- Ear Surgery and Otitis Media
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Tuberculosis Research and Epidemiology
- Ear and Head Tumors
- Congenital Ear and Nasal Anomalies
- Sinusitis and nasal conditions
- CAR-T cell therapy research
- Nasal Surgery and Airway Studies
- Immunotherapy and Immune Responses
- Infectious Diseases and Tuberculosis
- Head and Neck Anomalies
- Vestibular and auditory disorders
- Otitis Media and Relapsing Polychondritis
- Immune Response and Inflammation
- Tracheal and airway disorders
- Mycobacterium research and diagnosis
- Cystic Fibrosis Research Advances
- Cleft Lip and Palate Research
- vaccines and immunoinformatics approaches
- Asthma and respiratory diseases
- Immunodeficiency and Autoimmune Disorders
- Respiratory viral infections research
- Respiratory and Cough-Related Research
- Swearing, Euphemism, Multilingualism
University of Southampton
2013-2024
NIHR Southampton Biomedical Research Centre
2019-2024
Centre for Life
2024
Nottingham University Hospitals NHS Trust
2019-2023
Nottingham City Hospital
1995-2023
Desert Research Center
2021
Thermo Fisher Scientific (United States)
2020
Canadian Institute of Mining, Metallurgy and Petroleum
2020
Lebanese University
2005-2019
Zagazig University
2010-2018
Campomelic dysplasia (CMD) is a rare skeletal disorder that usually lethal. It characterised by bowing of the lower limbs, severe respiratory distress, and many chromosomal (XY) males show sex reversal. Because number reports familial campomelic it considered to be inherited in an autosomal recessive manner. In this study, details 36 patients with were collected from genetic centres, radiologists, pathologists United Kingdom. The ratio was approximately 1:1. There preponderance phenotypic...
Previously, we developed a 3-dimensional cell culture model of human tuberculosis (TB) and demonstrated its potential to interrogate the host-pathogen interaction (Tezera et al., 2017a). Here, use investigate mechanisms whereby immune checkpoint therapy for cancer paradoxically activates TB infection. In patients, PD-1 is expressed in Mycobacterium (Mtb)-infected lung tissue but absent areas immunopathology. microsphere model, ligands are up-regulated by infection, PD-1/PD-L1 axis further...
KIR2DS2, an activating natural killer cell receptor, recognizes conserved peptides derived from the RNA helicases of pathogenic flaviviruses.
Cell biology differs between traditional cell culture and 3-dimensional (3-D) systems, is modulated by the extracellular matrix. Experimentation in 3-D presents challenges, especially with virulent pathogens. Mycobacterium tuberculosis (Mtb) kills more humans than any other infection characterised a spatially organised immune response matrix remodelling. We developed system incorporating mycobacteria, primary human blood mononuclear cells collagen-alginate to dissect host-pathogen...
BACKGROUNDNovel biomarkers to identify infectious patients transmitting Mycobacterium tuberculosis are urgently needed control the global (TB) pandemic. We hypothesized that proteins released into plasma in active pulmonary TB clinically useful distinguish cases from healthy individuals and with other respiratory infections.METHODSWe applied a highly sensitive non-depletion tandem mass spectrometry discovery approach investigate protein expression compared controls South African Peruvian...
Significance Tuberculosis is a major global pandemic responsible for more deaths than any other infectious disease, yet no effective vaccine exists. Here, we demonstrate CD1b expression within human tuberculous granulomas, supporting role lipid antigen presentation in host immunity to infection. presents mycolates, the dominant Mycobacterium tuberculosis (Mtb) cell wall class and key virulence factors, αβ T cells. We reveal that mycolate tail moieties, distal head group, are antigenic...
Significance T cells autoreactive to cluster of differentiation 1c (CD1c) are abundant in human blood but lipid antigens recognized by these remained poorly understood. A new 2.4-Å structure CD1c and computational simulations thereof indicated substantial conformational plasticity with ligand-induced formation an F′ roof G′ portal, as well the potential present acylated sterols. Confirming predictions we demonstrated loading biophysical interaction CD1c–lipid complexes self-reactive T-cell...
To develop a radiologic classification of severity round window involvement in otosclerosis and describe the impact each class on hearing outcome stapes surgery.Retrospective chart review with computed tomographic scans.Hospital private otolaryngology clinics.We reviewed scans 930 ears clinical otosclerosis; 121 (13%) had involvement, no pericochlear 41 these-the primary subjects study. A control group consisted 15 stapedial otosclerosis.Round was classified into 5 groups from isolated edge...
Abstract Invariant NKT cells (iNKT) are potent immunoregulatory T that recognize CD1d via a semi-invariant TCR (iNKT-TCR). Despite the knowledge of defective iNKT pool in several autoimmune conditions, including rheumatoid arthritis (RA), clear understanding intrinsic mechanisms, qualitative and structural changes human repertoire at earlier stages disease, is lacking. In this study, we compared structure function early RA patients with age- gender-matched controls. We analyzed phenotype ex...
Isoglobotrihexosylceramide (iGb3) has been identified as a potent CD1d-presented self-antigen for mouse invariant natural killer T (iNKT) cells. The role of iGb3 in humans remains unresolved, however, there have conflicting reports about iGb3-dependent human iNKT-cell activation, and lack synthase, key enzyme synthesis. Given the importance immune responses, we conducted human-mouse cross-species analysis activation by iGb3-CD1d. Here show that iNKT cells were both able to recognise...
Tuberculosis is unfortunately once again killing more people than any other infection.Despite global biomedical and public health efforts, standard interventions to control the pandemic have not advanced in most resource-poor settings, contrast diseases such as malaria HIV infection.The authors propose that reconsidering concepts of optimal host immune response Mycobacterium tuberculosis required develop a paradigm will inform novel interventions.The development active associated with cancer...
Abstract Mycobacterium tuberculosis (Mtb) is one of the most successful human pathogens. Several cytokines are known to increase virulence bacterial pathogens, leading us investigate whether Interferon-γ (IFN-γ), a central regulator immune defense against Mtb , has direct effect on bacteria. We found that recombinant and T-cell derived IFN-γ rapidly induced dose-dependent in oxygen consumption rate (OCR) consistent with increased respiration. This was not observed attenuated Bacillus...
XPO1 (Exportin-1/CRM1) is a nuclear export protein that frequently overexpressed in cancer and functions as driver of oncogenesis. Currently small molecules target are being used the clinic anticancer agents. We identify for natural killer (NK) cells. Using immunopeptidomics, we have identified peptide derived from can be recognized by activating NK cell receptor KIR2DS2 context human leukocyte antigen–C. The endogenously processed presented to activate cells specifically through this...
Abstract Invariant NKT (iNKT) cells in healthy people express iNKT-TCRs with widely varying affinities for CD1d, suggesting different roles high- and low-affinity iNKT clones immune regulation. However, the functional implications of this heterogeneity have not yet been determined. Functionally aberrant responses previously demonstrated autoimmune diseases, including human type 1 diabetes, but their relationship to changes clonal repertoire addressed. In study, we directly compared recent...