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
GABA(B) Receptor Modulation Of Gastrointestinal Function In Health And Disease By Alpha-Conotoxins
Funder
National Health and Medical Research Council
Funding Amount
$689,050.00
Summary
Chronic visceral pain is a common and debilitating condition arising from numerous diseases that affect our internal organs. There is a desperate need for more information about the mechanisms responsible for signalling chronic visceral pain to provide therapies and potentially find a cure for it. Our research focuses on ?-conotoxins (small peptides from marine cone snail venom) as novel potential therapeutic agents for the treatment of chronic visceral pain.
Molecular Targets Of Amino Acid/neurotransmitter Conjugates Of Fatty Acids
Funder
National Health and Medical Research Council
Funding Amount
$846,390.00
Summary
This project investigates endogenous chemicals that affect cells important for detecting and responding to pain. We aim to discover how these compounds affect proteins important for nerve cell function, particularly proteins that have a prominent role in detecting and transmitting painful events. The compounds we examine are not themselves likely to be drugs, but future therapies may involve manipulating the levels of these chemicals in the body, or using drugs that mimic the activity of these c ....This project investigates endogenous chemicals that affect cells important for detecting and responding to pain. We aim to discover how these compounds affect proteins important for nerve cell function, particularly proteins that have a prominent role in detecting and transmitting painful events. The compounds we examine are not themselves likely to be drugs, but future therapies may involve manipulating the levels of these chemicals in the body, or using drugs that mimic the activity of these compounds.Read moreRead less
Targeting TRPV4 Activation Mechanisms To Reveal Novel Pain Therapies
Funder
National Health and Medical Research Council
Funding Amount
$580,938.00
Summary
Pain nerves sense painful chemical and physical stimuli, by opening protein "ion channels" which let small electric currents traverse the cell membrane. This pain signal is transmitted to the spinal cord and then the brain, where it is perceived as pain and elicits a reaction. But we don't know how the ion channels open. This project will investigate how receptors for painful substances open ion channels to cause pain. Understanding this mechanism will help us to make new drugs to treat pain.
Understanding Uterine Contractility: What Can We Learn From Obesity?
Funder
National Health and Medical Research Council
Funding Amount
$600,792.00
Summary
The incidence of failure to progress in labour has increased in recent years, being linked to the rise in obesity. The result is a significant escalation in the rate of delivery by Caesarean Section (CS) which increases the risk of serious complications during subsequent pregnancies. We have identified five dysfunctional systems associated with poor uterine contraction. We now aim to determine the mechanisms underlying these dysfunctional systems, particularly those mechanisms in common.
Identifying And Exploiting Novel Pharmacological Targets For Breast Cancer Treatment
Funder
National Health and Medical Research Council
Funding Amount
$442,214.00
Summary
Breast cancers are made up of different types of cancer cells, and not all cells contribute equally. A subset of cancer cells may be uniquely capable of driving tumor growth, rebuilding fatal tumors after therapy and establishing new tumors at distant sites. New therapies to inhibit the activity and survival of these cells will lead to better modes of treatment and greatly accelerate progress towards ending breast cancer.
The Awakening:GABA-A Receptors As Targets For Improving Motor Function
Funder
National Health and Medical Research Council
Funding Amount
$735,498.00
Summary
Zolpidem (Stilnox) is a “sleeping pill” that is reported "awaken" people with severe motor, memory and speech disabilities that result from stroke or other brain injury. We have identified a novel target by which zolpidem can exert these effects. This project will characterise this target and assess drug effects in models of stroke.
Towards The Rational Design Of Calcium Sensing Receptor Allosteric Modulators For The Treatment Of Osteoporosis And Calcium Handling Disorders
Funder
National Health and Medical Research Council
Funding Amount
$741,390.00
Summary
Drugs that target the human calcium sensing receptor can be too strong or too weak, resulting in side effects or lack of efficacy. This proposal thus seeks to establish whether the strength of drug activity can be rationally altered and exploited to treat different disease states by fine-tuning CaSR activity in a disease-specific manner.
Engendering Biased Signalling At The Human Calcium Sensing Receptor (CaSR) To Correct Pathophysiology
Funder
National Health and Medical Research Council
Funding Amount
$633,860.00
Summary
The human calcium sensing receptor (CaSR) has been targeted therapeutically in hyperparathyroidism and osteoporosis, but current CaSR therapeutics exhibit problematic side effects or are ineffective. Thus, the current research proposal seeks to understand the specific properties of CaSR drugs required to selectively control whole body calcium and bone mineral metabolism, to identify ligands that can mediate desired therapeutic effects at the exclusion of adverse effects.
Is Overactive Bladder A 'Bladder Itch'? Identification Of Itch Specific Pathways Within The Bladder
Funder
National Health and Medical Research Council
Funding Amount
$720,585.00
Summary
Overactive bladder is a leading cause of nocturia, urgency and incontinence. These symptoms arise from sensory nerve fibres in the bladder. We have identified key irritant mechanisms, including the bile acid receptor TGR5 and Mrgpr family, thought to only exist in the skin, also innervate the bladder. We hypothesis that the clinical entity overactive bladder, is triggered by pathological activation of bladder afferents by such irritants and that overactive bladder is essentially a bladder itch.