DEVELOPING MOLECULAR THERAPEUTICS AND DIAGNOSTICS FOR PREGNANCY COMPLICATIONS
Grant number: 1050765 | Funding period: 2013 - 2016
Pregnancy complications still causes the death of mothers, and their babies. During this fellowship, we will be developing new treatments and clinical tests for three important complications of pregnancy. We will run clinical trials of a new medication based treatment to cure ectopic pregnancies. We will also develop a blood test that can identify those babies still in the womb but suffering dangerously low oxygen levels. Lastly, we will develop drugs to treat preeclampsia, a serious condition of pregnancy.
Related publications (40)
High-dose compared with low-dose oxytocin for induction of labour of nulliparous women at term
Natasha Prichard, Anthea Lindquist, Richard Hiscock, Sophie Ruff, Stephen Tong, Fiona C Brownfoot
BACKGROUND: The optimal oxytocin infusion regimen to induce labour with the lowest caesarean section rate, instrumental delivery r..
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
Natalie J Hannan, Natalie K Binder, Sally Beard, Nguyen Tuong-Vi, Tu'uhevaha J Kaitu'u-Lino, Stephen Tong
Preeclampsia is one of the most serious complications of pregnancy. Currently there are no medical treatments. Given placental oxi..
Vinorelbine Potently Induces Placental Cell Death, Does Not Harm Fertility and is a Potential Treatment for Ectopic Pregnancy
Roxanne Hastie, Elgene Lim, Pavel Sluka, Lisa Campbell, Andrew W Horne, Lenore Ellett, Natalie J Hannan, Fiona Brownfoot, Tu'uhevaha J Kaitu'u-Lino, Stephen Tong
Ectopic pregnancies complicate 1-2 pregnancies and are a leading cause of maternal death. An effective oral drug therapy that repl..
Combining metformin and esomeprazole is additive in reducing sFlt-1 secretion and decreasing endothelial dysfunction - implications for treating preeclampsia
Tu'uhevaha J Kaitu'u-Lino, Fiona C Brownfoot, Sally Beard, Ping Cannon, Roxanne Hastie, Tuong V Nguyen, Natalie K Binder, Stephen Tong, Natalie J Hannan
INTRODUCTION: The discovery of new treatments that prevent or treat preeclampsia would be a major advance. Antiangiogenic factors ..
Resveratrol inhibits release of soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin and improves vascular dysfunction - implications as a preeclampsia treatment
Natalie J Hannan, Fiona C Brownfoot, Ping Cannon, Minh Deo, Sally Beard, Tuong V Nguyen, Kirsten R Palmer, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino
Preeclampsia is a disease of pregnancy associated with placental oxidative stress, inflammation and elevated release of anti-angio..
Key players of the necroptosis pathway RIPK1 and SIRT2 are altered in placenta from preeclampsia and fetal growth restriction
Natalie J Hannan, Sally Beard, Natalie K Binder, Kenji Onda, Tu'uhevaha J Kaitu'u-Lino, Qi Chen, Laura Tuohey, Manarangi De Silva, Stephen Tong
INTRODUCTION: Preeclampsia (PE) and fetal growth restriction (FGR) are among the leading causes of perinatal morbidity and mortali..
Maternal plasma concentrations of the placental specific sFLT-1 variant, sFLT-1 e15a, in fetal growth restriction and preeclampsia
Kirsten R Palmer, Tu'uhevaha J Kaitu'u-Lino, Ping Cannon, Laura Tuohey, Manarangi S De Silva, Manuel Varas-Godoy, Stephanie Acuna, Jose Galaz, Stephen Tong, Sebastian E Illanes
OBJECTIVE: sFLT-1 e15a is a recently described sFlt-1 variant that is placental and primate specific. As such, it may have potenti..
Placental-specific sFLT-1: role in pre-eclamptic pathophysiology and its translational possibilities for clinical prediction and diagnosis
KR Palmer, S Tong, TJ Kaitu'u-Lino
Pre-eclampsia is a common obstetric complication globally responsible for a significant burden of maternal and perinatal morbidity..
