A5057296989- Trace Elements in Health
- Iron Metabolism and Disorders
- Hippo pathway signaling and YAP/TAZ
- Cell death mechanisms and regulation
- Virus-based gene therapy research
- Redox biology and oxidative stress
- Sulfur Compounds in Biology
- Lipid metabolism and biosynthesis
- Heat shock proteins research
- RNA regulation and disease
- Zebrafish Biomedical Research Applications
- Adipose Tissue and Metabolism
- Cancer-related Molecular Pathways
- Peptidase Inhibition and Analysis
- Liver physiology and pathology
- Liver Disease Diagnosis and Treatment
- Glutathione Transferases and Polymorphisms
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Chemical Synthesis and Analysis
- Endoplasmic Reticulum Stress and Disease
- Genomics, phytochemicals, and oxidative stress
- Epigenetics and DNA Methylation
- Glycosylation and Glycoproteins Research
- Pancreatic function and diabetes
Peter MacCallum Cancer Centre
2019-2024
The University of Melbourne
2019-2024
Harvard University
2011-2021
Brigham and Women's Hospital
2012-2021
Harvard Stem Cell Institute
2012-2020
Organogenesis (United States)
2019
Dana-Farber Brigham Cancer Center
2011
Dana-Farber Cancer Institute
2011
University of Otago
2007-2010
Christchurch Clinical Studies Trust
2009
Mitochondrial dysfunction is associated with a spectrum of human disorders, ranging from rare, inborn errors metabolism to common, age-associated diseases such as neurodegeneration. How these lesions give rise diverse pathology not well understood, partly because their proximal consequences have been well-studied in mammalian cells. Here we provide two lines evidence that mitochondrial respiratory chain leads alterations one-carbon pathways. First, using hypothesis-generating metabolic,...
The liver exhibits a remarkable capacity to regenerate following injury. Despite this unique attribute, toxic injury is leading cause of failure. temporal processes by which the senses and initiates regeneration remain unclear. Here, we developed transgenic zebrafish model wherein hepatocyte-specific expression uracil phosphoribosyltransferase (UPRT) enabled implementation SLAM-ITseq investigate nascent transcriptome during initiation regeneration. Using approach, identified rapid metabolic...
Novel β-sheet-forming peptide 33-mers, βpep peptides, have been designed by using a combination approach employing basic folding principles and incorporating short sequences from the β-sheet domains of anti-angiogenic proteins. One these peptides (βpep-25), named anginex, was observed to be potently anti-angiogenic. Anginex specifically inhibits vascular endothelial cell proliferation induces apoptosis in cells, as shown flow-cytometric detection sub-diploid TUNEL (terminal...
Peroxiredoxins (Prxs) are a ubiquitous family of thiol peroxidases that protect cells from peroxides and have putative role in redox signaling. In this study, we investigated the properties human Prx 3, typical 2-Cys is localized to mitochondrial matrix. We found 3 displayed strong reactivity with H2O2, competitive kinetic approach generating second order rate constant 2 × 107 M−1 s−1. This considerably higher than thiols similar values for other mammalian Prxs. contrast, reacted very slowly...
The Prxs (peroxiredoxins) are a family of cysteine-dependent peroxidases that decompose hydrogen peroxide. become hyperoxidized when sulfenic acid formed during the catalytic cycle reacts with In present study, Western blot methodology was developed to quantify hyperoxidation individual 2-Cys in cells. It revealed Prx 1 and 2 were at lower doses peroxide than would be predicted from vitro data, suggesting intracellular factors promote hyperoxidation. contrast, mitochondrial 3 considerably...
The maintenance of redox and metabolic homeostasis is integral to embryonic development. Nuclear factor erythroid 2-related 2 (NRF2) a stress-induced transcription that plays central role in the regulation balance cellular metabolism. Under homeostatic conditions, NRF2 repressed by Kelch-like ECH-associated protein 1 (KEAP1). Here, we demonstrate Keap1 deficiency induces Nrf2 activation postdevelopmental lethality. Loss viability preceded severe liver abnormalities characterized an...
Novel β-sheet-forming peptide 33-mers, βpep peptides, have been designed by using a combination approach employing basic folding principles and incorporating short sequences from the β-sheet domains of anti-angiogenic proteins. One these peptides (βpep-25), named anginex, was observed to be potently anti-angiogenic. Anginex specifically inhibits vascular endothelial cell proliferation induces apoptosis in cells, as shown flow-cytometric detection sub-diploid TUNEL (terminal...
Significance Dietary selenium and selenoproteins play important roles in regulating redox processes that impact human health. The genome includes 25 genes for selenoproteins, which have diverse homeostasis, thyroid hormone metabolism, endoplasmic reticulum quality control, transport, other functions. Selenoprotein H ( seph ) is a recently identified nucleolar oxidoreductase with DNA-binding properties whose function not well understood. In this work, we used unique combination of unbiased...
Prxs (peroxiredoxins) are a ubiquitous family of cysteine-dependent peroxidases that react rapidly with H2O2 and alkyl hydroperoxides provide defence against these reactive oxidants. Hydroperoxides also formed on amino acids proteins during oxidative stress, they too potential cause biological damage. We have investigated whether acid, peptide protein hydroperoxides, the reactions sufficiently rapid for enzymes to antioxidant protection Isolated Prx2, which is cytosolic protein, Prx3,...
Toxic liver injury is a leading cause of failure and death because the organ's inability to regenerate amidst massive cell death, few therapeutic options exist. The mechanisms coordinating damage protection repair are poorly understood. Here, we show that S-nitrosothiols regulate growth during development after in vivo; zebrafish, nitric-oxide (NO) enhanced formation independently cGMP-mediated vasoactive effects. After acetaminophen (APAP) exposure, inhibition enzymatic regulator...
Cancer cell metabolism is increasingly recognized as providing an exciting therapeutic opportunity. However, a drug that directly couples targeting of metabolic dependency with the induction death in cancer cells has largely remained elusive. Here we report drug-like small-molecule ironomycin reduces mitochondrial iron load, resulting potent disruption metabolism. Ironomycin promotes recruitment and activation BAX/BAK, but outer membrane permeabilization (MOMP) does not lead to apoptotic...
Abstract Sarcopenia, the age‐related decline in muscle function, places a considerable burden on health‐care systems. While stereotypic hallmarks of sarcopenia are well characterized, their contribution to wasting remains elusive, which is partly due limited availability animal models. Here, we have performed cellular and molecular characterization skeletal from African killifish—an extremely short‐lived vertebrate—revealing that while many characteristics deteriorate with increasing age,...