A5087358285- Pregnancy and preeclampsia studies
- Birth, Development, and Health
- Reproductive System and Pregnancy
- Neonatal Respiratory Health Research
- Prenatal Screening and Diagnostics
- Gestational Diabetes Research and Management
- MicroRNA in disease regulation
- Acute Myeloid Leukemia Research
- Renal and related cancers
- Maternal and fetal healthcare
- Platelet Disorders and Treatments
- Congenital Diaphragmatic Hernia Studies
- Adrenal Hormones and Disorders
- Blood disorders and treatments
- Nutrition and Health in Aging
- Ear Surgery and Otitis Media
- Reproductive Biology and Fertility
- Hearing, Cochlea, Tinnitus, Genetics
- RNA modifications and cancer
- Heparin-Induced Thrombocytopenia and Thrombosis
- Immune Cell Function and Interaction
- Galectins and Cancer Biology
- GDF15 and Related Biomarkers
- T-cell and B-cell Immunology
- Blood Coagulation and Thrombosis Mechanisms
Mercy Hospital for Women
2016-2025
The University of Melbourne
2015-2024
University of Mississippi Medical Center
2024
Walter and Eliza Hall Institute of Medical Research
2008-2022
Olivia Newton-John Cancer Wellness & Research Centre
2017
La Trobe University
2017
Tokyo University of Pharmacy and Life Sciences
2015
Hudson Institute of Medical Research
2015
Institute of Molecular Medicine
2008
Homerton University Hospital
2001
Abstract— Preeclampsia is a major pregnancy complication where excess placental release of soluble fms-like tyrosine kinase-1 (sFlt-1) and endoglin causes maternal endothelial multisystem organ injury. Clinical trials have commenced examining whether pravastatin can be used to treat preeclampsia. However, the preclinical evidence supporting as treatment limited animal models, with almost no studies in human tissues. Therefore, we examined reduced sFlt-1 secretion decreased dysfunction...
Autoimmune regulator (AIRE) is an important transcription that mediates a role in central tolerance via promoting the "promiscuous" expression of tissue-specific Ags thymus. Although several mouse models Aire deficiency have been described, none has analyzed phenotype induced by mutation emulates common 13-bp deletion human APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy) disrupting first plant homeodomain exon 8. Aire-deficient mice with corresponding showed some...
Plasmodium falciparum is predicted to transport over 300 proteins the cytosol of its chosen host cell, mature human erythrocyte, including 19 members Hsp40 family. Here, we have generated transfectant lines expressing GFP- or HA-Strep-tagged versions these proteins, and used investigate both localization other properties co-chaperones. These fusion labelled punctate structures within infected initially suggestive a Maurer's clefts localization. Further experiments demonstrated that were...
First reported in 1999, germline runt-related transcription factor 1 (RUNX1) mutations are a well-established cause of familial platelet disorder with predisposition to myeloid malignancy (FPD-MM). We present the clinical phenotypes and genetic detected 10 novel RUNX1-mutated FPD-MM families. Genomic analyses on these families 2 partial gene deletions, 3 mutations, 5 recurrent as RUNX1 alterations leading FPD-MM. Combining genomic data from herein aggregated published sets resulted 130...
Abstract Background The RUNX1 transcription factor gene is frequently mutated in sporadic myeloid and lymphoid leukemia through translocation, point mutation or amplification. It also responsible for a familial platelet disorder with predisposition to acute (FPD-AML). disruption of the largely unknown biological pathways controlled by likely be development leukemia. We have used multiple microarray platforms bioinformatic techniques help identify these aid understanding why mutations lead...
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is an autoimmune disorder caused by mutations in the regulator gene AIRE. We examined expression of Aire different organs (thymus, spleen, and lymph nodes) C57BL/6 mice, using a novel rat mAb, specific for murine Aire. Using flow cytometry, directly fluorochrome-labeled mAb revealed rare thymic cellular subset that was CD45(-), expressed low levels Ly51, high MHC-II EpCam. This also pattern costimulatory molecules, including...
In preeclampsia, the antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFLT-1) is released from placenta into maternal circulation, causing endothelial dysfunction and organ injury. A recently described splice variant, sFLT-1 e15a, primate specific most abundant placentally derived sFLT-1. Therefore, it may be major isoform contributing to pathophysiology of preeclampsia. e15a protein remains poorly characterized: its bioactivity has not been comprehensively examined, serum levels in...
Preeclampsia is a hypertensive disorder of pregnancy characterized by maternal endothelial dysfunction and end-organ damage. The antiangiogenic factor, sFlt-1 (soluble FMS-like tyrosine kinase-1) has been strongly implicated in the pathogenesis preeclampsia. secreted into circulation where it antagonizes VEGF (vascular growth factor) ultimately disrupts vascular homeostasis. However, upstream mechanisms regulating release are poorly characterized. We investigated roles key prosurvival...
