Reproductive Sciences

Prostaglandin-nuclear receptor-angiogenic signaling axis during embryo implantation with special emphasis to cPLA2α-Cox2-PPARδ-Vegf network in the uterus; cytokine-growth factor-homeobox-morphogen signaling axis in implantation involving Lif-Hb-Egf-Hoxa10/Msx1-Ihh/Bmp/Wnt network in the uterus; immunophilin/cochaperone-nuclear signaling in the mouse uterus during implantation involving Fkbp52-PR; ligand-receptor signaling with endocannabinoids during the periimplantation events in mice in the context of anandamide interacting with G-protein coupled receptors, CB1 and CB2; molecular and genetic basis of epithelial ovarian cancer with special reference to prostaglandin-PPAR signaling; miRNA and Cox-2 regulation in uterine biology and cancer; Pten and uterine carcinoma: conditionally gene deleted mouse models

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Biography

Dr. Dey received his PhD from The University of Calcutta College of Sciences in 1972, after which he received postdoctoral training at the University of Kansas Medical Center from 1973-1977, followed by his faculty appointment in 1977 where he rose to the rank of University Distinguished Professor. He moved to Vanderbilt University as Dorothy Overall Wells professor of pediatrics, cell and developmental biology and pharmacology in 2002. In both places he directed NIH-funded reproductive biology training grants. In 2008, Dr. Dey moved to Cincinnati Children’s Hospital Medical Center as Lova Riekert Chair and professor of pediatrics within the University of Cincinnati College of Medicine to start a new Division of Reproductive Sciences. He has published over 300 original articles and has been funded by two MERIT Awards, RO1 grants and a Program Project Grants from NIH, and grants from the Bill and Melinda Gates Foundation and March of Dimes Foundation. His research mission has been to define the molecular road map to embryo-uterine interactions during pregnancy. His recent work published in Developmental Cell, Nat Med, PNAS and JCI provides novel information in the context of cell polarity in implantation, ectopic pregnancy, progesterone resistance to pregnancy failure and premature decidual senescence in preterm delivery. In 2008, Dr. Dey received Carl G. Hartman Award, the highest honor of the Society for the Study of Reproduction. In 2009, he received IVI Award sponsored by Schering-Plough for best contribution in reproductive medicine.

He has graduated seven PhD students and mentored over 40 postdoctoral fellows, 20 of whom are currently independent faculty members, and most others are investigators in major research institutions. His laboratory currently consists of one junior faculty, four postdoctoral fellows, one MD/PhD student, and two research assistants.

BSc: Presidency College, Calcutta, India, 1965.

MSc: University of Calcutta, India, 1967.

PhD: University of Calcutta, India, 1972.

Cha J, Bartos A, Egashira M, Haraguchi H, Saito-Fujita T, Leishman E, Bradshaw H, Dey SK, and Hirota Y. Combinatory approaches prevent preterm birth profoundly exacerbated by gene-environment interactions. J Clin Invest. 2013 Sep 3;123(9):4063-75.

Raines AM, Adam M, Magella B, Meyer SE, Grimes HL, Dey SK, Potter SS. Recombineering-based dissection of flanking and paralogous Hox gene functions in mouse reproductive tracts. Development. 2013 Jul;140(14):2942-52.

Cha J, Sun X, Bartos A, Fenelon J, Lefevre P, Daikoku T, Shaw G, Maxson R, Murphy BD, Renfree MB, Dey SK. A new role for muscle segment homeobox genes in mammalian embryonic diapause. Open Biol. 2013 Apr 24;3(4):130035.

Cha J, Sun X, Dey SK. Mechanisms of implantation: strategies for successful pregnancy. Nat Med. 2012 Dec:18(12):1754-67.

Xie H, Sun X, Piao Y, Jegga AG, Handwerger S, Ko MS, Dey SK. Silencing or amplification of endocannabinoid signaling in blastocysts via CB1 compromises trophoblast cell migration. J Biol Chem. 2012 Sep 14;287(38):32288-97.

