From Pathogenesis To Therapeutics: Targeting Two Signalling Pathways As A Therapeutic Strategy To Treat Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$499,048.00
Summary
Preeclampsia is a serious complication of pregnancy that claims the lives of thousands of mothers and babies each year. There is no efficacious medical treatment besides delivery of the baby and placenta. Our lack of therapeutics is largely a result of our poor understanding of the disease. In this application we plan to thoroughly characterise two pathways we believe responsible for preeclampsia, effectively identifying many points at which new therapies could be targeted.
Improving The Prediction And Detection Of Contributors To Term Stillbirth
Funder
National Health and Medical Research Council
Funding Amount
$570,358.00
Summary
Stillbirths are a global human tragedy, with 1 in 130 of all pregnancies in Australia ending in stillbirth. We propose to use ultrasound and blood markers to improve the detection of babies who are not growing well, a leading risk factor for stillbirth. Sleep position has also been associated with stillbirth, so we will study fetal heart rate responses during an overnight sleep study to see if breathing events overnight may be an important contributor to stillbirth in growth restricted fetuses.
Endometriosis affects up to 10% of reproductive aged women causing a range of debilitating symptoms including pelvic pain and infertility. Our team has discovered that small nerve fibres can be found in the endometrium of women with endometriosis that are not present in women without the condition. We will investigate how these nerve fibres grow and the mechanisms of pain generation. This will potentially allow the development of more targeted and effective treatment modalities.
The Role Of Vitamin D In Placental Development And Pregnancy Success
Funder
National Health and Medical Research Council
Funding Amount
$723,235.00
Summary
Vitamin D deficiency affects about 1 billion people worldwide, including up to 80% of Australians depending on age, skin colour and sun exposure. Vitamin D deficiency has now been associated with a large number of common diseases of aging and with pregnancy complications. This proposal will use human pregnancy serum and placenta, as well as mouse gene knockout models, to determine the hitherto unknown roles of vitamin D in development of the placenta and health of mother and baby.
Priming The Maternal Immune Response To Resist Inflammatory Disorders Of Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$920,972.00
Summary
Preeclampsia and preterm birth are common conditions affecting >15 million pregnancies annually. An underlying cause is the mother’s immune response, which can react adversely to the fetus causing an inflammatory reaction. This project seeks to find ways to strengthen the maternal immune system beginning before conception. The work will provide insights upon which to advise intending parents and will inform development of new treatments options to protect susceptible women.
Stillbirth is a global public health problem affecting 3 million babies annually. In Australia, almost 3,000 stillbirths occur each year, many of which are preventable if the pregnancy is recognised as being at risk. This fellowship will develop novel non-invasive techniques to identify these at risk pregnancies using biomarkers in the mother's blood and cutting edge imaging. The efficacy of these novel techniques to prevent stillbirths and improve pregnancy outcomes will then be assessed.
The Cellular And Molecular Mechanisms In The Initaition Of Human Labour
Funder
National Health and Medical Research Council
Funding Amount
$460,904.00
Summary
Being born too early is the major cause of perinatal morbidity and mortality and accounts for the majority of neonatal deaths. The aim of this project is to gain a better understanding of the mechanisms involved in premature birth with a view to future development of clinically useful interventions to reduce the high rates of mortality and long-term disability.
Role Of Endogenous Opioid Peptides In Endometrial Receptivity And Placentation
Funder
National Health and Medical Research Council
Funding Amount
$523,884.00
Summary
Infertility affects 1 in 10 couples. In early pregancy miscarriage is the commonest complication resulting in the loss of 10-15% of all conceptions. During the latter part of pregnancy, complications such fetal growth restriction and preeclampsia, affects up to 10% of women resulting in considerable suffering to the mother and her newborn. Many of these births are premature with neonates requiring intensive care. There is also good evidence that children who are born prematurely with low birth w ....Infertility affects 1 in 10 couples. In early pregancy miscarriage is the commonest complication resulting in the loss of 10-15% of all conceptions. During the latter part of pregnancy, complications such fetal growth restriction and preeclampsia, affects up to 10% of women resulting in considerable suffering to the mother and her newborn. Many of these births are premature with neonates requiring intensive care. There is also good evidence that children who are born prematurely with low birth weight are much more likely to develop a host of diseases including cardiovascular disease, diabetes and obestiy in adult life increasing the long term burden of health care support. Infertility is often due to the lack of uterine endometrial receptivity while the pregnancy complications arise from the reduced growth of the placenta and sub-optimal interactions between the mother's uterus and the growing placenta. Endometrial infertility, placental growth and interactions with the endometrium is stringently regulated by substances produced at the maternal endometrial- placental interface. To understand how infertility and pregnancy complications arise, develop diagnostic, monitoring and therapeutic tests it is critical to understand the roles played by these regulatory substances. We have novel data suggesting that small proteins known as endogenous opioids could be enchancing endometrial receptivity and the growth and development of the placenta. Interstingly these substances are closely related to exogenous opioids such as heroin and morphine. We will investigate the manner in which these substances regulate endometrial immune cell function, maintain the endometrial stromal cell bed in preparation for pregnancy and direct the growth and differentiation of the placenta. The findings will give novel insights into infertility, improve the success rates of in vitro fertilization, reduce maternal and neonatal complications of pregnancy.Read moreRead less
I am a reproductive biologist specialised in the cell and molecular biology of placental development in pregnancy. I focus on determining the molecular mechanisms that govern placental invasion, growth and function and how these are altered in defective placentation which underlies common complications of pregnancy that can be life threatening to the mother and her baby compromising a healthy start to life. I am developing screening tests to identify couples at risk to improve patient care.
Measuring Hypoxia Induced MRNA In Maternal Blood To Monitor Wellbeing Of Growth-restricted Fetuses
Funder
National Health and Medical Research Council
Funding Amount
$421,358.00
Summary
Severely growth restricted fetuses are at peril of stillbirth from low oxygenation. While ultrasound monitoring improves outcomes, babies are still lost. Better ways to monitor the health the unborn baby are needed. We have recently discovered fetuses’ starved of oxygen leak RNA into mother's blood. Thus, measuring RNA molecules in blood could be used to assess fetal health. We will examine whether measuring mRNA in maternal blood could be used to monitor wellbeing of growth-restricted fetuses.