Resistance To Herceptin (trastuzumab) In HER2 Positive Breast Cancers: The Role Of Calcium Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$620,292.00
Summary
The monoclonal antibody therapy trastuzumab has revolutionized the treatment of women with Her2 positive breast cancer. Unfortunately some Her2 positive breast cancers do not respond to this therapy or gradually develop resistance. This project will define how an important cellular signal is remodeled in breast cancers resistant to trastuzumab. The ability of modulators of this signaling pathway to alter the sensitivity of breast cancers to trastuzumab will also be determined.
Repurposing Amiloride Into Breast Cancer Drugs With A Dual-Targeting Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$611,966.00
Summary
This project aims to transform a diuretic drug (amiloride) into a breast cancer drug that acts via a novel molecular mechanism. The science of medicinal chemistry will be used to remove amiloride's diuretic effects whilst gaining potent dual-activity against two breast cancer targets, uPA and NHE1. Our study will validate a new pharmacological approach in cancer treatment and produce patented drugs suitable for development into first-in-class breast cancer drugs.
Research Fellowship: Understanding G Protein-coupled Receptors (GPCRs)
Funder
National Health and Medical Research Council
Funding Amount
$444,177.00
Summary
This project focuses on drug action at G protein-coupled receptors (GPCRs), the largest class of drug targets. It builds on key discoveries by the applicant that novel sites on GPCRs can be targeted by small molecules in a selective manner, thus minimizing side effects and maximizing therapeutic efficacy. Because this approach can work across most GPCR families, the relevance to the pharmaceutical industry and GPCR-related diseases, such as schizophrenia and diabetes, is very high.
Allosteric Modulation And Biased Signalling At The Calcium-sensing Receptor
Funder
National Health and Medical Research Council
Funding Amount
$636,242.00
Summary
The calcium-sensing receptor is a major target for the treatment of endocrine and bone disorders. However, the development of drugs for this receptor is challenging due to limited understanding of potential sites of drug interaction and how individual drugs may differentially change signalling from the receptor. This project will address these critical knowledge gaps, which may allow for improved therapeutic outcomes.
Exploiting The Overexpression Of A Specific Calcium Permeable Ion Channel In Breast Cancer Cells: A New Pharmacological Approach To Targeting Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$577,717.00
Summary
We have identified that a specific protein that controls the entry of calcium into cells is found at much higher levels in some breast cancer cells. We have also identified that drugs that control the activity of this protein can promote the death of some breast cancer cells. This grant will help further define the mechanism of this effect and determine the applicability of this approach as a therapy for some women with breast cancer.
Rational Co-targeting Of G Protein-coupled Receptors As A Novel Approach Towards Treating Neuropsychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$620,399.00
Summary
Schizophrenia is a common mental disorder with multiple symptoms. Current therapeutics only treat some of these symptoms. This project will focus on two important brain proteins implicated in schizophrenia. With the hypothesis that the rational targeting of these two proteins will lead to the design of more effective medicines for treatment of schizophrenia we will develop novel methods to selectively and simultaneously and target these two proteins.
Molecular Mechanisms And Pharmacology Of The Dynamins
Funder
National Health and Medical Research Council
Funding Amount
$883,375.00
Summary
His research focuses on the molecular mechanisms of synaptic transmission in the nervous system to: a) understand the basic science of nerve communication and b) develop drugs to control diseases of nerve terminals like epilepsy. The main focus is on proteins called the dynamins, which are self-assembling molecular machines acting in many intracellular functions. There are three dynamin genes: dynI, II and III with diverse functions in the different parts of the body.
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.
I am a molecular physiologist investigating the structure and function of the inhibitory neurotransmitter glycine receptor (GlyR) and GABA type- A receptor (GABAAR) chloride channels. We are interested in understanding how these receptors open and close