RAGE And ACE2 Shedding As Therapeutic Targets In Diabetes And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$748,447.00
Summary
We have previously demonstrated the pivotal role of two shed proteins, Receptor for Advanced Glycation End-products (RAGE) and Angiotensin Converting Enzyme Receptor 2 (ACE2) in heart disease and diabetic complications. In this project, we will use a novel technologies to modify shedding of these proteins from the cell surface and alter their ability to cause disease.
Non-invasive Detection Of Hypoglycaemia In People With Diabetes Using Brain Wave Activity
Funder
National Health and Medical Research Council
Funding Amount
$330,447.00
Summary
Hypoglycaemia remains a major cause of morbidity and mortality in people with both type 1 diabetes and type 2 diabetes who require insulin therapy. Current treatments for nocturnal hypoglycaemia are usually ineffective. Combining brain wave recording and artificial intelligence, we will identify the changes that precipitate an episode of hypoglycaemia allowing the development of a non-invasive device to prevent or alleviate these fearful and potentially life-threatening events.
Epigenetic Determinants Of Nephropathy In Adults With Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$532,118.00
Summary
The prevention and successful management of diabetic complications are issues of utmost importance for the health of Australians. We hypothesize that epigenetic pathways partly determine why some individuals with diabetes develop complications of their disease, while others do not, despite a similar duration of diabetes, treatment intensity and mean glucose exposure.
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
Preclinical Evaluation Of A Novel Allosteric IL-1R Inhibitor (rytvela) For The Prevention Of Perinatal Inflammation-induced Fetal Injury
Funder
National Health and Medical Research Council
Funding Amount
$1,377,827.00
Summary
Interleukin-1 (IL-1) is a potent inflammatory protein involved in many inflammatory disorders, including preterm birth (PTB). Blocking the actions of IL-1 in pregnancies at risk of delivering preterm may protect the fetus from PTB and the long-term harm of exposure to inflammation before birth. Using four different models of antenatal inflammation, we will explore the use of a new IL-1 inhibitor to see if it blocks inflammation ‘in utero’ and improve neonatal health and development.
How The Placental Protein Syncytin Impairs Maternal Immune Responses To Influenza
Funder
National Health and Medical Research Council
Funding Amount
$609,862.00
Summary
Pregnant women are known to be highly susceptible to certain viral infections, especially influenza, which results in severe illness and even death. The reason for this transitory susceptibility are unknown. We have found that a protein, Syncytin, has the ability to impair maternal immune responses to influenza We now will determine how it does this and discover potential interventions to reverse these effects.
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.
Investigating The Relationship Between Depression, Anxiety And Nausea And Vomiting During Pregnancy: Causation Or Shared Liability?
Funder
National Health and Medical Research Council
Funding Amount
$600,874.00
Summary
Recent studies showing women who experience severe Nausea and vomiting during pregnancy (NVP) have higher rates of Anxiety and Depression prior to pregnancy have revived earlier hypotheses that NVP may have a psychogenic component. We hypothesize that Anxiety and Depression do not play a causal role in NVP but rather, the relationship is due to shared risk from genetic effects that influence both traits. We will test this hypothesis using genetic and epidemiological approaches.
The Protective Effects Of Fenofibrate In Diabetes-related Susceptibility To Ischaemia
Funder
National Health and Medical Research Council
Funding Amount
$630,571.00
Summary
Blood flow reduction (blockage of arteries) to local tissue is a common problem for diabetic people. Fenofibrate, a cholesterol lowering drug, dramatically reduces the diabetes-related limb amputation and other vascular disorders. We plan to study the mechanism of fenofibrate to facilitate growth of new blood vessels to sites affected by vascular disease. Ultimately, this may result in new treatment for diabetic vascular complications.
Targeting Epigenetic Pathways That Lead To Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$989,948.00
Summary
Glucose remains the major cause of complications in diabetes with prior episodes of high glucose having long lasting effects on blood vessels leading to heart attacks, kidney disease and blindness. We have identified an enzyme Set7 which plays a key role in promoting glucose induced injury. By validating this target using drug and molecular approaches we will strengthen the rationale to develop potent inhibitors of this enzyme in order to reduce the major burden of diabetes, its complications.