Pauline M Rudd

Pauline M Rudd
University College Dublin | UCD · National Institute for Bioprocessing Research and Training

About

551
Publications
105,867
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
34,306
Citations
Citations since 2016
130 Research Items
14807 Citations
201620172018201920202021202205001,0001,5002,0002,500
201620172018201920202021202205001,0001,5002,0002,500
201620172018201920202021202205001,0001,5002,0002,500
201620172018201920202021202205001,0001,5002,0002,500

Publications

Publications (551)
Article
Full-text available
Traumatic spinal cord injury (SCI) results in disruption of tissue integrity and loss of function. We hypothesize that glycosylation has a role in determining the occurrence of regeneration and that biomaterial treatment can influence this glycosylation response. We investigated the glycosylation response to spinal cord transection in Xenopus laevi...
Article
The Minimum Information Required for a Glycomics Experiment (MIRAGE) is an initiative to standardize the reporting of glycoanalytical methods and to assess their reproducibility. To date, the MIRAGE Commission has published several reporting guidelines that describe what information should be provided for sample preparation methods, mass spectromet...
Article
Intravenous immunoglobulin (IVIG) is used as an immunomodulatory agent in the treatment of various autoimmune/inflammatory diseases although its mechanism of action remains elusive. Recently, nonfucosylated IgG has been shown to be preferentially bound to Fcγ receptor IIIa (FcγRIIIa) on circulating natural killer cells; therefore, we hypothesized t...
Chapter
GlycoStore (http://www.glycostore.org) is an open access chromatographic and electrophoretic retention database of glycans characterized from glycoproteins, glycolipids, and biotherapeutics. It is a continuation of the GlycoBase project (Oxford Glycobiology Institute and National Institute for Bioprocessing Research and Training, Ireland) but addre...
Article
Full-text available
Background Glycosylation, one of the most fundamental post-translational modifications, is altered in cancer and is subject in part, to epigenetic regulation. As there are many epigenetic-targeted therapies currently in clinical trials for the treatment of a variety of cancers, it is important to understand the impact epi-therapeutics have on glyco...
Chapter
Glycosylation is important in biology, contributing to both protein conformation and function. Structurally, glycosylation is complex and diverse. This complexity is reflected in the topology, composition, monosaccharide linkages, and isomerism of each oligosaccharide. Glycoanalytics is a discipline that addresses the understanding and characteriza...
Chapter
Therapeutic monoclonal antibodies (mAbs) are mostly of the IgG class and constitute highly efficacious biopharmaceuticals for a wide range of clinical indications. Full-length IgG mAbs are large proteins that are subject to multiple posttranslational modifications (PTMs) during biosynthesis, purification, or storage, resulting in micro-heterogeneit...
Chapter
The complex diantennary-type oligosaccharides at Asn297 residues of the IgG heavy chains have a profound impact on the safety and efficacy of therapeutic IgG monoclonal antibodies (mAbs). Fc glycosylation of a mAb is an established critical quality attribute (CQA), and its oligosaccharide profile is required to be thoroughly characterized by state-...
Article
Full-text available
Study question Could glycosylation changes on serum and/or urine glycoproteins be suitable biomarkers for the non-invasive diagnosis of endometriosis? Summary answer The glycosylation pattern on serum and urine glycoproteins differed significantly in endometriosis patients compared to controls, suggesting a novel role as biomarkers of the disease....
Article
Full-text available
O-Glycosylation changes in misfolded proteins are of particular interest in understanding neurodegenerative conditions such as Parkinson’s disease (PD) and incidental Lewy body disease (ILBD). This work outlines optimizations of a microwave-assisted nonreductive release to limit glycan degradation and employs this methodology to analyze O-glycosyla...
Article
Full-text available
Therapeutic-induced-senescent (TIS) Cal51 TNBC cells display differential N -glycan moieties compared to non-senescent cells, depending on cellular location and EV progeny.
Article
Full-text available
The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular...
