The critical role of the class III histone deacetylase SIRT2 in stabilizing N-Myc oncoprotein. Cancer is the commonest cause of death from disease in children. Neuroblastoma is the commonest solid tumor in early childhood. This project will investigate the critical roles of SIRT2 protein in increasing the expression of N-Myc oncoprotein and consequently inducing neuroblastoma, and SIRT2 inhibitors as anticancer agents.
Mitochondrially targeted anti-cancer drugs modulate the mitochondrial genome. Successful cancer management requires novel therapeutical approaches. This project will test the effect of a new class of compounds that target mitochondria, the powerhouse of the cells, where they suppress expression of mitochondrial genes. By this mechanism, cancers that are resistant to apoptosis induction can be inhibited.
Molecular hallmarks of androgen receptor targeting in prostate cancer. There is a critical need in oncology drug development for better biomarkers of response to prostate cancer therapies, clinically to assist with treatment decision making, and pre-clinically to facilitate translation of emerging agents into clinical practice. Using a unique explant culture model, this project will identify protein and lipid markers that can be used to accurately and reliably assess response to androgen recepto ....Molecular hallmarks of androgen receptor targeting in prostate cancer. There is a critical need in oncology drug development for better biomarkers of response to prostate cancer therapies, clinically to assist with treatment decision making, and pre-clinically to facilitate translation of emerging agents into clinical practice. Using a unique explant culture model, this project will identify protein and lipid markers that can be used to accurately and reliably assess response to androgen receptor (AR)-targeting therapies in human prostate tumours. The identification and functional assessment of these biomarkers will identify those that can be used as surrogate endpoints in clinical trials, facilitate earlier approval of investigational agents and lead to improved options for therapeutic management of prostate cancer.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220100165
Funder
Australian Research Council
Funding Amount
$451,900.00
Summary
Engineering T cells to promote peripheral immunity. Tissue-resident memory T cells (TRM) are key for immune protection against infections and cancer. This has led to much interest in understanding how these immune cells develop, although elucidation of molecules that regulate TRM are still scarce. This project aims to (i) identify genetic drivers of TRM in peripheral organs and (ii) modulate TRM generation utilising state-of-the-art genetic engineering techniques. Expected outcomes include gener ....Engineering T cells to promote peripheral immunity. Tissue-resident memory T cells (TRM) are key for immune protection against infections and cancer. This has led to much interest in understanding how these immune cells develop, although elucidation of molecules that regulate TRM are still scarce. This project aims to (i) identify genetic drivers of TRM in peripheral organs and (ii) modulate TRM generation utilising state-of-the-art genetic engineering techniques. Expected outcomes include generating new knowledge that will contribute to the development of novel therapeutics against infectious disease and cancer, together with the benefit of promoting national and international collaboration with the ultimate goal of improving health.Read moreRead less
Osteosarcoma is the most common tumour of bone. Recent success in targeting immune checkpoint blockers such as Programmed death-1 (PD-1) in genomically complex tumours suggests that osteosarcomas may be amenable to such strategies. We will characterise the role of the PD-1 pathway in osteosarcoma development and growth. Using preclinical mouse models we will investigate the biology of the PD-1 pathway and study its potential as a therapeutic target in advanced and resectable osteosarcoma.
EGFR-directed radioimmunotherapy combined with chemotherapy and DNA repair inhibition: development towards clinical application for aggressive cancers. Pancreatic ductal adenocarcinoma (PDAC) and triple negative breast cancer (TNBC) are aggressive diseases which lack effective therapies in clinical use. A novel and curative therapy was developed against PDAC and TNBC which involves targeted radiotherapy combined with chemotherapy and DNA damage response inhibition. This project will develop a “p ....EGFR-directed radioimmunotherapy combined with chemotherapy and DNA repair inhibition: development towards clinical application for aggressive cancers. Pancreatic ductal adenocarcinoma (PDAC) and triple negative breast cancer (TNBC) are aggressive diseases which lack effective therapies in clinical use. A novel and curative therapy was developed against PDAC and TNBC which involves targeted radiotherapy combined with chemotherapy and DNA damage response inhibition. This project will develop a “preclinical data package” comprising a biological rationale and preclinical evidence of safety and efficacy that together would justify an early phase clinical trial. This package includes the choice of formulations, mechanism of action and safety studies. This development will have an immediate impact for PDAC and TNBC patients and a future impact on other EGFR-positive cancers.Read moreRead less
Tailoring Targeted Therapy To DNA Repair-defective High-Grade Serous Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$802,247.00
Summary
Ovarian cancer is a major cause of cancer death in women because current treatments are inadequate. Half of aggressive ovarian cancers have abnormalities in DNA repair and should be susceptible to new PARP inhibitor therapy, yet not all those respond. By developing a new model of studying human ovarian cancers in mice, we can discover markers to predict which ovarian cancers will respond best to these exciting new treatments.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100082
Funder
Australian Research Council
Funding Amount
$180,000.00
Summary
FACSAria III - Fluorescence activated cell sorter. Flow cytometry is a technique for counting and examining microscopic particles, such as cells and chromosomes, by suspending them in a stream of fluid and passing them by an electronic detection apparatus. The FACSAria III cell sorter will be used to establish a core facility for sorting cells. The outcomes from using this technology are a better understanding cellular and genetic understanding of cancer, respiratory diseases, reproduction and ....FACSAria III - Fluorescence activated cell sorter. Flow cytometry is a technique for counting and examining microscopic particles, such as cells and chromosomes, by suspending them in a stream of fluid and passing them by an electronic detection apparatus. The FACSAria III cell sorter will be used to establish a core facility for sorting cells. The outcomes from using this technology are a better understanding cellular and genetic understanding of cancer, respiratory diseases, reproduction and birth. Read moreRead less
An Integrated Systems Biology Approach For The Development Of New Therapeutic Strategies For The Treatment Of High Grade Glioma
Funder
National Health and Medical Research Council
Funding Amount
$696,404.00
Summary
Glioma, the most common adult brain cancer, is incurable. Recent advances now allow us to grow glioma cells directly from patients in the laboratory in a way that preserves the features of the original tumor. In this proposal we will systematically analyze such cells using state-of-the-art technologies to identify new processes important to glioma, which in turn should facilitate the identification of innovative therapeutic approaches.