- Antimicrobial Peptides and Activities
- Glycosylation and Glycoproteins Research
- Biochemical and Structural Characterization
- Proteoglycans and glycosaminoglycans research
- Monoclonal and Polyclonal Antibodies Research
- Phagocytosis and Immune Regulation
- Cell Adhesion Molecules Research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- Fibroblast Growth Factor Research
- Cell death mechanisms and regulation
- Extracellular vesicles in disease
- X-ray Diffraction in Crystallography
- Immune Response and Inflammation
- Crystallization and Solubility Studies
- Carbohydrate Chemistry and Synthesis
- Mast cells and histamine
- Immunotherapy and Immune Responses
- Transgenic Plants and Applications
- Inflammasome and immune disorders
- RNA and protein synthesis mechanisms
- Peptidase Inhibition and Analysis
- Protease and Inhibitor Mechanisms
- Platelet Disorders and Treatments
La Trobe University
2015-2024
Institute for Molecular Science
2019-2024
QIMR Berghofer Medical Research Institute
2024
Hexima (Australia)
2011-2012
Australian National University
1999-2010
Pediatrics and Genetics
2008
Canberra (United Kingdom)
2006
Heidelberg Repatriation Hospital
1999-2002
Austin Hospital
1991-1999
Austin Health
1999
Exosomes are nanovesicles released by a variety of cells and detected in body fluids including blood. Recent studies have highlighted the critical application exosomes as personalized targeted drug delivery vehicles reservoirs disease biomarkers. While these research applications created significant interest can be translated into practice, stability needs to assessed exosome isolation protocols from blood plasma need optimized. To optimize methods isolate plasma, we performed comparative...
Abstract Disassembly of apoptotic cells into smaller fragments (a form extracellular vesicle called bodies) can facilitate removal debris and intercellular communication. However, the mechanism underpinning this process is unclear. While observing monocytes undergoing apoptosis by time-lapse microscopy, we discovered a new type membrane protrusion that resembles ‘beads-on-a-string’ structure. Strikingly, ‘beads’ are frequently sheared off ‘string’ to bodies. Generation bodies via sorting...
Heparanase is a β-D-endoglucuronidase that cleaves heparan sulfate (HS), facilitating degradation of the extracellular matrix (ECM) and release HS-bound biomolecules including cytokines. The remodeling ECM by heparanase important for various physiological pathological processes, inflammation, wound healing, tumour angiogenesis metastasis. Although has been proposed to facilitate leukocyte migration through ECM, its role in inflammation regulating expression cytokines not fully defined. In...
Currently most attempts at cancer immunotherapy involve the generation of CD8+ cytotoxic T lymphocytes (CTLs) against tumor-associated antigens. Many tumors, however, have been immunoselected to evade recognition by CTLs and thus alternative approaches are urgently needed. Here we demonstrate that CD4+ cells recognize a secreted tumor-specific antigen exhibit cytokine secretion profile characteristic Th2 cells, capable clearing established lung visceral metastases CTL-resistant melanoma....
Cationic antimicrobial peptides (CAPs) such as defensins are ubiquitously found innate immune molecules that often exhibit broad activity against microbial pathogens and mammalian tumor cells. Many CAPs act at the plasma membrane of cells leading to destabilization permeabilization. In this study, we describe a novel cell lysis mechanism for fungal by plant defensin NaD1 acts via direct binding phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2). We determined crystal structure...
The defensin and defensin-like proteins are an extensive group of small, cationic, disulfide-rich found in animals, plants, fungi mostly perform roles host defense. term was originally used for small mammalian neutrophils subsequently applied to insect plant γ-thionins based on their perceived sequence structural similarity. Defensins often described as ancient innate immunity molecules classified a single superfamily both alignments phylogenies have been constructed. Here, we present...
Apoptosis is a form of programmed cell death that occurs throughout life as part normal development well pathologic processes including chronic inflammation and infection. Although the often considered only biological outcome committed to apoptosis, it becoming increasingly clear dying can actively communicate with other cells via soluble factors membrane-bound extracellular vesicles (EVs) regulate clearance, immunity tissue repair. Compared EVs generated from viable such exosomes...
Over 200 billion cells undergo apoptosis every day in the human body order to maintain tissue homeostasis. Increased can also occur under pathological conditions including infection and autoimmune disease. During apoptosis, fragment into subcellular membrane-bound vesicles known as apoptotic bodies (ApoBDs). We recently developed a flow cytometry-based method accurately differentiate ApoBDs from other particles (e.g. debris). In present study, we aim further characterize subsets of based on...
NK cells are highly efficient at preventing cancer metastasis but infrequently found in the core of primary tumors. Here, have we demonstrated that freshly isolated mouse and human express low levels endo-β-D-glucuronidase heparanase increase upon cell activation. Heparanase deficiency did not affect development, differentiation, or tissue localization under steady-state conditions. However, mice lacking specifically (Hpsefl/fl NKp46-iCre mice) were tumor prone when challenged with...
COVID-19 is primarily known as a respiratory disease caused by SARS-CoV-2. However, neurological symptoms such memory loss, sensory confusion, severe headaches, and even stroke are reported in up to 30% of cases can persist after the infection over (long COVID). These thought be produced virus infecting central nervous system, however we don't understand molecular mechanisms triggering them. The effects share similarities neurodegenerative diseases which presence cytotoxic aggregated amyloid...
Heparanase is a β-d-endoglucuronidase that cleaves heparan sulfate (HS) and has been implicated in many important physiological pathological processes, including tumor cell metastasis, angiogenesis, leukocyte migration. We report herein the identification of active-site residues human heparanase. Using PSI-BLAST PHI-BLAST searches sequence databases, similarities were identified between heparanase members several glycosyl hydrolase families (10, 39, 51) from clan A (GH-A), strong local...
Apoptotic bodies (ApoBDs) are membrane-bound extracellular vesicles that can mediate intercellular communication in physiological and pathological settings. By combining recently developed analytical strategies with fluorescence-activated cell sorting (FACS), we have a method enables the isolation of ApoBDs from cultured cells to 99% purity. In addition, this approach also identification type-specific tissue, bodily fluid blood-derived samples.