocrinology and Metabolism 89(4):1926-33
Y.-M. Kuo, J. Duncan, S. Westaway,H. Yang, G. Nune, Xu, E. Y., S. Hayflick, and J. Gitschier (2004) Deficiency in pantothenate kinase 2 in a mouse model for Hallervorden-Spatz Syndrome leads to retinal degeneration and azoospermia Human Molecular Genetics 14(1):49-57
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Laurie Zoloth, PhD
Director of the Center for Bioethics
Professor of Medical Humanities and Bioethics
Professor of Religion
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Laurie Zoloth is Director the Center for Bioethics at Northwestern University,
a Professor of Medical Humanities and Bioethics, and Professor of Religion, at
Northwestern. From 1995-2003, she was Professor of Ethics and Director of the
Program in Jewish Studies at San Francisco State University. In 2001, she was
the President of the American Society for Bioethics and Humanities, and in 2002
was Vice President of the Society for Jewish Ethics. She is a member of the both
the NASA National Advisory Council, NASA’s Planetary Protection Advisory
Committee, the Boards of the International Society for Stem Cell Research, and
the Society of Women’s Health Research. She is the Chair of the Howard Hughes
Medical Institute's Bioethics Advisory Board., as well as being on the founding
boards of 4 national academic societies. She has published extensively in the
areas of ethics, family, feminist theory, religion and science, Jewish Studies,
and social policy. Her books are Health Care and The Ethics of Encounter, Notes
From a Narrow Ridge: Religion and Bioethics, Margin of Error: The Ethics of Mistakes
in the Practice of Medicine and The Human Embryonic Stem Cell Debate: Ethics,
Religion and Public Policy, and her 29 book chapters include work on the emerging
issues in basic research and in the problems of social justice in health care.
She has testified about science and ethics for the US Senate, the states of Illinois,
Texas, and California, and the European Union Commission on Bioethics and Humanities.
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