Daikoku T, Cha J, Sun X, Tranguch S, Xie H, Fujita T, Hirota Y, Lydon J, DeMayo F, Maxson R, Dey SK. Conditional Deletion of MSX Homeobox Genes in the Uterus Inhibits Blastocyst Implantation by Altering Uterine Receptivity. Dev Cell. 2011 Dec 13;21(6):1014-25.

Sun X, Xie H, Yang J, Wang H, Bradshaw HB, Dey SK. Endocannabinoid signaling directs differentiation of trophoblast cell lineages and placentation. Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16887-92.

Hirota Y, Acar N, Tranguch S, Burnum KE, Xie H, Kodama A, Osuga Y, Ustunel I, Friedman DB, Caprioli RM, Daikoku T, Dey SK. Uterine FK506-binding protein 52 (FKBP52)-peroxiredoxin-6 (PRDX6) signaling protects pregnancy from overt oxidative stress. Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15577-82.

Hirota Y, Daikoku T, Tranguch S, Xie H, Bradshaw HB, Dey SK. Uterine-specific p53 deficiency confers premature uterine senescence and promotes preterm birth in mice. J Clin Invest. 2010 Mar;120(3):803-15.

Burnum KE, Cornett DS, Puolitaival SM, Milne SB, Myers DS, Tranguch S, Brown HA, Dey SK, RM Caprioli. Spatial and temporal alterations of phospholipids determined by mass spectrometry during mouse embryo implantation. J Lipid Res. 2009 Nov;50(11);2290-8.

Faculty

Sanjoy K. Das, PhD

Sanjoy K. Das, PhD, focuses on two independent areas: 1) Characterization of non-genomic actions of natural estrogen and xenoestrogens in the uterus without involving the nuclear ERα and ERβ, and 2) Aspects of uterine cell cycle regulation for decidualization in implantation.
Visit the Das Lab.

513-803-1159 sanjoy.das@cchmc.org

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Sanjoy K. Das, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-1159

Fax 513-803-1160

Email sanjoy.das@cchmc.org

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Characterization of non-genomic actions of natural estrogen and xenoestrogens in the uterus without involving the nuclear ERa and ERb; aspects of uterine cell cycle regulation for decidualization in implantation

Visit the Das Lab.

PhD: Biochemistry, University of Calcutta, Calcutta, India.

MSc: Biochemistry, University of Calcutta, Calcutta, India.

BSc: Chemistry (Honors), University of Calcutta, Calcutta, India.

Gao F, Ma X, Ostmann AB, Das SK. GPR30 activation opposes estrogen-dependent uterine growth via inhibition of stromal ERK1/2 and estrogen receptor alpha (ERα) phosphorylation signals. Endocrinology. 2011 Apr;152(4):1434-47.

Das SK. Regional development of uterine decidualization: molecular signaling by Hoxa-10. Mol Reprod Dev. 2010 May;77(5):387-96. Review.

Das SK. Cell cycle regulatory control for uterine stromal cell decidualization in implantation. Reproduction. 2009 Jun;137(6):889-99.

Davies SM, Borowitz MJ, Rosner GL, Ritz K, Devidas M, Winick N, Martin PL, Bowman P, Elliott J, Willman C, Das S, Cook EH, Relling MV. Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2008 Mar 15;111(6):2984-90.

Ray S, Xu F, Wang H, Das SK. Cooperative Control via Lymphoid Enhancer Factor 1/T Cell Factor 3 and Estrogen Receptor-a for Uterine Gene Regulation by Estrogen. Molecular Endocrinology. 2008;22:1125-40.

Xie H, Tranguch S, Jia X, Zhang H, Das SK, Dey SK, Kuo CJ, Wang H. Inactivation of nuclear Wnt-b-catenin signaling limits blastocyst competency for implantation. Development. 2008;135:717-27.

