A5061321901- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Estrogen and related hormone effects
- Advanced Breast Cancer Therapies
- MicroRNA in disease regulation
- Circular RNAs in diseases
- Ferroptosis and cancer prognosis
- Cancer-related Molecular Pathways
- Bioinformatics and Genomic Networks
- Cancer, Lipids, and Metabolism
- Protein Degradation and Inhibitors
- Cancer-related molecular mechanisms research
- Peptidase Inhibition and Analysis
- Cancer Treatment and Pharmacology
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Pharmacogenetics and Drug Metabolism
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- Prostate Cancer Treatment and Research
- Advanced Biosensing Techniques and Applications
- Click Chemistry and Applications
- Glycosylation and Glycoproteins Research
- Histone Deacetylase Inhibitors Research
- Renal and related cancers
Royal College of Surgeons in Ireland
2016-2025
Sanofi (United States)
2018-2023
Australian National University
2007-2022
Charles River Laboratories (United Kingdom)
2006-2019
University College Dublin
2004-2018
Dublin City University
2010-2018
Charles River Laboratories (Netherlands)
2015-2018
Beaumont Hospital
2017-2018
St. Vincent's University Hospital
2011-2018
Cancer Trials Ireland
2012-2018
Immune-regulated pathways influence multiple aspects of cancer development. In this article we demonstrate that both macrophage abundance and T-cell in breast represent prognostic indicators for recurrence-free overall survival. We provide evidence response to chemotherapy is part regulated by these leukocytes; cytotoxic therapies induce mammary epithelial cells produce monocyte/macrophage recruitment factors, including colony stimulating factor 1 (CSF1) interleukin-34, which together...
Weighted gene coexpression network analysis (WGCNA) is a powerful 'guilt-by-association'-based method to extract coexpressed groups of genes from large heterogeneous messenger RNA expression data sets. We have utilized WGCNA identify 11 coregulated clusters across 2342 breast cancer samples 13 microarray-based studies. A number these transcriptional modules were found be correlated clinicopathological variables (e.g. tumor grade), survival endpoints for as whole (disease-free survival,...
The Wilms tumor suppressor gene wt1 encodes a zinc finger DNA binding protein, WT1, that functions as transcriptional repressor. fetal mitogen insulin-like growth factor II (IGF-II) is overexpressed in tumors and may have autocrine effects progression. major IGF-II promoter was defined transient transfection assays region spanning from nucleotides -295 to +135, relative the transcription start site. WT1 bound multiple sites this functioned potent repressor of vivo. Maximal repression...
The wt1 gene, a putative tumor suppressor gene located at the Wilms (WT) locus on chromosome 11p13, encodes zinc finger-containing protein that binds to same DNA sequence as EGR-1, mitogen-inducible immediate-early product activates transcription. transcriptional regulatory potential of WT1 has not been demonstrated. In transient transfection assays, functioned repressor transcription when bound EGR-1 site. repression function was mapped glutamine- and proline-rich NH2-terminus WT1; fusion...
The metabolism of clozapine by human liver has been investigated in vitro. Irreversible protein-binding and conjunction with model nucleophiles have used as markers for bioactivation clozapine, while stable metabolite formation assessed using radiometric HPLC. In all nine microsomal preparations investigated, was extensively metabolized to the products desmethylclozapine (range 19%-27.2%), N-oxide (1.5-20.5%) three polar metabolites (0-20.8%), bioactivated a protein-reactive (0.6-2.1%)....
The Wilms' tumor locus on chromosome 11p13 contains a suppressor gene, wt1, which encodes DNA binding protein (WT1) with four zinc fingers and glutamine-proline-rich N terminus functions as repressor of transcription. platelet-derived growth factor (PDGF) A-chain gene potent factor, is expressed in high levels number cell lines. We initiated search for WT1 target genes now report that strikingly represses transcription the PDGF transient transfection assays interacts directly highly G+C-rich...
Abstract Oncogenic osteomalacia (OOM) is associated with primitive mesenchymal tumors that secrete phosphaturic factors resulting in low serum concentrations of phosphate and calcitriol, phosphaturia, defective bone mineralization. To identify overexpressed genes these tumors, we compared gene expression profiles resected from patients OOM histologically similar control using serial analysis (SAGE). Three hundred sixty-four were expressed at least twofold greater tumors. A subset 67 highly...
Abstract The molecular signature that defines tumor microvasculature will likely provide clues as to how vascular-dependent proliferation is regulated. Using purified endothelial cells, we generated a database of gene expression changes accompanying vascular in invasive breast cancer. In contrast normal mammary vasculature, cancer vasculature expresses extracellular matrix and surface proteins characteristic proliferating migrating cells. We define validate the up-regulated VE-cadherin...
