Translational Obstetrics Group

• 
  Professor of Obstetrics and Gynaecology
  Professor Stephen Tong

  stong@unimelb.edu.au

  View researcher's webpage

  +61 3 8458 4377

Research Overview

The Translational Obstetrics Group is a team of 10-15 scientists and clinician-scientists, lead by Professor Stephen Tong.

The team is focused on developing diagnostics and therapeutics to improve the care of pregnant women and their fetuses.  They have a focus on developing treatments for ectopic pregnancy and preeclampsia, and developing diagnostics to avert stillbirth.

Three concepts conceived by the Translational Obstetrics Group have progressed from preclinical laboratory studies to international multi-centre trials and prospective studies:

The team has transitioned a novel drug treatment for ectopic pregnancy from preclinical studies to a large multicentre phase III clinical trial that is recruiting across 25-50 hospitals in the United Kingdom.

The Translational Obstetrics Group has also developed a preclinical pipeline to screen drugs that are safe in pregnancy and may be highly effective in treating or preventing preeclampsia. His team has published work identifying such drug candidates for preeclampsia, such as pravastatin, metformin and solfacone. Finally, his team has a strong interest in further understanding the molecular mechanisms in preeclampsia.

As a result of preclinical studies performed by the team they are now investigating – in collaboration with academics at Tygerberg Hospital - whether esomeprazole could be used to treat preterm preeclampsia in a phase II randomized trial in South Africa.

A large study lead by the team to develop a maternal blood test to identify fetuses critically starved of oxygen (and at high risk of stillbirth) has just completed recruitment across eight hospitals in Australia and New Zealand. Lastly, the Translational Obstetrics Group is collaborating with the Perinatal research unit at Mercy Hospital for Women in a large prospective study to develop a maternal blood test to identify fetuses that are growth restricted (and also at higher risk of stillbirth). These two large biomarker studies arose from concepts developed by the team in the laboratory.

Staff

• Professor Stephen Tong, Clinician-Scientist, head of The Translational Obstetrics Group
• Associate Professor Natalie Hannan, Senior Scientist
• Associate Professor Tu'uhevaha Kaitu'u-Lino, Senior Scientist
• Dr Lisa Hui, Clinician-Scientist
• Dr Fiona Brownfoot, Clinician-Scientist
• Dr Roxanne Hastie, Perinatal Research Fellow
• Dr Anthea Lindquist, Perinatal Senior Research Fellow
• Sally Beard, Research Assistant
• Ping Cannon, Research Assistant
• Natalie Binder, Research Assistant
• Laura Tuohey, Research Assistant
• Vi Nguyen, Research Assistant
• Carole-Ann Whigham, PhD student
• Natasha De Alwis, PhD student
• Natasha Pritchard, PhD student
• Amber Kenney, PhD student

Collaborators

1. Dr Cathy Cluver, Professor Gerald Theron, Professor David Hall - South Africa
   These eminent academics are based at Tygerberg Hospital in South Africa and are running the PIE trial. PIE is a phase II randomised clinical trial that examines whether esomeprazole may be a useful treatment for women with severe preterm preclampsia. This is a severe pregnancy complication that continues to claim many lives globally.
2. Professor Andrew Horne, Scotland
   Professor Horne and Professor Tong are leading the GEM III trial, a phase III randomised clinical to examine whether combining gefitinib (a molecularly targeted EGFR inhibitor) with methotrexate could be an effective way to medically cure ectopic pregnancy.
3. Professor Sebastian Ilanes
   Professor Ilanes is a clinician-scientist in Chile. He is collaborating with the team to further unravel the mechanisms of preeclampsia.
4. Maternal Fetal Medicine Specialists across Australia
   We are collaborating with clinicians across Australia to develop a blood test that may identify fetuses that are critically starved of oxygen and at imment risk of stillbirth. Our value collaborators are: Dr Scott Petersen (Mater Hospital, QLD), Dr Sean Seeho (Royal North Shore, Sydney), Dr Amanda Henry (Royal Hospital for Women, Sydney), Dr Katie Groom,  (Auckland City Hospital, New Zealand), A/Prof Jo Said (Sunshine Hospital).
5. Lynda Harris, University of Manchester
   Lynda is working with the team to develop nanoparticles to deliver drugs directly to the placenta.
6. Professor Laura Parry
   Professor Parry is a vasular biologist who is working with the team to develop treatments for preeclampsia, and to discover new insights into disease pathogenesis.

