Hayley L. Belnoue-Davis
A5061087285- Cancer Immunotherapy and Biomarkers
- Cancer Cells and Metastasis
- Cancer-related gene regulation
- Immunotherapy and Immune Responses
- Genetic factors in colorectal cancer
- Cell Adhesion Molecules Research
- Colorectal and Anal Carcinomas
- Immune Cell Function and Interaction
- Cancer Genomics and Diagnostics
- Peptidase Inhibition and Analysis
- Colorectal Cancer Treatments and Studies
- Cytokine Signaling Pathways and Interactions
- Wnt/β-catenin signaling in development and cancer
- Digestive system and related health
- Ubiquitin and proteasome pathways
- Hippo pathway signaling and YAP/TAZ
- TGF-β signaling in diseases
- Cancer-related Molecular Pathways
- Monoclonal and Polyclonal Antibodies Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Genomic variations and chromosomal abnormalities
- Colorectal Cancer Screening and Detection
- Inflammatory Bowel Disease
- Pancreatic and Hepatic Oncology Research
- T-cell and B-cell Immunology
University of Oxford
2016-2025
Centre for Human Genetics
2015-2025
National Institute for Health Research
2024
NIHR Biomedical Research Centre at The Royal Marsden and the ICR
2024
John Radcliffe Hospital
2024
Oxford University Hospitals NHS Trust
2017
Intestinal homeostasis is underpinned by LGR5+ve crypt-base columnar stem cells (CBCs), but following injury, dedifferentiation results in the emergence of LGR5−ve regenerative cell populations (RSCs), characterized fetal transcriptional profiles. Neoplasia hijacks signaling, so we assessed distribution CBCs and RSCs mouse human intestinal tumors. Using combined molecular-morphological analysis, demonstrate variable expression markers across a range lesions. The degree CBC-RSC admixture was...
Abstract Molecular stratification using gene-level transcriptional data has identified subtypes with distinctive genotypic and phenotypic traits, as exemplified by the consensus molecular (CMS) in colorectal cancer (CRC). Here, rather than data, we make use of gene ontology biological activation state information for initial class discovery. In doing so, defined three pathway-derived (PDS) CRC: PDS1 tumors, which are canonical/LGR5 + stem-rich, highly proliferative display good prognosis;...
The Fbxw7 (F-box/WD repeat–containing protein 7; also called CDC4, Sel10, Ago, and Fbw7) component of the SCF (Skp1/Cullin/F-box protein) E3 ubiquitin ligase complex acts as a tumor suppressor in several tissues targets multiple transcriptional activators protooncogenes for ubiquitin-mediated degradation. To understand function murine intestine, this study, we specifically deleted gut using Villin-Cre (Fbxw7ΔG). In wild-type mice, loss altered homeostasis intestinal epithelium, resulted...
IBD confers an increased lifetime risk of developing colorectal cancer (CRC), and colitis-associated CRC (CA-CRC) is molecularly distinct from sporadic (S-CRC). Here we have dissected the evolutionary history CA-CRC using multiregion sequencing.
The risk of developing advanced neoplasia (AN; colorectal cancer and/or high-grade dysplasia) in ulcerative colitis (UC) patients with a low-grade dysplasia (LGD) lesion is variable and difficult to predict. This major challenge for effective clinical management. We aimed provide accurate AN stratification UC LGD. hypothesised that the pattern burden somatic genomic copy number alterations (CNAs) LGD lesions could predict future risk. performed retrospective multicentre validated...
<h3>Objective</h3> Wnt signalling is critical for normal intestinal development and homeostasis. dysregulation occurs in almost all human murine tumours an optimal but not excessive level of activation considered favourable tumourigenesis. The authors assessed effects pan-intestinal on tissue homeostasis, taking into account underlying physiological activity stem-cell number each region the bowel. <h3>Design</h3> generated mice that expressed temporally controlled, stabilised β-catenin along...
Objective Pathological Wnt pathway activation is a conserved hallmark of colorectal cancer. Wnt-activating mutations can be divided into: i) ligand-independent (LI) alterations in intracellular signal transduction proteins ( Adenomatous polyposis coli , β-catenin), causing constitutive and ii) ligand-dependent (LD) affecting the synergistic R-Spondin axis RNF43 RSPO -fusions) acting through amplification endogenous transmembrane transduction. Our aim was to exploit differential target gene...
<h3>Background and aims</h3> Adenomatous polyposis coli (<i>APC</i>) is a tumour suppressor gene mutated in the germline of patients with familial adenomatous (FAP) somatically most colorectal cancers. <i>APC</i> mutations impair β-catenin degradation, resulting increased Wnt signalling. The frequent mutation codon 1309 truncation that associated severe FAP. A previous study compared two mouse models intestinal tumorigenesis, Apc<sup>R850X</sup> (Min) Apc<sup>1322T</sup> (1322T), latter...
Abstract Intraepithelial lymphocytes (IEL) expressing γδ T-cell receptors (γδTCR) play key roles in elimination of colon cancer. However, the precise mechanisms by which progressing cancer cells evade immunosurveillance these innate T are unknown. Here, we investigated how loss Apc tumor suppressor gut tissue could enable nascent to escape cytotoxic γδIELs. In contrast with healthy intestinal or colonic tissue, found that γδIELs were largely absent from microenvironment both mouse and human...
<h3>Objective</h3> <i>FBXW7</i> encodes the substrate recognition component of a ubiquitin ligase that degrades targets such as Notch1, c-Jun, c-Myc and cyclin E. mutations occur in several tumour types, including colorectal cancers. The mutation spectrum cancers is unusual. Some tumours have biallelic loss function but most monoallelic missense involving specific arginine residues at β-propellor tips involved recognition. <h3>Design</h3> FBXW7 functional studies generally used null systems....
A rare germline duplication upstream of the bone morphogenetic protein antagonist GREM1 causes a Mendelian-dominant predisposition to colorectal cancer (CRC). The underlying disease mechanism is strong, ectopic overexpression in intestinal epithelium. Here, we confirm that common polymorphism, rs16969681, also associated with CRC susceptibility, conferring ∼20% differential risk general population. We hypothesized cause be moderate differences expression. showed rs16969681 lies region active...
Abstract The functional role of bone morphogenetic protein ( BMP ) signalling in colorectal cancer CRC is poorly defined, with contradictory results cell line models reflecting the inherent difficulties assessing a pathway that context‐dependent and subject to genetic constraints. By transcriptional response diploid human colonic epithelial ligand stimulation, we generated prognostic signature, which was applied multiple datasets investigate heterogeneity across molecular subtypes. We linked...
The V600EBRAF oncogenic mutation is detected in a wide range of human cancers and induces hyperactivation the downstream MEK–ERK signalling cascade. Although output BRAF–MEK–ERK pathway regulated by feed-forward RAF activity, feedback control also plays an important role. One such has been identified Caenorhabditis elegans involves ERK-mediated phosphorylation BRAF within CDC4 phosphodegron (CPD), targeting for degradation via (also known as FBXW7), component SKP1/CUL1/F-box (SCF) E3...