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Investigating The Effects Of Macrolides On Excessive Synthesis And Secretion Of Airway Mucins Using Novel Ex Vivo And In Vivo Approaches
Funder
National Health and Medical Research Council
Funding Amount
$520,821.00
Summary
Many people have difficulty breathing because the airway tubes that move air in and out of their lungs are blocked by excessive amounts of sticky mucus. Our project will use new techniques developed in our laboratories to investigate whether a group of medicines called “macrolides” can prevent the excessive production and release of mucus in the airways, and thus be beneficial in treating asthma, and potentially other lung diseases.
Targeting Small Airways To Overcome Resistance To Therapy In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$531,045.00
Summary
There is a pressing need to overcome resistance to current therapies for severe asthma. Targetting inflammation-induced changes in small airway contraction offers an alternative strategy. We have identified a novel bronchodilator that relaxes maximally contracted mouse small airways when current treatment is ineffective. We will demonstrate its efficacy in animal models mimicking key features of human asthma, and define new ways to improve outcomes in poorly-controlled asthma.
Novel Treatments Of Fibrosis For Hypertensive Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$912,536.00
Summary
A recognised risk factor for cardiovascular disease is high blood pressure which contributes to a stiffer heart that can ultimately lead to heart failure. There are very few treatments that can reduce heart stiffening, called fibrosis. This project is focused on the preclinical testing of novel compounds that we have developed to reverse the build-up of fibrosis in the heart, which will lead to better treatment of elderly patients with high blood pressure and poorly-functioning hearts.
M2 Macrophage Polarization As A Cause Of Vascular Fibrosis And Stiffening In Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$657,028.00
Summary
Blood vessel stiffening is a hallmark of hypertension (A.K.A. high blood pressure) and is thought to be a major contributor to the clinical complications of the condition, which include heart failure, stroke and renal impairment. Here we will test the novel concept that this stiffening process is caused by certain types of white blood cells (macrophages), which enter the walls of blood vessels and signal the surrounding cells to produce a rigid scaffolding protein called collagen.
Pharmacological Inhibition Of IRAP As A Novel Antifibrotic Strategy
Funder
National Health and Medical Research Council
Funding Amount
$1,036,370.00
Summary
There are very few treatments that can reduce heart stiffening, called fibrosis, which is seen in patients with high blood pressure or in patients who have had a heart attack. This project will test new drugs that we have developed that act by a unique mechanism to reverse or prevent cardiovascular disease in patients with poorly-functioning hearts and blood vessels.
Formyl Peptide Receptor Biased Agonists As Novel Cardioprotective Agents Against Myocardial Infarction.
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Heart attack and its resulting heart failure are the leading causes of death in Australia. Examining a promising new target (formyl peptide receptors), I will use my knowledge of drug action at the single cell level to identify new drugs that act via a unique biased mechanism. These will be tested in pre-clinical animal models of heart attack to uncover critical new potential therapies that will protect the heart post heart attack and prevent the development heart failure.
Specific Roles Of The Transmembrane Exoloops And The LDLa Module In The Activity Of Relaxin And INSL3 Receptors
Funder
National Health and Medical Research Council
Funding Amount
$598,863.00
Summary
The peptide hormone relaxin is currently in clinical trials to treat acute heart failure. The related hormone INSL3 has important roles in fertility. We will continue our previously successful approaches to study the interaction of relaxin and INSL3 with their cell surface receptors and the mechanisms by which the receptors function. The knowledge gained will aid in the design of smaller, more potent and orally active forms of relaxin and INSL3 for future clinical applications.
Research Fellowship: Protection Of Myocardial Function In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
Heart failure (HF) is a major cause of death in Australia. A/Prof Rebecca Ritchie heads Heart Failure Pharmacology at Baker IDI. Her research focuses on new drug strategies to maintain heart function in response to diabetes & heart attack, common precursors of HF. Many of the treatments discovered from this work are naturally-occurring antioxidants; enhancing their activity will ultimately reduce progression to HF & death in the >3 million Australians affected by these disorders.