A5088858231- HER2/EGFR in Cancer Research
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Advanced Breast Cancer Therapies
- Neuroblastoma Research and Treatments
- Cell death mechanisms and regulation
- PI3K/AKT/mTOR signaling in cancer
- Monoclonal and Polyclonal Antibodies Research
- Cervical Cancer and HPV Research
- Cancer Treatment and Pharmacology
- Prostate Cancer Treatment and Research
- Breast Cancer Treatment Studies
- Genetic factors in colorectal cancer
- Cancer-related Molecular Pathways
- Ethics in Clinical Research
- Colorectal Cancer Surgical Treatments
- RNA Research and Splicing
- Cell Adhesion Molecules Research
- Gut microbiota and health
- Signaling Pathways in Disease
- Immunotherapy and Immune Responses
- Inflammasome and immune disorders
- Virus-based gene therapy research
- Lung Cancer Treatments and Mutations
- Cancer, Lipids, and Metabolism
Beaumont Hospital
2013-2024
Royal College of Surgeons in Ireland
2012-2024
Dublin City University
2016-2018
University College Dublin
2016-2018
St. Vincent's University Hospital
2016-2018
Cancer Trials Ireland
2016-2018
University of Toronto
2016
St. James's Hospital
2016
National Children’s Research Centre
2011-2012
Children's Health Ireland at Crumlin
2012
Transforming growth factor-β (TGF-β) signaling regulates many diverse cellular activities through both canonical (SMAD-dependent) and non-canonical branches, which includes the mitogen-activated protein kinase (MAPK), Rho-like guanosine triphosphatase phosphatidylinositol-3-kinase/AKT pathways. Here, we demonstrate that miR-335 directly targets downregulates genes in TGF-β pathways, including Rho-associated coiled-coil containing (ROCK1) MAPK1, resulting reduced phosphorylation of downstream...
Neuroblastoma remains a major cause of cancer-linked mortality in children. miR-204 has been used microRNA expression signatures predictive neuroblastoma patient survival. The aim this study was to explore the independent association with survival cohort, and investigate phenotypic effects mediated by neuroblastoma. cell lines were transiently transfected mimics assessed for viability using MTS assays. Apoptosis levels evaluated FACS analysis Annexin V-/propidium iodide-stained cells treated...
Abstract Colorectal cancer (CRC) is one of the most common cancers in Western world. 5-Fluorouracil (5FU)-based chemotherapy (CT) remains mainstay treatment CRC advanced setting, and activates executioner caspases target cells. Executioner are key proteins involved cell disassembly during apoptosis. Activation also has a role tissue regeneration repopulation by stimulating signal transduction proliferation neighbouring, non-apoptotic cells as reported recently. Tissue microarrays (TMAs)...
Recent legislative changes within the United Kingdom have stimulated professional debate about access to patient data research. However, there is currently little awareness of public views such The authors sought explore attitudes public, and their lay representatives, towards use primary care medical record for research when consent was not being sought.49 members four non-medical local community health councils in South Wales, UK gave on value acceptability three current scenarios, each...
Colorectal cancer (CRC) is a leading cause of mortality in the Western world and commonly treated with genotoxic chemotherapy. Stress endoplasmic reticulum (ER) was implicated to contribute chemotherapeutic resistance. Hence, ER stress related protein may be prognostic or therapeutic significance.The expression levels proteins calnexin, calreticulin, GRP78 GRP94 were determined n = 23 Stage II III colon fresh frozen tumour matched normal tissue samples. Data validated cohort 11 rectal...
The contribution of somatic variants to epilepsy has recently been demonstrated, particularly in the etiology malformations cortical development. aim this study was determine diagnostic yield genes that have previously associated with a or germline model, ascertained from resected brain tissue patients multidrug-resistant focal epilepsy.
Abstract The expression profile of a panel RNA‐binding proteins (heterogeneous ribonucleoprotein (hnRNP) A1, hnRNP C1/C2, H, I, ASF/SF2, SR proteins, HuR and U2AF 65 ) markers differentiation, proliferation neoplasia (cytokeratin (CK) 13, CK‐14, proliferating cell nuclear antigen (PCNA), Syndecan‐1 p16INK4a) were analyzed in 50 formalin fixed paraffin embedded cervical tissues using immunohistochemistry. samples included histologically normal epithelium, human papillomavirus (HPV) induced...
The mainstay of treatment in rectal cancer is neoadjuvant radio chemotherapy prior to surgery, an attempt downstage the tumour, allowing for more complete removal during surgery. In 40 % cases however, this fails achieve tumour regression, partly due insufficient apoptosis signaling. X-linked Inhibitor Apoptosis Protein (XIAP) anti-apoptotic protein that has been reported contribute disease progression and resistance.We obtained biopsy normal matched tissue from 29 patients with varying...
