A5069358983- DNA Repair Mechanisms
- Telomeres, Telomerase, and Senescence
- Microtubule and mitosis dynamics
- Mitochondrial Function and Pathology
- Pancreatic and Hepatic Oncology Research
- Neonatal Respiratory Health Research
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- S100 Proteins and Annexins
- Cancer Genomics and Diagnostics
- TGF-β signaling in diseases
- Immune Response and Inflammation
- Amyotrophic Lateral Sclerosis Research
- bioluminescence and chemiluminescence research
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA regulation and disease
- Immune cells in cancer
- Immunotherapy and Immune Responses
- Neurogenetic and Muscular Disorders Research
- interferon and immune responses
- Inflammasome and immune disorders
- CRISPR and Genetic Engineering
Children's Medical Research Institute
2018-2025
The University of Sydney
2018-2025
Walter and Eliza Hall Institute of Medical Research
2018-2024
The University of Melbourne
2020-2024
The Francis Crick Institute
2024
Victorian Comprehensive Cancer Centre
2021-2022
Cytoplasmic accumulation of TDP-43 is a disease hallmark for many cases amyotrophic lateral sclerosis (ALS), associated with neuroinflammatory cytokine profile related to upregulation nuclear factor κB (NF-κB) and type I interferon (IFN) pathways. Here we show that this inflammation driven by the cytoplasmic DNA sensor cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) when invades mitochondria releases via permeability transition pore. Pharmacologic inhibition or genetic deletion cGAS...
Abstract Coatomer complex I (COPI) mediates retrograde vesicular trafficking from Golgi to the endoplasmic reticulum (ER) and within compartments. Deficiency in subunit alpha causes COPA syndrome is associated with type IFN signalling, although upstream innate immune sensor involved was unknown. Using vitro models we find aberrant activation of STING pathway due deficient but probably not intra-Golgi transport. Further cytosolic DNA cGAS as essentially required drive signalling. Genetic...
Abstract Mitotic catastrophe is a broad descriptor encompassing unclear mechanisms of cell death. Here we investigate replication stress-driven mitotic in human cells and identify that stress principally induces death signalled through two independent pathways. In p53-compromised find lethal confers WAPL-dependent centromere cohesion defects maintain spindle assembly checkpoint-dependent arrest the same cycle. then drives fatigue triggers primary pathway BAX/BAK-dependent apoptosis....
Abstract Epithelial-mesenchymal transition (EMT) is a continuum that includes epithelial, partial EMT, and mesenchymal states, each of which associated with cancer progression, invasive capabilities, ultimately, metastasis. We used lineage-traced sporadic model pancreatic to generate murine organoid biobank from primary secondary tumors, including sublines underwent EMT complete EMT. Using an unbiased proteomics approach, we found morphology predicts the state, solid organoids are signature....
Abstract Telomeres prevent ATM activation by sequestering chromosome termini within telomere loops (t-loops). Mitotic arrest promotes linearity and a localized ATM-dependent DNA damage response (DDR) through an unknown mechanism. Using unbiased interactomics, biochemical screening, molecular biology, super-resolution imaging, we found that mitotic arrest-dependent (MAD) deprotection requires the combined activities of Chromosome passenger complex (CPC) on shelterin, BLM-TOP3A-RMI1/2 (BTR)...
Abstract Gastrointestinal epithelial cells provide a selective barrier that segregates the host immune system from luminal microorganisms, thereby contributing directly to regulation of homeostasis. We have shown early embryonic development Bcl-G, Bcl-2 protein family member with unknown function, was highly expressed in gastrointestinal cells. While Bcl-G dispensable for normal growth and mice, loss resulted accelerated progression colitis-associated cancer. A label-free quantitative...
SUMMARY We used super-resolution microscopy to investigate the role of macromolecular telomere structure in chromosome end protection. In murine and human cells with reduced TRF2, we find that ATM-activation at ends occurs a structural change from t-loops linearized through t-loop unfolding. Comparably, Aurora B kinase regulates linearity concurrent ATM activation telomeres during mitotic arrest. Using separation function allele, TRFH domain TRF2 formation while suppressing activity....
Telomeres prevent ATM activation by sequestering chromosome termini within telomere loops (t-loops). Mitotic arrest promotes linearity and a localized ATM-dependent DNA damage response (DDR) through an unknown mechanism. Using unbiased interactomics, biochemical screening, molecular biology, super-resolution imaging, we found that mitotic arrest-dependent (MAD) deprotection requires the combined activities of Chromosome passenger complex (CPC) on shelterin, BLM-TOP3A-RMI1/2 (BTR) t-loops....
ABSTRACT Mitotic catastrophe is a broad descriptor encompassing unclear mechanisms of cell death. Here we investigate replication stress-driven mitotic in human cells and identify that stress principally induces death signalled through two independent pathways. In p53-compromised find lethal confers WAPL-dependent centromere cohesion defects maintain spindle assembly checkpoint-dependent arrest the same cycle. then drives fatigue triggers primary pathway BAX/BAK-dependent apoptosis....
Abstract The shelterin component telomeric repeat-binding factor 2 (TRF2) is an essential regulator of telomere homeostasis and genomic stability. Mutations in the TRF2 TRFH domain physically impair t-loop formation prevent recruitment several factors that promote efficient replication, resulting a DNA damage response. Here, we design, synthesize, biologically test covalent cyclic peptides irreversibly target domain. We identify APOD53 as our most promising compound. forms adduct with...
SUMMARY Epithelial-mesenchymal transition (EMT) is a continuum that includes epithelial, partial EMT (P-EMT) and mesenchymal states, each of which are associated with cancer progression, invasive capabilities ultimately metastasis. We have employed lineage traced sporadic model pancreatic to generate murine organoid biobank from primary secondary tumors, including sublines undergone P-EMT complete (C-EMT). Using an unbiased proteomics approach, we found the morphology organoids predicts...