Wang H, Xie H, Sun X, Tranguch S, Zhang H, Jia X, Wang D, Das SK, Desvergne B, Wahli W, Dubois RN, Dey SK. Stage-specific integration of maternal and embryonic Peroxisome Proliferator-activated Receptor d signaling is critical to pregnancy success. Journal of Biological Chemistry. 2007;282:37770-82.

Xie H, Wang H, Tranguch S, Iwamoto R, Mekada E, DeMayo FJ, Lydon JP, Das SK, Dey SK. Maternal heparin-binding-EGF deficiency limits pregnancy success in mice. Proceedings of the National Academy of Science USA. 2007;104:18315-20.

Ray S, Xu F, Li P, Sanchez NS, Wang H, Das SK. Increased level of cellular Bip critically determines estrogenic potency for a xenoestrogen kepone in the mouse uterus. Endocrinology. 2007;148:4774-85.

Tony J. De Falco, PhD

Tony J. De Falco, PhD, has basic research programs in gonad differentiation and homeostasis. His lab investigates how the initially undifferentiated gonad primordium transforms into a testis or ovary, as well as how the adult testis maintains sperm production over a long reproductive lifespan. His specific interests are in the novel and diverse roles of myeloid immune cells in reproductive biology.

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513-803-3988 tony.defalco@cchmc.org

High Res

Tony J. De Falco, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-3988

Email tony.defalco@cchmc.org

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Specialties

Differentiation of the fetal gonad into a sexually dimorphic and structurally specialized organ; spermatogonial differentiation; roles of myeloid cells in tissue remodeling, organ vascularization and spermatogonial development.

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BA: University of Virginia, Charlottesville, VA.

PhD: Johns Hopkins University, Baltimore, MD.

Postdoc: Duke University Medical Center, Durham, NC.

Postdoc: National Institute of Genetics, Mishima, Japan.

Sun X, Ito J, Potter SJ, Dey SK, DeFalco T. Extra-gonadal oocytes residing in the mouse ovarian hilum contribute to fertility. Biol Reprod. 2017;96(5):1060-1070.

Lin YT, Barske L, DeFalco T, Capel B. Numb regulates somatic cell lineage commitment during early gonadogenesis in mice. Development. 2017;144(9):1607-1618. (This article was featured in an “In This Issue” preview article in the May 1, 2017 issue of Development.)

Potter SJ, DeFalco T. Role of the testis interstitial compartment in spermatogonial stem cell function. Reproduction. 2017;153(4):R151-R162.

DeFalco T*, Potter SJ, Williams AV, Waller B, Kan MJ, Capel B. Macrophages Contribute to the Spermatogonial Niche in the Adult Testis**. Cell Rep. 2015;12(7):1107-19. (*corresponding author) (**Featured Article on the cover of the August 18th issue of Cell Reports, and also highlighted as a Preview in Cell Reports and as a featured article in the “World of Reproductive Biology” in Biology of Reproduction)

Potter SJ, DeFalco T. Using ex vivo upright droplet cultures of whole fetal organs to study developmental processes during mouse organogenesis. J Vis Exp. 2015;104:e53262.

DeFalco T*, Bhattacharya I, Williams AV, Sams, DM, Capel, B.* Yolk-sac-derived macrophages regulate fetal testis vascularization and morphogenesis. Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):E2384-2393. (*co-corresponding authors)

DeFalco T, Saraswathula A, Briot A, Iruela-Arispe ML, Capel B. Testosterone levels influence mouse fetal Leydig cell progenitors through Notch signaling. Biol Reprod. 2013 Apr 11;884:91.

Jameson S, Natarajan A, Cool J, DeFalco T, Maatouk D, Mork L, Munger SC, Capel B. Temporal transcriptional profiling of somatic and germ cells reveals biased lineage priming of sexual fate in the fetal mouse gonad. PLoS Genet. 2012;8(3):e1002575.

DeFalco T, Takahashi S, Capel B. Two distinct origins for Leydig cell progenitors in the fetal testis. Dev Biol. 2011 Apr 1;352(1):14-26.