Rat kidney WT1 cDNAs contain either a thymidine or cytosine residue at position 839. Genomic DNA contains only T839. To explain these results, we propose the transcript undergoes RNA editing in which U839 is converted to C, resulting replacement of leucine 280 by proline. same nucleotide was observed from human testis. In functional assays, WT1-leucine280 polypeptide repressed EGR-1 promoter vitro assays approximately 30% more efficiently than WT1-proline. Edited WT1-C839 mRNA barely...
Increased metabolism is a requirement for tumor cell proliferation. To understand the dependence of cells on fatty acid metabolism, we evaluated various nodes synthesis pathway. Using RNAi have demonstrated that depletion fatty-acid pathway enzymes SCD1, FASN, or ACC1 in HCT116 colon cancer results cytotoxicity reversible by addition exogenous acids. This conditional phenotype most pronounced when SCD1 depleted. We used this rescue strategy to characterize several small-molecule inhibitors...
Abstract Annually, ovarian cancer (OC) affects 240,000 women worldwide and is the most lethal gynecological malignancy. High‐grade serous OC (HGSOC) common aggressive subtype, characterized by widespread genome changes chromosomal instability consequently poorly responsive to chemotherapy treatment. The objective of this study was investigate role microRNA miR‐433 in cellular response cells paclitaxel We show that stable expression A2780 results induction senescence demonstrated...
Breast cancer is the second leading cause of death for women in United States. Of different subtypes, estrogen receptor-negative (ER(-)) tumors, which are ErbB2+ or triple-negative, carry a relatively poor prognosis. In this study, we used system-wide analysis breast proteomes to identify proteins that associated with progression ER(-) tumors. Our two-step approach included an initial deep cultured cells were obtained from tumors defined stages, followed by validation set using human Using...
Breast cancer is a complex heterogeneous disease for which substantial resource of transcriptomic data available. Gene expression have facilitated the division breast into, at least, five molecular subtypes, namely luminal A, B, HER2, normal-like and basal. Once identified, subtypes can inform clinical decisions surrounding patient treatment prognosis. Indeed, it important to identify patients risk developing aggressive so as tailor level intervention. We developed user-friendly, web-based...
Evaluation of the safety new chemicals and pharmaceuticals requires combination information from various sources (e.g. in vitro, silico vivo) to provide an assessment risk human health environment. The authors have identified opportunities maximize predictivity this humans while reducing animal use four key areas; (i) accelerating uptake vitro methods; (ii) incorporating latest science into pharmacology assessments; (iii) optimizing rodent study design biological development (iv)...
Abstract Triple-negative breast cancer (TNBC) patients commonly exhibit poor prognosis and high relapse after treatment, but there remains a lack of biomarkers effective targeted therapies for this disease. Here, we report evidence highlighting the cell-cycle–related kinase CDK7 as driver candidate therapeutic target in TNBC. Using publicly available transcriptomic data from collated set TNBC (n = 383) METABRIC dataset 217), found mRNA levels to be correlated with patient prognosis. High...
The Wilms' tumor suppressor, WT1, is a zinc finger transcriptional regulator which exists as multiple forms owing to alternative mRNA splicing. most abundant splicing variants contain nine-nucleotide insertion encoding lysine, threonine, and serine (KTS) in the H-C link region between third fourth WT1 fingers disrupts binding previously defined WT1-EGR1 site. We have identified WT1[+KTS] sites insulin-like growth factor II gene show that represses transcription from P3 promoter. highest...
Screening for the early detection of colorectal cancer is important to improve patient survival. The aim this study was investigate potential circulating cell-free miRNAs as biomarkers CRC, and their efficiency at delineating patients with polyps benign adenomas from normal groups. expression 667 assessed in a discovery set 48 plasma samples comprising normal, polyp, adenoma, advanced samples. Three (miR-34a, miR-150, miR-923) were further examined validation cohort 97 subjects divided into...
To study the role of microRNA (miRNA) in regulation Chinese hamster ovary (CHO) cell growth, qPCR, microarray and quantitative LC-MS/MS analysis were utilised for simultaneous expression profiling miRNA, mRNA protein. The sample set under investigation consisted clones with variable cellular growth rates derived from same population. In addition to providing a systems level perspective on integration multiple datasets can facilitate identification non-seed miRNA targets, complement...
Abstract Purpose: Here, we describe an integrated bioinformatics, functional analysis, and translational pathology approach to identify novel miRNAs involved in breast cancer progression. Experimental Design: Coinertia analysis (CIA) was used combine a database of predicted miRNA target sites gene expression data. Using two independent cohorts, CIA combined with correspondence between group produce ranked list associated disease Ectopic studies were carried out MCF7 cells evaluated...