Dimitriadis Group Reproductive Biology and Co-Head Gynaecology Research Centre

Research Overview

This group is interested in reproductive biology.

Staff

  • Ms Emily Jane Bromley, Research Support Officer
  • Ms Judi Hocking, SRN
  • Dr Ellen Menkhorst, Decidual Biology Group Leader, Research Fellow in Reproductive biology
  • Dr Leilani Santos, Senior Research Support Officer https://www.findanexpert.unimelb.edu.au/display/person665840>
  • Ms Kelly Sorby, PhD Student
  • Ms Teresa So, Research Support Officer
  • Dr Wei Zhou, Research Fellow in Reproductive Biology

Collaborators

  • A/Prof Kaori Koga, University of Tokyo, Japan
  • A/Prof Daniel Rolnik, Monash University, Australia
  • Prof Kypros Nicolaides, NHS, London, United Kingdom
  • Dr Jemma Evans, Hudson Institute, Australia

Funding

  • Grant funding last 5 years (2013-19) $5,777,014
  • Grant funding overall as CIA $8,291,120
  • NHMRC funding last 5 years (as CIA 2013-19) $3,222,414
  • NHMRC funding overall as CIA $5,886,520
  • Industry Grant funding last 5 years as CIA (2013-19) $282,000
  • Industry Grant funding overall as CIA $2,404,600

Research Outcomes

mbryo implantation and infertility

Takamura M, Zhou W, Dimitriadis E revisions after review this is now accepted <more information needed on title of article>

Van Sinderen M, Oyanedel J, Menkhorst E, Cuman C, Rainczuk K, Winship A, Salamonsen LA, Edgell TA, Dimitriadis E.  Soluble Delta-like ligand 1 alters human endometiral epithelial cell adhesive capacity.  Reproduction, Fertility and Development, 2017;29(4):694-702.

Winship A, Dimitriadis E.  Interleukin 11 induces preterm birth and modulates decidual inflammasome gene expression in mice.  Placenta 2017;50:99-101.

Evans J, Salamonsen LA, Winship A, Menkhorst E, Nie G, Gargett CE, Dimitriadis E.  Fertile ground:  human endometrial programming and lessons in health and disease.  Nature Reviews Endocrinology.  2017;12:654-667. Review.

Monhasery N, Moll J, Cuman C, Franke M, Lamertz L, Nitz R, Gorg B, Haussinger D, Lokau J, Floss DM, Piekorz R, Dimitriadis E, Garbers C, Scheller J.  Transcytosis of IL-11 and Apical Redirection of gp130 is Mediated by IL-11alpha receptor. Cell Reports. 2016;16(4):1067-81.

Van Sinderen M, Cuman C, Gamage T, Rainczuk K, Osianlis T, Rombauts L, Dimitriadis E.  Localisation of the Notch family in the human endometrium of fertile and infertile women. Journal of Molecular Histology. 2014;45(6):697-706.

Cuman C, Menkhorst EM, Rombauts LJ, Holden S, Webster D, Bilandzic M, Osianlis T, Dimitriadis E. Preimplantation human blastocysts release factors that differentially alter human endometrial epithelial cell adhesion and gene expression relative to IVF success.  Human Reproduction. 2013;28(5):1161-71. Epub 2013 Mar 10.

Aschenbach LC, Hester KE, Rothenheber NC, Zhang J, Dimitriadis E*, Duffy DM* (co-last authors).  The LIF receptor antagonist PEGLA is effectively delivered to the uterine endometrium and blocks LIF activity in cynomolgus monkeys. Contraception. 2013;87(6):813-23.   doi: 10.1016/j.

Nejatbakhsh R, Kabir-Salmani M, Dimitriadis E, Hosseini A, Taheripanah R, Sadeghi Y, Akimoto Y, Iwashita M. Subcellular localization of L-selectin ligand in the endometrium implies a novel function for pinopodes in endometrial receptivity. Reproductive Biology Endocrinology. 2012;10(1):46.

Lay V, Yap J, Sonderegger S, Dimitriadis E. Interleukin (IL) 11 regulates adhesion and migration of endometrial cancer cells via STAT3. International Journal of Oncology.  2012;41(2):759-764.

Donoghue JF, McGavigan CJ, Lederman FL, Cann LM, Fu L, Dimitriadis E, Girling JE, Rogers PAW. Dilated thin-walled blood and lymphatic vessels in human endometrium: a potential role for VEGF-D in progestin-induced break-through bleeding. PLoS One. 2012;7(2):e30916.

