A5038116733- Renal and related cancers
- Epigenetics and DNA Methylation
- Neuroblastoma Research and Treatments
- Cancer-related gene regulation
- Cancer, Hypoxia, and Metabolism
- Renal cell carcinoma treatment
- Genetic Syndromes and Imprinting
- Ethics and Legal Issues in Pediatric Healthcare
- Hippo pathway signaling and YAP/TAZ
- Metabolism, Diabetes, and Cancer
- Ubiquitin and proteasome pathways
- Cancer, Lipids, and Metabolism
- Prenatal Screening and Diagnostics
- Wnt/β-catenin signaling in development and cancer
- Genetics and Neurodevelopmental Disorders
- T-cell and Retrovirus Studies
- Vector-Borne Animal Diseases
- Cancer-related Molecular Pathways
- Tumors and Oncological Cases
- Colorectal Cancer Treatments and Studies
- Organ Donation and Transplantation
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Childhood Cancer Survivors' Quality of Life
- Autophagy in Disease and Therapy
University of Bristol
2016-2025
Bristol Robotics Laboratory
2019
Crescent University
2019
University of Edinburgh
2019
Cancer Research UK
2006
Fuji Chemical Industries (Japan)
1992
University of Cambridge
1987-1988
Cambridge School
1988
Summary We report the first complete nucleotide sequence of an adult T cell leukaemia virus/human virus type I (ATLV/HTLV-I) isolate from a British patient Caribbean origin. Sequence comparisons our proviral clone (HS-35) with other molecular clones are shown. note strong conservation between isolates and Japanese origin (2.3% divergence), but demonstrate higher homologies existing originating similar geographical areas (approximately 1% divergence). Implications for origin, evolution...
Wilms' tumour (WT) is a pediatric tumor of the kidney that arises via failure fetal developmental program. The absence identifiable mutations in majority WTs suggests frequent involvement epigenetic aberrations WT. We therefore conducted genome-wide analysis promoter hypermethylation and identified at chromosome 5q31 spanning 800 kilobases (kb) more than 50 genes. methylated genes all belong to α-, β-, γ-protocadherin (PCDH) gene clusters (Human Genome Organization nomenclature PCDHA@,...
Research Article24 August 2018Open Access Source DataTransparent process Cancer cell adaptation to hypoxia involves a HIF-GPRC5A-YAP axis Alexander Greenhough Corresponding Author [email protected] orcid.org/0000-0002-8306-811X UK Colorectal Tumour Biology Group, School of Cellular & Molecular Medicine, Faculty Life Sciences, University Bristol, Epigenetics Laboratory, Search for more papers by this author Clare Bagley Kate J Heesom Proteomics Facility, David B Gurevich Biochemistry, Gay...
Mammalian kidney development requires the functions of Wilms tumor gene WT1 and WNT/beta-catenin signaling pathway. Recent studies have shown that negatively regulates signaling, but molecular mechanisms by which inhibits are not completely understood. In this study, we identified a gene, CXXC5, renamed WID (WT1-induced Inhibitor Dishevelled), as novel transcriptional target signaling. activates transcription through upstream enhancer region. developing kidney, Wid Wt1 coexpressed in...
// Gabriella Cunha Vieira 1, * , S. Chockalingam Zsombor Melegh 2 Alexander Greenhough 3 Sally Malik 1 Marianna Szemes Ji Hyun Park Abderrahmane Kaidi Li Zhou 4 Daniel Catchpoole Rhys Morgan David O. Bates 5 Peter Gabb Karim Cancer Epigenetics Laboratory and, School of Cellular & Molecular Medicine, University Bristol, UK Department Pathology, Southmead Hospital, Colorectal Laboratory, The Kids Research Institute, Children's Hospital at Westmead, New South Wales, Australia Biology, Division...
The serine/threonine kinase glycogen synthase kinase-3 (GSK3) plays an important role in balancing pro- and anti-inflammatory cytokines. We have examined the of GSK3 production IL-10 by subsets CD4(+) T helper cells. Treatment naive murine cells with inhibitors did not affect their IL-10. However, treatment Th1 Th2 dramatically increased inhibition also led to upregulation among Th1, Th2, Th17 isolated from human blood. encephalitogenic potential inhibitor treated was significantly reduced...
Degraders with dual activity against BRD4 and CBP/EP300 were designed. A structure-guided design approach was taken to assess test potential exit vectors on the inhibitor, ISOX-DUAL. Candidate Degrader panels revealed that VHL-recruiting moieties could mediate dose-responsive ubiquitination of BRD4. panel CRBN-recruiting thalidomide-based unable induce or degradation target proteins. High-resolution protein co-crystal structures an unexpected interaction between thalidomide moiety Trp81...
Many mammalian genes contain overlapping antisense RNAs, but the functions and mechanisms of action these transcripts are mostly unknown. WT1 is a well-characterized developmental gene that mutated in Wilms’ tumor (WT) acute myeloid leukaemia (AML) has an transcript ( WT1-AS ), which we have previously found to regulate protein levels. In this study, show present multiple spliceoforms usually expressed parallel with RNA human mouse tissues. We demonstrate expression correlates methylation...
