A5051172094- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Burn Injury Management and Outcomes
- Wound Healing and Treatments
- Immune cells in cancer
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Asthma and respiratory diseases
- Genomics and Rare Diseases
- Thermal Regulation in Medicine
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- CRISPR and Genetic Engineering
- Occupational and environmental lung diseases
- Immune Response and Inflammation
- Heme Oxygenase-1 and Carbon Monoxide
- Influenza Virus Research Studies
- Genetics and Neurodevelopmental Disorders
- Respiratory viral infections research
- Cell Adhesion Molecules Research
- Hedgehog Signaling Pathway Studies
- Protein Kinase Regulation and GTPase Signaling
- Inhalation and Respiratory Drug Delivery
- Climate Change and Health Impacts
- Cancer Cells and Metastasis
The University of Western Australia
2016-2025
The Kids Research Institute Australia
2014-2024
Asbestos Diseases Research Institute
2018-2024
Perth Children's Hospital
2022-2023
Princess Margaret Hospital for Children
2019-2023
Institute for Respiratory Health
2021
ORCID
2021
Queen Elizabeth II Medical Centre
2018-2019
A STAT1-driven inflammatory phenotype associated with response to checkpoint blocking antibodies sensitizes cancers immunotherapy.
Immune checkpoint therapy (ICT) results in durable responses individuals with some cancers, but not all patients respond to treatment. ICT improves CD8+ cytotoxic T lymphocyte (CTL) function, changes tumor antigen-specific CTLs post that correlate successful have been well characterized. Here, we studied murine models dichotomous ICT. We tracked CTL frequencies and phenotype before after responding non-responding animals. Tumor increased within draining lymph nodes ICT, exhibited an effector...
In disease settings, vitamin D may be important for maintaining optimal lung epithelial integrity and suppressing inflammation, but less is known of its effects prior to onset. Female BALB/c dams were fed a D3-supplemented (2280 IU/kg, VitD+) or nonsupplemented (0 VitD−) diet from 3 weeks age, mated at 8 age. Male offspring the same as their mother. Some initially VitD− switched VitD+ age (VitD−/+). At 12 signs low-level inflammation observed in bronchoalveolar lavage fluid (BALF) mice (more...
Abstract The biological determinants of the response to immune checkpoint blockade (ICB) in cancer remain incompletely understood. Little is known about dynamic events that underpin therapeutic efficacy due inability frequently sample tumours patients. Here, we map transcriptional profiles 144 responding and non-responding within two mouse models at four time points during ICB. We find display on/fast-off kinetics type-I-interferon (IFN) signaling. Phenocopying this using time-dependent...
Mesothelioma is an aggressive asbestos induced cancer with extremely poor prognosis and limited treatment options. Immune checkpoint blockade (ICPB) has demonstrated effective therapy in melanoma now being applied to other cancers, including mesothelioma. However, the efficacy of ICPB which immune combinations constitute best therapeutic option for mesothelioma have yet be fully elucidated. Here, we used our well characterised tumour model investigate different ICBP treatments generate We...
Surgical resection of cancer remains the frontline therapy for millions patients annually, but post-operative recurrence is common, with a relapse rate around 45% non-small cell lung cancer. The tumour draining lymph nodes (dLN) are resected at time surgery staging purposes, and this cannot be null event patient survival future response to immune checkpoint blockade treatment. This project investigates surgery, lymphadenectomy, onset metastatic disease, immunotherapy in novel model that...
Recurrences frequently occur following surgical removal of primary tumors. In many cancers, adjuvant therapies have limited efficacy. Surgery provides access to the tumor microenvironment, creating an opportunity for local therapy, in particular immunotherapy, which can induce and systemic anti-cancer effects. Here, we develop a surgically optimized biodegradable hyaluronic acid-based hydrogel sustained intraoperative delivery Toll-like receptor 3 agonist poly(I:C) demonstrate that it...
Abstract Lung cancer remains the leading cause of cancer‐related death worldwide. The disease is classified into two major subtypes, small‐cell lung ( SCLC ) and more prevalent non‐small‐cell NSCLC ). First‐line conventional therapies, such as chemotherapy, radiotherapy surgery, have offered limited benefit, patient prognosis poor with post‐treatment recurrences representing a morbidity. Consequently, there an urgent need for improved therapeutic options. Historically, has been considered...
Despite advances in immunotherapy, metastatic melanoma remains a considerable therapeutic challenge due to the complexity of tumor microenvironment. Intratumoral type I interferon (IFN-I) has long been associated with improved clinical outcomes. However, several IFN-I subtypes can also paradoxically promote growth some contexts. We investigated this further by engineering murine B16 cells overexpress various subtypes, where spectrum outcomes was observed. Characterization these tumors RNA...
