Therapeutics Discovery and Vascular Function Group

Research Overview

Therapeutics Discovery and Vascular Function Group is focused on improving Women’s health, principally understanding serious pregnancy complications and identifying and developing novel treatment strategies for these conditions, particularly preeclampsia, hypertension in pregnancy, fetal growth restriction and preterm birth. Our research program focuses on understanding placental development and how inappropriate development can lead to dangerous consequences for both the mother and her fetus.

Understanding placental and vascular dysfunction in major complications of pregnancy

Preeclampsia is a shocking syndrome of pregnancy, where the failing placenta releases excess levels of anti-angiogenic and pro-inflammatory factors into the maternal circulation, causing serious systemic maternal vascular dysfunction and organ failure. The team has led and contributed to many important publications in this area uncovering the early development of the placenta, the critical roles anti-angiogenic and pro-inflammatory meditators play in severity of vascular dysfunction and injury. These findings were predominantly uncovered through the use of primary human placental and vascular tissues (and isolated cells) obtained via established tissue biobanks.

Developing novel therapies and innovative drug delivery for pregnancy complications

We established a primary human tissue screening pipeline, to develop therapeutics for preeclampsia. Importantly, this utilises primary human cells, tissue, vessels and blood samples (collected from women during pregnancy) to design key experiments to model the pathophysiology; allowing testing of novel drugs for prevention/treatment of preeclampsia. We have also developed several exciting mouse models of preeclampsia, one of which uses sophisticated lentiviral embryo manipulation techniques to produce a placental specific disease model (a model that best recapitulates the disease as seen in women). Notably these models have been used to test the possibility of delivering therapeutics to the dysfunctional placenta using nanomedicine technology as well as the discovery of small molecule targets.

Staff

  • A/Professor Natalia Hannan Research Group Leader
  • Dr Natalie Binder Post-doctoral Scientist
  • Sally Beard Research Assistant and Masters Student
  • Natasha de Alwis PhD Student
  • Bridget Arman PhD Student
  • Bianco Fato Honours Student

Collaborators

  • Dr Lynda Harris, The University of Manchester, UK
  • Professor Jenny Myers, University of Manchester, St. Mary’s Hospital, UK
  • A/Professor Cathy Cluver, Stellenbosch University, Tygerberg Hospital, South Africa
  • A/Professor Kenji Onda, Tokyo University of Life Sciences, Japan
  • A/Professor Lara Friel, University of Texas Houston, USA
  • Professor Stephen Tong, The University of Melbourne and Mercy Perinatal, Australia
  • Professor Jon Hyett, The University of Sydney, Australia
  • Jennifer MacDiarmid, EnGENeic Pty Ltd., Australia
  • A/Professor Lisa Hui, The University of Melbourne and Mercy Perninatal, Australia
  • Dr Amanda Henry, St Georges Hospital and the University of New South Wales, Australia
  • Dr Clare Arnott, Heart Research Institute, Australia
  • Professor Tom Marwick, Baker IDI, Australia
  • A/Professor Jo Said, University of Melbourne and the Western Hospital, Australia
  • Professor Laura Mackay, Peter Doherty Institute, University of Melbourne, Australia
  • Professor Laura Parry, University of Adelaide, Australia

Funding

The research activities of the group are funded by a variety of sources including National Health & Medical Research Council, Baker IDI, Mercy Perinatal, University of Melbourne and philanthropic and industry funding.

Research Publications

Recent research publications from Therapeutics Discovery and Vascular Function Group:

1. Binder NK, Brownfoot FC, Beard S, Cannon P, Nguyen TV, Tong S, Kaitu'u-Lino TJ, Hannan NJ. Esomeprazole and sulfasalazine in combination additively reduce sFlt-1 secretion and diminish endothelial dysfunction: potential for a combination treatment for preeclampsia. Pregnancy Hypertens. 2020; 22:86-96. doi: 10.1016/j.preghy.2020.07.013