Article
High-throughput glycan analysis has become an important part of biopharmaceutical production and quality control. However, it is still a significant challenge in the field of glycomics to easily deduce isomeric glycan structures, especially in a high-throughput manner. Ion mobility spectrometry (IMS) is an excellent tool for differentiating isomeri...
Article
Full-text available
The accurate assessment of antibody glycosylation during bioprocessing requires the high-throughput generation of large amounts of glycomics data. This allows bioprocess engineers to identify critical process parameters that control the glycosylation critical quality attributes. The advances made in protocols for capillary electrophoresis-laser-ind...
Article
N--glycan alterations in the nervous system can result in different neuropathological symptoms like mental retardation, seizures and epilepsy. Studies have reported the characterization of N-glycans in rodent brains but there is a lack of spatial resolution as either the tissue samples were homogenized or specific proteins were selected for analysi...
Article
Full-text available
Background: Glycosylation is one of the most fundamental post-translational modifications. Importantly, glycosylation is altered in many cancers. These alterations have been proven to impact on tumor progression and to promote tumor cell survival. From the literature, it is known that there is a clear link between chemoresistance and hypoxia, hypox...
Preprint
High resolution glycan analysis has become an important part of biopharmaceutical API production and quality control. Liquid chromatography (LC) is now a well-established technique in this field but the resolution of similar isomeric glycan structures is still a challenge. Here we show that the addition of ion mobility spectroscopy (IMS) in a hyphe...
Article
Full-text available
Anti-D immunoglobulin (Anti-D Ig) prophylaxis prevents haemolytic disease of the fetus and newborn. Monoclonal IgG anti-Ds (mAb-Ds) would enable unlimited supplies but have differed in efficacy in FcγRIIIa-mediated ADCC assays and clinical trials. Structural variations of the oligosaccharide chains of mAb-Ds are hypothesised to be responsible. Quan...
Article
Full-text available
The mass spectrometry (MS)-based analysis of free polysaccharides and glycans released from proteins, lipids and proteoglycans increasingly relies on databases and software. Here, we review progress in the bioinformatics analysis of protein-released N- and O-linked glycans (N- and O-glycomics) and propose an e-infrastructure to overcome current def...
Article
Full-text available
Glycosylation is a topic of intense current interest in the development of biopharmaceuticals since it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy‑six laboratories from industry, universit...
Article
Sialic acids are cell surface sugars present in many animal glycoproteins and are of particular interest in biopharmaceuticals, where lack of sialylation can reduce bioactivity. Here we describe how α-2,6-sialyltransferase from Photobacterium damselae can be used to markedly increase sialylation of CHO produced alpha-1-antitrypsin. Detailed analysi...
Article
Full-text available
IgG Fc glycans were characterized in 225 healthy children and 40 children with unexplained recurrent respiratory infections, revealing age-dependent variation and suggesting a role for IgG glycosylation in immunocompetence.
Article
Full-text available
The direct association of the genome, transcriptome, metabolome, lipidome and proteome with the serum glycome has revealed systems of interconnected cellular pathways. The exact roles of individual glycoproteomes in the context of disease have yet to be elucidated. In a move towards personalized medicine, it is now becoming critical to understand d...
Article
Glycan head-groups attached to glycosphingolipids (GSLs) found in the cell membrane bilayer can alter in response to external stimuli and disease, making them potential markers and/or targets for cellular disease states. To identify such markers, comprehensive analyses of glycan structures must be undertaken. Conventional analyses of fluorescently...
Preprint
Sialic acids are cell surface sugars present in many animal glycoproteins and are of particular interest in biopharmaceuticals, where lack of sialylation can reduce bioactivity. Here we describe how α-2,6-sialyltransferase from Photobacterium Damselae can be used to markedly increase sialylation of CHO produced alpha-1-antitrypsin. Detailed analysi...
Article
The leading proteomic method for identifying N-glycosylated peptides is liquid chromatography coupled with tandem fragmentation mass spectrometry (LCMS/MS) followed by spectral matching of MS/MS fragment masses to a database of possible glycan and peptide combinations. Such database-dependent approaches come with challenges such as needing high qua...
