A5091328614- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- TGF-β signaling in diseases
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Pancreatic and Hepatic Oncology Research
- Cancer Cells and Metastasis
- Pregnancy and preeclampsia studies
- Kruppel-like factors research
- Reproductive Biology and Fertility
- RNA Research and Splicing
- Heterotopic Ossification and Related Conditions
- Medical Imaging and Pathology Studies
- Metabolism, Diabetes, and Cancer
- Fibroblast Growth Factor Research
- Renal and related cancers
- Genetic factors in colorectal cancer
- Cancer Risks and Factors
- Phagocytosis and Immune Regulation
- Amoebic Infections and Treatments
- T-cell and B-cell Immunology
- Genetic and Kidney Cyst Diseases
- Gene expression and cancer classification
- Diabetes Treatment and Management
- Bone Metabolism and Diseases
University of Auckland
2002-2025
The Francis Crick Institute
2018-2022
University of Oxford
2010-2015
John Radcliffe Hospital
2010-2015
The Honourable Society of Lincoln's Inn
2012-2015
Cancer Research UK
2012-2013
MRC Weatherall Institute of Molecular Medicine
2012
Cancer Society of New Zealand
2009
Background Hypoxia in cancers results the upregulation of hypoxia inducible factor 1 (HIF-1) and a microRNA, hsa-miR-210 (miR-210) which is associated with poor prognosis. Methods Findings In human cancer cell lines tumours, we found that miR-210 targets mitochondrial iron sulfur scaffold protein ISCU, required for assembly iron-sulfur clusters, cofactors key enzymes involved Krebs cycle, electron transport, metabolism. Down regulation ISCU was major cause induction reactive oxygen species...
To investigate small-nucleolar RNAs (snoRNAs) as reference genes when measuring miRNA expression in tumour samples, given emerging evidence for their role cancer. Four snoRNAs, commonly used normalisation, RNU44, RNU48, RNU43 and RNU6B, known to be associated with pathological factors, were measured by real-time polymerase chain reaction two patient series: 219 breast cancer 46 head neck squamous cell carcinoma (HNSCC). SnoRNA then correlated clinicopathological features prognosis....
The best characterized signaling pathway downstream of transforming growth factor β (TGF-β) is through SMAD2 and SMAD3. However, TGF-β also induces phosphorylation SMAD1 SMAD5, but the mechanism this its functional relevance not known. Here, we show that TGF-β-induced SMAD1/5 requires members two classes type I receptor, TGFBR1 ACVR1, establish a new paradigm for receptor activation where phosphorylates activates which SMAD1/5. We demonstrate biological significance by showing approximately...
In vivo cells receive simultaneous signals from multiple extracellular ligands and must integrate interpret them to respond appropriately. Here we investigate the interplay between pathways downstream of two transforming growth factor β (TGF-β) superfamily members, bone morphogenetic protein (BMP) TGF-β. We show that in cell lines, TGF-β potently inhibits BMP-induced transcription at level both BMP-responsive reporter genes endogenous BMP target genes. This inhibitory effect requires type I...
Hypoxia leads to the stabilisation of hypoxia-inducible factor (HIF) transcription that drives expression target genes including microRNAs (miRNAs). MicroRNAs are known regulate many involved in tumourigenesis. The aim this study was identify hypoxia-regulated miRNAs (HRMs) bladder cancer and investigate their functional significance. Bladder cell lines were exposed normoxic hypoxic conditions interrogated for 384 by qPCR. Functional studies carried out using siRNA-mediated gene knockdown...
Non-muscle invasive (NMI) bladder cancer is characterised by increased expression and activating mutations of FGFR3. We have previously investigated the role microRNAs in shown that FGFR3 a target miR-100. In this study, we effects hypoxia on miR-100 expression, link between hypoxia. Bladder cell lines were exposed to normoxic or hypoxic conditions examined for quantitative PCR (qPCR) western blotting, qPCR. The effect viability two-dimensional (2-D) three-dimensional (3-D) was transfecting...
Abstract Fibrodysplasia ossificans progressiva (FOP) and diffuse intrinsic pontine glioma (DIPG) are debilitating diseases that share causal mutations in ACVR1, a TGF‐β family type I receptor. ACVR1 R206H is frequent mutation both diseases. Pathogenic signaling via the SMAD1/5 pathway mediated by Activin A, but how triggers aberrant not known. We show essential for A‐mediated phosphorylation activated two distinct mechanisms. Wild‐type receptors, ACVR1B/C. In contrast, activation does...
The immune response exhibits strong circadian rhythmicity, with enhanced bacterial clearance often synchronized an organism’s active phase. Despite providing the bulk of cellular antibacterial defense, neutrophil clockwork is poorly understood. Here, we used larval zebrafish to explore role clock genes in neutrophils during infection. Per2 was required for reactive oxygen species (ROS) production and killing by enhancing infection-responsive expression high-mobility group box 1a ( hmgb1a )....
Appropriate growth, development, and function of the placenta is central to success nutrient partitioning between mother, placenta, fetus. Hormones such as placental lactogen (PL) leptin are produced in bovine play an important role regulation fetal growth. Nuclear transfer pregnancies associated with a number abnormalities, including increased growth macrosomia, hence represent unique situation gain insight into fetoplacental regulation. We have examined expression PL (bPL) placentomes...
Although the gene MEN1 has a long-standing association with cancer, its mechanisms of action remain incompletely understood, acting both as tumour suppressor in neuroendocrine tumours and an oncogene leukaemia. The best-characterised isoform encoded protein, MENIN, is 610-amino acid MENIN 2. We hypothesise that some complexity biology can be attributed to currently unappreciated contribution different isoforms. Through silico data mining, we show alternative splicing along entire length ....
Abstract There are currently 6 FDA approved therapies in metastatic renal cell carcinoma and their introduction has improved both time to progression survival these patients. Despite treatment with targeted approximately 20% of patients do not respond the remaining will most likely develop resistance during first 18 months treatment. The aim this study was identify a link between differences sensitivity therapies, vHL status expression genes involved mTOR pathway historic primary cancer...
Abstract Purpose: Administering hypoxia modifying therapy to patients with head and neck squamous cell carcinoma (HNSCC) improves outcomes in those identified hypoxic tumors. As no method for measuring tumor has demonstrated clinical utility, this study aimed validate use of a gene expression signature TaqMan Low Density Array (TLDA) platform. Experimental design: Tumor samples (n=201) from 80 HNSCC were collected prospectively two centers. Fifty-three received pimonidazole prior surgery....