2. Hannan NJ, Stock O, Spencer R, Whitehead C, David A, Groom K, Petersen S, Henry A, Said J, Seeho S, Kane S, Gordon L, Beard S, Karegodar S, Chindera K, Hiscock R, Pritchard N, Kaitu'u-Lino T, Walker S, Tong S. Circulating mRNAs are differentially expressed in pregnancies with severe placental insufficiency and at high risk of stillbirth. BMC Medicine. 2020 May;18:145. doi: 10.1186/s12916-020-01605-x

3. Beard S, Pritchard N,  Binder NK, Karen Schindler, de Alwis N, Kaitu'u-Lino TJ, Tong S, Hannan NJ. Aurora kinase mRNA expression is reduced with increasing gestational age and in severe early onset fetal growth restriction. Placenta. 2020 Jun;95:53-61. doi: 10.1016/j.placenta.2020.04.012

4. de Alwis N, Beard S, Mangwiro YT, Binder NK, Kaitu'u-Lino TJ, Brownfoot FC, Tong S, Hannan NJ. Pravastatin as the statin of choice for reducing pre-eclampsia-associated endothelial dysfunction. Pregnancy Hypertens. 2020 Mar 4;20:83-91

EGFL7 gene expression is regulated by hypoxia in trophoblast and altered in the plasma of patients with early preeclampsia. Pregnancy Hypertens. 2018 Oct. doi: 10.1016/j.preghy.2018.09.001

5. Cluver CA, Hannan NJ, van Papendorp E, Hiscock R, Beard S, Mol BW, Theron GB, Hall DR, Decloedt EH, Stander M, Adams KT, Rensburg M, Schubert P, Walker SP, Tong S. Esomeprazole to treat women with preterm preeclampsia: a randomized placebo controlled trial. Am J Obstet Gynecol. 2018 Oct;219(4):388.e1-388.e17

6. Hannan NJ, Binder NK, Beard S, Nguyen TV, Kaitu’u-Lino TJ and Tong S. Melatonin enhances antioxidant molecules in the placenta, reduces secretion of soluble fms-like tyrosine kinase 1 (sFLT) from primary trophoblast but does not rescue endothelial dysfunction: An evaluation of its potential to treat preeclampsia. PLoS One. 2018 Apr 11;13(4):e0187082

7. Kaitu'u-Lino TJ, Brownfoot FC, Beard S, Cannon P, Hastie R, Nguyen TV, Binder NK, Tong S, Hannan NJ. Combining metformin and esomeprazole is additive in reducing sFlt-1 secretion and decreasing endothelial dysfunction - implications for treating preeclampsia. PLoS One. 2018 Feb 21;13(2):e0188845

8. Pendlebury A, Hannan NJ, Binder N, Beard S, Mcgauran M, Grant P, Tong S, Whitehead CL.  The circulating microRNA-200 family in whole blood are potential biomarkers for high-grade serous epithelial ovarian cancer. Biomed Rep. 2017 Mar;6(3):319-322. doi: 10.3892/br.2017.847. Epub 2017 Jan 25

9. Hannan NJ, Beard S, Binder NK, Onda K, Kaitu'u-Lino TJ, Chen Q, Tuohey L, De Silva M, Tong S. Key players of the necroptosis pathway RIPK1 and SIRT2 are altered in placenta from preeclampsia and fetal growth restriction. Placenta. 2017 Mar;51:1-9. doi: 10.1016/j.placenta.2017.01.002. Epub 2017 Jan 4

10. Onda K, Tong S, Beard S, Binder N, Muto M, Senadheera SN, Parry L, Dilworth M, Renshall L, Brownfoot F, Hastie R, Tuohey L, Palmer K, Hirano T, Ikawa M, Kaitu'u-Lino T, Hannan NJ. Proton Pump Inhibitors Decrease Soluble fms-Like Tyrosine Kinase-1 and Soluble Endoglin Secretion, Decrease Hypertension, and Rescue Endothelial Dysfunction. Hypertension. 2017 Mar;69(3):457-468. doi: 10.1161/HYPERTENSIONAHA.116.08408. Epub 2017 Jan 23

Research Projects


School Research Themes

Women's Health



Key Contact

For further information about this research, please contact Associate Professor Natalie Hannan

Department / Centre

Obstetrics and Gynaecology

Node

Mercy Health

Unit / Centre

Therapeutics Discovery and Vascular Function Group

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