A5064960876- Neuroinflammation and Neurodegeneration Mechanisms
- Cellular transport and secretion
- Immune cells in cancer
- Immunotherapy and Immune Responses
- Peroxisome Proliferator-Activated Receptors
- T-cell and B-cell Immunology
- Lipid Membrane Structure and Behavior
- Alzheimer's disease research and treatments
- vaccines and immunoinformatics approaches
- Neuroscience and Neuropharmacology Research
- Botulinum Toxin and Related Neurological Disorders
- Cancer Immunotherapy and Biomarkers
- Amyotrophic Lateral Sclerosis Research
- Nuclear Receptors and Signaling
- RNA regulation and disease
- Brain Metastases and Treatment
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Nerve injury and regeneration
- Virus-based gene therapy research
- Cancer Cells and Metastasis
- RNA Research and Splicing
- Ion channel regulation and function
- Analytical Chemistry and Sensors
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
QIMR Berghofer Medical Research Institute
2007-2025
University of Iowa
2025
University of California, Los Angeles
2020
University of Wisconsin–La Crosse
2020
The University of Queensland
2010-2016
Park Centre for Mental Health
2015-2016
The Alfred Hospital
2014
Griffith University
2003-2010
Queensland Eye Institute
2009
Center for Cancer Research
2007
Dynamin GTPase activity increases when it oligomerizes either into helices in the presence of lipid templates or rings SH3 domain proteins. Dynasore is a dynamin inhibitor moderate potency ( IC 50 ˜ 15 μM vitro ). We show that dynasore binds stoichiometrically to detergents used for drug screening, drastically reducing its = 479 μM) and research tool utility. synthesized focused set dihydroxyl trihydroxyl analogs called Dyngo™ compounds, five which had improved potency, reduced detergent...
The botulinum neurotoxins (BoNTs) are di-chain bacterial proteins responsible for the paralytic disease botulism. Following binding to plasma membrane of cholinergic motor nerve terminals, BoNTs internalized into an endocytic compartment. Although several pathways have been characterized in neurons, molecular mechanism underpinning uptake at presynaptic terminal is still unclear. Here, a recombinant BoNT/A heavy chain domain (Hc) was used unravel internalization pathway by fluorescence and...
To understand how neural-immune-associated genes and pathways contribute to neurodegenerative disease pathophysiology, we performed a systematic functional genomic analysis in purified microglia bulk tissue from mouse human AD, FTD, PSP. We uncover complex temporal trajectory of microglial-immune involving the type 1 interferon response associated with tau pathology early stages, followed by later signatures partial immune suppression and, subsequently, 2 response. find that genetic risk for...
Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease characterised by the loss of upper and lower motor neurons. Increasing evidence indicates that neuroinflammation mediated microglia contributes to ALS pathogenesis. This microglial activation evident in post-mortem brain tissues neuroimaging data from patients with ALS. However, role pathogenesis progression amyotrophic remains unclear, partly due lack model system able faithfully recapitulate clinical...
Abstract Background Alzheimer’s disease (AD) is an incurable neurodegenerative disorder with a rapidly increasing prevalence worldwide. Current approaches targeting hallmark pathological features of AD have had no consistent clinical benefit. Neuroinflammation major contributor to neurodegeneration and hence, microglia, the brain’s resident immune cells, are attractive target for potentially more effective therapeutic strategies. However, there current in vitro model system that captures...
ABSTRACT A single blind, randomized, placebo-controlled, single-center phase I clinical trial of a CD8 + T-cell peptide epitope vaccine against infectious mononucleosis was conducted with 14 HLA B*0801-positive, Epstein-Barr virus (EBV)-seronegative adults. The comprised the B*0801-restricted FLRGRAYGL and tetanus toxoid formulated in water-in-oil adjuvant, Montanide ISA 720. FLRGRAYGL-specific responses were detected 8/9 peptide-vaccine recipients 0/4 placebo by gamma interferon...
Axonal retrograde transport of signalling endosomes from the nerve terminal to soma underpins survival. As each endosome carries a quantal amount activated receptors, we hypothesized that it is frequency reaching determines scale trophic signal. Here show upregulating synaptic activity markedly increased flux plasma membrane-derived (labelled using cholera toxin subunit-B: CTB) in hippocampal neurons cultured microfluidic devices, and live Drosophila larval motor neurons. Electron...