Funding

Our team are chief investigators on five NHMRC Project Grants

1. 2016-2019 NHMRC Project Grant – Systematic screening approach to identify new therapeutics for preeclampsia (ID 1101871, $727,529). CIs Tong S, Kaitu’u-Lino T, Hannan N, Parry L
2. 2014-2016 NHMRC Project Grant  - Developing diagnostics and therapeutics for preeclampsia: targeting a novel placental specific sFlt-1 variant (ID 1061977, $698,622).  CIs Tong S, Palmer K, Kaitu’u-Lino T
3. 2014-2016  NHMRC Project Grant  - Improving the prediction and detection of contributors to term stillbirth (ID 1065854, $551,111). CIs Walker S, Tong S, Whitehead C, Howard M
4. 2014-2016  NHMRC Project Grant  - Relaxin treatment of preeclampsia (ID 1064845, $633,901). CIs Parry L, Tong S, Tare M
5. 2014-2016  NHMRC Project Grant - The Critical Role of Corin and Atrial Natriuretic Peptide in human placentation. CI Hannan N.

Other major funding

6. 2016-2019 Efficacy and Mechanisms Evaluation/National Institute for Health Research (EME/NIHR, part of MRC/NHS UK) (£ 999,811, ie 2,048,849 AUD). GEM3: A multi-centre double-blind randomised trial of a combination of methotrexate and gefitinib versus methotrexate alone as a treatment for ectopic pregnancy. Role Chief Investigator B (Horne AW, Tong S, Duncan WC, Mol B, Bhattacharya S, Daniels J, Coomaraswamy A, Jorkovic D, Bourne T, Bottomley C, Peace-Gadsby A.

Fellowship Funding (salary support):

7. NHMRC Career Development Fellowship Level II - Awarded to Professor Stephen Tong
8. CR Roper Fellowship - Awarded to Dr Natalie Hannan
9. NHMRC Career Development Fellowship Level I - Awarded to Dr Tu'uhevaha Kaitu'u-Lino.

Other funding:

We have received philanthropic grants from many funding bodies, including the Norman Beischer Medical Research Foundation, RANZCOG, Stillbirth Foundation. The Kilvington Trust, the Veski Foundation and others.

Research Publications

Developing therapeutics for ectopic pregnancy

We have pioneered a new treatment  to medially treat ectopic pregnancy, taking it successfully from preclinical studies to clinical trials:

1. Skubisz MM, Horne AW, Johns TG, Nilsson UW, Duncan WC, Wallace EM, Critchley HO, Tong S. Combination gefitinib and methotrexate compared to methotrexate alone to treat ectopic pregnancy. Obstetrics and Gynecology 2013; 122(4):745-51
2. Horne AW, Skubisz M, Doust A, Duncan WC, Wallace EM, Critchley HOD, Johns T, Norman JE, Bhattacharya S, Mollison J, Rassmusen M, Tong S. Phase II single arm open label multicentre clinical trial to evaluate the efficacy and side effects of combination gefitinib and methotrexate to treat tubal ectopic pregnancies (GEM II): study protocol. BMJ Open 2013; Jul 19;3(7) e002902
3. Horne A, Skubisz MM, Tong S, Duncan WC, Neil P, Wallace EM, Johns TG. Combination gefitinb and methotrexate treatment for non-tubal ectopic pregnancies: a case series. Human Reproduction 2014;29(7):1375-9.

