A5014633387- Immune Response and Inflammation
- Immune Cell Function and Interaction
- interferon and immune responses
- Viral-associated cancers and disorders
- Cytomegalovirus and herpesvirus research
- Cytokine Signaling Pathways and Interactions
- NF-κB Signaling Pathways
- Herpesvirus Infections and Treatments
- Neuroblastoma Research and Treatments
- T-cell and B-cell Immunology
- Influenza Virus Research Studies
- Glycosylation and Glycoproteins Research
- Neuroscience and Neuropharmacology Research
- Polyamine Metabolism and Applications
- Neurogenesis and neuroplasticity mechanisms
- Microbial Metabolism and Applications
- T-cell and Retrovirus Studies
- Cancer, Hypoxia, and Metabolism
- Pharmacological Effects of Natural Compounds
- CAR-T cell therapy research
- Cannabis and Cannabinoid Research
- RNA Interference and Gene Delivery
- Pancreatic function and diabetes
- Respiratory viral infections research
- Inflammasome and immune disorders
Trinity College Dublin
2008-2022
Pfizer (United States)
2021
Park University
2011
Cardiff University
2005
Leiden University Medical Center
2005
University of Wales
2002-2005
Abstract The mammalian target of rapamycin complex 1 (mTORC1) is a key regulator cellular metabolism and also has fundamental roles in controlling immune responses. Emerging evidence suggests that these two functions mTORC1 are integrally linked. However, little known regarding function the NK cells, lymphocytes play antiviral antitumor immunity. This study investigated hypothesis mTORC1-controlled underpins normal cell proinflammatory function. We demonstrate robustly stimulated cells...
Abstract Human NK cells can be classified into phenotypically and functionally distinct subsets based on levels of CD56 receptor. CD56dim are generally considered more cytotoxic, whereas the CD56bright potent producers IFN-γ. In this study, we define metabolic changes that occur in peripheral blood response to cytokine. Metabolic analysis showed upregulate glycolysis oxidative phosphorylation either IL-2 or IL-12/15 cytokine combinations. Despite fact both these combinations robustly...
Toll-like receptor (TLR) signaling is known to involve interleukin-1 receptor-associated kinases (IRAKs), however the particular role of IRAK-2 has remained unclear. Further, although IRAK-1 was originally thought be central for TLR-NFkappaB axis, recent data have shown that it dispensable NFkappaB activation some TLRs and demonstrated an alternative in interferon regulatory factor activation. Here we show critical TLR-mediated pathway. The poxviral TLR antagonist A52 inhibited by TLR2, -3,...
Abstract: Pigs were treated with N 2 O which is known to impair vitamin B 12 function in vivo. Such pigs demonstrated an inability gain weight, progressive ataxia, and spinal neuropathy. The ataxia was totally the neuropathy partially preventable by dietary methionine supplementation. Methionine synthase activity inhibited both liver brain. There a marked elevation of S ‐adenosylhomocysteine neural tissues concomitant failure ‐adenosylmethionine rise thus maintain methylation ratio, except...
ABSTRACT Epstein-Barr virus (EBV) resides as a persistent infection in human leukocyte antigen (HLA) class II + B lymphocytes and is associated with number of malignancies. The EBV lytic-phase protein gp42 serves at least two functions: acts the coreceptor for viral entry into cells hampers T-cell recognition via HLA molecules through steric hindrance receptor-class II-peptide interactions. Here, we show that associates their various stages maturation, including immature αβIi heterotrimers...
Human herpesviruses utilize an impressive range of strategies to evade the immune system during their lytic replicative cycle, including reducing expression cell surface major histocompatibility complex (MHC) and immunostimulatory molecules required for recognition lysis by virus-specific cytotoxic T cells. Study possible evasion Epstein-Barr virus (EBV) in lytically infected cells has been hampered lack appropriate permissive culture model. Using two-color immunofluorescence staining...
Human herpesviruses, including EBV, persist for life in infected individuals. During the lytic replicative cycle that is required production of infectious virus and transmission to another host, many viral Ags are expressed. Especially at this stage, immune evasion strategies likely be advantageous avoid elimination virus-producing cells. However, little known about escape during productive EBV infection because no fully permissive model available. In study, we have developed a novel...
Epstein-Barr virus (EBV) is a potent growth-transforming agent of human B cells. It has previously been shown that viral latent membrane protein 1 (LMP1) essential for EBV-induced transformation normal cells and contributes to maintenance latency in vitro. Using the EBV-positive Burkitt's lymphoma line P3HR1-c16, which lacks LMP1 during can readily be activated into virus-productive lytic cycle, we found inhibits cycle induction via transcription factor NF-kappa B. In addition, progress two...
Toll-like receptors (TLRs) are pattern-recognition that recognize microbial ligands and subsequently trigger intracellular signaling pathways involving transcription factors such as NFκB MAPKs p38. TLR can regulate both transcriptional post-transcriptional events leading to altered gene expression thus appropriate immune responses. The interleukin-1 receptor-associated kinase (IRAK) family comprises four kinases signaling. However, the role of IRAK-2 has remained unclear, especially in human...
Host pattern recognition receptors (PRRs) such as Toll-like (TLRs) detect viruses and other pathogens, inducing production of cytokines that cause inflammation mobilize cells to control infection. Vaccinia virus (VACV) encodes proteins antagonize these host innate immune responses, elucidating the mechanisms action viral helped shed light on PRR signaling mechanisms. The VACV virulence factor E3 is one most intensely studied has multiple effects cells, many which cannot be explained by...
Abstract Neuroblastoma is the most common extra‐cranial solid tumour in children. Natural killer ( NK ) cells are innate lymphocytes that known to mediate direct cytotoxicity of neuroblastoma cells. variation highly polymorphic immunoglobulin‐like receptors KIR and their cognate human leukocyte antigen HLA class I ligands results considerable diversity cell function. As early onset suggests contribution genetic factors, we investigated if individual genes, combined gene haplotypes or...
We report here the discovery and optimization of a novel T cell retargeting anti-GUCY2C x anti-CD3ε bispecific antibody for treatment solid tumors. Using combination hybridoma, phage display rational design protein engineering, we have developed fully humanized manufacturable CD3 that demonstrates favorable pharmacokinetic properties potent in vivo efficacy. Anti-GUCY2C antibodies derived from mouse hybridomas were first into well-behaved human variable region frameworks with full retention...
High risk neuroblastoma is responsible for 15% of deaths in pediatric cancer patients. The introduction anti-GD2 immunotherapy has significantly improved outcomes but there still only approximately a 50% 5 year event-free-survival these children and improvements treatments are urgently required. Anti-GD2 uses the patients' own immune system to kill cells. In particular, Natural Killer (NK) cells antibody coated tumor by process called dependent cellular cytotoxicity (ADCC). However, our...