Immunological homeostasis in the respiratory tract is thought to require balanced interactions between networks of dendritic cell (DC) subsets lung microenvironments order regulate tolerance or immunity inhaled antigens and pathogens. Influenza A virus (IAV) poses a serious threat long-term disruption this balance through its potent pro-inflammatory activities. In study, we have used BALB/c mouse model A/PR8/34 H1N1 Type Virus infection examine effects IAV on tissue DC during recovery phase...
Immune checkpoint therapy (ICT) causes durable tumour responses in a subgroup of patients, but it is not well known how T cell receptor beta (TCRβ) repertoire dynamics contribute to the therapeutic response. Using murine models that exclude variation host genetics, environmental factors and mutation burden, limiting between animals naturally diverse TCRβ repertoires, we applied TCRseq, single RNAseq flow cytometry study ICT responders non-responders. Increased oligoclonal expansion...
Abstract Background Over 400 million people worldwide are living with a rare disease. Next Generation Sequencing (NGS) identifies potential disease causative genetic variants. However, many identified as variants of uncertain significance (VUS) and require functional laboratory validation to determine pathogenicity, this creates major diagnostic delays . Methods In study we test rapid variant assessment pipeline using CRISPR homology directed repair introduce single nucleotide into inducible...
Burn injury initiates an acute inflammatory response that subsequently drives wound repair. However, disruption to the immune is also common, leading susceptibility sepsis and increased morbidity mortality. Despite understanding of impact burn on system in phase, little known about long-term consequences function. This study was established determine whether has clinical impacts patients' responses.Using a population-based retrospective longitudinal linked hospital death data from Western...
Abstract The integrin CD 103 is the α E chain of β 7 that important in maintenance intraepithelial lymphocytes and recruitment T cells dendritic ( DC ) to mucosal surfaces. role intestinal immune homeostasis has been well described, however, its allergic airway inflammation less understood. In this study, we used an ovalbumin OVA )‐induced, 103‐knockout KO BALB /c mouse model experimental airways disease EAAD investigate expression, 4 + T‐cell activation function lymph nodes. We found...
While chemotherapy remains the first-line treatment for many cancers, it is still unclear what distinguishes responders from non-responders. Here, we characterize chemotherapy-responsive tumor microenvironment in mice, using RNA sequencing on tumors before and after cyclophosphamide, compare gene expression profiles of with progressors. Responsive have an inflammatory highly immune infiltrated pre-treatment characterized by enrichment pathways associated CD4+ T cells, interferons (IFNs),...
Epidemiological studies have demonstrated that survivors of acute burn trauma are at long-term increased risk developing a range morbidities. The mechanisms underlying this remain unknown. This study aimed to determine whether injury leads sustained immune dysfunction may underpin morbidity. Plasma and peripheral blood mononuclear cells were collected from 36 pediatric >3 years after non-severe (<10% total body surface area) age/sex-matched non-injured controls. Circulating cytokine vaccine...
Cancer vaccination drives the generation of anti-tumor T cell immunity and can be enhanced by inclusion effective immune adjuvants such as type I interferons (IFNs). Whilst IFNs have been shown to promote cross-priming cells, role individual subtypes remains unclear. Here we systematically compared capacity distinct IFN enhance responses a whole-cell strategy in pre-clinical murine model. We show that combination with IFNβ induces significantly greater expansion tumor-specific CD8 + cells...
There are an estimated > 400 million people living with a rare disease globally, genetic variants the cause of approximately 80% cases. Next Generation Sequencing (NGS) rapidly identifies however they often unknown significance. Low throughput functional validation in specialist laboratories is current ad hoc approach for variants, which creating major bottlenecks patient diagnosis. This study investigates application CRISPR gene editing followed by genome wide transcriptomic profiling to...
Introduction Burn injury in children causes prolonged systemic effects on physiology and metabolism leading to increased morbidity mortality, yet much remains undefined regarding the metabolic trajectory towards specific health outcomes. Methods A multi-platform strategy was implemented evaluate long-term immuno-metabolic consequences of burn combining metabolite, lipoprotein, cytokine panels. Plasma samples from 36 aged 4–8 years were collected 3 after a together with 21 non-injured age sex...
The Australian Genomics Cardiovascular Disorders Flagship was a national multidisciplinary collaboration. It aimed to investigate the feasibility of genome sequencing (GS) and functional genomics resolve variants uncertain significance (VUS) in clinical management patients families with cardiomyopathies, primary arrhythmias, congenital heart disease (CHD).
Immune checkpoint blockade (ICPB) is a powerfully effective cancer therapy in some patients. Tumor neo-antigens are likely main targets for attack but it not clear which and how many tumor mutations individual cancers actually antigenic, with or without ICPB their role as neo-antigen vaccines predictors of responses. To examine this, we interrogated the immune response to murine model induced by natural human carcinogen (i.e. asbestos) mimics its counterpart mesothelioma). We identified...