Examination Of The Molecular Pharmacology Of Anthracyclines Induced Via Their Interaction With Iron
Funder
National Health and Medical Research Council
Funding Amount
$618,401.00
Summary
Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and ....Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and haem synthesis. Hence, this effect probably contributes to the cytotoxic activity of anthracyclines on the heart. We showed that novel drugs developed in my lab that bind Fe called chelators show high activity in animals (DR4) and prevent anthracycline-mediated Fe accumulation in ferritin. Importantly, Fe chelators have been shown to inhibit anthracycline-mediated cardiotoxicity. Indeed, the clinically used cardioprotective agent, ICRF-187, is actually an Fe chelator (5, DR6). However, ICRF-187 is not totally successful in terms of its cardioprotective effects and can cause myelosuppression (5, DR6). While the clinically used chelator, desferrioxamine (DFO), can prevent anthracycline-mediated cardiotoxicity, its poor membrane permeability limits its effectiveness. Our chelators are highly permeable and overcome the disadvantages of DFO (DR4). Thus, they are vital to examine for preventing anthracycline-mediated cardiotoxicity. In this proposal we will examine the changes in Fe metabolism induced by anthracyclines and test the hypothesis that novel Fe chelators may prevent the cardiotoxicity of these agents. We also aim to be the first to assess if preparation of anthracyclines which cannot bind iron prevents their cardiotoxicity. This will be done by preparing metal complexes of these drugs which prevent Fe-binding eg. anthracycline-zinc complexes. These studies are important for the development of less cardiotoxic forms of these very useful anti-tumour agents.Read moreRead less
Pharmacology Of Potential Anti-Tumour Agents: Iron Chelators Of The BpT Class
Funder
National Health and Medical Research Council
Funding Amount
$585,455.00
Summary
Pharmacology of Potential Anti-Tumour Agents: Iron Chelators of the BpT Class Cancer cells have a high iron requirement for DNA synthesis and many clinical trials showed Fe chelators are effective anti-cancer drugs. Their potential to act as anti-tumour agents has been confirmed by the entrance of Triapine into widespread NCI clinical trials. In this NHMRC Renewal, we will perform pharmacological and preclinical studies to promote the development of BpT chelators as novel anti-tumour agents.
Industrial Transformation Research Hubs - Grant ID: IH220100017
Funder
Australian Research Council
Funding Amount
$4,808,669.00
Summary
ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals. Radiopharmaceuticals are emerging as next generation medical technologies for addressing complex health challenges, and their manufacture offers significant economic benefit to Australia. The ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals (AMTAR) aims to establish a manufacturing platform for new medical technologies combining innovations in biotechnology and pharmaceutical science. The progra ....ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals. Radiopharmaceuticals are emerging as next generation medical technologies for addressing complex health challenges, and their manufacture offers significant economic benefit to Australia. The ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals (AMTAR) aims to establish a manufacturing platform for new medical technologies combining innovations in biotechnology and pharmaceutical science. The program addresses industry-led challenges for translation of biologics as molecular radiopharmaceuticals, building capacity in biomanufacturing, radiobiology and radiochemistry. The program establishes a dedicated manufacturing pipeline, future-proofing production and securing supply chain of next generation medical technologies.Read moreRead less
Examining scientific, philosophical, and folk perspectives on time=. This project aims to consider three very different physical theories, each of which reconciles quantum mechanics and general and special relativity in a different way. While science is more accessible than ever, we are increasingly faced with a scientific world-view that is antithetical to the way we see the world and experience ourselves in it. This project will consider the tension between the scientific picture of the world ....Examining scientific, philosophical, and folk perspectives on time=. This project aims to consider three very different physical theories, each of which reconciles quantum mechanics and general and special relativity in a different way. While science is more accessible than ever, we are increasingly faced with a scientific world-view that is antithetical to the way we see the world and experience ourselves in it. This project will consider the tension between the scientific picture of the world and our experience of the world, and aims to reconcile the two by bridging the gap between lived experience and scientific findings. The project will provide a range of ways of bridging the tension between these physical theories with our lived experience.Read moreRead less
Early Career Industry Fellowships - Grant ID: IE230100245
Funder
Australian Research Council
Funding Amount
$460,237.00
Summary