Article
Full-text available
Background: The sequelae of Kawasaki disease (KD) vary widely with the greatest risk for future cardiovascular events among those who develop giant coronary artery aneurysms (CAA). We sought to define the molecular signature associated with different outcomes in pediatric and adult KD patients. Methods: Molecular profiling was conducted using ma...
Article
Alpha-1 antitrypsin (AAT) is an acute phase protein that possesses immune-regulatory and anti-inflammatory functions independent of antiprotease activity. AAT deficiency (AATD) is associated with early-onset emphysema and chronic obstructive pulmonary disease. Of interest are the AATD nonsense mutations (termed null or Q0), the majority of which ar...
Article
Full-text available
Many eukaryotic proteins are modified by N-glycans. Liquid chromatography (ultra-performance -UPLC and high-performance-HPLC) coupled with mass spectrometry (MS) is conventionally used to characterize N-glycan structures. Software can automatically assign glycan structures by matching their observed retention times and masses with standardized valu...
Article
The Minimum Information Required for A Glycomics Experiment (MIRAGE) is an initiative created by experts in the fields of glycobiology, glycoanalytics and glycoinformatics to design guidelines that improve the reporting and reproducibility of glycoanalytical methods. Previously, the MIRAGE Commission has published guidelines for describing sample p...
Article
Full-text available
N-Glycosylation is a fundamentally important protein modification with a major impact on glycoprotein characteristics such as serum half-life and receptor interaction. More than half of the proteins in human serum are glycosylated, and the relative abundances of protein glycoforms often reflect alterations in health and disease. Several analytical...
Data
Equation S1. Model equation to estimate the probability of indolent, significant and aggressive disease for each patient. Fig. S1. Heatmaps for indolent, significant and aggressive disease type. Fig. S2. Alternate layout of Fig. 1 information. Table S1. Summary statistics for full Clinical Cohort. Table S2. Cross tabulation of the known indolen...
Preprint
Full-text available
Glycomics targets released glycans from proteins, lipids and proteoglycans. High throughput glycomics is based on mass spectrometry (MS) that increasingly depends on exchange of data with databases and the use of software. This requires an agreed format for accurately recording of experiments, developing consistent storage modules and granting publ...
Article
Full-text available
Many eukaryotic proteins are modified by N-glycans. Liquid chromatography (ultra-performance -UPLC and high-performance - HPLC) coupled with mass spectrometry (MS) is conventionally used to characterize N-glycan structures. Software can automatically assign glycan structures by matching their observed retention times and masses with standardized va...
Article
Full-text available
Glycosylation, one of the most fundamental post-translational modifications, is altered in many cancers. These alterations have been proven to impact on the progression of the tumor cell and promote survival. In literature published over the last half century, it is obvious there is a clear link between (a) chemo-resistance and hypoxia (b) hypoxia...
Article
Full-text available
Exoglycosidases are often used for detailed characterization of glycan structures. Bovine kidney α-fucosidase is commonly used to determine the presence of core α1-6 fucose on N-glycans, an important modification of glycoproteins. Recently, several studies have reported that removal of core α1-6-linked fucose from N-glycans labeled with the reactiv...
Article
Full-text available
Aberrant glycosylation has been associated with a number of diseases including cancer. Our aim was to elucidate changes in whole plasma N-glycosylation between colorectal cancer (CRC) cases and controls in one of the largest cohorts of its kind. A set of 633 CRC patients and 478 age and gender matched controls was analysed. Additionally, patients w...
Data
Table S3. Glycan peaks and corresponding N‐glycan features.
Data
Fig. S3. The segregation of MDG BC cancer and normal serum based on the level of five N‐glycans groups exhibited differential abundance across TIF, NIF and matched serum.
Data
Table S1. The biopsies with ≥ 1% of the invasive cancer cells positively stained for ER‐ and PgR were classified as positive.
Data
Table S4. N‐glycans identified as differentially abundant between samples with high and low tumor TILs. N‐glycans are reported with associated log fold changes and adjusted P‐values.
