A5078763991- Melanoma and MAPK Pathways
- DNA Repair Mechanisms
- Cancer Cells and Metastasis
- Computational Drug Discovery Methods
- Protein Degradation and Inhibitors
- Alzheimer's disease research and treatments
- Cell Adhesion Molecules Research
- Mathematical Biology Tumor Growth
- Cell Image Analysis Techniques
- Cancer therapeutics and mechanisms
- Cutaneous Melanoma Detection and Management
- Gene Regulatory Network Analysis
- Microtubule and mitosis dynamics
- Cancer Immunotherapy and Biomarkers
- melanin and skin pigmentation
- Trace Elements in Health
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Cellular Mechanics and Interactions
- Phagocytosis and Immune Regulation
- Monoclonal and Polyclonal Antibodies Research
- Genomics and Chromatin Dynamics
- Immunotherapy and Immune Responses
- Cancer Research and Treatments
- CRISPR and Genetic Engineering
The University of Queensland
2013-2024
Translational Research Institute
2013-2021
Australia Telescope National Facility
2019
Commonwealth Scientific and Industrial Research Organisation
2019
Astronomy and Space
2019
The University of Melbourne
2012-2018
Retina Institute
2013
Diamant (Germany)
2013
While invasion and metastasis of tumour cells are the principle factor responsible for cancer related deaths, mechanisms governing process remain poorly defined. Moreover, phenotypic divergence sub-populations is known to underpin alternative behaviors linked progression such as proliferation, survival invasion. In context melanoma, heterogeneity between two transcription factors, BRN2 MITF, has been associated with switching predominantly invasive proliferative respectively. Epigenetic...
Abstract Approaches to prolong responses BRAF targeting drugs in melanoma patients are challenged by phenotype heterogeneity. Melanomas of a “MITF‐high” usually respond well inhibitor therapy, but these melanomas also contain subpopulations the de novo resistance “AXL‐high” phenotype. > 50% progress with enriched populations, and because AXL is linked de‐differentiation invasiveness avoiding an “AXL‐high relapse” desirable. We discovered that heterogeneity supported during response phase...
Tumour spheroids are widely used to pre-clinically assess anti-cancer treatments. They an excellent compromise between the lack of microenvironment encountered in adherent cell culture conditions and great complexity vivo animal models. Spheroids recapitulate intra-tumour microenvironment-driven heterogeneity, a pivotal aspect for therapy outcome that is, however, often overlooked. Likely due their ease, most assays measure overall spheroid size and/or death as readout. However, different...
Abstract The identification of factors that regulate myelination provides important insight into the molecular mechanisms coordinate nervous system development and myelin regeneration after injury. In this study, we investigated role amyloid precursor protein (APP) its paralogue precursor‐like 2 (APLP2) in using APP APLP2 knockout (KO) mice. Given BACE1 regulates sheath thickness both peripheral central systems, sought to determine if APLP2, as alternate substrates, also modulate...
A hallmark of cancer is genomic instability that considered to provide the adaptive capacity cancers thrive under conditions in which normal precursors would not survive. Recent analysis has revealed a very high degree melanomas, although mechanism by this arises known. Here we report proportion (68%) melanoma cell lines are either partially (40%) or severely (28%) compromised for G2 phase decatenation checkpoint normally functions ensure sister chromatids able separate correctly during...
Purpose: Checkpoint kinase 1 inhibitors (CHEK1i) have single-agent activity in vitro and vivo Here, we investigated the molecular basis of this activity.Experimental Design: We assessed a panel melanoma cell lines for their sensitivity to CHEK1i GNE-323 GDC-0575 The effects these compounds on responses DNA replication stress were analyzed hypersensitive lines.Results: A subset is CHEK1i-induced death vitro, drug effectively inhibits tumor growth In lines, triggers without cells entering...
Abstract Phenotypic heterogeneity of cancer cells plays a critical role in shaping treatment response. This type is organized spatially with specific phenotypes, such as sharply demarcated clusters proliferating and cell cycle-arrested cells, predominating within discrete domains tumor. What determines the occurrence tumor phenotypes distinct microdomains solid cancers poorly understood. Here, we show that melanoma spatial organization phenotypic dictated by expression activity MITF. We...
Summary Melanomas have high levels of genomic instability that can contribute to poor disease prognosis. Here, we report a novel defect the ATM ‐dependent cell cycle checkpoint in melanoma lines promotes instability. In defective cells, signalling CHK 2 is intact, but cells are unable maintain arrest due elevated PLK 1 driving recovery from arrest. Reducing activity recovered arrest, and over‐expressing was sufficient overcome increase Loss did not affect sensitivity ionizing radiation...
Summary Melanoma cell lines are commonly defective for the G2‐phase cycle checkpoint that responds to incomplete catenation of replicated chromosomes. Here, we demonstrate melanomas this response less sensitive genotoxic stress, suggesting compensated loss by increasing their ability cope with DNA damage. We performed an si RNA kinome screen identify kinases responsible and identified PI 3K pathway components. Checkpoint‐defective were three‐fold more small molecule inhibitors 3K. The...
Abstract Three-dimensional (3D) in vitro tumour spheroid experiments are an important tool for studying cancer progression and potential drug therapies. Standard involve growing imaging spheroids to explore how different experimental conditions lead rates of growth. These kinds experiments, however, do not reveal any information about the spatial distribution cell cycle within expanding spheroid. Since 2008, a new technology called fluorescent ubiquitination-based indicator (FUCCI), has...