DEVELOPMENT OF NOVEL THERAPEUTICS TO PREVENT OR TREAT PREECLAMPSIA

Sulfasalazine for the treatment of preeclampsia in a nitric oxide synthase antagonist mouse model.

Natalie K Binder, Natasha de Alwis, Sally Beard, Elif Kadife, Alesia Harper, Tu'uhevaha J Kaitu'u-Lino, Fiona C Brownfoot, Natalie J Hannan

2023-02-01

INTRODUCTION: Development of a therapeutic that targets the pathophysiological elements of preeclampsia would be a major advance f..

Endothelial protein C receptor is increased in preterm preeclampsia and fetal growth restriction.

Faith Andres, Natalie J Hannan, Susan P Walker, Teresa M MacDonald, Georgia P Wong, Ciara Murphy, Ping Cannon, Manju Kandel, Joshua Masci, Tuong-Vi Nguyen, Alison Abboud, Danica Idzes, Valerie Kyritsis, Natasha Pritchard, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino

2022-12-01

Placental dysfunction is the leading cause of both preeclampsia and fetal growth restriction. This study aimed to characterize end..

The L-NAME mouse model of preeclampsia and impact to long-term maternal cardiovascular health

Natasha de Alwis, Natalie K Binder, Sally Beard, Yeukai Tm Mangwiro, Elif Kadife, James SM Cuffe, Emerson Keenan, Bianca R Fato, Tu'uhevaha J Kaituiu-Lino, Fiona C Brownfoot, Sarah A Marshall, Natalie J Hannan

2022-12-01

Preeclampsia affects ∼2-8% of pregnancies worldwide. It is associated with increased long-term maternal cardiovascular disease ris..

The effect of metformin on cardiovascular markers in female mice consuming a high fat diet.

Natasha de Alwis, Natalie K Binder, Yeukai TM Mangwiro, Natasha Pritchard, Sally Beard, Tu'uhevaha J Kaitu'u-Lino, Fiona Brownfoot, Natalie J Hannan

2022-11-01

BACKGROUND: Metformin, widely used to treat diabetes, is now considered a candidate therapeutic for treatment of cardiovascular di..

Placental galectin-3 is reduced in early-onset preeclampsia

Manju Kandel, Stephen Tong, Susan P Walker, Ping Cannon, Tuong-Vi Nguyen, Teresa M MacDonald, Natalie J Hannan, Tu'uhevaha J Kaitu'u-Lino, Lucy A Bartho

2022-10-14

Preeclampsia is a disease of pregnancy responsible for significant maternal and neonatal mortality. Galectin-3 is a β-Galactoside ..

RNA-Seq of amniotic fluid cell-free RNA: a discovery phase study of the pathophysiology of congenital cytomegalovirus infection

Lisa Hui, Luc De Catte, Sally Beard, Jovana Maksimovic, Neeta L Vora, Alicia Oshlack, Susan P Walker, Natalie J Hannan

2022-10-01

BACKGROUND: Congenital cytomegalovirus infection is the most common perinatal infection and a significant cause of sensorineural h..

Assessment of the Proton Pump Inhibitor, Esomeprazole Magnesium Hydrate and Trihydrate, on Pathophysiological Markers of Preeclampsia in Preclinical Human Models of Disease

Natasha de Alwis, Bianca R Fato, Sally Beard, Natalie K Binder, Tu'uhevaha J Kaitu'u-Lino, Kenji Onda, Natalie J Hannan

2022-09-01

Previously, we demonstrated that the proton pump inhibitor, esomeprazole magnesium hydrate (MH), could have potential as a repurpo..

Placental OLAH Levels Are Altered in Fetal Growth Restriction, Preeclampsia and Models of Placental Dysfunction

Natasha de Alwis, Sally Beard, Natalie K Binder, Natasha Pritchard, Tu'uhevaha J Kaitu'u-Lino, Susan P Walker, Owen Stock, Katie Groom, Scott Petersen, Amanda Henry, Joanne M Said, Sean Seeho, Stefan C Kane, Stephen Tong, Lisa Hui, Natalie J Hannan

2022-09-01

Previously, we identified elevated transcripts for the gene Oleoyl-ACP Hydrolase (OLAH) in the maternal circulation of pregnancies..

Serum Collected from Preeclamptic Pregnancies Drives Vasoconstriction of Human Omental Arteries-A Novel Ex Vivo Model of Preeclampsia for Therapeutic Development

Bianca R Fato, Natasha de Alwis, Sally Beard, Natalie K Binder, Natasha Pritchard, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino, Natalie J Hannan

2022-09-01

New-onset maternal hypertension is a hallmark of preeclampsia, driven by widespread endothelial dysfunction and systemic vasoconst..