Nuclear factor of activated T-cells (NFAT) regulates soluble fms-like tyrosine kinase-1 secretion (sFlt-1) from human placenta
Louie Ye, Amy Gratton, Natalie J Hannan, Ping Cannon, Minh Deo, Kirsten R Palmer, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino, Fiona C Brownfoot
INTRODUCTION: Preeclampsia is a serious complication affecting 5-8% of pregnancies. Central to its pathogenesis is placental hypox..
Steroid sulfatase is increased in the placentas and whole blood of women with early-onset preeclampsia
Amy M Gratton, Louie Ye, Fiona C Brownfoot, Natalie J Hannan, Clare Whitehead, Ping Cannon, Minh Deo, Peter J Fuller, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino
INTRODUCTION: Preeclampsia is a serious complication of pregnancy affecting 5% of pregnancies. Our team identified 137 genes highl..
ATF3 is a negative regulator of inflammation in human fetal membranes
Ratana Lim, Gillian Barker, Stella Liong, Caitlyn Nguyen-Ngo, Stephen Tong, Tu'uhevaha Kaitu'u-Lino, Martha Lappas
INTRODUCTION: Infection and inflammation stimulate pro-inflammatory cytokines, prostaglandins and matrix metalloproteinase (MMP)-9..
Abnormal plasma DNA profiles in early ovarian cancer using a non-invasive prenatal testing platform: implications for cancer screening
Paul A Cohen, Nicola Flowers, Stephen Tong, Natalie Hannan, Mark D Pertile, Lisa Hui
BACKGROUND: Non-invasive prenatal testing (NIPT) identifies fetal aneuploidy by sequencing cell-free DNA in the maternal plasma. P..
A comparison of sample collection methods for quantifying cell-free fetal neurodevelopment transcripts in amniotic fluid.
Lisa Hui, Stephen Tong, Tu'Uhevaha J Kaitu'u-Lino, Natalie J Hannan
BACKGROUND: Cell-free RNA (cfRNA) transcripts known to be expressed by the fetal brain are detectable by quantitative reverse tran..
Effects of simvastatin, rosuvastatin and pravastatin on soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sENG) secretion from human umbilical vein endothelial cells, primary trophoblast cells and placenta
Fiona C Brownfoot, Stephen Tong, Natalie J Hannan, Roxanne Hastie, Ping Cannon, Tu'uhevaha J Kaitu'u-Lino
BACKGROUND: Preeclampsia is associated with the placental release of soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endog..
Identifying late-onset fetal growth restriction by measuring circulating placental RNA in the maternal blood at 28 weeks' gestation
Clare L Whitehead, Helen McNamara, Susan P Walker, Maria Alexiadis, Peter J Fuller, Daniel K Vickers, Natalie J Hannan, Roxanne Hastie, Laura Tuohey, Tu'uhevaha J Kaitu'u-Lino, Stephen Tong
BACKGROUND: Late-onset fetal growth restriction (FGR) is often undetected prior to birth, which puts the fetus at increased risk o..
Loss of Akt increases soluble endoglin release from endothelial cells but not placenta
Tu'uhevaha J Kaitu'u-Lino, Roxanne Hastie, Natalie J Hannan, Fiona Brownfoot, Manarangi De Silva, Ping Cannon, Laura Tuohey, Stephen Tong
INTRODUCTION: Preeclampsia is a serious pregnancy complication for which there are no medical treatments. Soluble endoglin is an a..
Placental Insufficiency in Fetuses That Slow in Growth but Are Born Appropriate for Gestational Age: A Prospective Longitudinal Study
Nadia Bardien, Clare L Whitehead, Stephen Tong, Antony Ugoni, Susan McDonald, Susan P Walker
OBJECTIVES: To determine whether fetuses that slow in growth but are then born appropriate for gestational age (AGA, birthweight >..
Expectant management of severe preterm preeclampsia: a comparison of maternal and fetal indications for delivery
Samantha S Mooney, Rilka M Lee, Stephen Tong, Fiona C Brownfoot
OBJECTIVE: To examine the delivery indication (maternal or fetal) for patients with preterm preeclampsia and assess whether diseas..
Placental-Specific sFLT-1 e15a Protein Is Increased in Preeclampsia, Antagonizes Vascular Endothelial Growth Factor Signaling, and Has Antiangiogenic Activity
Kirsten R Palmer, Tu'uhevaha J Kaitu'u-Lino, Roxanne Hastie, Natalie J Hannan, Louie Ye, Natalie Binder, Ping Cannon, Laura Tuohey, Terrance G Johns, Alexis Shub, Stephen Tong
In preeclampsia, the antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFLT-1) is released from placenta into the maternal..