Cool J, DeFalco TJ, Capel B. Vascular-mesenchymal cross-talk through Vegf and Pdgf drives organ patterning. Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):167-172.

Grants

Macrophage regulation of the spermatogonial stem cell niche. Principal Investigator. National Institutes of Health Maximizing Investigators’ Research Award (MIRA/R35)/National Institute of General Medical Sciences. Sep 2016 - May 2021.

Satoshi H. Namekawa, PhD

Satoshi H. Namekawa, PhD, examines the mechanisms and evolution of epigenetic events during mammalian reproduction, using a male germ cell model.
Visit the Namekawa Lab.

513-803-1377 satoshi.namekawa@cchmc.org

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Satoshi H. Namekawa, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-1377

Fax 513-803-1160

Email satoshi.namekawa@cchmc.org

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The long-term goal of Dr. Namekawa's research is to understand the mechanisms and evolution of epigenetic events during mammalian reproduction. One of the focus areas is epigenetic regulation of sex chromosomes in germ cell development. Recently, his laboratory demonstrated that DNA damage response pathways trigger epigenetic programming on the sex chromosomes in germ cells. An on-going direction of the laboratory is to pursue a general link between DNA damage response pathways and epigenetic programming. Another goal of the laboratory is to identify novel factors and related pathways that control epigenetic programming during mouse reproduction, especially focusing on the events occurring on sex chromosomes during spermatogenesis as well as the regulatory mechanisms in germline stem cells.

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Biography

Dr. Namekawa received his PhD from Tokyo University of Science in 2005. He completed postdoctoral training in the laboratory of Dr. Jeannie T. Lee at Massachusetts General Hospital and Harvard Medical School in 2009, followed by his faculty appointment at Cincinnati Children's in 2009. He is funded by NIH R01 Award and the Basil O’Connor Award from March of Dimes Foundation.

He received the 2015 New Investigator Award from the Society for the Study of Reproduction.

PhD: Tokyo University of Science, Japan, 2005.

BS: Tokyo University of Science, Japan, 2000.

Alavattam KG, Kato Y, Sin HS, Maezawa S, Kowalski IJ, Zhang F, Pang Q, Andreassen PR, Namekawa SH. Elucidation of the Fanconi Anemia Protein Network in Meiosis and Its Function in the Regulation of Histone Modifications. Cell Rep. 2016 Oct 18;17(4):1141-1157.

Sin HS, Kartashov AV, Hasegawa K,Barski A, Namekawa SH. Poised chromatin and bivalent domains facilitate the mitosis-to-meiosis transition in the male germline. BMC Biol. 2015 Jul 22;13:53.

Kato Y, Alavattam KG, Sin HS, Meetei A, Pang Q, Andreassen PR, Namekawa SH. FANCB is essential in the male germline and regulates H3K9 methylation on the sex chromosomes during meiosis. Hum Mol Genet. 2015 Jun 29.

Broering TJ, Wang YL, Pandey RN, Hegde RS, Wang SC, Namekawa SH. BAZ1B is dispensable for H2AX phosphorylation on Tyrosine 142 during spermatogenesis. Biol Open. 2015 May 15.

Hu YC, Namekawa SH. Functional significance of the sex chromosomes during spermatogenesis. Reproduction. 2015 Jun;149(6):R265-R277.

Hasegawa K, Sin HS, Maezawa S, Broering TJ, Kartashov AV, Alavattam KG, Ichijima Y, Zhang F, Bacon WC, Greis KD, Andreassen PR, Barski A, Namekawa SH. SCML2 establishes the male germline epigenome through regulation of histone H2A ubiquitination. Dev Cell. 2015 Mar 9;32(5):574-88.

Broering TJ*, Alavattam KG*, Sadreyev RI, Ichijima Y, Kato Y, Hasegawa K, Camerini-Otero RD, Lee JT, Andreassen PR, Namekawa SH. BRCA1 establishes DNA damage signaling and pericentric heterochromatin of the X chromosome in male meiosis. (*equal contribution) J Cell Biol. 2014 Jun 9;205(5):663-75.