Associations Between Soluble fms-Like Tyrosine Kinase-1 and Placental Growth Factor and Disease Severity Among Women With Preterm Eclampsia and Preeclampsia

Roxanne Hastie, Lina Bergman, Susan P Walker, Tu'uhevaha Kaitu'u-Lino, Natalie J Hannan, Fiona Brownfoot, Sonja Schell, Alesia Harper, Ping Cannon, Catherine A Cluver, Stephen Tong

2022-08-16

Background The angiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are postulated to..

Placental DAAM2 is unaltered in preeclampsia, but upregulated by treatment with proton pump inhibitors

Natasha De Alwis, Sally Beard, Natalie K Binder, Natasha Pritchard, Stephen Tong, Tu'uhevana J Kaitu'u-Lino, Natalie J Hannan

2022-08-04

BACKGROUND: Dishevelled Associated Activator Of Morphogenesis 2 (DAAM2) levels are elevated in the maternal circulation and placen..

Actions of Esomeprazole on the Maternal Vasculature in Lean and Obese Pregnant Mice with Impaired Nitric Oxide Synthesis: A Model of Preeclampsia

Natasha de Alwis, Natalie K Binder, Yeukai TM Mangwiro, Sally Beard, Natasha Pritchard, Elif Kadife, Bianca R Fato, Emerson Keenan, Fiona C Brownfoot, Tu'uhevaha J Kaitu'u-Lino, Natalie J Hannan

2022-08-01

Preeclampsia is a devastating, multisystem disorder of pregnancy. It has no cure except delivery, which if premature can impart si..

PSG7 and 9 (Pregnancy-Specific beta-1 Glycoproteins 7 and 9): Novel Biomarkers for Preeclampsia

Manju Kandel, Teresa M MacDonald, Susan P Walker, Catherine Cluver, Lina Bergman, Jenny Myers, Roxanne Hastie, Emerson Keenan, Natalie J Hannan, Ping Cannon, Tuong-Vi Nguyen, Natasha Pritchard, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino

2022-04-05

Background Preeclampsia is pregnancy specific, involving significant maternal endothelial dysfunction. Predictive biomarkers are l..

Circulating Activin A is elevated at 36 weeks' gestation preceding a diagnosis of preeclampsia

Georgia P Wong, Faith Andres, Susan P Walker, Teresa M MacDonald, Ping Cannon, Tuong-Vi Nguyen, Emerson Keenan, Natalie J Hannan, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino

2022-03-26

Activin A is aberrantly expressed by the preeclamptic placenta and circulating levels have been investigated as a potential biomar..

Pravastatin, proton-pump inhibitors, metformin, micronutrients, and biologics: new horizons for the prevention or treatment of preeclampsia

Stephen Tong, Tu'uhevaha J Kaitu'u-Lino, Roxanne Hastie, Fiona Brownfoot, Catherine Cluver, Natalie Hannan

2022-02-15

There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, dr..

Circulating SPINT1 Is Reduced in a Preeclamptic Cohort with Co-Existing Fetal Growth Restriction.

Ciara N Murphy, Catherine A Cluver, Susan P Walker, Emerson Keenan, Roxanne Hastie, Teresa M MacDonald, Natalie J Hannan, Fiona C Brownfoot, Ping Cannon, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino

2022-02-09

Fetal growth restriction (FGR), when undetected antenatally, is the biggest risk factor for preventable stillbirth. Maternal circu..

Silencing of Nrf genes in the human placenta as measured by SDS-PAGE and Western Blotting techniques

Yann W Yap, Natalie J Hannan, Euan M Wallace, Sarah A Marshall

2022-01-16

Nuclear factor erythroid 2-related factor-2 (Nrf2), and the less well characterised proteins Nrf1 and Nrf3, are member of the cap ..

A disintegrin and metalloproteinase 12 (ADAM12) is reduced at 36 weeks' gestation in pregnancies destined to deliver small for gestational age infants

Faith Andres, Georgia P Wong, Susan P Walker, Teresa M MacDonald, Emerson Keenan, Ping Cannon, Tuong-Vi Nguyen, Natalie J Hannan, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino

2022-01-01

First trimester circulating ADAM12 is reduced in fetal growth restriction (FGR) and preeclampsia. We measured plasma ADAM12 at 36 ..

