A5018749993- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Kruppel-like factors research
- Cancer-related gene regulation
- Cancer Research and Treatments
- Genetic Syndromes and Imprinting
- Cancer Cells and Metastasis
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Esophageal Cancer Research and Treatment
- Metabolism, Diabetes, and Cancer
- Microtubule and mitosis dynamics
- Peptidase Inhibition and Analysis
- Peroxisome Proliferator-Activated Receptors
- Click Chemistry and Applications
- DNA Repair Mechanisms
- TGF-β signaling in diseases
- Gastric Cancer Management and Outcomes
- CRISPR and Genetic Engineering
- Telomeres, Telomerase, and Senescence
- RNA Research and Splicing
- BRCA gene mutations in cancer
- Breast Cancer Treatment Studies
- Genetics, Bioinformatics, and Biomedical Research
University of Southampton
2012-2022
Southampton General Hospital
2003-2016
Cancer Research UK
2011-2016
Faculty (United Kingdom)
2015
University of Dundee
1998-2003
Ninewells Hospital
1998-2003
University of Wales
1992-1998
University of Bath
1991
National Eye Institute
1982
Federal Government of Germany
1982
Interactions between cancer cells and cancer-associated fibroblasts (CAFs) play an important role in tumour development progression. In this study we investigated the functional of CAFs oesophageal adenocarcinoma (EAC). We used immunochemistry to analyse a cohort 183 EAC patients for CAF markers related disease mortality. characterized normal (NOFs) using western blotting, immunofluorescence gel contraction. Transwell assays, 3D organotypic culture xenograft models were examine effects on...
Replicative senescence in human fibroblasts is absolutely dependent on the function of phosphoprotein p53 and correlates with activation p53-dependent transcription. However, no evidence for posttranslational modification has been presented, raising possibility that changes transcriptional activity result from upregulation a coactivator. Using series antibodies phosphorylation-sensitive epitopes, we now show associated major at putative regulatory sites N C termini consistent increased...
When cells transform, phenotypic and genetic profiles can be dramatically altered. Nevertheless, a recent report identifying IgG in breast cancer was unexpected, revealing differentiation features normally associated with B lymphocytes. To extend these findings, we focused on immunoglobulin variable (V) region gene analysis using well-defined cell lines expressing the epithelial marker, adhesion molecule (EpCAM). V(H) transcripts were identifiable by nested reverse transcription-PCR either...
Click DNA ligation promises an alternative to the current enzymatic approaches for assembly, with ultimate goal of using efficient chemical reactions total synthesis and assembly genes genomes. Such approach would enable incorporation various chemically modified bases throughout long stretches DNA, a feat not possible polymerase-based methods. An unequivocal requirement this is biocompatibility resulting triazole-linked DNA. The correct function unnatural linker in human cells demonstrated...
eIF4E is over-expressed in many tumours, including a high proportion of breast cancers. an oncogene, and signalling pathways which promote activity represent potential targets for therapeutic intervention cancer. MNKs phosphorylate on serine 209, modification that can be required eIF4E-dependent cell transformation. There therefore clear requirement to determine the role proliferation survival cells from major human such as Phosphorylated protein was readily detectable some tumour samples,...
Abstract Aminoimidazole carboxamide ribonucleotide transformylase/ inosine monophosphate cyclohydrolase (ATIC) is a bifunctional homodimeric enzyme that catalyzes the last two steps of de novo purine biosynthesis. Homodimerization ATIC, protein–protein interaction with an interface over 5000 Å 2 , required for its aminoimidazole (AICAR) transformylase activity, active sites forming at interacting proteins. Here, we report development small‐molecule inhibitor AICAR functions by preventing...
Identification of direct modulators transcription factor protein–protein interactions is a key challenge for ligand discovery that promises to significantly advance current approaches cancer therapy. Here, we report an inhibitor NADH-dependent dimerization the C-terminal binding protein (CtBP) transcriptional repressor, identified by screening genetically encoded cyclic peptide libraries up 64 million members. CtBP dimers form core complexes associated with epigenetic regulation multiple...
Increased glycolytic stress in cancer cells stimulates p53 production to maintain metabolic homeostasis.
p53 protein activity as a transcription factor can be activated <i>in vivo</i> by antibodies that target its C-terminal negative regulatory domain suggesting cellular enzymes this may play role in stimulating p53-dependent gene expression. A phospho-specific monoclonal antibody to the Ser<sup>315</sup>phospho-epitope was used determine whether phosphorylation of endogenous at Ser<sup>315</sup> detected vivo</i>, steady-state increases or decreases an irradiated cell, and event activates...
Background information. CtBPs [C-terminal (of E1A) binding protein] have roles in the nucleus as transcriptional co-repressors, and cytoplasm maintenance of vesicular membranes. are expressed from two genes, CTBP1 CTBP2, mRNA products which alternatively spliced at their 5′-ends to generate distinct protein isoforms. Extensive molecular cellular analyses identified regulators pathways critical for tumour initiation, progression response therapy. However, little is known expression or...
Glycolysis and hypoxia are key regulators of human embryonic stem cell (hESC) self-renewal, but how changes in metabolism affect gene expression is poorly understood. C-terminal binding proteins (CTBPs) glycolytic sensors that through NADH link the metabolic state to its expression, by acting as transcriptional corepressors, or coactivators. However, role CTBPs hESCs has not previously been investigated. A direct interaction between hypoxia-inducible factor 2α (HIF-2α) CTBP proximal...
CtBPs (CtBP1 and CtBP2) act in the nucleus as transcriptional corepressors cytoplasm regulators of Golgi apparatus fission. Studies which expression or function has been inhibited have independently identified roles for both suppressing apoptosis promoting cell cycle progression. Here, we analyzed consequences ablating CtBP breast cancer-derived lines. We found that loss suppresses proliferation through a combination apoptosis, reduction progression, aberrations transit mitosis. The third...
The p53 regulatory network is critically involved in preventing the initiation of cancer. In unstressed cells, maintained at low levels and largely inactive, mainly through action its two essential negative regulators, HDM2 HDMX. abundance activity are up-regulated response to various stresses, including DNA damage oncogene activation. Active initiates transcriptional transcription-independent programs that result cell cycle arrest, cellular senescence, or apoptosis. also activates...
Altered flux through major metabolic pathways is a hallmark of cancer cells and provides opportunities for therapy. Stem cell-like (SCLC) can cause metastasis therapy resistance. They possess plasticity, theoretically enabling resistance to therapies targeting specific state. The C-terminal binding protein (CtBP) transcriptional regulators are potential therapeutic targets in highly glycolytic cells, as they activated by the coenzyme nicotinamide adenine dinucleotide (NADH). However, SCLC...