A5060466019- Amino Acid Enzymes and Metabolism
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Cancer, Lipids, and Metabolism
- Pancreatic and Hepatic Oncology Research
- Cancer-related Molecular Pathways
- Prostate Cancer Treatment and Research
- Neuroendocrine Tumor Research Advances
- Cancer Immunotherapy and Biomarkers
- Metabolism and Genetic Disorders
- RNA modifications and cancer
- Polyamine Metabolism and Applications
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- T-cell and B-cell Immunology
- MicroRNA in disease regulation
- Glioma Diagnosis and Treatment
- Natural Compounds in Disease Treatment
- Angiogenesis and VEGF in Cancer
- Immune cells in cancer
- X-ray Diffraction in Crystallography
- Fatty Acid Research and Health
- Crystallization and Solubility Studies
- Cell Adhesion Molecules Research
UNSW Sydney
2003-2025
The University of Sydney
2011-2023
Centenary Institute
2011-2023
Prince of Wales Hospital
2022
Thomas Jefferson University
2021
The University of Adelaide
2011
Royal Prince Alfred Hospital
2011
St Vincent's Hospital Sydney
2000-2010
St. Jude Children's Research Hospital
2006-2010
St Vincent's Hospital
2002
Highlights•Activated T cell signatures/populations drive response to anti-PD-1-based therapies•EOMES+CD69+CD45RO+ effector memory cells are associated with response•EOMES+CD69+CD45RO+ expression is longer PFS and tumor shrinkage•Non-responders TIL-hot tumors express other immune drug targetsSummaryCancer immunotherapies provide survival benefits in responding patients, but many patients fail respond. Identifying the biology of treatment resistance a priority optimize selection improve...
Alanine, serine, cysteine-preferring transporter 2 (ASCT2; SLC1A5) mediates uptake of glutamine, a conditionally essential amino acid in rapidly proliferating tumour cells. Uptake glutamine and subsequent glutaminolysis is critical for activation the mTORC1 nutrient-sensing pathway, which regulates cell growth protein translation cancer This particular interest breast cancer, as dependence increased high-risk subtypes. Pharmacological inhibitors ASCT2-mediated transport significantly reduced...
Obesity is associated with increased recurrence and reduced survival of breast cancer. Adipocytes constitute a significant component tissue, yet their role in provisioning metabolic substrates to support cancer progression poorly understood. Here, we show that co-culture cells adipocytes revealed cell-stimulated depletion adipocyte triacylglycerol. Adipocyte-derived free fatty acids were transferred cells, driving acid metabolism via CPT1A electron transport chain complex protein levels,...
Abstract Glutamine is conditionally essential in cancer cells, being utilized as a carbon and nitrogen source for macromolecule production, well anaplerotic reactions fuelling the tricarboxylic acid ( TCA ) cycle. In this study, we demonstrated that glutamine transporter ASCT2 SLC1A5 highly expressed prostate patient samples. Using LNCaP PC ‐3 cell lines, showed chemical or shRNA ‐mediated inhibition of function vitro decreases uptake, cycle progression through E2F transcription factors,...
Amino acids, especially leucine and glutamine, are important for tumor cell growth, survival metabolism. A range of different transporters deliver each specific amino acid into cells, some which increased in cancer. These acids consequently activate the mTORC1 pathway drive cycle progression. The transporter LAT1/4F2hc heterodimer assembles as part a large complex with glutamine ASCT2 to transport acids. In this study, we show that expression LAT1 is significantly human melanoma samples...
Fatty acid β-oxidation (FAO) is the main bioenergetic pathway in human prostate cancer (PCa) and a promising novel therapeutic vulnerability. Here we demonstrate efficacy of targeting FAO clinical tumors cultured ex vivo, identify DECR1, encoding rate-limiting enzyme for oxidation polyunsaturated fatty acids (PUFAs), as robustly overexpressed PCa tissues associated with shorter relapse-free survival. DECR1 negatively-regulated androgen receptor (AR) target gene and, therefore, may promote...
