A5009202375- NF-κB Signaling Pathways
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Liver Disease Diagnosis and Treatment
- Retinal and Optic Conditions
- Long-Term Effects of COVID-19
- Immune responses and vaccinations
- Retinal Diseases and Treatments
- Liver Disease and Transplantation
- Evolution and Genetic Dynamics
- Retinal Imaging and Analysis
- Aquatic Ecosystems and Biodiversity
- COVID-19 Clinical Research Studies
- Genetic diversity and population structure
- Lymphoma Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- Pancreatic and Hepatic Oncology Research
- Immune Cell Function and Interaction
- DNA Repair Mechanisms
- Spaceflight effects on biology
- Cancer Genomics and Diagnostics
- Endoplasmic Reticulum Stress and Disease
- Evolution and Paleontology Studies
- Genomics and Phylogenetic Studies
- Aquatic Ecosystems and Phytoplankton Dynamics
University of Liverpool
2020-2024
Newcastle University
2021-2024
NIHR Newcastle Biomedical Research Centre
2022
University of York
2020
Abstract Non-alcoholic fatty liver disease (NAFLD) is a common, progressive strongly associated with the metabolic syndrome. It unclear how progression of NAFLD towards cirrhosis translates into systematic changes in circulating proteins. Here, we provide detailed proteo-transcriptomic map steatohepatitis and fibrosis during NAFLD. In this multicentre proteomic study, characterize 4,730 proteins 306 patients histologically characterized integrate transcriptomic analysis paired tissue. We...
Abstract Age-related macular degeneration (AMD) is the most prevalent cause of blindness in developed world. Vision loss advanced stages disease caused by atrophy retinal photoreceptors, overlying pigment epithelium (RPE) and choroidal endothelial cells. The molecular events that underline development these cell types from utero to adult as well progression intermediate AMD are not yet fully understood. We performed single-cell RNA-sequencing (RNA-Seq) human fetal RPE–choroidal tissues,...
The deepest marine ecosystem, the hadal zone, hosts endemic biodiversity resulting from geographic isolation and environmental selection pressures. However, pan-ocean distribution of some fauna challenges concept that zone is a series isolated island-like habitats. Whether this remains true at population genomic level untested. We investigated phylogeographic patterns amphipod, Bathycallisoma schellenbergi, 12 features across Pacific, Atlantic, Indian, Southern oceans analyzed genome-wide...
DNA replication stress resulting from the activity of oncogenes such as MYC, is a common feature cancer cells. To cope with this challenge, tumours become addicted to ATR/CHK1 signalling, thus making these kinases attractive targets for anti-cancer therapies. Here, we demonstrate that RelA(p65) NF-κB subunit an important regulator MYC induced in vivo. Using Eμ-Myc model B-cell lymphoma, mice mutated at putative CHK1 T505 phosphosite (T505A) RelA transactivation domain, exhibited reduced...
Conjunctival epithelial cells, which express viral-entry receptors angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine type (TMPRSS2), constitute the largest exposed epithelium of ocular surface tissue may represent a relevant route. To address this question, we generated an organotypic air-liquid-interface model conjunctival epithelium, composed basal, suprabasal, superficial fibroblasts, could be maintained successfully up to day 75 differentiation. Using single-cell...
Previously, we discovered that deletion of c-Rel in the Eµ-Myc mouse model lymphoma results earlier onset disease, a finding contrasted with expected function this NF-κB subunit B-cell malignancies. Here report Eµ-Myc/cRel−/− cells have an unexpected and major defect CHK1 pathway. Total phospho proteomic analysis revealed lymphomas highly resemble wild-type (WT) treated acute dose inhibitor (CHK1i) CCT244747. Further demonstrated is consequence having lost expression protein itself, effect...
The development of resistance and the activation bypass pathway signalling represents a major problem for clinical application protein kinase inhibitors. While investigating effect either c-Rel deletion or RelAT505A phosphosite knockin on Eµ-Myc mouse model B-cell lymphoma, we discovered that both NF-κB subunit mutations resulted in CHK1 inhibitor resistance, arising from loss alteration activity, respectively. However, since lymphomas depend activity to cope with high levels DNA replication...
Abstract Background New-onset diabetes mellitus (NOD) can manifest as a consequence of pancreatic ductal adenocarcinoma (PDAC), although not all PDAC patients develop NOD. For many patients, hyperglycaemia begins 3 years prior to diagnosis, with 30% experiencing NOD by the time their cancer is diagnosed. The mechanisms underlying onset (DM) in and its consequences for disease development, detection treatment are well understood. aim this study was characterise transcriptomic differences...
Abstract Understanding how genetic, nongenetic, and environmental cues are integrated during development may be critical in understanding if, how, organisms will respond to rapid change. Normally, only post‐embryonic studies possible. But this study, we developed a real‐time, high‐throughput confocal microscope assay that allowed us link Daphnia embryogenesis offspring life history variation at the individual level. Our identified eight clear developmental phenotypes linked by seven stages,...
Abstract We previously discovered that deletion of c-Rel in the Eμ-Myc mouse model lymphoma results earlier onset disease, a finding contrasted with expected function this NF-κB subunit B-cell malignancies. Here we report c-rel -/- Eµ-Myc cells have an unexpected and major defect CHK1 pathway, almost undetectable levels CLSPN protein leading to therapeutic resistance highly specific inhibitor (CHK1i) CCT244747. Similar downregulation was also seen CCT244747 resistant U20S osteosarcoma cells....
Abstract Although tropism of SARS-CoV-2 for respiratory tract epithelial cells is well established, an open question whether the conjunctival epithelium also a target SARS-CoV-2. Conjunctival cells, which express viral entry receptors ACE2 and TMPRSS2, constitute largest exposed ocular surface tissue, may represent relevant route. To address this question, we generated organotypic air-liquid-interface model epithelium, composed progenitor, basal superficial fibroblasts, could be maintained...