A5009316764- Gene expression and cancer classification
- Cancer Genomics and Diagnostics
- Bioinformatics and Genomic Networks
- Colorectal Cancer Treatments and Studies
- Genetic factors in colorectal cancer
- Single-cell and spatial transcriptomics
- Cancer Immunotherapy and Biomarkers
- Ferroptosis and cancer prognosis
- Computational Drug Discovery Methods
- Molecular Biology Techniques and Applications
- Sphingolipid Metabolism and Signaling
- Cell Image Analysis Techniques
- Pancreatic and Hepatic Oncology Research
- Liver Disease Diagnosis and Treatment
- Cancer Research and Treatments
- Esophageal Cancer Research and Treatment
- Colorectal Cancer Screening and Detection
- Radiomics and Machine Learning in Medical Imaging
- Liver Disease and Transplantation
- Colorectal Cancer Surgical Treatments
- Genetic Associations and Epidemiology
- Gastrointestinal Tumor Research and Treatment
- Drug-Induced Hepatotoxicity and Protection
- Calcium signaling and nucleotide metabolism
- Autophagy in Disease and Therapy
Queen's University Belfast
2019-2025
Queens University
2024
Cancer Research UK
2022
Keele University
2013-2018
University of Michigan
2012-2018
Michigan Medicine
2013
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;...
OBJECTIVES: We aimed to understand and improve patient knowledge about self-management of cirrhosis. METHODS: gave 150 outpatients with cirrhosis a survey test disease knowledge. then them concise educational booklet and, 3 months later, follow-up survey. analyzed demographic clinical correlates baseline knowledge, compared scores before after the intervention. RESULTS: Only 53% 15 questions were answered correctly in The most commonly missed items related diet, such as sodium content sea...
Abstract Background Colorectal cancer (CRC) primary tumours are molecularly classified into four consensus molecular subtypes (CMS1–4). Genetically engineered mouse models aim to faithfully mimic the complexity of human cancers and, when appropriately aligned, represent ideal pre-clinical systems test new drug treatments. Despite its importance, dual-species classification has been limited by lack a reliable approach. Here we utilise, develop and set options for human-to-mouse CMS...
Abstract Purpose: Precise mechanism-based gene expression signatures (GES) have been developed in appropriate vitro and vivo model systems, to identify important cancer-related signaling processes. However, some GESs originally represent specific disease processes, primarily with an epithelial cell focus, are being applied heterogeneous tumor samples where the of genes signature may no longer be epithelial-specific. Therefore, unknowingly, even small changes stroma percentage can directly...
Background: A small cluster of up to four cells, defined as tumour budding (TB), has been well studied an independent promising prognostic marker in CRC. However, its underlying mechanism CRC is unclear. Methods: Multi-omic approaches from bulk RNA regional GeoMx were used identify the TB and possible correlation with microenvironment tissue. The results validated using immunohistochemistry (IHC) multiplex immunofluorescence (mIF) staining. Results: Patients high have a worse outcome...
Abstract Background: Bowel cancer screening has increased detection of colorectal precursors. Despite this incidence, while transcriptional characterisation and molecular subtyping approaches are well established in tumours, similar biological discovery polyps have been limited. While some multi-omics studies defined patterns aligned to serrated adenoma histological pathways, these generally performed small collections samples. This project aims define, for the first time, a comprehensive...
Abstract Colorectal cancer (CRC) has been classified into molecular subtypes using gene-level data from both bulk and single-cell RNA sequencing (scRNA-seq), leading to the development of consensus (CMS) intrinsic CMS (iCMS). In addition CRC studies, scRNA-seq spatial transcriptomics characterization human polyps, aligned with conventional adenoma serrated identified distinct driver mutations, cells-of-origin iCMS traits associated each polyp type. These transcriptional classification...
Obatoclax belongs to a class of compounds known as BH3 mimetics which function antagonists Bcl-2 family apoptosis regulators. It has undergone extensive preclinical and clinical evaluation cancer therapeutic. Despite this, it is clear that obatoclax additional pharmacological effects contribute its cytotoxic activity. been claimed obatoclax, either alone or in combination with other molecularly targeted therapeutics, induces an autophagic form cell death. In addition, shown inhibit lysosomal...
Bariatric surgery leads to changes in mental health, quality of life and social functioning, yet these outcomes differ among individuals. In this study, we explore patients' psychosocial experiences following bariatric elucidate the individual-level factors that may drive variation outcomes.Eleven semi-structured focus groups with Michigan Surgery Collaborative (MBSC) patients (n = 77). Interviews were audio recorded, transcribed verbatim, analyzed using a grounded theory approach. Data on...
