A5101473409- Virus-based gene therapy research
- CAR-T cell therapy research
- Cytomegalovirus and herpesvirus research
- Viral Infectious Diseases and Gene Expression in Insects
- X-ray Diffraction in Crystallography
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Herpesvirus Infections and Treatments
- Cancer Research and Treatments
- Complement system in diseases
- Crystallization and Solubility Studies
- Blood groups and transfusion
- Platelet Disorders and Treatments
- Nuclear Materials and Properties
- Bacterial Infections and Vaccines
- Immunotherapy and Immune Responses
- Palliative Care and End-of-Life Issues
- Animal Virus Infections Studies
- Greenhouse Technology and Climate Control
- Nuclear materials and radiation effects
- Toxoplasma gondii Research Studies
- Insect symbiosis and bacterial influences
- Pneumonia and Respiratory Infections
- Monoclonal and Polyclonal Antibodies Research
- Antimicrobial Resistance in Staphylococcus
Cardiff University
2015-2024
United Hospice
2023
University of Limerick
2021
Invicro (United Kingdom)
2019-2020
Imperial College London
2020
Hammersmith Hospital
2020
Cancer Genetics (United States)
2019
Institute of Infection and Immunity
2011-2019
National Institutes of Health
2019
University of Calgary
2006
Human cytomegalovirus (HCMV) in clinical material cannot replicate efficiently vitro until it has adapted by mutation. Consequently, wild-type HCMV differ fundamentally from the passaged strains used for research. To generate a genetically intact source of HCMV, we cloned strain Merlin into self-excising BAC. The BAC clone had mutations RL13 gene and UL128 locus that were acquired during limited replication prior to cloning. complete complement was reconstructed reference original sample....
NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both identification characterization...
Human cytomegalovirus (HCMV) extensively modulates host cells, downregulating >900 human proteins during viral replication and degrading ≥133 shortly after infection. The mechanism of degradation most remains unresolved, the functions many are incompletely characterised. We performed a mass spectrometry-based interactome analysis 169 tagged, stably-expressed canonical strain Merlin HCMV proteins, two non-canonical in infected cells. This identified network >3400 virus-host >150 virus-virus...
Adenoviruses are clinically important agents. They cause respiratory distress, gastroenteritis, and epidemic keratoconjunctivitis. As non-enveloped, double-stranded DNA viruses, they easily manipulated, making them popular vectors for therapeutic applications, including vaccines. Species D adenovirus type 26 (HAdV-D26) is both a of EKC other diseases promising vaccine vector. HAdV-D26-derived vaccines under investigation as protective platforms against HIV, Zika, syncytial virus infections...
To examine as randomly possible the role of beta-ketoacyl and acyl carrier protein (ACP) components bacterial type II polyketide synthases (PKSs), homologs chain-length-factor (CLF) genes were cloned from environmental community microorganisms. With PCR primers derived conserved regions known ketosynthase (KSalpha) ACP specifying formation 16- to 24-carbon polyketides, two CLF (KSbeta) unclassified streptomycetes isolated soil, soil DNA without prior isolation parent microorganism. The...
Human cytomegalovirus (HCMV) UL141 induces protection against natural killer cell-mediated cytolysis by downregulating cell surface expression of CD155 (nectin-like molecule 5; poliovirus receptor), a ligand for the activating receptor DNAM-1 (CD226). However, is also recognized to bind second ligand, CD112 (nectin-2). We now show that HCMV targets proteasome-mediated degradation 48 h post-infection, thus removing both ligands from during productive infection. Significantly, and was restored...
Abstract TLR overactivation may lead to end organ damage and serious acute chronic inflammatory conditions. responses must therefore be tightly regulated control disease outcomes. We show in this study the ability of soluble form TLR2 (sTLR2) regulate proinflammatory responses, demonstrate mechanisms underlying sTLR2 regulatory capacity. Cells overexpressing sTLR2, or stimulated presence protein, are hyporesponsive ligands. Regulation was specific, affected NF-κB activation, phagocytosis,...
The human cytomegalovirus (HCMV) US12 family consists of ten sequentially arranged genes (US12-21) with poorly characterized function. We now identify novel natural killer (NK) cell evasion functions for four members: US12, US14, US18 and US20. Using a systematic multiplexed proteomics approach to quantify ~1300 surface ~7200 whole proteins, we demonstrate that the selectively targets plasma membrane proteins plays key roles in regulating NK ligands, adhesion molecules cytokine receptors....
Significance Human cytomegalovirus (HCMV) is the major infectious cause of developmental disorders in babies due to its capacity cross placenta. HCMV also a pathogen transplant recipients and HIV–AIDS patients. Despite inducing strongest immune responses observed for any human pathogen, evades host defenses persists life. Herein, we report another viral stealth strategy. UL148 reduces surface expression key cell adhesion molecule (CD58), impairing ability NK T cells be activated by...
