Relaxin family peptides are small proteins that have numerous essential biological roles in the vascular system, brain and gut. The hormone relaxin is currently in Phase III clinical trials to treat heart failure and the other peptides show great potential as drugs to treat diseases including mental illnesses and obesity. My research focuses on developing drugs targeting the receptors for these important peptide systems and understanding how these drugs can be best used therapeutically
Determining Modes Of Binding And Activation Of Peptide G-protein Coupled Receptor Targets
Funder
National Health and Medical Research Council
Funding Amount
$576,538.00
Summary
The neuropeptide relaxin-3 and the peptide hormone INSL5 are recently discovered members of the relaxin peptide family. Relaxin-3 has important roles in stress and feeding whereas INSL5 is a gut hormone. We will study the interaction of relaxin-3 and INSL5 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-3 and INSL5 for future clinical applications
Discovery And Development Of Novel Venom Peptide Analgesics
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
Professor Lewis will discover and develop new research tools and potential therapeutics from toxins acting on pain pathways. The Fellowship will leverage (i) well-funded collaborations with top Australian and international scientists (ii) the recently established IMB Centre for Pain Research that I lead as inaugural Director, and (iii) an outstanding Institute equipped with leading edge technologies for high throughput and high content discovery and proteomic and transcriptomic analysis.
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.
Improving Endothelial Dysfunction In Diabetes-associated Vascular Diseases With Nrf2 Activators
Funder
National Health and Medical Research Council
Funding Amount
$340,039.00
Summary
Diabetic patients have a greater risk of developing cardiovascular diseases as compared to the general population. This is largely attributed to the impact the diabetic environment has on the endothelium (inner layer of the blood vessel). Indeed, clinical studies have shown that impaired endothelial function occurs prior to the development of cardiovascular diseases. Hence, we propose to study a novel way to improve endothelial function by limiting oxidative stress and inflammatory pathways.
G protein-coupled receptors are proteins that exist on every human cell, where they sense, and respond to environmental stimuli. Because of their importance they are targeted by drugs to treat many diseases. However little is known about how drugs activate these receptors and this has hindered new drug development. I use state-of-the-art technology to determine how drugs activate receptors and develop new methods for drug discovery. This work will have major impact on the Pharmaceutical industry
Professor Lewis is a molecular pharmacologist interested in discovering new venom peptides and ciguatoxins and determining how they interact with the membrane proteins they target using advanced biochemical and spectroscopic methods. Peptides of interest are then modified to improve potency and selectivity. Those with appropriate properties are patented and developed for clinical applications using approaches successfully applied to Xen2174, a conopeptide analogue I co-discovered that is now in ....Professor Lewis is a molecular pharmacologist interested in discovering new venom peptides and ciguatoxins and determining how they interact with the membrane proteins they target using advanced biochemical and spectroscopic methods. Peptides of interest are then modified to improve potency and selectivity. Those with appropriate properties are patented and developed for clinical applications using approaches successfully applied to Xen2174, a conopeptide analogue I co-discovered that is now in Phase II clinical trials for severe pain.Read moreRead less
Discovery and characterisation of novel spider-venom peptides targeting the human sodium ion channel Nav1.7. Drugs that selectively block the human sodium ion channel Nav1.7 are likely to be powerful analgesics for treating a wide variety of pain conditions. However, it has proved difficult to obtain selective blockers of this channel. The aim of this project is to determine whether spider-venoms might provide a source of highly selective Nav1.7 blockers.
Blood-Brain Barrier Penetrating Antisense Therapy For Spinal Muscular Atrophy
Funder
National Health and Medical Research Council
Funding Amount
$635,005.00
Summary
Spinal muscular atrophy (SMA) is a genetic disease caused by the deficiency of a protein known as survival motor neuron.This results in the degeneration of motor neurons (nerve cells controlling muscles) leading to progressive muscle weakness, paralysis, and eventual death. Currently, there is no known cure for SMA. The aim of proposed research is to develop gene-modifying molecules that prevent degeneration of motor neuron and extend the life-span of mice as a potential therapy for SMA.
Novel Approaches To Understanding Peptide G-protein-coupled Receptor Activation
Funder
National Health and Medical Research Council
Funding Amount
$665,043.00
Summary
G protein-coupled receptors (GPCRs) are proteins that exist on every human cell, where they sense, and respond to environmental stimuli. Because of their importance they are targeted by drugs to treat many diseases. However little is known about the molecular steps that underlie cellular responses upon drug binding and this has hindered new drug development. This project uses new technology to determine the complex pathway of GPCR activation upon drug binding which will aid new drug development.