Clinical tools and biomarkers to predict preeclampsia

Teresa M MacDonald, Susan P Walker, Natalie J Hannan, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino

2022-01-01

Preeclampsia is pregnancy-specific, and significantly contributes to maternal, and perinatal morbidity and mortality worldwide. An..

Hydroxychloroquine reduces soluble Flt-1 secretion from human cytotrophoblast, but does not mitigate markers of endothelial dysfunction in vitro.

Elif Kadife, Natalie Hannan, Alesia Harper, Natalie Binder, Sally Beard, Fiona C Brownfoot

2022-01-01

Preeclampsia is a multi-system disease that can have severe, even fatal implications for the mother and fetus. Abnormal placentati..

NR4A2 expression is not altered in placentas from cases of growth restriction or preeclampsia, but is reduced in hypoxic cytotrophoblast

Natasha de Alwis, Sally Beard, Natalie K Binder, Natasha Pritchard, Tu'uhevaha J Kaitu'u-Lino, Susan P Walker, Owen Stock, Katie M Groom, Scott Petersen, Amanda Henry, Joanne M Said, Sean Seeho, Stefan C Kane, Stephen Tong, Natalie J Hannan

2021-10-19

Nuclear Receptor Subfamily 4 Group A Member 2 (NR4A2) transcripts are elevated in the circulation of individuals whose pregnancies..

Circulating Growth Differentiation Factor 15 Is Increased Preceding Preeclampsia Diagnosis: Implications as a Disease Biomarker

Tess Cruickshank, Teresa M MacDonald, Susan P Walker, Emerson Keenan, Kirsten Dane, Anna Middleton, Valerie Kyritsis, Jenny Myers, Catherine Cluver, Roxanne Hastie, Lina Bergman, Damanpreet Garcha, Ping Cannon, Elizabeth Murray, Tuong-Vi Nguyen, Richard Hiscock, Natasha Pritchard, Natalie J Hannan, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino

2021-08-17

Background We investigated the biomarker potential of growth differentiation factor 15 (GDF-15), a stress response protein highly ..

Circulating syndecan-1 is reduced in pregnancies with poor fetal growth and its secretion regulated by matrix metalloproteinases and the mitochondria

Damanpreet Garcha, Susan P Walker, Teresa M MacDonald, Jon Hyett, Jessica Jellins, Jenny Myers, Sebastian E Illanes, Jhy K Nien, Manuel Schepeler, Emerson Keenan, Carole-Anne Whigham, Ping Cannon, Elizabeth Murray, Tuong-Vi Nguyen, Manju Kandel, Joshua Masci, Ciara Murphy, Tess Cruickshank, Natasha Pritchard, Natalie J Hannan

2021-08-16

Fetal growth restriction is a leading cause of stillbirth that often remains undetected during pregnancy. Identifying novel biomar..

Pre-Clinical Investigation of Cardioprotective Beta-Blockers as a Therapeutic Strategy for Preeclampsia

Natalie K Binder, Teresa M MacDonald, Sally A Beard, Natasha de Alwis, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino, Natalie J Hannan

2021-08-01

Despite significant maternal and fetal morbidity, a treatment for preeclampsia currently remains an unmet need in clinical care. A..

Pre-eclampsia: Challenges for Nanomedicine Development in Pregnancy

Natasha de Alwis, Natalie K Binder, Natalie J Hannan

2021-07-29

LOX-1 expression is reduced in placenta from pregnancies complicated by preeclampsia and in hypoxic cytotrophoblast

Natasha de Alwis, Sally Beard, Natalie K Binder, Natasha Pritchard, Tu'uhevaha J Kaitu'u-Lino, Susan P Walker, Owen Stock, Katie M Groom, Scott Petersen, Amanda Henry, Joanne M Said, Sean Seeho, Stefan C Kane, Stephen Tong, Natalie J Hannan

2021-07-27

OBJECTIVES: The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is upregulated in the maternal vasculature in pree..

Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction

Ciara N Murphy, Susan P Walker, Teresa M MacDonald, Emerson Keenan, Natalie J Hannan, Mary E Wlodek, Jenny Myers, Jessica F Briffa, Tania Romano, Alexandra Roddy Mitchell, Carole-Anne Whigham, Ping Cannon, Tuong-Vi Nguyen, Manju Kandel, Natasha Pritchard, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino

2021-07-01

Biomarkers for placental dysfunction are currently lacking. We recently identified SPINT1 as a novel biomarker; SPINT2 is a functi..