Abstract Although many cytokine receptors generate their signals via the STAT3 pathway, IL-10R appears unique in promoting a potent anti-inflammatory response (AIR) to antagonize proinflammatory that activate innate immune response. We found heterologous receptor systems but are naturally refractory (the IL-22R), or engineered be IL-6, leptin, and erythropoietin receptors), suppressor of signaling-3-mediated inhibition an AIR indistinguishable from IL-10. conclude is generic signaling...
L-type amino acid transporters (LATs) uptake neutral acids including L-leucine into cells, stimulating mammalian target of rapamycin complex 1 signaling and protein synthesis. LAT1 LAT3 are overexpressed at different stages prostate cancer, they responsible for increasing nutrients cell growth.We examined expression in human cancer tissue microarrays. LAT function was inhibited using a leucine analog (BCH) androgen-dependent -independent environments, with gene analyzed by microarray. A PC-3...
Abstract l-Type amino acid transporters such as LAT1 and LAT3 mediate the uptake of essential acids. Here, we report that prostate cancer cells coordinate expression to maintain sufficient levels leucine needed for mTORC1 signaling cell growth. Inhibiting LAT function was decrease growth in cells. These maintained influx through androgen receptor–mediated regulation ATF4 after deprivation. responses remained intact primary cancer, indicated by high disease, increased hormone ablation...
Abstract While intron retention (IR) is considered a widely conserved and distinct mechanism of gene expression control, its regulation poorly understood. Here we show that DNA methylation directly regulates IR. We also find reduced occupancy MeCP2 near the splice junctions retained introns, mirroring at these sites. Accordingly, depletion in tissues cells enhances By analysing interactome using mass spectrometry RNA co-precipitation, demonstrate decreased binding facilitates IR via...
Abstract Cancer-associated fibroblasts (CAF) are major contributors to pancreatic ductal adenocarcinoma (PDAC) progression through protumor signaling and the generation of fibrosis, latter which creates a physical barrier drugs. CAF inhibition is thus an ideal component any therapeutic approach for PDAC. SLC7A11 cystine transporter that has been identified as potential target in PDAC cells. However, no prior study evaluated role tumor stroma its prognostic significance. Here we show high...
The neutral amino acid transporter solute carrier family 1 member 5 (SLC1A5 or ASCT2) is overexpressed in many cancers. To identify its roles tumors, we employed 143B osteosarcoma cells and HCC1806 triple-negative breast cancer with without ASCT2 deletion. ASCT2ko grew well standard culture media, but was required for optimal growth at <0.5 mm glutamine, tumor spheroid monolayer migration of being strongly impaired lower glutamine concentrations. However, the deletion did not affect...
Prostate cancer cells exhibit altered cellular metabolism but, notably, not the hallmarks of Warburg metabolism. increased de novo synthesis fatty acids (FA); however, little is known about how extracellular FAs, such as those in circulation, may support prostate progression. Here, we show that increasing FA availability intracellular triacylglycerol content cultured patient-derived tumor explants, LNCaP and C4-2B spheroids, a range (LNCaP, C4-2B, 22Rv1, PC-3), epithelial (PNT1)....
Abstract Loss of the retinoblastoma (RB) tumor suppressor protein is a critical step in reprogramming biological networks that drive cancer progression, although mechanistic insight has been largely limited to impact RB loss on cell-cycle regulation. Here, isogenic modeling identified disease stage–specific rewiring E2F1 function, providing first-in-field mapping cistrome and transcriptome after across progression. Biochemical functional assessment using both vitro vivo models an unexpected,...
Background Micro-RNAs (miRNAs) control gene expression by destabilizing targeted transcripts and inhibiting their translation. Aberrant of miRNAs has been described in many human cancers, including chronic myeloid leukemia. Current first-line therapy for newly diagnosed leukemia is imatinib mesylate, which typically produces a rapid hematologic response. However the effect on miRNA vivo not thoroughly examined.Design Methods Using TaqMan Low-Density Array system, we analyzed blood samples...
Live animal imaging is becoming an increasingly common technique for accurate and quantitative assessment of tumor burden over time. Bioluminescence systems rely on a bioluminescent signal from cells, typically generated expression the firefly luciferase gene. However, previous reports have suggested that either high level or resultant light reaction produced upon addition D-luciferin substrate can negative influence cell growth. To address this issue, we designed vector allows simultaneous...