Menkhorst EM, Lane N, Winship AL, Li P, Yap J, Meehan K, Rainczuk A, Stephens A, Dimitriadis E.  Decidual-secreted factors alter invasive trophoblast membrane and secreted proteins implying a role for decidual cell regulation of placentation. PLoS One. 2012;7(2):e31418.

Howlett M, Chalinor HV, Buzzelli JN, Nguyen N, van Driel IR, Bell KM, Fox JG, Dimitriadis E, Menheniott TR, Giraud AS, Judd L. IL-11 is a parietal cell cytokine that induces 1 atrophic gastritis.  Gut.  2012;61(10):1398-409.  (Epub Dec 16 2011).

Shuya LL, Menkhorst EM, Yap J, Li P, Lane N, Dimitriadis E (2011) Leukemia Inhibitory Factor enhances endometrial stromal cell differentiation in humans and mice. PLoS One. 2011;6(9): e25288.

Sonderegger S, Yap J, Menkhorst E, Weston G, Stanton PG, Dimitriadis E.   Interleukin (IL)11 mediates protein secretion and modification in human extravillous trophoblasts. Human Reproduction. 2011;26(10):2841-2849.

Yap J, Foo CF, Lee MY, Stanton PG, Dimitriadis E.  Proteomic analysis identifies interleukin 11 regulated plasma membrane proteins in human endometrial epithelial cells in vitro. Reproductive Biology Endocrinology. 2011;9(1):73.

Menkhorst E, Zhang J-G, Sims NA, Morgan PO, Soo P, Poulton IJ, Metcalf D,  Alexandrou E, Gresle M, Salamonsen LA, Buzkueven H4, Nicola NA, Dimitriadis E. Vaginally administered PEGylated LIF antagonist blocked embryo implantation and eliminated non-target effects on bone in mice. PLoS One. 2011;6(5):e19665.

Paiva P, Hannan NJ, Hincks C, Meehan KL, Pruysers E, Dimitriadis E, Salamonsen LA.  Human chorionic gonadotrophin regulates FGF2 and other cytokines produced by human endometrial epithelial cells, providing a mechanism for enhancing endometrial receptivity. Human Reproduction.  2011;26(5):1153-62.

Yap J, Salamonsen LA, Jobling T, Nicholls PK, Dimitriadis E. Interleukin 11 is upregulated in uterine lavage and endometrial cancer cells in women with endometrial carcinoma. Reproductive Biology and Endocrinology 2010;8(1):63.

Stoikos CJ, Salamonsen LA, Hannan NJ, O’Connor A, Rombauts L, Dimitriadis E.  Activin A decreases trophoblast cell adhesion: implications for implantation failure in women with endometriosis-associated infertility. Human Reproduction. 2010;25(7): 1767-1774.

Menkhorst E, Zhang J, Salamonsen L, Harrison C, Gu J and Dimitriadis E. IL11 and activin A synergise to regulate progesterone-induced but not cAMP-induced decidualization. Journal of Reproductive Immunology. 2010;84(2):124-132.

Novakovic B, Sibson M, Ng HK, Manuelpillai U, Rakyan V, Down T, Beck S, Fournier T, Evain-Brion D, Dimitriadis E, Craig JM, Morley R, Saffery R.  Placenta-specific methylation of the vitamin D 24-hydroxylase gene: implications for feedback autoregulation of active vitamin D levels at the fetomaternal interface. Journal of Biological Chemistry. 2009:284(22):14838-14848.

Marwood M, Visser K, Salamonsen LA, Dimitriadis E. Interleukin 11 and leukaemia inhibitory factor regulate the adhesion of endometrial epithelial cells: implications in fertility regulation. Endocrinology. 2009;150(6):2915-2923. IF=5.045. Citations: 64.

Menkhorst E, Salamonsen LA, Robb L, Dimitriadis E. IL-11 antagonist inhibits uterine stromal differentiation causing pregnancy failure in mice. Biology of Reproduction. 2009;80:920-927. IF=3.769.

Paiva P, Salamonsen LA, Manuelpillai U, Dimitriadis E. Interleukin 11 inhibits human trophoblast invasion indicating a likely role in the decidual restraint of trophoblast invasion during placentation. Biology of Reproduction. 2009;80(2):302-310. IF=3.769.

Stoikos C, Salamonsen LA, Harrison C, Dimitriadis E. A distinct cohort of TGFβ superfamily members are expressed in human endometrium that regulate decidualisation.  Human Reproduction. 2008;23(6):1447-1456. IF=3.769.

