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Cellular Response To Modulation Of Iron Levels: Studies Examining ASK1, Thioredoxin And Ribonucleotide Reductase
Funder
National Health and Medical Research Council
Funding Amount
$33,055.00
Summary
Iron is crucial for many essential biological processes. Recently, I demonstrated that iron-depletion can affects signalling pathways that play important roles in cellular growth and death. This study is designed to investigate the cellular and molecular effects of iron depletion which currently remains unclear. My proposed research is crucial for understanding: (1) the effects of iron-deficiency and (2) for understanding the effects of iron chelators that are used for treating various diseases.
Understanding The Major Class Of Cell Surface Drug Targets
Funder
National Health and Medical Research Council
Funding Amount
$7,595,840.00
Summary
G Protein-Coupled Receptors (GPCRs) form the largest family of receptors and drug targets in living organisms. Currently, the major reason that new drugs fail to reach the clinic is lack of appropriate drug effect (approx. 30%). Thus, we need a better understanding of how GPCRs work and how this relates to disease. Our Program addresses this knowledge gap, using GPCR models that are relevant to treatment of metabolic, inflammatory, cardiovascular and central nervous system disease.
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.
Biased Allosteric Modulators Of Metabotropic Glutamate Receptors: Novel Therapeutic Targets For CNS Disorders
Funder
National Health and Medical Research Council
Funding Amount
$611,534.00
Summary
Metabotropic glutamate receptor 5 (mGlu5) is a major therapeutic target for depression and schizophrenia. The proposed studies will improve our understanding of how drug-like chemicals interact with mGlu5 and therefore change the activity of these receptors and in turn the activity of brain cells leading to therapeutic effectiveness. The research undertaken in this program will allow us to be smarter in developing new mGlu5 drugs that are both effective and have minimal side effects.
Molecular Pharmacology Of Chemokine Receptor Signalling In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$371,770.00
Summary
Molecular pharmacology is the study of how hormones, neurotransmitters and pharmaceuticals interact with our cells through receptors, which transfer a signal across the cell membrane to change the function of that cell. Chemokine receptors are recognised to play a role in the development of many cancers. Understanding how these receptors work has enormous implications for improving our ability to develop better anti-cancer treatments with fewer side effects.
Understanding The Physiological Consequences Of Biased Signalling Mediated By The Glucagon-like Peptide-1 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$636,508.00
Summary
The glucagon-like peptide 1 receptor is a major target for treatment of Type 2 diabetes and obesity. However, the development of drugs targeting this receptor is challenging as activation by different ligands can result in distinct signalling biases, a paradigm for which there is limited understanding of the physiological consequences. This project will address this critical knowledge gap and may allow for development of novel drugs with improved therapeutic outcomes.
Understanding Allosteric Modulation And Biased Signalling At Family B GPCRs
Funder
National Health and Medical Research Council
Funding Amount
$428,065.00
Summary
Family B GPCRs are therapeutic targets for drugs treating osteoporosis, hypercalcaemia, Paget’s disease, type II diabetes and are being actively pursued for other diseases that represent major global health burdens. Despite huge financial input, there are no orally available drugs that act on these receptors. This speaks to a lack of mechanistic understanding of how they work. My research focuses on addressing this question and how to exploit these receptors to design and identify better drugs.
Allosteric Targeting Of The Dopamine D2 Receptor: A Novel Approach For The Treatment Of Parkinson’s Disease And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$469,644.00
Summary
The dopamine D2 receptor is a brain protein that is the target for drugs that are used in the treatment of schizophrenia and Parkinson's disease (PD). In both cases the current drugs have significant side effects because they simply act to switch the receptor off or on respectively. We will focus on a new class of drugs that, because they act to tune up or tune down the activity of the D2 receptor, may be a safer more effective approach to treat these disorders.
Pharmacological Targeting Of Integrated Oncogenic And Tumour Suppressive Pathways Using Novel Therapeutics.
Funder
National Health and Medical Research Council
Funding Amount
$510,953.00
Summary
We will investigate NDRG1, a novel molecular target that has been demonstrated to inhibit the progression of numerous cancers. We aim to better understand the underlying function of NDRG1 in pancreatic cancer and how we can potentially target this gene with novel therapeutics being developed in our lab. We hope that this new approach will lead to promising treatments and a better outcome for those suffering from pancreatic cancer.
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.