A5024890079- Adipose Tissue and Metabolism
- Atherosclerosis and Cardiovascular Diseases
- Coronary Interventions and Diagnostics
- Adipokines, Inflammation, and Metabolic Diseases
- Nanoplatforms for cancer theranostics
- Nanoparticle-Based Drug Delivery
- Inflammasome and immune disorders
- Birth, Development, and Health
- interferon and immune responses
- Cancer, Lipids, and Metabolism
- Angiogenesis and VEGF in Cancer
- Tryptophan and brain disorders
- Circadian rhythm and melatonin
- Cancer Mechanisms and Therapy
- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Cholesterol and Lipid Metabolism
- Optical Coherence Tomography Applications
- Platelet Disorders and Treatments
- Systemic Lupus Erythematosus Research
- Dendrimers and Hyperbranched Polymers
- Dietary Effects on Health
- Climate Change and Health Impacts
- Cerebrovascular and Carotid Artery Diseases
- Circular RNAs in diseases
South Australian Health and Medical Research Institute
2018-2025
The University of Adelaide
2019-2025
Australian Research Council
2023-2025
ARC Centre for Nanoscale BioPhotonics
2023-2024
University of South Australia
2022
Australian Regenerative Medicine Institute
2022
Monash University
2022
South Australia Pathology
2022
Bond University
2022
Abstract Despite the emergence of novel diagnostic, pharmacological, interventional, and prevention strategies, atherosclerotic cardiovascular disease remains a significant cause morbidity mortality. Nanoparticle (NP)-based platforms encompass diverse imaging, delivery, pharmacological properties that provide opportunities for refining diagnostic therapeutic interventions atherosclerosis at cellular molecular levels. Macrophages play critical role in therefore represent an important...
Objective: In-stent neoatherosclerosis is a phenomenon of percutaneous coronary intervention with stenting. Whilst similar to de novo atherosclerosis, it develops rapidly over 1-5 years rather than lifetime. No preclinical small animal models exist that allow full elucidation biology and future treatments. The aim this study was establish validate novel murine model in-stent neoatherosclerosis. Approach Results: Murine stainless-steel stents (2.5 x 0.7 mm) were deployed into donor descending...
BACKGROUND: Impaired angiogenic responses to ischemia underlie diabetic vascular complications. Reconstituted high-density lipoproteins (rHDLs) have proangiogenic effects in diabetes. The PDK4 (pyruvate dehydrogenase kinase 4)/PDC complex) axis is an oxygen-conserving mechanism that preserves endothelial cell function hypoxia. We aimed determine the role of PDK4/PDC angiogenesis, effect diabetes on its regulation response ischemia, and properties rHDL. METHODS: Expression phosphorylated PDC...
Abstract Atherosclerosis is the build-up of fatty plaques within blood vessel walls, which can occlude vessels and cause strokes or heart attacks. It gives rise to both structural biomolecular changes in walls. Current single-modality imaging techniques each measure one these two aspects but fail provide insight into combined changes. To address this, our team has developed a dual-modality system combines optical coherence tomography (OCT) fluorescence that optimized for porphyrin lipid...
ABSTRACT Background High-density lipoprotein (HDL) nanoagents have unrealized potential for atherosclerosis theranostics. Porphyrin-lipid HDL mimetic nanoparticles (Por-HDL-NPs) incorporate porphyrin-lipid which permits near infrared fluorescence imaging and positron emission tomography (PET) through chelation of Copper-64 ( 64 Cu). The outer shell contains apolipoprotein A-I peptide R4F that interacts with scavenger receptor SR-BI, enabling macrophage targeting therapeutic effects. We...
Circadian disruption increases the development of cardiovascular disease and diabetes. We found that circadian causes glucose intolerance, cardiac fibrosis adipocyte tissue dysfunction in male sand rats, Psammomys obesus. Whether these effects occur female P. obesus is unknown. Male were fed a high energy diet exposed to neutral (12 light:12 dark, control) or short (5 light:19 disruption) photoperiod for 20 weeks. impaired tolerance males but not females. It also increased perivascular...
Circadian disruption causes glucose intolerance, cardiac fibrosis, and adipocyte dysfunction in sand rats (Psammomys obesus). Exercise intervention can improve metabolism, insulin sensitivity, adipose tissue function protect against inflammation. We investigated the influence of exercise on male P. obesus exposed to a short photoperiod (5 h light:19 dark) high-energy diet. reduced intolerance. expression inflammatory marker Ccl2 Bax:Bcl2 apoptosis ratio. increased heart:body weight ratio...
Diabetic vascular complications are associated with impaired ischaemia-driven angiogenesis. We recently found that reconstituted high-density lipoproteins (rHDL) rescue diabetes-impaired microRNAs (miRNAs) regulate angiogenesis and transported within HDL to sites of injury/repair. The role miRNAs in the by rHDL is unknown. Using a miRNA array, we inhibits hsa-miR-181c-5p expression vitro using mimic antimiR identify novel anti-angiogenic for miR-181c-5p. was tracked over time post-hindlimb...