Adenovirus based vectors are of increasing importance for wide ranging therapeutic applications. As vaccines, derived from human adenovirus species D serotypes 26 and 48 (HAdV-D26/48) demonstrating promising efficacy as protective platforms against infectious diseases. Significant clinical progress has been made, yet definitive studies underpinning mechanisms entry, infection, receptor usage currently lacking. Here, we perform structural biological analysis the binding fiber-knob protein...
The RGD-integrin, αvβ6, plays a role in the pathogenesis of pulmonary fibrosis through activation transforming growth factor beta (TGFβ). This study sought to quantify expression αvβ6 lungs healthy humans and subjects with using αvβ6-selective [
Abstract TLR and complement activation ensures efficient clearance of infection. Previous studies documented synergism between TLRs the receptor for pro‐inflammatory peptide C5a (C5aR/CD88), regulation TLR‐induced responses by C5aR, suggesting crosstalk C5aR. However, it is unclear whether how modulate C5a‐induced responses. We demonstrate a marked positive modulatory effect on cell sensitivity to in vitro ex vivo identify an underlying mechanistic target. Pre‐exposure PBMCs whole blood...
Abstract Metastatic pancreatic ductal adenocarcinomas (PDAC) are incurable due to the rapid development of resistance all current therapeutics. Oncolytic adenoviral mutants have emerged as a promising new strategy that negates such resistance. In contrast normal tissue, majority PDACs express αvβ6 integrin receptor. To exploit this feature, we modified our previously reported oncolytic adenovirus, AdΔΔ, selectively target integrins facilitate systemic delivery. Structural modifications AdΔΔ...
Purpose: Virotherapies are maturing in the clinical setting. Adenoviruses (Ad) excellent vectors for manipulability and tolerance of transgenes. Poor tumor selectivity, off-target sequestration, immune inactivation hamper efficacy. We sought to completely redesign Ad5 into a refined, tumor-selective virotherapy targeted αvβ6 integrin, which is expressed range aggressively transformed epithelial cancers but nondetectable healthy tissues.Experimental Design: Ad5NULL-A20 harbors mutations each...
The GacS/GacA two-component regulatory system in pseudomonads regulates genes involved virulence, secondary metabolism and biofilm formation. Despite these functions, some Pseudomonas species are prone to spontaneous inactivating mutations gacA gacS. A gacS(-) strain of aeruginosa PA14 was constructed study the physiological role this sensor histidine kinase. This loss-of-function mutation associated with hypermotility, reduced production acylhomoserine lactones, impaired maturation,...
The effect of rifampin on nasopharyngeal carriage Neisseria meningitidis was studied in a relatively closed population approximately 1,600 military trainees at time when the rate among subpopulations ranged between 43% and 86%. Cultures were taken from volunteers who immediately started drug regimen 600 mg daily for four days; no side reactions observed. one two weeks after treatment, again men left camp. meningococcal reduced 65.1% just before treatment to 10.1% days treatment. This...
Oncolytic virotherapies based on adenovirus 5 (Ad5) hold promise as adjunctive cancer therapies; however, their efficacy when delivered systemically is hampered by poor target cell specificity and preexisting anti-Ad5 immunity. Ovarian represents a promising for virotherapy, since the virus can be locally into peritoneal cavity. Both epidermal growth factor receptor (EGFR) fibroblast 1 (FGFR1) are overexpressed in majority of human tumors, including ovarian cancer. To generate adenoviral...
// Hanni Uusi-Kerttula 1 , James Davies Lynda Coughlan 2 Sarah Hulin-Curtis Rachel Jones 3 Louise Hanna John D. Chester 1, Alan L. Parker Department of Cancer and Genetics, School Medicine, Cardiff University, CF14 4XN, UK Nuffield The Jenner Institute, University Oxford, Oxford OX3 7DQ, Velindre Centre, 2TL, Correspondence to: Parker, e-mail: parkeral@cardiff.ac.uk Keywords: adenovirus, re-targeting, neutralizing antibody, ovarian cancer, αvβ6 integrin Received: February 05,...
Glioblastoma (GBM) is the most common and aggressive adult brain cancer with an average survival rate of around 15 months in patients receiving standard treatment. Oncolytic adenovirus expressing therapeutic transgenes represent a promising alternative treatment for GBM. Of many human adenoviral serotypes described to date, 5 (HAdV-C5) has been utilised clinically experimentally. However, use Ad5 as anti-cancer agent may be hampered by naturally high seroprevalence rates HAdV-C5 coupled...