Targeting The Anti-angiogenic Factors Of Preeclampsia: Soluble Endoglin And SFlt1
Funder
National Health and Medical Research Council
Funding Amount
$447,024.00
Summary
Preeclampsia is a severe disease of pregnancy - the placenta releases toxins in to mum's bloodstream that circulate her body and damage her organs. As there are no efficacious treatments, clinicians are forced to deliver babies irrespective of gestation. Although the two toxins of preeclampsia have been identified, little is known about their regulation. This project aims to elucidate the regulation of these toxins and design therapeutics that can prevent their release in the clinic.
Most pregnancy complications, including miscarriage, pre-eclampsia, fetal growth restriction and stillbirth, stem from poor development of the placenta early in pregnancy. Restricted fetal growth in the uterus increases the babies risk of cardiovascular and other disorders in later life. This research will investigate whether Corin, an enzyme discovered in the heart, helps the mothers uterus prepare for pregnancy. Disruptions in Corin production during early pregnancy is likely to be involved in ....Most pregnancy complications, including miscarriage, pre-eclampsia, fetal growth restriction and stillbirth, stem from poor development of the placenta early in pregnancy. Restricted fetal growth in the uterus increases the babies risk of cardiovascular and other disorders in later life. This research will investigate whether Corin, an enzyme discovered in the heart, helps the mothers uterus prepare for pregnancy. Disruptions in Corin production during early pregnancy is likely to be involved in major pregnancy complications and loss.Read moreRead less
Combination Methotrexate And Gefitinib To Cure Ectopic Pregnancies: Phase I-II Clinical Trials
Funder
National Health and Medical Research Council
Funding Amount
$235,875.00
Summary
Ectopic pregnancies are dangerous emergencies that can cause fatal bleeding. Most require surgery. We plan to test a novel medication-based treatment that could be used to cure most ectopics. If successful, it could revolutionise current management.
Soluble Endoglin In The Pathogenesis Of Preeclampsia: Investigation Of Mechanisms And The Development Of Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$572,733.00
Summary
Preeclampsia is a severe disease of pregnancy. As the pathogenesis is poorly understood, the only treatment is for clinicians to deliver babies irrespective of gestation. We have identified MMP-14 as the molecular scissors that release soluble endoglin from placenta, a toxin centrally responsible for severe preeclampsia. In this project we aim to further investigate the mechanisms governing soluble endoglin release and to begin developing a potential therapeutic for use in the clinic.
Development Of Novel Medical Therapies To Cure Ectopic Pregnancies
Funder
National Health and Medical Research Council
Funding Amount
$601,156.00
Summary
Ectopic pregnancies are conceptions implanting outside the womb, mainly the fallopian tube. They are pathological, and can erode straight through the tube into large blood vessels causing fatal bleeding and death. We plan to assess three medication based approaches to treat this condition that would avoid surgery entirely. If we succeed, and subsequently translate one or more of these treatments to the clinic, it would revolutionise management of this serious gynaecological emergency.
Proprotein Convertase 6: A Master Regulator For The Development Of Endometrial Receptivity And Embryo Implantation
Funder
National Health and Medical Research Council
Funding Amount
$424,846.00
Summary
Implantation of an embryo into the womb (uterus) is a key step for human development, without which the embryo will only be able to develop to a very early stage the blastocyst stage (about 8 days after fertilization). For successful implantation, the uterus has to prepare itself to be receptive; this preparation is crucial as an ill-prepared uterus will reject the embryo. Such implantation failure is a major cause of early pregnancy loss and female infertility; ~30% of pregnancies end in sponta ....Implantation of an embryo into the womb (uterus) is a key step for human development, without which the embryo will only be able to develop to a very early stage the blastocyst stage (about 8 days after fertilization). For successful implantation, the uterus has to prepare itself to be receptive; this preparation is crucial as an ill-prepared uterus will reject the embryo. Such implantation failure is a major cause of early pregnancy loss and female infertility; ~30% of pregnancies end in spontaneous abortion. How the uterus becomes receptive is not well understood. Our recent research has identified that proprotein convertase 6 (PC6), an important master switch responsible for activating other proteins, is tightly regulated in the uterus during its preparation for receptivity and critical for implantation. This project will examine how PC6 acts in the human uterus to make it receptive, by identifying the factors that PC6 controls and how this controlling works. We will use a cell culture model with cells isolated from human term placenta. In addition, there is no means of readily testing whether the uterus is receptive owing to the lack of reliable biomarkers. In this study we will determine whether PC6 (and those molecules controlled by PC6) are potential biomarkers for uterine receptivity. This will be achieved by examining uterine biopsies and uterine washings collected from proven fertile volunteers and patients of proven endometrial infertility. This study will greatly enhance our understanding of how a critical molecule, PC6, acts in the uterus for implantation. The results will provide new knowledge regarding uterine preparation for implantation. The study has considerable implication for developing much-needed diagnostic and therapeutic tools for uterine receptivity and infertility.Read moreRead less
Critical Role Of Proprotein Convertase 6 In Human Uterine Epithelium For Embryo Implantation And Clinical Implications
Funder
National Health and Medical Research Council
Funding Amount
$643,899.00
Summary
Implantation of an embryo into the uterus is a key step for human development. Implantation failure causes embryonic death, pregnancy loss and infertility. Conversely, preventing implantation is an attractive approach for contraception. We have established that proprotein convertase 6 (PC6) is a master regulator of implantation. We will investigate how PC6 works in a woman's uterus, and how we can use this knowledge to improve implantation in IVF and to develop PC6 drugs for new contraceptives.
The Insulin Signalling Pathway In Normal And Gestationally Diabetic Pregnancies
Funder
National Health and Medical Research Council
Funding Amount
$319,335.00
Summary
Gestational Diabetes Mellitus (GDM), which is defined as glucose intolerance of variable severity with onset or first recognition during pregnancy, affects 5% to 8% of pregnancies, and represents more than 10,000 women annually in Australia. The overall aim of this project is to increase our understanding of the causes of gestational diabetes. In particular, the role of various inflammatory pathways in the biochemical mechanisms involved in insulin resistance associated with GDM will be examined ....Gestational Diabetes Mellitus (GDM), which is defined as glucose intolerance of variable severity with onset or first recognition during pregnancy, affects 5% to 8% of pregnancies, and represents more than 10,000 women annually in Australia. The overall aim of this project is to increase our understanding of the causes of gestational diabetes. In particular, the role of various inflammatory pathways in the biochemical mechanisms involved in insulin resistance associated with GDM will be examined, with these pathways representing novel approaches to developing agents for efficacious clinical management strategies for the management of GDM. Although major advances have been made in our understanding of the molecular mechanisms of insulin action and identification of the defects leading to insulin resistance in type 2 diabetes, there is still a paucity of data available concerning GDM. A better understanding of the regulatory pathways that mediate insulin action may lead to the identification of molecular targets for therapy. Furthermore, the clinical effectiveness of current anti-diabetic therapies to improve insulin signal transduction will be assessed. Understanding how insulin signalling is regulated will have major and important implications for the treatment of insulin resistance and obesity. As multiple pro-inflammatory cytokines may have similar effects on insulin signalling, the shared, cytokine-induced second messenger pathways may be excellent therapeutic targets for the treatment of diabetes.Read moreRead less