Tapia A, Salamonsen LA, Manuelpillai U, Dimitriadis E. Leukemia inhibitory factor promotes human first trimester extravillous trophoblast adhesion to extracellular matrix and secretion of TIMP-1 and -2. Humanan Reproduction.  2008;23(8):1724-1732. IF=3.769.

Infertility White CA, Zhang JG, Salamonsen LA, Baca M, Fairlie WD, Metcalf D, Nicola NA, Robb L, Dimitriadis E. Blocking leukemia inhibitory factor action in the uterus using a novel PEGylated antagonist prevents implantation: a new non-hormonal contraceptive strategy. Proceedings of the National Academy of  Sciences of USA. 2007;104(49):19357-62. (Editorial in Science and PNAS cover feature) IF=10.2.

Developing biomarkers and therapeutics for preeclampsia and miscarriage

Novakovic B, Napier CE, Vryer R, Dimitriadis E, Manuelpillai U, Sharkey A, Craig JM, Reddel RR, Saffery R.  DNA methylation mediated up-regulation of TERRA non-coding RNA is coincident with elongated telomeres in the human placenta.  Molecular Human Reproduction, 2016;22(11):791-799.

Winship AL, Koga K, Menkhorst E, Van Sinderen M, Rainczuk K, Nagai M, Cuman C, Yap J, Zhang JG, Simmons D, Young MJ, Dimitriadis E. Interleukin-11 alters placentation and causes preeclampsia features in mice. Proceedings of the Nationall Academy of Sciences of USA. 2015;112(52):15928-33.

Evans J, Salamonsen LA, Menkhorst E, Dimitriadis E. Dynamic changes in hyperglycosylated human chorionic gonadotrophin throughout the first trimester of pregnancy and its role in early placentation. Human Reproduction. 2015;30(5):1029-38.

Evans J, Yap J, Gamage T, Salamonsen L, Dimitriadis E, Menkhorst E.  Galectin-7 is important for normal uterine repair following menstruation.  Molecular Human Reproduction 2014;20(8):787-98. Epub 2014 Apr 29. Citations: 12. Field Weighted Citation Impact: 0.85.

Menkhorst E, Koga K, Van Sinderen M, Dimitriadis E. Galectin-7 serum levels are altered prior to the onset of pre-eclampsia. Placenta. 2014;35(4):281-5.

Menkhorst EM, Gamage T, Cuman C, Kaitu’u-Lino TJ, Tong S, Dimitriadis E.  Galectin-7 acts as an adhesion molecule during implantation and increased expression is associated with miscarriage.  Placenta. 2014;35(3):195-201. Epub 2014 Jan 24.

Van Sinderen M, Cuman C, Winship A, Menkhorst E, Dimitriadis E. The chrondroitin sulfate proteoglycan (CSPG4) regulates human trophoblast function.  Placenta. 2013;34(10):907-12.  Epub 2013 Aug 15.

Lalitkumar S, Boggavarapu NR, Menezes J, Dimitriadis E, Zhang JG, Nicola NA, Gemzell-Danielsson K, Lalitkumar LP. Polyethylene glycated leukemia inhibitory factor antagonist inhibits human blastocyst implantation and triggers apoptosis by down-regulating embryonic AKT. Fertily Sterility. 2013;100(4);1160-9.e2.  Epub 2013 Jul 19.

Endometrial cancer development and new treatment options

Van Sinderen M, Griffiths M, Menkhorst E, Niven K, Dimitriadis E. “Restoration of microRNA-29c in type I endometioid cancer reduced endometrial cancer cell growth” Oncology Letters– miR29c in EC, in press online now.

Loke H, Rainczuk K, Dimitriadis E. MicroRNA biogenesis machinery is dysregulated in the endometrium of infertile women suggesting a role in receptivity and infertility. Journal of Histochemistry & Cytochemistry. 2019 Accepted for publication. Online now.

Menkhorst E, Griffiths M, Van Sinderen M, Rainczuk K, Niven K, Dimitriadis E. Galectin-7 is elevated in endometriod (type I) endometrial cancer and promotes cell migration.  Oncology Letters. 2018;16(4):4721-4728.

Menkhorst E, Van Sinderen M, Rainczuk K, Cuman C, Winship A, Dimitriadis E.  Invasive trophoblast promote stromal fibroblast decidualization via profiling 1 and ALOX5. Scientific Reports. 2017;7:1:8690 Article Number. Doi: 10.1038/s41598-017-05947-0.