Abstract Background Aberrant PI3K signalling is implicated in trastuzumab resistance HER2-positive gastric cancer (GC). The role of or MEK inhibitors sensitising GCs to overcoming unclear. Methods Using mass spectrometry-based genotyping we analysed 105 hotspot, non-synonymous somatic mutations PIK3CA and ERBB-family ( EGFR , ERBB2 ERBB3 ERBB4 ) genes tumour samples from 69 patients. A panel cell lines (N87, OE19, ESO26, SNU16, KATOIII) were profiled for anti-proliferative response the...
We have investigated the role of human papillomavirus type 16 (HPV-16) early untranslated region (3' UTR) in HPV-16 gene expression. found that deletion 3' UTR reduced utilization polyadenylation signal and, as a consequence, resulted read-through into late and production L1 L2 mRNAs. Deletion U-rich half had similar effect, demonstrating 57-nucleotide acted an enhancing upstream element on signal. In accordance with this, newly identified hFip1 protein, which has been shown to enhance...
ABSTRACT Production of human papillomavirus type 16 (HPV-16) virus particles is totally dependent on the differentiation-dependent induction viral L1 and L2 late gene expression. The early polyadenylation signal in HPV-16 plays a major role switch from to late, productive stage life cycle. Here, we show that coding region contains RNA elements are necessary for at signal. Consecutive mutations six GGG motifs located 174 nucleotides downstream resulted gradual decrease This caused...
Summary Caspases are a group of proteolytic enzymes involved in the co-ordination cellular processes, including homeostasis, inflammation and apoptosis. Altered activity caspases, particularly caspase-1, has been implicated development intestinal diseases, such as inflammatory bowel disease (IBD) colorectal cancer (CRC). However, involvement two related caspase members, caspases-4 -5, during homeostasis not yet established. This study demonstrates that -5 IBD-associated inflammation....
The Cancer Genome Atlas analysis revealed that somatic EGFR, receptor tyrosine-protein kinase erbB-2 (ERBB2), Erb-B2 tyrosine 3 (ERBB3) and 4 (ERBB4) gene mutations (ERBB family mutations) occur alone or co-occur with in the encoding phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) 19% of human epidermal growth factor 2 (HER2)-positive breast cancers. Because ERBB can activate PI3K/AKT pathway likely have similar canonical signalling effects to PI3K mutations, we investigated...
Two splice sites on the human papillomavirus type 16 (HPV-16) genome are used exclusively by late capsid protein L1 mRNAs: SD3632 and SA5639. These suppressed in mitotic cells. This study showed that serine/arginine-rich 30c (SRp30c), also named SFRS9, activated both SA5639 induced production of mRNA. Activation HPV-16 mRNA splicing SRp30c required an intact arginine/serine-repeat (RS) domain SRp30c. In addition to this effect, could enhance indirectly inhibiting early 3'-splice site SA3358,...
Abstract The intrinsic or mitochondrial apoptosis pathway is controlled by the interaction of antiapoptotic and pro-apoptotic members BCL-2 protein family. Activation this death plays a crucial role in cancer progression chemotherapy responses. BCL-2-related ovarian killer (BOK) possesses three homology domains has been proposed to act similar as proteins BAX BAK. In study, we showed that stage II III colorectal patients possessed decreased levels BOK their tumours compared matched normal...
Murine inflammatory caspase-11 has an important role in intestinal epithelial inflammation and barrier function. Activation of the non-canonical inflammasome, mediated by caspase-11, serves as a regulatory pathway for production pro-inflammatory cytokines IL-1β IL-18, key pyroptotic cell death. We have previously demonstrated protective during dextran sulphate sodium (DSS)-induced colitis, however importance colorectal tumour development remains unclear. Here, we show that Casp11−/− mice are...
PTPN11 encodes the SHP2 protein tyrosine phosphatase that activates mitogen-activated kinase (MAPK) pathway upstream of KRAS and MEK. PTPN11/Shp2 somatic mutations occur frequently in Juvenile myelomonocytic leukaemia (JMML); however, role mutated lung cancer tumourigenesis its utility as a therapeutic target has not been fully addressed. We applied mass-spectrometry-based genotyping to DNA extracted from tumour matched normal tissue 356 NSCLC patients (98 adenocarcinomas (LUAD) 258 squamous...
Trastuzumab treatment for women with HER2-positive breast cancer (BC) resulted in the significant improvement of both relapse free survival (RFS) and overall (OS). However, many who are classified as do not respond. Many studies have focused on role somatic mutations rather than germline polymorphisms trastuzumab resistance.We completed an Agena MassArray screen 10 ERBB-family single nucleotide (SNPs) 194 adjuvant treated BC patients. SNPs EGFR genes a association RFS OS. Patients minor...