A5073682028- Adipose Tissue and Metabolism
- Melanoma and MAPK Pathways
- Mitochondrial Function and Pathology
- Computational Drug Discovery Methods
- Synthesis and biological activity
- CRISPR and Genetic Engineering
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Adipokines, Inflammation, and Metabolic Diseases
- Protein Degradation and Inhibitors
- Cardiovascular Disease and Adiposity
- Cancer, Hypoxia, and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Bioinformatics and Genomic Networks
- Alzheimer's disease research and treatments
- Cancer-related Molecular Pathways
- Protein Kinase Regulation and GTPase Signaling
- Pancreatic function and diabetes
- RNA modifications and cancer
- Coenzyme Q10 studies and effects
- Sirtuins and Resveratrol in Medicine
- ATP Synthase and ATPases Research
- RNA and protein synthesis mechanisms
- Pluripotent Stem Cells Research
- Genetics, Aging, and Longevity in Model Organisms
The University of Melbourne
2014-2025
Monash University
2021-2025
Baker Heart and Diabetes Institute
2017-2025
Deakin University
2014-2024
Geelong Hospital
2017
Westmead Institute
2014
Peter MacCallum Cancer Centre
2014
Molecular Oncology (United States)
2014
Millennium Institute
2014
The University of Sydney
2014
Deregulated glucose metabolism fulfills the energetic and biosynthetic requirements for tumor growth driven by oncogenes. Because inhibition of oncogenic BRAF causes profound reductions in uptake a strong clinical benefit BRAF-mutant melanoma, we examined role energy responses to inhibition. We observed pronounced consistent decreases glycolytic activity melanoma cells. Moreover, identified network BRAF-regulated transcription factors that control glycolysis Remarkably, this factors,...
Drugs that recapitulate aspects of the exercise adaptive response have potential to provide better treatment for diseases associated with physical inactivity. We previously observed reduced skeletal muscle class IIa HDAC (histone deacetylase) transcriptional repressive activity during exercise. Here, we find exercise-like adaptations are induced by expression mutants cannot form a corepressor complex. Adaptations include increased metabolic gene expression, mitochondrial capacity, and lipid...
Human induced pluripotent stem cells (iPSCs) are a valuable tool for studying the cardiac developmental process in vitro, and cardiomyocytes derived from iPSCs putative cell source personalized medicine. Changes mitochondrial morphology have been shown to occur during cellular reprogramming differentiation. However, relationships between dynamics mesoderm commitment of remain unclear. Here we demonstrate that changes small granular fragmented phenotype filamentous reticular elongated network...
During mitochondrial damage, information is relayed between the mitochondria and nucleus to coordinate precise responses preserve cellular health. One such pathway integrated stress response (mtISR), which known be activated by DNA (mtDNA) damage. However, causal molecular signals responsible for activation of mtISR remain mostly unknown. A gene often associated with mtDNA mutations/deletions Polg1, encodes Polymerase γ (PolG). Here, we describe an inducible, tissue specific model PolG...
Metabolic conditions such as obesity, insulin resistance and glucose intolerance are frequently associated with impairments in skeletal muscle function metabolism. This is often linked to dysregulation of homeostatic pathways including an increase reactive oxygen species (ROS) oxidative stress. One the main sites ROS production mitochondria, where flux substrates through electron transport chain (ETC) can result generation free radicals. Fortunately, several mechanisms exist buffer bursts...
Reciprocal regulation of hepatic glycolysis and gluconeogenesis contributes to systemic metabolic homeostasis. Recent evidence from lower order organisms has found that reversible post-translational modification glyceraldehyde-3-phosphate dehydrogenase (GAPDH), particularly acetylation, the reciprocal glycolysis/gluconeogenesis. However, whether this occurs in mammalian hepatocytes vitro or vivo is unknown. Several proteomics studies have identified 4 lysine residues critical regions GAPDH...
Mitochondrial dysfunction is associated with a diverse array of diseases ranging from dystrophy and heart failure to obesity hepatosteatosis. One the major biochemical consequences impaired mitochondrial function an accumulation superoxide, or reactive oxygen species (ROS). Excessive ROS can be detrimental cellular health proposed underpin many diseases. Accordingly, much research has been committed understanding ways therapeutically prevent reduce accumulation. In white adipose tissue...
The effective storage of lipids in white adipose tissue (WAT) critically impacts whole body energy homeostasis. Many genes have been implicated WAT lipid metabolism, including tripartite motif containing 28 (Trim28), a gene proposed to primarily influence adiposity via epigenetic mechanisms embryonic development. However, the current study we demonstrate that mice with deletion Trim28 specifically committed adipocytes, also develop obesity similar global models, highlighting...