Objectives Obesity is an independent risk factor for cardiovascular disease. Reverse cholesterol transport (RCT) important cardioprotective mechanism. This study aimed to investigate RCT changes in a murine model of obesity. Methods Ob/ob and control mice were injected with [3H]-cholesterol-labelled macrophages accumulation quantified after 48 h. Ex vivo, efflux uptake determined hepatic adipose tissues. Results had more labelled their plasma (86%, p<0.001), suggesting impaired RCT....
Abstract Type 2 diabetes mellitus (T2DM) increases cardiac inflammation which promotes the development of fibrosis. We sought to determine impact circadian disruption on induction hyperglycaemia, and Methods: Psammomys obesus ( P. ) were exposed neutral (12 h light:12 dark) or short (5 light:19 photoperiods fed a low energy (LE) high (HE) diet for 8 20 weeks. To daily rhythmicity, euthanised at 2, 8, 14, after ‘lights on’. Results: photoperiod weeks had impaired glucose tolerance following...
Dysfunctional adipose tissue phenotype underpins type 2 diabetes mellitus (T2DM) development. The disruption of circadian rhythms contributes to T2DM We investigated the effects high-energy diet and photoperiod length on visceral subcutaneous phenotype. Psammomys obesus sand rats exposed neutral (12 light:12 dark) or short (5 light:19 were fed a low- (LE) high- (HE) energy diet. HE and/or reduced expression adipocyte differentiation/function markers C/ebpα, Pparδ, Pparγ Adipoq. Visceral...
While blood-contacting materials are widely deployed in medicine vascular stents, catheters, and cannulas, devices fail situ because of thrombosis restenosis. Furthermore, microbial attachment biofilm formation is not an uncommon problem for medical devices. Even incremental improvements hemocompatible can provide significant benefits patients terms safety patency as well substantial cost savings. Herein, a novel but simple strategy described coating range materials, that be applied to...
Aberrations in the excitatory/inhibitory balance within brain have been associated with both intellectual disability (ID) and schizophrenia (SZ). The bHLH-PAS transcription factors NPAS3 NPAS4 implicated controlling balance, targeted disruption of either gene mice results a phenotype resembling ID SZ. However, there are few human variants none that or neurodevelopmental disorders. From clinical exome sequencing database we identified three four could potentially disrupt protein function...
Angiogenesis is a critical physiological response to ischemia but becomes pathological when dysregulated and driven excessively by inflammation. We recently identified novel angiogenic role for tripartite-motif-containing protein 2 (TRIM2) whereby lentiviral shRNA-mediated TRIM2 knockdown impaired endothelial functions in vitro. This study sought determine whether these effects could be translated vivo the molecular mechanisms involved. CRISPR/Cas9-generated Trim2–/– mice that underwent...
Angiogenesis is a critical physiological response to ischemia but becomes pathological when dysregulated and driven excessively by inflammation. We recently identified novel angiogenic role for tripartite-motif-containing protein 2 (TRIM2) whereby lentiviral shRNA-mediated TRIM2 knockdown impaired endothelial functions in vitro. This study sought determine whether these effects could be translated vivo the molecular mechanisms involved. CRISPR/Cas9-generated Trim2-/- mice that underwent...
Objective: Impaired angiogenic responses to ischemia underlie diabetic vascular complications. Reconstituted high-density lipoproteins (rHDL) have proangiogenic effects in diabetes. The pyruvate dehydrogenase kinase 4 (PDK4)/pyruvate complex (PDC) axis is an oxygen-conserving mechanism that preserves EC functions hypoxia. We aimed determine the role of PDK4/PDC angiogenesis, effect diabetes on its regulation response ischemia, and properties rHDL. Approach Results: In a murine wound healing...
Abstract Background High-density lipoprotein (HDL) mimetic nanoagents have unrealized potential for atherosclerosis theranostics. Porphyrin-lipid HDL nanoparticles (Por-HDL-NPs) incorporate a porphyrin-lipid conjugate which permits near infrared fluorescence imaging and positron emission tomography (PET) through chelation of Copper-64 (64Cu). The outer shell contains apolipoprotein A-I peptide R4F designed to interact with scavenger receptor class B type I (SR-BI), enabling...
Abstract Introduction The asialoglycoprotein receptor 1 (ASGR1) is a hepatic that clears desialylated glycoproteins from the circulation. A loss-of-function mutation in ASGR1 was reported to associate with 34% reduction coronary artery disease (CAD) risk, suggesting role for CAD. Aim To determine of atherosclerosis and whether deletion elicits atheroprotective effects. Methods Western blotting, mass spectrometry flow cytometry assessed expression cultured macrophages or immune cells...
Reconstituted high-density lipoproteins (rHDL) improve wound healing in diabetes. We aimed to determine if rHDL elicit anti-inflammatory effects diabetic wounds, as a mechanism explain their benefits.
Introduction: ‘Porphysome’ nanoparticles contain porphyrin-lipid which permits fluorescent imaging and can be radiolabelled for positron emission tomography (PET) imaging. The outer shell contains the R4F peptide that interacts with scavenger receptor SR-B1, enabling macrophage targeting therapeutic effects. Aim: To investigate anti-atherosclerotic properties of porphysomes. Methods: In vitro, porphysome or PBS-treated macrophages were assessed uptake (fluorescence microscopy), [ 3...