A5058174847- Cell death mechanisms and regulation
- Histone Deacetylase Inhibitors Research
- Cancer, Hypoxia, and Metabolism
- Cancer-related Molecular Pathways
- Colorectal Cancer Treatments and Studies
- Cancer Research and Treatments
- BRCA gene mutations in cancer
- Advanced Breast Cancer Therapies
- Ubiquitin and proteasome pathways
- Cancer Mechanisms and Therapy
- interferon and immune responses
- Cancer, Lipids, and Metabolism
- MicroRNA in disease regulation
- Genomics and Chromatin Dynamics
- Lung Cancer Treatments and Mutations
- Genetics, Bioinformatics, and Biomedical Research
- RNA Interference and Gene Delivery
- Cancer therapeutics and mechanisms
- Autophagy in Disease and Therapy
- PI3K/AKT/mTOR signaling in cancer
- Melanoma and MAPK Pathways
- Cancer Genomics and Diagnostics
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Protein Degradation and Inhibitors
Almac (United Kingdom)
2021-2024
Queen's University Belfast
2013-2023
St. Patrick's Hospital
2020
Lund University
2011
Royal College of Surgeons in Ireland
2011
Beaumont Hospital
2011
National Taiwan University of Science and Technology
2011
Abstract Rewiring of host cytokine networks is a key feature inflammatory bowel diseases (IBD) such as Crohn’s disease (CD). Th1-type cytokines—IFN-γ and TNF-α—occupy critical nodes within these both are associated with disruption gut epithelial barrier function. This may be due to their ability synergistically trigger the death intestinal cells (IECs) via largely unknown mechanisms. In this study, through unbiased kinome RNAi drug repurposing screens we identified JAK1/2 kinases principal...
We carried out a yeast two-hybrid screen using BRCA1 bait composed of amino acids 1 to 1142 and identified BRD7 as novel binding partner BRCA1. This interaction was confirmed by coimmunoprecipitation endogenous in T47D HEK-293 cells. is bromodomain containing protein, which subunit PBAF-specific Swi/Snf chromatin remodeling complexes. To determine the functional consequences BRCA1-BRD7 interaction, we investigated role BRCA1-dependent transcription microarray-based expression profiling....
Abstract Background Understanding how to modulate the microenvironment of tumors that are resistant immune checkpoint inhibitors represents a major challenge in oncology.Here we investigate ability USP7 reprogram tumor (TME) by inhibiting secretion vascular endothelial growth factor (VEGF) from fibroblasts. Methods To understand role played TME, systematically evaluated effects potent, selective on co‐cultures comprising components using human primary cells. We also inhibition syngeneic...
Activating mutations in the BRAF oncogene are found 8% to 15% of colorectal cancer patients and have been associated with poor survival. In contrast BRAF-mutant (MT) melanoma, inhibition MAPK pathway is ineffective majority BRAFMT patients. Therefore, identification novel therapies for urgently needed.BRAFMT wild-type (WT) models were assessed vitro vivo. Small-molecule inhibitors MEK1/2, MET, HDAC used, overexpression siRNA approaches applied, cell death was by flow cytometry, Western...
Non-small cell lung carcinoma remains by far the leading cause of cancer-related deaths worldwide. Overexpression FLIP, which blocks extrinsic apoptotic pathway inhibiting caspase-8 activation, has been identified in various cancers. We investigated FLIP and procaspase-8 expression NSCLC effect HDAC inhibitors on expression, activation drug resistance normal line models. Immunohistochemical analysis cytoplasmic nuclear protein was carried out using a novel digital pathology approach. Both...
Article3 February 2020Open Access Source DataTransparent process A revised model of TRAIL-R2 DISC assembly explains how FLIP(L) can inhibit or promote apoptosis Luke M Humphreys The Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, UK Search more papers by this author Jennifer P Fox Catherine Higgins Joanna Majkut Tamas Sessler Kirsty McLaughlin Christopher McCann Jamie Z Roberts Nyree T Crawford Simon S McDade orcid.org/0000-0002-3024-4773 J Scott Timothy Harrison...
Transcriptomic-based subtyping, consensus molecular subtyping (CMS) and colorectal cancer intrinsic (CRIS) identify a patient subpopulation with mesenchymal traits (CMS4/CRIS-B) poorer outcome. Here, we investigated the relationship between prevalence of Fusobacterium nucleatum (Fn) Fusobacteriales, CMS/CRIS cell type composition, immune infiltrates host contexture to refine stratification druggable context-specific vulnerabilities.We coupled culture experiments characterisation...
