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.
Toxicological And Pre-clinical Assessment Of The Anti-cancer Compound Bp4eT
Funder
National Health and Medical Research Council
Funding Amount
$198,900.00
Summary
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 Development Grant, we will perform toxicological studies to enable clinical trials of our most promising novel iron chelator to commence.
I am a pharmacologist-cell biologist-molecular biologist and chemist examining the metabolism of iron in normal and neoplastic cells and the development of iron chelators for the treatment of a wide variety of diseases eg., ?-thalassaemia, cancer and Frie
Pharmacological Targeting Via AKT, PTEN, And TGF-beta Pathway Integration Using Novel Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$634,875.00
Summary
We have identified potentially important interactions of cellular pathways that vary between individual sufferers, but which also provide common molecular targets for novel drug development. Our suite of novel and potent drugs that markedly and selectively inhibit cancer cell growth will be studied to determine if these pharmaceutical agents act to inhibit tumour cell proliferation by targeting common effector molecules of integrated cellular pathways.
Perturbation of the extracellular architecture to promote the absorption and lymphatic transport of biological macromolecules. Macromolecules therapeutics such as proteins, antibodies or polymer conjugates pose a number of pharmaceutical challenges. Where the dose is high, drainage of that dose from a subcutaneous injection site into the circulation, poses a particular problem. Here the project aims to explore how recombinant hyaluronidase, an enzyme that breaks down a structural component (hya ....Perturbation of the extracellular architecture to promote the absorption and lymphatic transport of biological macromolecules. Macromolecules therapeutics such as proteins, antibodies or polymer conjugates pose a number of pharmaceutical challenges. Where the dose is high, drainage of that dose from a subcutaneous injection site into the circulation, poses a particular problem. Here the project aims to explore how recombinant hyaluronidase, an enzyme that breaks down a structural component (hyaluronan) of the interstitum, can be used promote absorption into the draining blood and lymph capillaries. The project aims to also explore the downstream effects of hyaluronidase on lymph nodes and evaluate whether the enzyme is able to temporarily disrupt the lymph node structure and promote drug penetration into the lymph node mass. This has significant potential for improved drug targeting.Read moreRead less
Understanding the Cellular Pathways of Nuclear Receptor Activation. The success of drug treatment depends critically on specificity, i.e., stimulation of a therapeutic response at a target site, and avoidance of activity at other (potentially toxic) locations. This project aims to explore how drug interactions with binding proteins in the cytosol can induce nuclear transport and tissue specific activation of nuclear receptors - a major drug target. The project intends to employ molecular, struct ....Understanding the Cellular Pathways of Nuclear Receptor Activation. The success of drug treatment depends critically on specificity, i.e., stimulation of a therapeutic response at a target site, and avoidance of activity at other (potentially toxic) locations. This project aims to explore how drug interactions with binding proteins in the cytosol can induce nuclear transport and tissue specific activation of nuclear receptors - a major drug target. The project intends to employ molecular, structural and cell biology approaches to map drug-binding protein-receptor interactions and to determine how the structure of these complexes dictates receptor activation. The data could provide a roadmap to design drugs that interact with the right protein in the right tissue and in doing so dramatically enhance drug specificity.Read moreRead less
Synergising nanoemulsion and lipid biomimetic design for advanced delivery. This project aims to identify the critical design characteristics of lipid formulations of lipid-modified probes or drugs (lipid biomimetics) that together promote integration into lipid absorption pathways and target the lymphatic system that drains the small intestine. This has significant potential since the intestinal lymphatic system is a key immune tissue, the site of immune response to autoantigens and antigens de ....Synergising nanoemulsion and lipid biomimetic design for advanced delivery. This project aims to identify the critical design characteristics of lipid formulations of lipid-modified probes or drugs (lipid biomimetics) that together promote integration into lipid absorption pathways and target the lymphatic system that drains the small intestine. This has significant potential since the intestinal lymphatic system is a key immune tissue, the site of immune response to autoantigens and antigens derived from food and the microbiome. The project will deliver a design roadmap of the required characteristics for lymphatic targeting, and in particular, will identify novel lipid nanoemulsions that work synergistically with lipid biomimetics to enhance lymphatic imaging and delivery applications.Read moreRead less
Biomedical Investigations Of Pharmacology And Pathology For Disease Treatment
Funder
National Health and Medical Research Council
Funding Amount
$863,413.00
Summary
I am an NHMRC SPRF & Director of the Molecular Pharmacology & Pathology Program consisting of 34 researchers. The breadth of our studies is diverse & continues to expand. Excitingly, we have recently obtained commercialisation support to develop our anti-tumour drug, DpC. My vision for the next 5 yrs is to direct development of these agents together with investigations of basic mechanism. These studies will be done with a team of outstanding researchers I am mentoring and an established group of ....I am an NHMRC SPRF & Director of the Molecular Pharmacology & Pathology Program consisting of 34 researchers. The breadth of our studies is diverse & continues to expand. Excitingly, we have recently obtained commercialisation support to develop our anti-tumour drug, DpC. My vision for the next 5 yrs is to direct development of these agents together with investigations of basic mechanism. These studies will be done with a team of outstanding researchers I am mentoring and an established group of experienced collaborators.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120103084
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Targeting bacterial superbugs: novel approaches for optimisation of antibiotic combinations and resistance prevention. This project will elucidate the mechanistic basis to optimally combine available beta-lactam antibiotics to prevent resistance of gram-negative 'superbugs'. The interdisciplinary project will substantially contribute to solving the global crisis due to multidrug-resistant bacteria and inform the design of effective new antibiotics.
Targeting an impending global disaster: the mismatch between increasingly drug-resistant superbugs and development of new antibiotics. This project will develop much-needed novel antibiotics for treating infections caused by bacteria that are resistant to all current antibiotics. It will make a significant contribution to the global medical challenge of a shortage of new antibiotics.