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
Stephen Tong, Tu'uhevaha J Kaitu'u-Lino, Kenji Onda, Sally Beard, Roxanne Hastie, Natalie K Binder, Cathy Cluver, Laura Tuohey, Clare Whitehead, Fiona Brownfoot, Manarangi De Silva, Natalie J Hannan
Elevated placental release of the antiangiogenic factors, soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sENG),..
A wash step at collection of placental biopsies from preeclamptic pregnancies does not adversely affect levels of sFlt-1 or endoglin
Tu'uhevaha J Kaitu'u-Lino, Natalie J Hannan, Manarangi De Silva, Natalie Binder, Laura Tuohey, Ping Cannon, Stephen Tong
There is recent interest for uniform placental collection protocols so laboratories can share samples. However, concerns have been..
Effects of Pravastatin on Human Placenta, Endothelium, and Women With Severe Preeclampsia
Fiona C Brownfoot, Stephen Tong, Natalie J Hannan, Natalie K Binder, Susan P Walker, Ping Cannon, Roxanne Hastie, Kenji Onda, Tu'uhevaha J Kaitu'u-Lino
UNLABELLED: Preeclampsia is a major pregnancy complication where excess placental release of soluble fms-like tyrosine kinase-1 (s..
Chorioamnionitis Occurring in Women With Preterm Rupture of the Fetal Membranes Is Associated With a Dynamic Increase in mRNAs Coding Cytokines in the Maternal Circulation
Owen Stock, Lavinia Gordon, Jada Kapoor, Susan P Walker, Clare Whitehead, Tu'uhevaha J Kaitu'u-Lino, Gabrielle Pell, Natalie J Hannan, Stephen Tong
BACKGROUND: Preterm prelabor rupture of the fetal membranes (PPROM) is a significant contributor to the morbidity and mortality of..
Paternal obesity in a rodent model affects placental gene expression in a sex-specific manner
Natalie K Binder, Sally A Beard, Tu'uhevaha J Kaitu'u-Lino, Stephen Tong, Natalie J Hannan, David K Gardner
Fetal growth restriction (FGR) is a major obstetric complication stemming from poor placental development. We have previously demo..
Sofalcone Upregulates the Nuclear Factor (Erythroid-Derived 2)-Like 2/Heme Oxygenase-1 Pathway, Reduces Soluble fms-Like Tyrosine Kinase-1, and Quenches Endothelial Dysfunction Potential Therapeutic for Preeclampsia
Kenji Onda, Stephen Tong, Anzu Nakahara, Mei Kondo, Hideaki Monchusho, Toshihiko Hirano, Tu'uhevaha Kaitu'u-Lino, Sally Beard, Natalie Binder, Laura Tuohey, Fiona Brownfoot, Natalie J Hannan
Preeclampsia is a severe complication of pregnancy, characterized by hypertension, oxidative stress, and severe endothelial dysfun..
Placental SEMA3B expression is not altered in severe early onset preeclampsia
TJ Kaitu'u-Lino, R Hastie, P Cannon, NK Binder, S Lee, O Stock, NJ Hannan, S Tong
Recent evidence suggests that Semaphorin 3B (SEMA3B) is upregulated in severe preeclampsia, and a major driver of cytotrophoblast ..
Stability of absolute copy number of housekeeping genes in preeclamptic and normal placentas, as measured by digital PCR
TJ Kaitu'u-Lino, R Hastie, P Cannon, S Lee, O Stock, NJ Hannan, R Hiscock, S Tong
Measuring mRNA expression is fundamental to placental research. Ideally, mRNA transcript numbers are directly quantified. However,..
Characterization of protocols for primary trophoblast purification, optimized for functional investigation of sFlt-1 and soluble endoglin
Tu'uhevaha J Kaitu'u-Lino, Stephen Tong, Sally Beard, Roxanne Hastie, Laura Tuohey, Fiona Brownfoot, Kenji Onda, Natalie J Hannan
OBJECTIVES: Soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) are the most studied molecules in preeclampsia..