Nicotinamide and its effects on endothelial dysfunction and secretion of antiangiogenic factors by primary human placental cells and tissues

Fiona Brownfoot, Natalie Binder, Roxanne Hastie, Alesia Harper, Sally Beard, Laura Tuohey, Emerson Keenan, Stephen Tong, Natalie Hannan

2021-06-01

Preeclampsia is a serious pregnancy complication associated with elevated antiangiogenic markers and endothelial dysfunction. Rece..

DAAM2 is elevated in the circulation and placenta in pregnancies complicated by fetal growth restriction and is regulated by hypoxia

Natasha de Alwis, Sally Beard, Natalie K Binder, Natasha Pritchard, Tu'uhevaha J Kaitu'u-Lino, Susan P Walker, Owen Stock, Katie Groom, Scott Petersen, Amanda Henry, Joanne M Said, Sean Seeho, Stefan C Kane, Lisa Hui, Stephen Tong, Natalie J Hannan

2021-03-10

Previously, we identified increased maternal circulating DAAM2 mRNA in pregnancies complicated by preterm fetal growth restriction..

Nanoparticles in pregnancy: the next frontier in reproductive therapeutics

Natasha Pritchard, Tu'uhevaha Kaitu'u-Lino, Lynda Harris, Stephen Tong, Natalie Hannan

2021-03-01

BACKGROUND: Nanotechnology involves the engineering of structures on a molecular level. Nanomedicine and nano-delivery systems hav..

Circulating Tissue Factor Pathway Inhibitor (TFPI) is increased preceding preeclampsia diagnosis and in established preeclampsia

Teresa M MacDonald, Stephen Tong, Jenny Myers, Ping Cannon, Nguyen Tuong-Vi, Emerson Keenan, Elizabeth Murray, Alesia Harper, Natasha Pritchard, Natalie J Hannan, Kirsten M Dane, Anna L Middleton, Valerie P Kyritsis, Susan P Walker, Tu'uhevaha J Kaitu'u-Lino

2021-02-01

INTRODUCTION: Tissue Factor Pathway Inhibitor (TFPI) is a part of the extrinsic coagulation pathway, and highly expressed in the p..

Novel approaches to combat preeclampsia: from new drugs to innovative delivery

Natasha de Alwis, Natalie K Binder, Sally Beard, Tu'uhevaha J Kaitu'u-Lino, Stephen Tong, Fiona Brownfoot, Natalie J Hannan

2020-12-01

Preeclampsia is a complex disease affecting 2-8% of pregnancies worldwide. It poses significant risk of maternal and perinatal mor..

MicroRNAs 363 and 149 are differentially expressed in the maternal circulation preceding a diagnosis of preeclampsia

Carole-Anne Whigham, Teresa M MacDonald, Susan P Walker, Richard Hiscock, Natalie J Hannan, Natasha Pritchard, Ping Cannon, Vi Nguyen Tuong, Manisha Miranda, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino

2020-10-22

Preeclampsia is a pregnancy complication associated with angiogenic dysbalance, maternal endothelial dysfunction and end-organ inj..

Esomeprazole and sulfasalazine in combination additively reduce sFlt-1 secretion and diminish endothelial dysfunction: potential for a combination treatment for preeclampsia

Natalie K Binder, Fiona C Brownfoot, Sally Beard, Ping Cannon, Tuong V Nguyen, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino, Natalie J Hannan

2020-10-01

Development and repurposing of therapies that show promise in the prevention or treatment of preeclampsia would be a major advance..

Aurora kinase mRNA expression is reduced with increasing gestational age and in severe early onset fetal growth restriction

Sally Beard, Natasha Pritchard, Natalie Binder, Karen Schindler, Natasha De Alwis, Tu'uhevaha J Kaitu'u-Lino, Stephen Tong, Natalie J Hannan

2020-06-01

INTRODUCTION: Oxidative damage and biochemical ageing are implicated in placental dysfunction and potentially fetal death. Cellula..

Circulating mRNAs are differentially expressed in pregnancies with severe placental insufficiency and at high risk of stillbirth

Natalie J Hannan, Owen Stock, Rebecca Spencer, Clare Whitehead, Anna L David, Katie Groom, Scott Petersen, Amanda Henry, Joanne M Said, Sean Seeho, Stefan C Kane, Lavinia Gordon, Sally Beard, Kantaraja Chindera, Smita Karegodar, Richard Hiscock, Natasha Pritchard, Tu'uhevaha J Kaitu'u-Lino, Susan P Walker, Stephen Tong

2020-05-22

Background Fetuses affected by placental insufficiency do not receive adequate nutrients and oxygenation, become growth restricted..