Failure to efficiently induce apoptosis contributes cisplatin resistance in non-small-cell lung cancer (NSCLC). Although BCL-2-associated X protein (BAX) and BCL-2 antagonist killer (BAK) are critical regulators of the mitochondrial pathway, their requirement has not been robustly established relation cisplatin. Here, we show that can bypass block caused by loss BAX BAK, via activation extrinsic death receptor pathway some model cell lines. Apoptosis following only be observed when both...
Here, we show for the first time, that familial breast/ovarian cancer susceptibility gene BRCA1 activates Notch pathway in breast cells by transcriptional upregulation of ligands and receptors both normal cells. We demonstrate through chromatin immunoprecipitation assays is localized to a conserved intronic enhancer region within ligand Jagged-1 (JAG1) gene, an event requiring ΔNp63. propose this BRCA1/ΔNp63-mediated induction JAG1 may be important regulation stem/precursor cells, as...
// Zenobia C. D’Costa 1 , Catherine Higgins Chee Wee Ong Gareth W. Irwin David Boyle Darragh G. McArt Karen McCloskey Niamh E. Buckley Nyree T. Crawford Lalitha Thiagarajan 3 James Murray 2 Richard D. Kennedy Karl A. Mulligan 4 Paul Harkin J.J. Waugh Chris J. Scott 5 Manuel Salto-Tellez Williams and B. Mullan Centre for Cancer Research Cell Biology, Queen’s University Belfast, UK Biomedical Science Institute, Trinity College Dublin, Green, Dublin 2, Ireland School of Biological...
Malignant pleural mesothelioma (MPM) is a highly pro-inflammatory malignancy that rapidly fatal and increasing in incidence. Cytokine signaling within the tumor microenvironment makes critical contribution to development of MPM its resistance conventional chemotherapy approaches. SMAC mimetic compounds (SMCs) are promising class anticancer drug dependent on necrosis factor alpha (TNFα) for their activity. As circulating TNFα expression significantly elevated patients, we examined sensitivity...
// Chris W.D. Armstrong 1 , Pamela J. Maxwell Chee Wee Ong Kelly M. Redmond Christopher McCann Jessica Neisen George A. Ward 3 Gianni Chessari Johnson Nyree T. Crawford Melissa LaBonte Kevin Prise Tracy Robson 2 Manuel Salto-Tellez Daniel B. Longley David J.J. Waugh Movember Centre of Excellence, for Cancer Research and Cell Biology, Queen's University Belfast, Northern Ireland School Pharmacy, Astex Pharmaceuticals, Cambridge, UK Correspondence to: DJJ Waugh, e-mail: d.waugh@qub.ac.uk...
Pevonedistat (MLN4924), a selective inhibitor of the NEDD8-activating enzyme E1 regulatory subunit (NAE1), has demonstrated significant therapeutic potential in several malignancies. Although multiple mechanisms-of-action have been identified, how MLN4924 induces cell death and its as combinatorial agent with standard-of-care (SoC) chemotherapy colorectal cancer (CRC) remains largely undefined. In an effort to understand MLN4924-induced CRC, we identified p53 important mediator apoptotic...
Little is known about the origin of basal-like breast cancers, an aggressive disease that highly similar to BRCA1-mutant cancers. p63 family proteins are structurally related p53 suppressor protein function in stem cell regulation and stratified epithelia development multiple tissues, expression may be a marker Here we report ΔNp63 isoforms transcriptional targets for positive by BRCA1. Our analyses cancer tissue microarrays BRCA1-modulated lines do not support earlier reports or BRCA1...
TRAIL-R2 (DR5) is a clinically-relevant therapeutic target and key for immune effector cells. Herein, we identify novel interaction between the Skp1-Cullin-1-F-box (SCF) Cullin-Ring E3 Ubiquitin Ligase complex containing Skp2 (SCFSkp2). We find that SCFSkp2 can interact with both TRAIL-R2's pre-ligand association (PLAC) ligand-activated death-inducing signalling (DISC). Moreover, Cullin-1 interacts in its active NEDDylated form. Inhibiting Cullin-1's DISC recruitment using NEDDylation...
Colorectal cancer is a molecularly heterogeneous disease. Responses to genotoxic chemotherapy in the adjuvant or palliative setting vary greatly between patients, and colorectal cells often resist by evading apoptosis. Antagonists of an inhibitor apoptosis proteins (IAPs) can restore defective signaling degrading cIAP1 cIAP2 inhibition XIAP. Due multiple molecular mechanisms-of-action these targets, responses IAP antagonist may differ distinct colon cells. In this study, Birinapant...