Identifying And Developing Novel Therapeutic Approaches For Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$638,517.00
Summary
Increasing rates of obesity, diabetes, and an ageing population increase the risk of heart disease & complications including heart failure (HF), atrial fibrillation (AF), and diabetic heart disease. There is a clinical need for i) improved therapies for patients with HF, AF, and diabetic heart, and ii) biomarkers which more effectively recognise people at risk of heart disease, to prevent clinical events. My research program is designed to develop novel therapies and identify new biomarkers.
Insulin Regulated Aminopeptidase: A New Cardiovascular Target
Funder
National Health and Medical Research Council
Funding Amount
$672,650.00
Summary
Cardiovascular disease, leading to heart attack or stroke is the largest cause of death in Australia. We have evidence that inhibition of a newly described enzyme (IRAP) by angiotensin IV is protective in a model of atherosclerosis. Excitingly we have preliminary data indicating that mice deficient in IRAP have better vascular function therefore we will further investigate this as well as the effectiveness of newly developed IRAP inhibitors in preventing development of cardiovascular disease.
Phospholipase Cbeta 1b, A Target To Limit Atrial Dilatation
Funder
National Health and Medical Research Council
Funding Amount
$544,847.00
Summary
We have identified a heart specific protein that is involved in perpetuating dilatation of the upper chambers of the heart and thereby contributing to cardiac disease. Inhibitors of this protein provide a suitable target for therapy to limit heart disease. The current studies aim to test such inhibitors in vivo as proof-of-concept that such treatment effectively limits cardiac dysfunction.
Novel GPCR Transactivation Of Serine Kinases In Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$386,565.00
Summary
All of biology and disease is based on cells receiving signals from hormones and growth factors via cell surface receptors. Cells integrate these signals to give a response which may be cell growth or the secretion of further hormones and growth factors. Signals from receptors can intersect to modify the response. This project will explore a new interaction we have discovered where a hormone activates its receptor to cause the activation of a growth factor receptor potentially providing new drug ....All of biology and disease is based on cells receiving signals from hormones and growth factors via cell surface receptors. Cells integrate these signals to give a response which may be cell growth or the secretion of further hormones and growth factors. Signals from receptors can intersect to modify the response. This project will explore a new interaction we have discovered where a hormone activates its receptor to cause the activation of a growth factor receptor potentially providing new drug targets in cardiovascular disease.Read moreRead less
SHANK3 As A Target To Reduce Hypertrophy And Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$548,908.00
Summary
We have identified a large protein in heart that functions to facilitate the heart's response to disease. The proposed studies will define how this protein mediates responses and whether we can successfully interfere with the process to limit disease progression.
Molecular Mechanisms In Pregnancy-indcuded Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$649,668.00
Summary
Approximately 5-10% of pregnancies are complicated by hypertension with associated health risks for both mother and child. To keep blood pressure at normal levels during pregnancy requires active regulation, but underlying processes are not yet fully understood. We have identified a molecule which crucially controls blood pressure during pregnancy. In this proposal we will study how the molecule remodels blood vessels in pregnant females to optimize pharmacological intervention and pregnancy out ....Approximately 5-10% of pregnancies are complicated by hypertension with associated health risks for both mother and child. To keep blood pressure at normal levels during pregnancy requires active regulation, but underlying processes are not yet fully understood. We have identified a molecule which crucially controls blood pressure during pregnancy. In this proposal we will study how the molecule remodels blood vessels in pregnant females to optimize pharmacological intervention and pregnancy outcomes in humans.Read moreRead less
G-alpha Proteins And Their Effectors (AC, PLC, Rho And ERK) In Central Cardiovascular Regulation In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$636,716.00
Summary
High blood pressure is a major risk factor for cardiovascular diseases such as stroke that are huge emotional and economic societal burdens. The brain is essential to the control of blood pressure. Specific sites within the brain are crucial in setting the resting level of blood pressure and controlling blood pressure in response to stimuli such as lying or standing. The activity of these brain sites is altered in conditions such as high blood pressure. We will determine the role specific protei ....High blood pressure is a major risk factor for cardiovascular diseases such as stroke that are huge emotional and economic societal burdens. The brain is essential to the control of blood pressure. Specific sites within the brain are crucial in setting the resting level of blood pressure and controlling blood pressure in response to stimuli such as lying or standing. The activity of these brain sites is altered in conditions such as high blood pressure. We will determine the role specific proteins within cells, which are important in cell to cell communication in the brain, have in the control of blood pressure. Cells in the brain communicate using chemical messengers that act at receptors on the cells surface. Three forms of these receptors exist. We are interested in the most abundant form of receptor that has about 860 members. When activated these receptors use a complex cascade of proteins within the cell to dictate that cell's response. We know that some of these receptors in the brain are involved in the regulation of blood pressure and that some of them are altered in conditions such as hypertension. We could target each of the receptors but for many of them we do not know the chemical than activates them. Fortunately each of 860 receptors act primarily via just a few specialised proteins. Initially we will target these proteins to determine the impact these receptors have in altering the resting levels of blood pressure, their role in response to stimuli that affect blood pressure and the role they play in hypertension. Three approaches will be used: altering function of the proteins, identifying the types of proteins present and identifying the cells involved, in brains sites important in regulation of the heart and blood vessels. This novel approach to understanding how the brain controls blood pressure will undoubtedly identify targets for novel blood pressure lowering therapies and targets for genetically determined causes of hypertension.Read moreRead less