Developing a maternal blood test for stillbirth

Our group is exploring whether measuring RNA released into the maternal blood from the stressed placenta can be a novel approach to identify fetuses at high risk of stillbirth

1. Whitehead CL, Teh WT, Walker SP, Leung C, Mendis S, Lamour L, Tong S. Quantifying circulating hypoxia-induced RNA transcripts in maternal blood to determine in utero fetal hypoxic status. BMC Medicine 2013,11:256 doi:10.1186/1741-7015-11-256
2. Whitehead CL, Teh WT, Walker SP, Leung C, Larmour L, Tong S. Circulating MicroRNAs as potential biomarkers for fetal hypoxia in utero. PLoS One 2013;8(11):e78487.
3. Whitehead C, Walker SP, Mendis S, Lappas M, Tong S. Quantifying mRNA coding growth genes in the maternal circulation to detect fetal growth restriction. American Journal of Obstetrics and Gynecology 2013;209(2):133.e1 9
4. Whitehead CL, McNamara H, Walker SP, Alexiadis M, Fuller P, Vickers DK, Hastie R, Tuohey L, Hannan NJ, Kaitu’u-Lino TJ, Tong S. Identifying late onset fetal growth restriction by measuring circulating placental RNA in the maternal blood at 28 weeks gestation. American Journal of Obstetrics and Gynecology 2016; 214(4): 521.e1-8.

Developing therapeutics for preelampsia

Our team are identifying new treatments for preeclampsia and testing them in human trials. We are also interrogating key mechanisms in the pathophysiology of preeclampsia.

1. Whitehead C, Tong S, Wilson D, Howard M, Walker SP. Treatment of early-onset preeclampsia with continuous positive airway pressure. Obstetrics and Gynecology 2015;5(1):131.
2. Onda K, Tong S, Nakahara A, Kondo M, Monchusho H, Hirano T, Kaitu'u-Lino T, Beard S, Binder N, Tuohey L, Brownfoot F and Hannan NJ. Sofalcone up-regulates the nuclear factor (erythroid-derived 2)-like 2 /heme-oxygenase-1 pathway, reduces sFlt-1 and quenches endothelial dysfunction: a potential therapeutic for preeclampsia. Hypertension  2015; 65(4):855-62.
3. Brownfoot F, Tong S, Hannan NJ, Binder NK, Walker SP, Cannon P, Hastie R, Onda K, Kaitu’u-Lino TJ. Effects of pravastatin on human placenta, endothelium and women with severe preeclampsia. Hypertension 2015;66(30):687-97.
4. Tong S, Kaitu’u-Lino TJ, Onda K, Beard Sm Binder NK, Cluver C, Tuohey L, Whitehead C, Brownfoot F, De Silva M, Hannan NJ. Heme oxygenase-1 is not decreased in preeclamptic placenta and does not negatively regulate placental soluble fms-like tyrosine kinase-1 or soluble endoglin secretion. Hypertension 2015;66(5):1073-81.
5. Palmer KR, Kaitu’u-Lino TJ, Hastie R, Ye L, Binder N, Cannon P, Tuohey L, Johns TG, Shub A, Tong S. Placental-specific sFlt-1 e15a protein is increased in preeclampsia, antagonises vascular endothelial growth factor signalling, and has anti-angiogenic activity. Hypertension 2015; 66(6):1251-9.
6. Cluver C, Walker SP, Mol B, Theron GB, Hall DR, Hiscock R, Tong S. A double-blind, randomised, placebo-controlled trial to evaluate the efficacy of esomeprazole to treat early onset preeclampsia (PIE Trial): study protocol. BMJ Open 2015; 28;5(20):e008211
7. Brownfoot FC, Hastie R, Hannan NJ, Cannon P, Tuohey L, Parry LJ, Senadheera S, Illanes SE, Kaitu’u-Lino, TJ, Tong S. Metformin: a potential agent for the prevention and treatment of preeclampsia based on its effects on anti-angiogenic factor secretion and endothelial dysfunction. American Journal of Obstetrics and Gynecology 2016;214(3);356.e1-356.e15.