Winship A, Menkhorst E, Van Sinderen M, Dimitriadis E. Interleukin 11 blockade during mid to late gestation does not affect maternal blood pressure, pregnancy viability or subsequent fertility in mice.  Reproductive BioMedicine Online.  2018;36(3):250-258.

Winship A, Ton A, Van Sinderen M, Menkhorst E, Rainczuk K, Griffiths M, Cuman C, Dimitriadis E.  Mouse double minute homologue 2 (MDM2) downregulation by miR-661 impairs human endometrial epithelial cell adhesive capacity.  Reproduction, Fertility and Development 2018;30(3):477-486. Doi: 10.1071/RD17095.

Bernasochi GB, Boon WC, Curl CL, Varma U, Pepe S, Tare M, Parry LJ, Dimitriadis E, Harrap SB, Nalliah CJ, Kalman JM, Delbridge LMD, Bell JR. Pericardial adipose and aromatase: A new translational target for aging, obesity and arrhythmogenesis? Journal Molecular Cellular Cardiology, 2017;111:96-101.

Winship AL, Sorby K, Correia J, Rainczuk A, Yap J, Dimitriadis E. Interleukin-11 up-regulates endoplasmic reticulum stress induced target, PDIA4 in human first trimester placenta and in vivo in mice.  Placenta. 2017;53:92-100.

Winship A, Van Sinderen M, Rainczuk K, Dimitriadis E. Therapeutically blocking Interleukin-11 receptor- enhanced doxorubicin cytotoxicity in high grade type 1 endometrioid tumours. Oncotarget, 2017;8(14):22716-29.

Winship A, van Sinderen M, Heffernan-Marks A, Dimitriadis E. Chondroitin sulfate proteoglycan protein is stimulated by interleukin 11 and promotes endometrial epithelial cancer cell proliferation and migration.  International Journal of Oncology. 2017;50:798-804.

Winship AL, Rainczuk K, Ton A, Dimitriadis E. Fibulin-5 localisation in human endometrial cancer shifts from epithelial to stromal with increasing tumour grade, and silencing promootes endometrial epithelial cancer call proliferation.  Oncology Letters 2016;12(1):651-657.

Winship A, Menkhorst E, Van Sinderen M, Dimitriadis E. Interleukin 11: similar or opposite roles in female reproduction and reproductive cancer? Reproduction, Fertility and Development. 2016;28(4):395-405.

Winship AL, Rainczuk K, Dimitriadis E.  Flotillin-1 protein is upregulated in human endometrial cancer and localization shifts from epithelial to stromal with increasing tumor grade.  Cancer Investigation. 2016;34(1):26-31.

Winship AL, Van Sinderen M, Donoghue J, Rainczuk K, Dimitriadis E.  Targeting Interleukin-11 receptor- impairs human endometrial cancer cell proliferation and invasion in vitro and reduces tumour growth and metastasis in vivo. Molecular Cancer Therapeutics. 2016;15(4):720-30.

Cuman C, Van Sinderen M, Gantier MP, Rainczuk K, Sorby K, Rombauts L, Osianlis T, Dimitriadis E.  Human Blastocyst Secreted microRNA Regulate Endometrial Epithelial Cell Adhesion.  EBioMedicine. 2015;2(10):1528-35. eCollection 2015 Oct. Citations: 21.

Winship A, Cuman C, Rainczuk K, Dimitriadis E.  Fibulin-5 is upregulated in decidualized human endometrial stromal cells and promotes primary human extravillous trophoblast outgrowth.  Placenta 2015;36(12):1405-11.

Winship A, Correia J, Zhang JG, Nicola NA, Dimitriadis E. Leukemia Inhibitory Factor (LIF) inhibition during mid-gestation impairs trophoblast invasion and spiral artery remodelling during pregnancy in mice.  PLoS One 2015;10(10):e0129110.

Winship A, Correia J, Krishnan T, Menkhorst E, Cuman C, Zhang JG, Nicola NA, Dimitriadis E.  Blocking Endogenous Leukemia Inhibitory Factor During Placental Development in Mice Leads to Abnormal Placentation and Pregnancy Loss. Scientific Reports 2015;5:13237.

Research Projects

This Research Group doesn't currently have any projects



Faculty Research Themes

Cancer

School Research Themes

Cancer in Medicine, Women's Health



Key Contact

For further information about this research, please contact Professor Eva Dimitriadis

Department / Centre

Obstetrics and Gynaecology , Gynaecology Research Centre

Unit / Centre

Dimitriadis Group Reproductive Biology and Co-Head Gynaecology Research Centre

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