Abstract Preeclampsia is a disease of pregnancy associated with placental oxidative stress, inflammation and elevated release anti-angiogenic factors sFlt-1 soluble endoglin. These cause generalized maternal endothelial dysfunction. There are no treatments to halt progression; delivery the only cure. Resveratrol modulates pathways involved in stress may offer potential therapeutic for preeclampsia. reduced sFlt-1, e15a endoglin secretion from primary trophoblasts HUVECs mRNA expression...
Preeclampsia is associated with the placental release of soluble fms-like tyrosine kinase 1 (sFlt-1) and endoglin (sENG). These anti-angiogenic factors cause hypertension multi-organ injury. Pravastatin decreases secretion sFlt-1 in vitro currently being examined clinical trials as a potential treatment for preeclampsia. However, it possible that different classes statins may be more potent at decreasing secretion. We compared relative potency three generations on sENG from human endothelial...
Abstract Placental insufficiency can cause fetal growth restriction and stillbirth. There are no reliable screening tests for placental insufficiency, especially near-term gestation when the risk of stillbirth rises. Here we show a strong association between low circulating plasma serine peptidase inhibitor Kunitz type-1 (SPINT1) concentrations at 36 weeks’ birthweight, an indicator insufficiency. We generate 4-tier model based on SPINT1 concentrations, where highest tier has approximately...
Building on our discovery that mutations in the transmembrane serine protease, TMPRSS3, cause nonsyndromic deafness, we have investigated contribution of other TMPRSS family members to auditory function. To identify which 16 known genes had a strong likelihood involvement hearing function, three types biological evidence were examined: 1) expression inner ear tissues; 2) location genomic interval contains yet unidentified gene for deafness; and 3) evaluation status any available Tmprss...
Introduction The discovery of new treatments that prevent or treat preeclampsia would be a major advance. Antiangiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and endoglin (sENG) are secreted in excess from the placenta, causing hypertension, endothelial dysfunction, multiorgan injury. We recently identified metformin esomeprazole as potential for preeclampsia. Both reduce placental secretion sFlt-1 endoglin, dysfunction. Objectives set out to assess whether combining...
Background We investigated the biomarker potential of growth differentiation factor 15 (GDF‐15), a stress response protein highly expressed in placenta, to predict preeclampsia. Methods and Results In 2 prospective cohorts (cohort 1: 960 controls, 39 women who developed preeclampsia; cohort 2: 950 41 preeclampsia), plasma concentrations GDF‐15 at 36 weeks' gestation were significantly increased among those preeclampsia ( P <0.001), area under receiver operating characteristic curves (AUC)...
Development of the cerebral cortex requires highly specific spatio-temporal regulation gene expression. It is proposed that transcriptome profiling at various developmental time points or regions will reveal candidate genes and associated molecular pathways involved in corticogenesis. Serial analysis expression (SAGE) libraries were constructed from C57BL/6 mouse cortices age embryonic day (E) 15.5, E17.5, postnatal (P) 1.5 4 to 6 months. Hierarchical clustering 561 differentially expressed...
Preeclampsia is a major pregnancy complication associated with poor placental perfusion and hypoxia. Systemic inflammation elevated secretion of the antiangiogenic factors sFlt-1 (soluble fms-like tyrosine kinase 1) sEng endoglin) are hallmarks preeclampsia, causing endothelial dysfunction multiorgan injury. A molecule that links hypoxia, inflammation, factor release has not been described. ATF3 (activating transcription 3) highly expressed in placenta. We assessed whether dysregulated...
Fetal growth restriction is a disorder of placental dysfunction with three to four-fold increased risk stillbirth. has pathophysiological features in common preeclampsia. We hypothesised that angiogenesis-related factors maternal plasma, known predict preeclampsia, may also detect fetal at 36 weeks' gestation. therefore set out determine the diagnostic performance soluble fms-like tyrosine kinase 1 (sFlt-1), factor (PlGF), and sFlt-1:PlGF ratio, measured gestation, identifying women who...
Background Preeclampsia is pregnancy specific, involving significant maternal endothelial dysfunction. Predictive biomarkers are lacking. We evaluated the biomarker potential, expression, and function of PSG7 (pregnancy-specific β-1 glycoprotein 7) PSG9 9) in preeclampsia. Methods Results At 36 weeks gestation preceding term preeclampsia diagnosis, (in Australian cohorts n=918 n=979, respectively) were significantly increased before onset (PSG7, P=0.013; PSG9, P=0.0011). In samples collected...