Peptides do not prevent cleavage of endoglin to produce soluble endoglin
Roxanne Hastie, Stephen Tong, Ping Cannon, Fiona Brownfoot, Natalie J Hannan, Tu'uhevaha Kaitu'u-Lino
MMP14 cleaves membrane bound endoglin to produce soluble endoglin (sEng), an anti-angiogenic factor that causes endothelial dysfun..
Soluble endoglin production is upregulated by oxysterols but not quenched by pravastatin in primary placental and endothelial cells
FC Brownfoot, N Hannan, K Onda, S Tong, T Kaitu'u-Lino
INTRODUCTION: Preeclampsia is a serious pregnancy complication. Soluble endoglin (sEng) is released from the placenta and contribu..
Combination gefitinib and methotrexate treatment for non-tubal ectopic pregnancies: a case series
AW Horne, MM Skubisz, S Tong, WC Duncan, P Neil, EM Wallace, TG Johns
Non-tubal ectopic pregnancies are a rare subgroup of ectopic pregnancies implanted at sites other than the Fallopian tube. Mortali..
A Bioplex Analysis of Cytokines and Chemokines in First Trimester Maternal Plasma to Screen for Predictors of Miscarriage
Natalie J Hannan, Katerina Bambang, Tu'uhevaha J Kaitu'u-Lino, Justin C Konje, Stephen Tong
BACKGROUND: We have previously shown in two independent cohorts that circulating first trimester Macrophage Inhibitory Cytokine-1 ..
Galectin-7 acts as an adhesion molecule during implantation and increased expression is associated with miscarriage
EM Menkhorst, T Gamage, C Cuman, TJ Kaitu'u-Lino, S Tong, E Dimitriadis
INTRODUCTION: Galectins are expressed at the fetal-maternal interface and have multiple roles including during blastocyst implanta..
Quantifying circulating hypoxia-induced RNA transcripts in maternal blood to determine in utero fetal hypoxic status
Clare Whitehead, Wan Tinn Teh, Susan P Walker, Cheryl Leung, Sonali Mendis, Luke Larmour, Stephen Tong
BACKGROUND: Hypoxia in utero can lead to stillbirth and severe perinatal injury. While current prenatal tests can identify fetuses..
Combination Gefitinib and Methotrexate Compared With Methotrexate Alone to Treat Ectopic Pregnancy
Monika M Skubisz, Andrew W Horne, Terrance G Johns, Ulrika W Nilsson, W Colin Duncan, Euan M Wallace, Hilary OD Critchley, Stephen Tong
OBJECTIVE: To determine the safety, tolerability, and efficacy of combination gefitinib and methotrexate to treat ectopic pregnanc..
Effects of Gefitinib, an Epidermal Growth Factor Receptor Inhibitor, on Human Placental Cell Growth
Ulrika W Nilsson, Terrance G Johns, Tania Wilmann, Tu'uhevaha Kaitu'u-Lino, Clare Whitehead, Eva Dimitriadis, Ellen Menkhorst, Burcu Saglam, Yane Gao, Sameer A Greenall, Andrew W Horne, Stephen Tong
OBJECTIVE: Placenta has the highest expression of epidermal growth factor (EGF) receptor of all tissues, a cell signaling pathway ..
Plasma MIC-1 and PAPP-A Levels Are Decreased among Women Presenting to an Early Pregnancy Assessment Unit, Have Fetal Viability Confirmed but Later Miscarry
Tu'uhevaha J Kaitu'u-Lino, Katerina Bambang, Joseph Onwude, Richard Hiscock, Justin Konje, Stephen Tong
BACKGROUND: We have recently shown first trimester Macrophage inhibitory cytokine-1 (MIC-1) and Pregnancy Associated Plasma Protei..
Measuring thyroid peroxidase antibodies on the day nulliparous women present for management of miscarriage: a descriptive cohort study
Mathis Grossmann, Rudolf Hoermann, Claire Francis, Emma J Hamilton, Aye Tint, Tu'uhevaha Kaitu'u-Lino, Kent Kuswanto, Martha Lappas, Ken Sikaris, Jeffery D Zajac, Michael Permezel, Stephen Tong
BACKGROUND: There has been recent evidence suggesting the presence of anti-thyroid peroxidase antibodies (TPOAb) increases the ris..