Abstract Obesity is a major risk factor underlying the development of metabolic disease and growing public health concern globally. Strategies to promote skeletal muscle metabolism can be effective limit progression disease. Here, we demonstrate that levels Hippo pathway transcriptional co-activator YAP are decreased in biopsies from obese, insulin-resistant humans mice. Targeted disruption Yap adult resulted incomplete oxidation fatty acids lipotoxicity. Integrated ‘omics analysis isolated...
Cardiac stem cell (CSC) therapy is a promising approach to treat ischemic heart disease. However, the poor survival of transplanted cells in myocardium has been major impediment achieving an effective cell-based against myocardial infarction. Inhibiting mitochondrial fission shown promote several types. role morphology human CSC remains unknown. In this study, we investigated whether division inhibitor-1 (Mdivi-1), inhibitor protein dynamin-related protein-1 (Drp1), can improve novel...
Mitochondrial dynamics refers to the constant remodeling of mitochondrial populations by multiple cellular pathways that help maintain health and function. Disruptions in often lead dysfunction, which is frequently associated with disease rodents humans. Consistent this, obesity reduced function white adipose tissue, partly via alterations dynamics. Several proteins, including E3 ubiquitin ligase membrane-associated RING-CH-type finger 5 (MARCH5), are known regulate dynamics; however, role...
Abstract Long ncRNAs (lncRNAs) have been shown to play a biological and physiological role in various tissues including the heart. We others previously established that lncRNA Oip5os1 ( 1700020I14Rik , OIP5‐AS1, Cyrano) is enriched striated muscles, its deletion mice leads defects both skeletal cardiac muscle function. In present study, we investigated impact of global on function setting streptozotocin (STZ)‐induced diabetes. Specifically, studied male WT KO with or without diabetes for 24...
Abstract There are epidemiological associations between obesity and type 2 diabetes, cardiovascular disease Alzheimer’s disease. The role of amyloid beta 42 (Aβ ) in these diverse chronic diseases is obscure. Here we show that adipose tissue releases Aβ , which increased from male mice with associated higher plasma . Increasing circulating levels without has no effect on systemic glucose homeostasis but obesity-like effects the heart, including reduced cardiac clearance impaired function....
Long non-coding RNAs (lncRNAs) have been demonstrated to influence numerous biological processes, being strongly implicated in the maintenance and physiological function of various tissues including heart. The lncRNA OIP5-AS1 (1700020I14Rik/Cyrano) has studied several settings; however its role cardiac pathologies remains mostly uncharacterized. Using a series vitro ex vivo methods, we demonstrate that is regulated during development rodent human models disease settings mice. CRISPR,...
Mild traumatic brain injuries (mTBIs) are the most common form of acquired injury. Symptoms mTBI thought to be associated with a neuropathological cascade, potentially involving dysregulation neurometabolites, lipids, and mitochondrial bioenergetics. Such alterations may play role in period enhanced vulnerability that occurs after mTBI, such second will exacerbate neuropathology. However, it is unclear whether mTBI-induced neurometabolites lipids involved energy metabolism other important...
CRISPR/Cas9 technology has revolutionized gene editing and fast tracked our capacity to manipulate genes of interest for the benefit both research therapeutic applications. Whilst many advances have, continue be made in this area, perhaps most utilized date been generation knockout cells, tissues animals. The advantages are fold, however some questions still remain regarding effects that long term expression foreign proteins such as Cas9, have on mammalian cell function. Several studies...
Type 2 diabetes mellitus (T2DM), a condition characterised by insulin resistance (IR) and skeletal muscle mitochondrial abnormalities, is leading cause of death in developed societies. Much work has postulated that improving pathways linked to health, including autophagy, may be potential avenue prevent or treat T2DM. Given the recent data indicating role for tripartite motif-containing 28 (TRIM28) autophagy pathways, we investigated whether muscle-specific deletion TRIM28 might impact on...
Protein kinase D (PKD) is emerging as an important regulating energy balance and glucose metabolism; however, whether hepatic PKD activity can be targeted to regulate these processes currently unclear. In this study, was reduced using adeno-associated virus vectors express a dominant-negative (DN) version of PKD1, which impairs the action all three isoforms. chow-fed mice, DN expression increased whole-body oxidation, but had only mild effects on insulin tolerance no homeostasis following...
ABSTRACT During mitochondrial damage, information is relayed between the mitochondria and nucleus to coordinate precise responses preserve cellular health. One such pathway integrated stress response (mtISR), which specifically activated by DNA (mtDNA) damage. However, causal molecular signals responsible for this activation remain elusive. A gene often associated with mtDNA mutations/deletions Polg1 , encodes Polymerase γ (PolG). Here, we describe what our knowledge first conditional muscle...