Abstract Background Limited studies examine the immune landscape in Esophageal Adenocarcinoma (EAC). We aim to identify novel associations, which may inform immunotherapy treatment stratification. Methods Three hundred twenty-nine EAC cases were available Tissue Microarrays (TMA) format. A discovery cohort of 166 stained immunohistochemically for range adaptive (CD3, CD4, CD8 and CD45RO) checkpoint biomarkers (ICOS, IDO-1, PD-L1, PD-1). validation 163 was also accessed. digital pathology...
Objective Stroma-rich tumours represent a poor prognostic subtype in stage II/III colon cancer (CC), with high relapse rates and limited response to standard adjuvant chemotherapy. Design To address the lack of efficacious therapeutic options for patients stroma-rich CC, we stratified our human tumour cohorts according stromal content, enabling identification biology underpinning potential vulnerabilities specifically within that could be exploited clinically. Following tumour-based...
Abstract Molecular stratification, across many tumour types, has used gene-level transcriptional data to identify subtypes associated with distinct genotypes and biological traits, as exemplified by the consensus molecular (CMS), more recently intrinsic CMS (iCMS), in colorectal cancer. In an attempt develop that closely align cancer-relevant phenotypic traits KRAS mutant tumours, here we present approach uses gene ontology activation state information, rather than data, for initial stages...
Tumour budding (TB) is an established prognostic feature in multiple cancers but not routinely assessed pathology practice. Efforts to standardise and automate assessment have shifted from haematoxylin eosin (H&E)-stained images towards cytokeratin immunohistochemistry. The aim of this study was compare manual H&E methods with a semi-automated approach built within QuPath open-source software.
Abstract The pro-tumourigenic role of epithelial TGFβ signalling in colorectal cancer (CRC) is controversial. Here, we identify a cohort born to be bad early-stage (T1) tumours, with aggressive features and propensity disseminate early, that are characterised by high cell-intrinsic signalling. In the presence concurrent Apc Kras mutations, activation rampantly accelerates tumourigenesis share transcriptional signatures those T1 human tumours predicts recurrence stage II CRC. Mechanistically,...
Abstract Gene set enrichment analysis (GSEA) tools can identify biological insights within gene expression-based studies. Although their statistical performance has been compared, the downstream implications that arise when choosing between range of pairwise or single sample forms GSEA methods remain understudied. We compare and results obtained from various pre-ranking methods/options for GSEA, followed by a stand-alone comparison (ssGSEA) variation (GSVA). Pairwise fGSEA provide similar...
Autotaxin is an extracellular phospholipase D that catalyzes the hydrolysis of lysophosphatidyl choline (LPC) to bioactive lipid lysophosphatidic acid (LPA). LPA has been implicated in many pathological processes relevant cancer, including cell migration and invasion, proliferation, survival. The most potent autotaxin inhibitor described date analogue S32826 (IC50 5.6 nM). other inhibitors are notably lipophilic, creating a need improve their physical properties. Polymers becoming...
Introduction: Best practices dictate that biobanks ensure accurate determination of tumor content before supplying formalin-fixed, paraffin-embedded (FFPE) tissue samples to researchers for nucleic acid extraction and downstream molecular testing. It is advisable trained competent individuals, who understand the requirements tests, perform microscopic morphological examination. However, special skills, time, costs associated with these assessments can be prohibitive, especially in large case...
Abstract BACKGROUND Colorectal cancer (CRC) primary tumours are molecularly classified into four consensus molecular subtypes (CMS1-4). Genetically engineered mouse models aim to faithfully mimic the complexity of human cancers and, when appropriately aligned, represent ideal pre-clinical systems test new drug treatments. Despite its importance, dual-species classification has been limited by lack a reliable approach. Here we utilise, develop and set options for human-to-mouse CMS...
Autotaxin is an extracellular phospholipase D that catalyzes the hydrolysis of lysophosphatidyl choline (LPC) to generate bioactive lipid lysophosphatidic acid (LPA). has been implicated in many pathological processes relevant cancer. Intraperitoneal administration autotaxin inhibitor may benefit patients with ovarian cancer; however, low molecular mass compounds are known be rapidly cleared from peritoneal cavity. Icodextrin a polymer already clinical use because it slowly eliminated Herein...
Abstract Background Gene set enrichment analysis (GSEA) tools can be used to identify biological insights from transcriptional datasets and have become an integral within gene expression-based cancer studies. Over the years, additional methods of GSEA-based been developed, providing field with ever-expanding range options choose from. Although several studies compared statistical performance these tools, downstream implications that arise when choosing between pairwise or single sample forms...