Transforming wastewater services in regional Australia. Wastewater treatment in regional Australia faces challenges of odour control, poor pollutant and pathogen removal, and greenhouse gas emissions. This project aims to innovatively use iron salts to realise highly efficient wastewater treatment in regional areas. With Partner, Western Australia Water Corporation, this project expects to leverage a recent breakthrough discovery on iron chemistry to co-develop and field test a solar system that ....Transforming wastewater services in regional Australia. Wastewater treatment in regional Australia faces challenges of odour control, poor pollutant and pathogen removal, and greenhouse gas emissions. This project aims to innovatively use iron salts to realise highly efficient wastewater treatment in regional areas. With Partner, Western Australia Water Corporation, this project expects to leverage a recent breakthrough discovery on iron chemistry to co-develop and field test a solar system that doses wastewater with iron, to overcome four challenges and a supply chain issue simultaneously. Expected outcomes include industry capacity to adopt and commercialise a novel technology with important global relevance. Outcomes should reduce the inequity of wastewater services in regional Australia.Read moreRead less
A Phase III Trial Comparing Adjuvant Versus Salvage Radiotherapy For High Risk Patients Post Radical Prostatectomy
Funder
National Health and Medical Research Council
Funding Amount
$819,138.00
Summary
About half of all patients Treated with an operation to remove their prostate cancer have a high chance of the cancer coming back. Giving immediate radiotherapy to all patients will improve cure rates but does not benefit all men and can cause significant side effects. This study explores whether it is safe to wait and only give radiotherapy when there is a rising PSA after surgery indicating active cancer. A total of 470 men from Australasia will enter this study comparing the two approaches.
Exemplary early childhood educators at work: A multi-level investigation. Exemplary early childhood educators at work: A multi-level investigation. This project aims to inform strategies to better attract, prepare, recognise, support and retain a high quality workforce, by investigating the complexity of early childhood educators’ work. Seemingly entrenched workforce shortages threaten the objectives that governments and families seek through investment in early childhood education. Popular imag ....Exemplary early childhood educators at work: A multi-level investigation. Exemplary early childhood educators at work: A multi-level investigation. This project aims to inform strategies to better attract, prepare, recognise, support and retain a high quality workforce, by investigating the complexity of early childhood educators’ work. Seemingly entrenched workforce shortages threaten the objectives that governments and families seek through investment in early childhood education. Popular images of work with young children as easy and instinctual, or of teaching as only school based, mislead potential workforce entrants and erode the status of educators, leading to attrition. This project’s audit and description of exemplary educators’ work, across each level of mandated qualification, will inform strategies to sustain a high quality early childhood workforce into the future.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE130100203
Funder
Australian Research Council
Funding Amount
$385,000.00
Summary
Autonomous benthic observing system. This project seeks to improve our ability to monitor marine habitats and characterise their variability by enhancing the Integrated Marine Observing system (IMOS) Autonomous Underwater Vehicle (AUV) Facility. The new AUV infrastructure will reduce operating costs, increase robustness of the sampling effort and insure continued operation for the next decade.
ARC Centre of Excellence for Children and Families over the Life Course. New solutions are needed to underpin the Australian social ideal of a fair go, and to drive future global economic productivity. The Australian Productivity Commission identifies deep and persistent disadvantage as a significant problem in Australia given the failure of growing national prosperity over the past two decades to benefit underprivileged Australians. Social disadvantage is a global challenge. This Centre will ad ....ARC Centre of Excellence for Children and Families over the Life Course. New solutions are needed to underpin the Australian social ideal of a fair go, and to drive future global economic productivity. The Australian Productivity Commission identifies deep and persistent disadvantage as a significant problem in Australia given the failure of growing national prosperity over the past two decades to benefit underprivileged Australians. Social disadvantage is a global challenge. This Centre will advance basic, applied and translational research to reduce intergenerational and long-term disadvantage. Through the maturation of longitudinal datasets and advanced data integration we can follow the journeys of Australian families over generations and across the life course. This data will provide evidence for new policies and make a real difference to the lives of children and families.Read moreRead less