Data
Fig. S1. The representative images of TILs distribution within a single tumor biopsy based on the IHC analysis.
Data
Fig. S2. Cox proportional‐hazard regression with known cause of death.
Data
Table S2. Complete characteristics of 85 breast cancer patients enrolled in the study.
Data
Table S5. N‐glycans with significantly correlated abundances between paired TIF and serum samples. N‐glycans are reported with associated pearsons correlation score and adjusted P‐value.
Article
Full-text available
Introduction: Classifying indolent prostate cancer represents a significant clinical challenge. We investigated whether integrating data from different omic platforms could identify a biomarker panel with improved performance compared to individual platforms alone. Methods: DNA methylation, transcripts, protein, and glycosylation biomarkers were...
Conference Paper
Full-text available
Introduction Glycosylation is epigenetically regulated and is a fundamental post-translational modification altered in cancer. These alterations impact on tumour progression, and promote tumour survival. In the literature, there is a clear link between chemoresistance and hypoxia, hypoxia and epigenetics and more recently glycosylation and epigenet...
Article
Full-text available
Particular N‐glycan structures are known to be associated with breast malignancies by coordinating various regulatory events within the tumor and corresponding microenvironment, thus implying that N‐glycan patterns may be used for cancer stratification and as predictive or prognostic biomarkers. However, the association between N‐glycans secreted b...
Article
GlycoStore is a curated chromatographic, electrophoretic and mass-spectrometry composition database of N-, O-, glycosphingolipid (GSL) glycans and free oligosaccharides associated with a range of glycoproteins, glycolipids and biotherapeutics. The database is built on publicly available experimental data sets from GlycoBase developed in the Oxford...
Article
Ion mobility mass spectrometry (IM-MS) holds great potential for structural glycobiology, in particular in its ability to resolve glycan isomers. Generally, IM-MS has largely been applied to intact glycoconjugate ions with reports focusing on the separation of different adduct types. Here, we explore IM separation and report the collision cross sec...
Article
Full-text available
Afamin is an 87 kDa glycoprotein with five predicted N-glycosylation sites. Afamin’s glycan abundance contributes to conformational and chemical inhomogeneity presenting great challenges for molecular structure determination. For the purpose of studying the structure of afamin, various forms of recombinantly expressed human afamin (rhAFM) with diff...
Article
Full-text available
BACKGROUND: Classical galactosaemia (OMIM 230400) is a rare disorder of carbohydrate metabolism caused by deficiency of the galactose-1-phosphate uridyltransferase enzyme. The pathophysiology of the long-term complications, mainly cognitive, neurological and female fertility problems, remains poorly understood. Current clinical methods of biochemic...
Article
Background -Heart failure (HF) is a leading cause of mortality and morbidity, and the search for novel therapeutic approaches continues. In the monogenic disease mucopolysaccharidosis (MPS) VI, loss of function mutations in arylsulfatase B (ASB) leads to myocardial accumulation of chondroitin sulfate (CS) glycosaminoglycans (GAGs), manifesting as a...
Article
Robust plate based antibody glycan analysis platforms are urgently needed for biopharmaceutical development and manufacturing as well as for clinical biomarker research. A 96-well plate based workflow has been developed to analyze both intact IgG antibodies and released N-glycans using an Orbitrap Fusion Mass Spectrometer and an LC/MS method on the...
Article
Full-text available
"N-Glycan sequencing of the released PSA N-glycans showed that the unbound fraction contained mainly monosialylated glycans and a few disialylated glycans that were digested to neutral structures with a specific a2,3-sialidase (NAN1) treatment (Figure 4B, middle panel)". should be modified to be: ""N-Glycan sequencing of the released PSA N-glycans...
Article
Full-text available
Introduction: Glycosylation is recognized as a Critical Quality Attribute for therapeutic glycoproteins such as monoclonal antibodies, fusion proteins and therapeutic replacement enzymes. Hence, efficient and quantitative glycan analysis techniques have been increasingly important for their discovery, development and quality control. The aim of thi...