Zellweger syndrome is the archetypical peroxisome biogenesis disorder and characterized by defective import of proteins into peroxisome, leading to peroxisomal metabolic dysfunction widespread tissue pathology. In humans, mutations in PEX13 gene, which encodes a membrane protein necessary for import, can lead phenotype. To develop mouse models this disorder, we have generated targeted with loxP-modified Pex13 gene enable conditional Cre recombinase-mediated inactivation Pex13. studies...
Background Tigilanol tiglate (TT) is a protein kinase C (PKC)/C1 domain activator currently being developed as an intralesional agent for the treatment of various (sub)cutaneous malignancies. Previous work has shown that intratumoral (I.T.) injection TT causes vascular disruption with concomitant tumor ablation in several preclinical models cancer, addition to tumors presenting veterinary clinic. completed Phase I dose escalation trials, some patients showing signs abscopal effects. However,...
Pancreatic ductal adenocarcinoma (PDAC) has a high incidence of perineural invasion (PNI), pathological feature the cancer nerves. PNI is associated with poor prognosis, local recurrence and pain. It been suggested that interactions between nerves tumor microenvironment (TME) play role in PDAC tumorigenesis. Here, we used Nanostring GeoMx Digital Spatial Profiler to analyze whole transcriptome both nerve cells non-PNI foci from 13 patients. We identified previously reported pathways involved...
SUMMARY Delayed cerebellar development is a hallmark of Zellweger syndrome (ZS), severe neonatal neurodegenerative disorder. ZS caused by mutations in PEX genes, such as PEX13, which encodes protein required for import proteins into the peroxisome. The molecular basis pathogenesis not known. We have created conditional mouse mutant with brain-restricted deficiency PEX13 that exhibits morphological defects. brain mutants survive postnatal period, majority dying 35 days, and survival inversely...
ABSTRACT Mounting evidence suggests that human immunodeficiency virus type 1 (HIV-1) Gag-specific T helper cells contribute to effective antiviral control, but their functional characteristics and the precise epitopes targeted by this response remain be defined. In study, we generated CD4 + T-cell clones specific for Gag from HIV-1-infected persons with vigorous responses detectable in peripheral blood mononuclear cells. Multiple peptides containing were identified, including a minimal...
Bulk endocytosis contributes to the maintenance of neurotransmission at amphibian neuromuscular junction by regenerating synaptic vesicles. How nerve terminals internalize adequate portions presynaptic membrane when bulk is initiated before end a sustained stimulation unknown. A maturation process, occurring stimulation, hypothesised precisely restore pools Using confocal time-lapse microscopy FM1-43-labeled junction, we confirm that during tetanic and reveal shortly after undergo process....
Activity-dependent bulk endocytosis allows neurons to internalize large portions of the plasma membrane in response stimulation. However, whether this critical type compensatory is unique or also occurs other excitable cells currently unknown. Here we used fluorescent 70 kDa dextran demonstrate that secretagogue-induced bovine chromaffin cells. The relatively size endosomes found model allowed us investigate how neck budding constricts allow efficient recruitment fission machinery. Using...
Abstract Neuronal communication relies on synaptic vesicles undergoing regulated exocytosis and recycling for multiple rounds of fusion. Whether all have identical protein content has been challenged, suggesting that their ability may differ greatly. Botulinum neurotoxin type-A (BoNT/A) is a highly potent internalized in at motor nerve terminals induces flaccid paralysis. Recently, BoNT/A was also shown to undergo retrograde transport, it might enter specific pool with trafficking fate....
Abstract In vitro, ACE2 translocates to the nucleus induce SARS-CoV-2 replication. Here, using digital spatial profiling of lung tissues from SARS-CoV-2-infected golden Syrian hamsters, we show that a specific and selective peptide inhibitor nuclear (NACE2i) inhibits viral replication two days after infection. Moreover, also prevents inflammation macrophage infiltration, increases NK cell infiltration in bronchioles. NACE2i treatment levels active histone mark, H3K27ac, restores host...
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disorder with minimally effective treatment options. An important hurdle in ALS drug development the non-invasive therapeutic access to motor cortex currently limited by presence of blood-brain barrier (BBB). Focused ultrasound and microbubble (FUS
In contrast to peroxisomes in normal cells, remnant cultured skin fibroblasts from a subset of the clinically severe peroxisomal disorders that includes biogenesis disorder Zellweger syndrome and single-enzyme defect D-bifunctional protein (D-BP) deficiency, are enlarged significantly less abundant. We tested whether these features could be related known role microtubules peroxisome trafficking mammalian cells. found patients with PEX1-null or D-BP deficiency exhibited clustering loss...