Pharmacogenetic And Structural Investigation Of The Omega Class Glutathione Transferases
Funder
National Health and Medical Research Council
Funding Amount
$490,020.00
Summary
Members of the family of enzymes known as glutathione transferases are known to be responsible for the metabolism and detoxification of a wide range of compounds including therapeutic drugs and cancer causing chemicals. Genetic variation in an individual's compliment of glutathione transferases can alter their response to drug treatment or their susceptibility to cancer. The Omega class of glutathione transferases are important because they are involved in the metabolism of arsenic and because t ....Members of the family of enzymes known as glutathione transferases are known to be responsible for the metabolism and detoxification of a wide range of compounds including therapeutic drugs and cancer causing chemicals. Genetic variation in an individual's compliment of glutathione transferases can alter their response to drug treatment or their susceptibility to cancer. The Omega class of glutathione transferases are important because they are involved in the metabolism of arsenic and because they have been shown to influence the age-at-onset of both Alzheimer s and Parkinson s diseases. The present studies will investigate the structure and function of different Omega class glutathione transferases and determine how they interact with arsenic based drugs. These studies will attempt to determine why the toxicity of arsenic varies between individuals and aims to prevent adverse reactions to arsenic containing drugs used in cancer therapy. These studies will also investigate the mechanism by which the inheritance of certain forms of Omega class glutathione transferase can affect the age at-onset of Alzheimer s disease and Parkinson s disease. The understanding of this mechanism may provide the basis for a therapy that could delay or prevent the onset of these common diseases.Read moreRead less
Identification Of Cardiac Sarcoplasmic Reticulum Targets For Cardiotoxic Drugs
Funder
National Health and Medical Research Council
Funding Amount
$265,986.00
Summary
Anthracyclines are drugs which are used successfully in chemotherapy. Unfortunately, these drugs can lead to serious heart problems which sometimes result in death, and the mechanisms behind this remain elusive. Finding the specific targets of these drugs and how these drugs affect heart contraction may lead to designing drug cocktails which protect the heart from side effects.
Effects Of Ageing On Hepatic Drug Clearance And Mechanisms Of Drug Induced Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$581,892.00
Summary
With increasing age, there is increase in disease, for which medications may provide benefit, and an increase in the risk of adverse drug reactions, even after considering the increase in medication use by older people. We will investigate how the liver clears drugs from the blood in old age. This will guide dosing of medications for older people. We will also study how drugs injure the liver in old age and test interventions to prevent this toxicity.
SULT4A1 is not a sulfotransferase, but a sulfotransferase inhibitor. It forms high affinity heterodimers with other sulfotransferases via a conserved dimerisation site in its carboxyl terminus attenuating catalytic activity. Consequently, it is important for the metabolism of numerous important molecules including estrogens, thyroid hormones, neurotransmitters and many therapeutic agents.
Pesonalised Risk Prediction For Severe Treatment-related Gastrointestinal Toxicity In Paediatric Cancer Patients Using Pre-treatment Gut Microbiome Analysis
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
The gut is home to trillions of good and bad bacteria, critical to human health. Each person has a different balance of bacteria, unique to their gut, which shapes their immune system and susceptibility to disease. I will investigate how the unique gut bacteria, in children with blood cancer, can be used to predict which children will develop severe gut side effects (diarrhoea) from their chemotherapy. This will identify high-risk children, enable personalised treatment and improve survival.
Radiotherapy Treatment For Prostate Cancer - A Change In Practice Based On Direct Evidence For Targeting And Toxicity Effects Using Real Outcomes Data
Funder
National Health and Medical Research Council
Funding Amount
$555,129.00
Summary
Radiotherapy for prostate cancer treatment will be more effective when we have better knowledge of what patient anatomy needs to be targeted, and what needs to be avoided. This project will combine data collected during a large Australasian prostate cancer radiotherapy trial, ‘RADAR’, with data collected using new patient imaging methods to determine how patient anatomy impacts on the effectiveness of their treatment and the side-effects they experience.
Evaluation Of The Safety Of Lead Compounds For Allergic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$310,568.00
Summary
Asthma is one of the most common chronic respiratory diseases in developed countries and is typically treated with corticosteroids which provide symptomatic relief and coarse non-specific treatment of the underlying disease. We are pursuing innovative therapies by targeting a different enzyme, HPGD2S, involved in the inflammatory mechanisms of asthma. We have developed potent, anti-inflammatory drug candidates and aim to profile the safety of these compounds before entering clinical studies.