Sin HS, Barski A, Zhang F, Kartashov AV, Nussenzweig A, Chen J, Andreassen PR, Namekawa SH. RNF8 regulates active epigenetic modifications and escape gene activation from inactive sex chromosomes in postmeiotic spermatids. Genes Dev. 2012 Dec 15:26(24)2737-2748.

Sin HS, Ichijima Y, Koh E, Namiki M, Namekawa SH. Human post meiotic sex chromatin and its impact on sex chromosome evolution. Genome Res. 2012 May;22(5):827-36.

Ichijima, Y, Ichijima M, Lou Z, Nussenzweig A, Camerini-Otero RD, Chen J, Andreassen PR, Namekawa SH. MDC1 directs chromosome-wide silencing of the sex chromosomes in male germ cells. Genes Dev. 2011 May 1;25(9):959-71.

Yuya Ogawa, PhD

Yuya Ogawa, PhD, is interested in how non-coding RNAs impact gene regulation and development in animals using X-chromosome inactivation as a model system.

513-803-1949 yuya.ogawa@cchmc.org

High Res

Yuya Ogawa, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-1949

Fax 513-803-1160

Email yuya.ogawa@cchmc.org

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In mammalian females, one of the two X-chromosomes is silenced to correct the imbalance of X-linked gene dosage between males (Xy) and females (XX). This chromosome-wide gene silencing is induced by a long noncoding RNA, Xist RNA.

The laboratory is interested in the mechanisms of: (1) how the chromosome-wide silencing is induced by Xist RNA and (2) how the long-range silencing is maintained and organized. Their long-term goal is to understand how noncoding RNAs impact gene regulation and development in animals.

BS: Molecular Biology, Nagoya University, Japan, 1992.

MS: Molecular Biology, Nagoya University, Japan, 1994.

PhD: Biology, Osaka University, Japan, 1998.

Daikoku T, Ogawa Y, Terakawa J, Ogawa A, DeFalco T, Dey SK. Lactoferrin-iCre: a new mouse line to study uterine epithelial gene function. Endocrinology. 2014 Jul;155(7):2718-24.

Sun S, Del Rosario BC, Szanto A, Ogawa Y, Jeon Y, Lee JT. Jpx RNA activates Xist by evicting CTCF. Cell. 2013 Jun 20;153(7):1537-51.

Sato A, Yamada N, Ogawa Y, Ikegami M. CCAAT/enhancer-binding protein-α suppresses lung tumor development in mice through the p38α MAP kinase pathway. PLoS One. 2013;8(2):e57013.

Zhao J, Ohsumi TK, Kung JT, Ogawa Y, Grau DJ, Sarma K, Song JJ, Kingston RE, Borowsky M, Lee JT. Genome-wide identification of polycomb-associated RNAs by RIP-seq. Mol Cell. 2010 Dec 22;40(6):939-53.

Zhang LF, Ogawa Y, Ahn JY, Namekawa SH, Silva SS, Lee JT. Telomeric RNAs mark sex chromosomes in stem cells. Genetics. 2009 182,685-98.

Ogawa Y, Sun BK, Lee JT. Intersection of the RNA interference and X-inactivation pathways. Science. 2008 320,1336-41.

Xiaofei Sun, PhD

Xiaofei Sun, PhD, investigates the effects of cannabinoid/endocannabinoid signaling in different pregnancy events spanning from preimplantation embryo development to parturition. He is also interested in studies of signaling pathways on periimplantation events.
Visit the Dey-Sun Lab.

513-803-2091 xiaofei.sun@cchmc.org

Xiaofei Sun, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-2091

Email xiaofei.sun@cchmc.org

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Reproductive biology; endocannabinoid signaling in reproduction

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BSc: Zhejiang University, China, 2002.

PhD: Vanderbilt University, Nashville, TN, 2010.