- Muscle Physiology and Disorders
- Adipose Tissue and Metabolism
- Exercise and Physiological Responses
- Cancer Cells and Metastasis
- Muscle metabolism and nutrition
- Pharmacological Effects and Assays
- Autophagy in Disease and Therapy
- Single-cell and spatial transcriptomics
- Cancer, Stress, Anesthesia, and Immune Response
- Sirtuins and Resveratrol in Medicine
- Pluripotent Stem Cells Research
- Mitochondrial Function and Pathology
- Tissue Engineering and Regenerative Medicine
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Diet and metabolism studies
- Muscle activation and electromyography studies
- Histone Deacetylase Inhibitors Research
- Calcium signaling and nucleotide metabolism
- Heat shock proteins research
- Adenosine and Purinergic Signaling
- CRISPR and Genetic Engineering
- Spaceflight effects on biology
- Pain Mechanisms and Treatments
- Cancer Genomics and Diagnostics
The University of Melbourne
2013-2023
National Institutes of Health
2009-2017
National Institute of Arthritis and Musculoskeletal and Skin Diseases
2009-2017
Google (United States)
2017
Significance Engineered cardiac muscle can be used to promote the structural and functional maturation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). However, previous studies have not yet produced tissues with metabolic proliferative maturation. Here, we develop a 96-well screening platform screen for conditions in engineered muscle. We found that simulating postnatal switch substrates from carbohydrates fatty acids promoted metabolism, DNA damage response, cell cycle...
A modified Chromium 10x droplet-based protocol that subsamples cells for both short-read and long-read (nanopore) sequencing together with a new computational pipeline (FLAMES) is developed to enable isoform discovery, splicing analysis, mutation detection in single cells. We identify thousands of unannotated isoforms find conserved functional modules are enriched alternative transcript usage different cell types species, including ribosome biogenesis mRNA splicing. Analysis at the level...
Satellite cells (SCs) sustain muscle growth and empower adult skeletal with vigorous regenerative abilities. Here, we report that EZH2, the enzymatic subunit of Polycomb-repressive complex 2 (PRC2), is expressed in both Pax7 + /Myf5 − stem committed myogenic precursors required for homeostasis SC pool. Mice conditional ablation Ezh2 SCs have fewer postnatal reduced mass fail to appropriately regenerate. These defects are associated impaired proliferation derepression genes nonmuscle cell...
β1–3-Adrenoreceptor (AR)-deficient mice are unable to regulate energy expenditure and develop diet-induced obesity on a high-fat diet. We determined previously that β2-AR agonist treatment activated expression of the mRNA encoding orphan nuclear receptor, NOR-1, in muscle cells plantaris muscle. Here we show significantly transiently NOR-1 (and other members NR4A subgroup) slow-twitch oxidative soleus fast-twitch glycolytic tibialis anterior The activation induced by β-adrenergic signaling...
The activation of AMP-activated protein kinase (AMPK) and phosphorylation/inhibition acetyl-CoA carboxylase 2 (ACC2) is believed to be the principal pathway regulating fatty acid oxidation. However, during exercise AMPK activity ACC Ser-221 phosphorylation does not always correlate with rates To address this issue we have investigated requirement for skeletal muscle in controlling aminoimidazole-4-carboxymide-1-beta-d-ribofuranoside (AICAR) contraction-stimulated oxidation utilizing...
β-Adrenergic receptor (β-AR) agonists induce Nur77 mRNA expression in the C2C12 skeletal muscle cell culture model and elicit hypertrophy. We previously demonstrated that (NR4A1) is involved lipolysis gene associated with regulation of lipid homeostasis. Subsequently it was by another group β-AR cold exposure-induced brown adipocytes adipose tissue, respectively. Moreover, NOR-1 (NR4A3) hyperinduced exposure nur77−/− animal model. These studies underscored importance understanding role...
Excess lipid accumulation resulting from an elevated supply of plasma fatty acids is linked to the pathogenesis metabolic syndrome and heart disease. The term 'lipotoxicity' was coined describe how leads cellular dysfunction death in non-adipose tissues including heart, pancreas liver. While lipotoxicity has been shown cultured skeletal muscle cells, degree vivo functional consequences are unresolved. We studied three models acid overload male mice: 5 h Intralipid((R)) heparin infusion,...
Elucidating the epigenetic mechanisms underlying muscle mass determination and skeletal wasting holds potential of identifying molecular pathways that constitute possible drug targets. Here, we report methyltransferase SMYD3 modulates myostatin c-Met transcription in primary cells C2C12 myogenic cells. targets genes participates recruitment bromodomain protein BRD4 to their regulatory regions through protein–protein interaction. By recruiting BRD4, favors chromatin engagement pause–release...
beta(2)-Adrenoceptor agonists provide a potential therapy for muscle wasting and weakness, but their use may be limited by adverse effects on the heart, mediated in part, beta(1)-adrenoceptor activation. Two beta(2)-agonists, formoterol salmeterol, are approved treating asthma have an extended duration of action increased safety, associated with greater beta(2)-adrenoceptor selectivity. The pharmacological profiles salmeterol skeletal cardiac mass were investigated 12-week-old, male F344...
The beta2-adrenoceptor agonist (beta2-agonist) fenoterol has potent anabolic effects on rat skeletal muscle. We conducted an extensive dose-response study to determine the most efficacious dose of for increasing muscle mass in adult rats and used this testing hypothesis that may have therapeutic potential ameliorating age-related wasting weakness. (16-month-old) had completed their growth development, old (28-month-old) exhibited characteristic weakness, treated them daily with either (1.4...
Beta(2)-adrenoceptor agonists such as fenoterol are anabolic in skeletal muscle, and because they promote hypertrophy improve force-producing capacity, have potential application for enhancing muscle repair after injury. No previous studies measured the beta(2)-adrenoceptor population regenerating or determined whether can functional recovery myotoxic In present study, extensor digitorum longus (EDL) of right hindlimb deeply anesthetized rats was injected with bupivacaine hydrochloride,...
Systemic administration of beta-adrenoceptor (beta-AR) agonists has been found to induce skeletal muscle hypertrophy and significant metabolic changes. In the context energy homeostasis, importance beta-AR signaling highlighted by inability beta(1-3)-AR-deficient mice regulate expenditure susceptibility diet induced obesity. However, molecular pathways gene expression changes that initiate maintain these phenotypic modulations are poorly understood. Therefore, aim this study was identify...