Circulating SPINT1 is a biomarker of pregnancies with poor placental function and fetal growth restriction

Tu'uhevaha J Kaitu'u-Lino, Teresa M MacDonald, Ping Cannon, Nguyen Tuong-Vi, Richard J Hiscock, Nick Haan, Jenny E Myers, Roxanne Hastie, Kirsten M Dane, Anna L Middleton, Intissar Bittar, Amanda N Sferruzzi-Perri, Natasha Pritchard, Alesia Harper, Natalie J Hannan, Valerie Kyritsis, Nick Crinis, Lisa Hui, Susan P Walker, Stephen Tong

2020-05-15

Purpose To investigate the relationship between patient-reported outcome (PRO) questionnaire responses and time to late age-relate..

Pravastatin as the statin of choice for reducing pre-eclampsia-associated endothelial dysfunction

Natasha de Alwis, Sally Beard, Yeukai T Mangwiro, Natalie K Binder, Tu'uhevaha J Kaitu'u-Lino, Fiona C Brownfoot, Stephen Tong, Natalie J Hannan

2020-04-01

OBJECTIVES: There is avid interest in pravastatin as a therapeutic intervention for pre-eclampsia, however little is known on stat..

Death associated protein kinase 1 (DAPK-1) is increased in preeclampsia

Cameron Yung, Teresa M MacDonald, Susan P Walker, Ping Cannon, Alesia Harper, Natasha Pritchard, Natalie J Hannan, Tu'uhevaha J Kaitu'u-Lino, Stephen Tong

2019-12-01

INTRODUCTION: Death associated protein kinase-1 (DAPK-1) is highly expressed in the placenta relative to all other human tissues. ..

Sulfasalazine decreases soluble fms-like tyrosine kinase-1 secretion potentially via inhibition of upstream placental epidermal growth factor receptor signalling

Roxanne Hastie, Fiona C Brownfoot, Ping Cannon, Nguyen Vi, Laura Tuohey, Natalie J Hannan, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino

2019-11-01

OBJECTIVES: Preeclampsia is a hypertensive disorder of pregnancy with no available medical treatment. We recently reported sulfasa..

The untapped potential of placenta-enriched molecules for diagnostic and therapeutic development

Carole-Anne Whigham, Teresa M MacDonald, Susan P Walker, Natalie J Hannan, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino

2019-09-01

Pregnancy complications such as fetal growth restriction and preeclampsia are diseases with limited biomarkers for prediction, and..

Proton Pump Inhibitors and Preeclampsia Risk Among 157 720 Women A Swedish Population Register-Based Cohort Study

Roxanne Hastie, Lina Bergman, Catherin A Cluver, Anna Wikman, Natalie J Hannan, Susan P Walker, Anna-Karin Wikstrom, Stephen Tong, Susanne Hesselman

2019-05-01

Preeclampsia is a hypertensive disorder of pregnancy characterized by maternal endothelial dysfunction and end-organ damage. The a..

Circulating adrenomedullin mRNA is decreased in women destined to develop term preeclampsia

Carole-Anne Whigham, Teresa M MacDonald, Susan P Walker, Natasha Pritchard, Natalie J Hannan, Roxanne Hastie, Natasha De Alwis, Ping Cannon, Vi Nguyen Tuong, Stephen Tong, Tu'uhevaha Kaitu'u-Lino

2019-04-01

Preeclampsia is a pregnancy complication associated with elevated placental secretion of anti-angiogenic factors, maternal endothe..

Circulating GATA2 mRNA is decreased among women destined to develop preeclampsia and may be of endothelial origin

Carole-Anne Whigham, Teresa M MacDonald, Susan P Walker, Natasha Pritchard, Natalie J Hannan, Ping Cannon, Vi Nguyen Tuong, Roxanne Hastie, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino

2019-01-18

Preeclampsia is a pregnancy complication associated with elevated placental secretion of anti-angiogenic factors, maternal endothe..

A Systematic Review of Proton Pump Inhibitors for the Prevention and Treatment of Preeclampsia and Gestational Hypertension

Manarangi De Silva, Fiona Brownfoot, Natalie J Hannan, Susan P Walker, Catherine A Cluver, Anthea Lindquist, Stephen Tong, Roxanne Hastie

2019-01-01

Disulfiram inhibits placental soluble FMS-like tyrosine kinase-1 and soluble endoglin secretion independent of the proteasome

Roxanne Hastie, Louie Ye, Natalie J Hannan, Fiona C Brownfoot, Ping Cannon, Vi Nguyen, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino

2018-10-01

Preeclampsia is associated with intermittent placental hypoxia, inflammation and the release of antiangiogenic factors, namely sFL..