The Wilms' tumor suppressor gene (WT1) encodes a zinc finger transcription factor that is vital during development of several organs including metanephric kidneys. Despite the critical regulatory role WT1, pathways and mechanisms by which WT1 orchestrates remain elusive. To identify target genes, we performed genome-wide expression profiling analysis in cells expressing inducible WT1. We identified number direct epidermal growth (EGF)-family ligands epiregulin HB-EGF, chemokine CX3CL1,...
Approximately half of poor prognosis neuroblastomas (NBs) are characterized by pathognomonic MYCN gene amplification and over-expression. Here we present data showing that short-interfering RNA mediated depletion the protein arginine methyltransferase 5 (PRMT5) in cell-lines representative NBs with leads to greatly impaired growth apoptosis. Growth suppression is not apparent MYCN-negative SH-SY5Y NB cell-line, or two immortalized human fibroblast cell-lines. Immunoblotting shows high PRMT5...
Neuroblastoma is one of the commonest and deadliest solid tumours childhood, thought to result from disrupted differentiation developing sympathoadrenergic lineage neural crest. exhibits intra- intertumoural heterogeneity, with high risk characterised by poor differentiation, which can be attributable MYCN-mediated repression genes involved in neuronal differentiation. MYCN known co-operate oncogenic signalling pathways such as Alk, Akt MEK/ERK signalling, and, together c-MYC has been shown...
Although tumour suppressor gene hypermethylation is a universal feature of cancer cells, little known about the necessary molecular triggers. Here, we show that Wilms' 1 (WT1), developmental master regulator can also act as or oncoprotein, transcriptionally regulates de novo DNA methyltransferase 3A (DNMT3A) and cellular WT1 levels influence methylation promoters genome-wide. Specifically, demonstrate depletion by short-interfering RNAs leads to reduced DNMT3A in cells human embryonal...
Neuroblastoma is a biologically and clinically heterogeneous pediatric malignancy that includes high-risk subset for which new therapeutic agents are urgently required. As well as MYCN amplification, activating point mutations of ALK NRAS associated with relapsing neuroblastoma. both RAS signal through the MEK/ERK pathway, we sought to evaluate two previously reported inhibitors ETS-related transcription factors, transcriptional mediators Ras-MEK/ERK pathway in other cancers. Here show...
Abstract Aberrant expression of protein arginine methyltransferases (PRMTs) has been implicated in a number cancers, making PRMTs potential therapeutic targets. But it remains not well understood how impact specific oncogenic pathways. We previously identified as important regulators cell growth neuroblastoma, deadly childhood tumor the sympathetic nervous system. Here, we demonstrate critical role for PRMT1 neuroblastoma survival. depletion decreased ability murine sphere cells to grow and...
Wilms tumors (WTs) have a complex etiology, displaying genetic and epigenetic changes, including loss of imprinting (LOI) tumor suppressor gene silencing. To identify new regions perturbation in WTs, we screened kidney DNA using CpG island (CGI) tags associated with cancer-specific methylation changes. One such tag corresponded to paralog the glioma pathogenesis-related 1/related testis-specific, vespid, pathogenesis proteins 1 (GLIPR1/RTVP-1) gene, previously reported be tumor-suppressor...
We have shown previously that AWT1 and WT1-AS are functionally imprinted in human kidney. In the adult kidney, expression of both transcripts is restricted to paternal allele, with silent maternal allele retaining methylation at WT1 antisense regulatory region (WT1 ARR). Here, we report characterization ARR differentially methylated show it contains a transcriptional silencer element acting on promoters. DNA results increased repression, also be an vitro vivo target site for imprinting...
Neuroblastoma is a childhood cancer in which many children still have poor outcomes, emphasising the need to better understand its pathogenesis. Despite recent genome‐wide mutation analyses, primary neuroblastomas do not contain recognizable driver mutations, implicating alternate molecular pathologies such as epigenetic alterations. To discover genes that become epigenetically deregulated during neuroblastoma tumorigenesis, we took novel approach of comparing neural crest precursor cells,...
Recent studies have identified antisense WT1 mRNAs whose expression is regulated by a promoter located in the first intron of gene. Transcription directed positively autoregulated protein implicating RNA control gene expression. To elucidate further biological role developing kidney, its distribution has been examined relative to sense mRNA and protein. Using strand-specific riboprobes, message were situ hybridization human fetal kidney at different gestational ages. The strand was strongest...
The human Wilms tumour suppressor gene, WT1, encodes a zinc‐finger protein which can function as transcriptional activator or suppressor. This study reports the analysis of WT1 gene promoter, and demonstrates that high levels expression lead to autosuppression promoter. Deletion analyses promoter region implicate sequences 5′ 3′ start site being crucial in autosuppression. Loss alteration this may be important tumourigenesis.
The neural crest (NC), which has been referred to as the fourth germ layer, comprises a multipotent cell population will specify diverse cells and tissues, including craniofacial cartilage bones, melanocytes, adrenal medulla peripheral nervous system. These fates are known be determined by gene regulatory networks (GRNs) acting at various stages of NC development, such induction, specification, migration. Although transcription factor hierarchies some their interplay with morphogenetic...