A5088946916- Antifungal resistance and susceptibility
- Fungal Infections and Studies
- Antimicrobial Peptides and Activities
- Asthma and respiratory diseases
- Peptidase Inhibition and Analysis
- Respiratory viral infections research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Oral health in cancer treatment
- Oral microbiology and periodontitis research
- Gut microbiota and health
- RNA Research and Splicing
- Immune Response and Inflammation
- Delphi Technique in Research
- Pediatric health and respiratory diseases
- Psoriasis: Treatment and Pathogenesis
- Probiotics and Fermented Foods
- RNA modifications and cancer
- COVID-19 Clinical Research Studies
- RNA and protein synthesis mechanisms
- Long-Term Effects of COVID-19
- SARS-CoV-2 and COVID-19 Research
King's College London
2018-2024
University of Pittsburgh
2022-2024
Candida albicans is a fungal pathobiont, able to cause epithelial cell damage and immune activation. These functions have been attributed its secreted toxin, candidalysin, though the molecular mechanisms are poorly understood. Here, we identify epidermal growth factor receptor (EGFR) as critical component of candidalysin-triggered responses. We find that both C. candidalysin activate human EGFR receptors candidalysin-deficient mutants induce phosphorylation during murine oropharyngeal...
Candida albicans is an opportunistic fungal pathogen responsible for superficial and life-threatening infections in humans. During mucosal infection, C. undergoes a morphological transition from yeast to invasive filamentous hyphae that secrete candidalysin, 31-amino-acid peptide toxin required virulence. Candidalysin damages epithelial cell plasma membranes stimulates the activating protein 1 (AP-1) transcription factor c-Fos (via p38-mitogen-activated kinase [MAPK]), MAPK phosphatase MKP1...
Candidalysin is the first cytolytic peptide toxin identified in any human fungal pathogen. secreted by Candida albicans and critical for driving infection host immune responses several model systems. However,
Protection against microbial infection by the induction of inflammation is a key function IL-1 superfamily, including both classical and new IL-36 cytokine families. Candida albicans frequent human fungal pathogen causing mucosal infections. Although initiators effectors important in protective host responses to C. are well described, players driving these remain poorly defined. Recent work has identified central role played inducing innate Type-17 immune clear Despite this, lack signaling...
Abstract SARS-CoV-2 has caused an estimated 7 million deaths worldwide to date. A secreted accessory protein, known as open reading frame 8 (ORF8), elicits inflammatory pulmonary cytokine responses and is associated with disease severity in COVID-19 patients. Recent reports proposed that ORF8 mediates downstream signals macrophages monocytes through the IL-17 receptor complex (IL-17RA, IL-17RC). However, generally are found be restricted nonhematopoietic compartment, thought due...
Candida albicans (C. albicans) is a dimorphic commensal human fungal pathogen that can cause severe oropharyngeal candidiasis (oral thrush) in susceptible hosts. During invasive infection, C. hyphae invade oral epithelial cells (OECs) and secrete candidalysin, pore-forming cytolytic peptide required for pathogenesis at mucosal surfaces. Candidalysin produced the hyphal invasion pocket triggers cell damage responses OECs. also activates multiple MAPK-based signaling events collectively drive...
Oropharyngeal candidiasis (OPC) is the most common human fungal infection, arising typically from T cell immune impairments. IL-17 and IL-22 contribute individually to OPC responses, but here we demonstrate that combined actions of both cytokines are essential for resistance OPC. Mice lacking IL-17RA IL-22RA1 exhibited high loads in esophagus- intestinal tract, severe weight loss, symptoms colitis. Ultimately, mice succumbed infection. Dual loss IL-22RA impaired expression small proline rich...
Abstract Glucocorticoids (GCs) are one of the most used anti-inflammatory drugs worldwide. Despite their widespread use, our understanding post-transcriptional effects remains poorly understood. The tristetraprolin (TTP) RNA binding protein (RBP) family (ZFP36, ZFP36L1 and ZFP36L2) has been implicated in inflammation regulation via to AU-rich elements (ARE) mRNAs, with TTP being GC modulation. We hypothesised that ZFP36L2 part pathway tested this hypothesis bronchial epithelium, which...
Candida albicans is a ubiquitous fungus in the human gut microbiome as well prevalent cause of opportunistic mucosal and systemic disease. There currently little understanding, however, to how crosstalk between C. host regulates colonization this key niche. Here, we performed expression profiling on ileal colonic tissues germ-free mice colonized with define global response fungus. We reveal that Duox2 Duoxa2 , encoding dual NADPH oxidase activity, are upregulated both ileum colon, induction...
Candida albicans is a fungal pathobiont colonizing mucosal surfaces of the human body, including oral cavity. Under certain predisposing conditions, C. invades tissues activating EGFR-MAPK signalling pathways in epithelial cells via action its peptide toxin candidalysin. However, our knowledge mechanisms involved during colonization rudimentary. Here, we describe role transcription factor early growth response protein 1 (EGR1) (OECs) to albicans. EGR1 expression increases OECs when exposed...
Abstract Candida albicans ( C. ) is a dimorphic human fungal pathogen that can cause severe oropharyngeal candidiasis (OPC, oral thrush) in susceptible hosts. During invasive infection, hyphae invade epithelial cells (OECs) and secrete candidalysin, pore-forming cytolytic peptide required for pathogenesis at mucosal surfaces. Candidalysin induces cell damage activates multiple MAPK-based innate signaling events collectively drive the production of downstream inflammatory mediators. The...
<b>Background:</b> Asthma is the most common chronic inflammatory disease of airways. ~4% patients have severe asthma, which remains uncontrolled despite treatment with steroids. The profile these has been extensively characterised; however, mechanisms underpinning asthma epithelial biology remain poorly understood. <b>Aim:</b> To determine role RNA binding proteins (RBPs) in epithelium integrity and glucocorticoid responses asthma. <b>Results:</b> Employing Frac-seq (subcellular...
Candida albicans is a fungal pathobiont colonising mucosal surfaces of the human body, including oral cavity. Under certain predisposing conditions, C. invades tissues activating EGFR-MAPK signalling pathways in epithelial cells via action its peptide toxin candidalysin. However, our knowledge mechanisms involved during colonisation rudimentary. Here, we describe role transcription factor early growth response protein 1 (EGR1) (OECs) to albicans. EGR1 expression increases OECs when exposed...
<b>Background:</b> Rhinovirus (RV) is the main cause of upper respiratory infections and asthma exacerbations. Patients with severe (SA) have deficient antiviral immunity but underlying mechanisms remain poorly understood. Viral RNA sensing undertaken by helicases such as MDA5 RIG-I, role host factors UPF1, central in decay, <b>Methods:</b> We undertook Frac-seq (subcellular fractionation RNA-sequencing) to compare transcriptional post-transcriptional mRNA expression, qPCR, siRNA, ELISA,...
<b>Background:</b> Common cold (rhinovirus, RV) remain as the major cause of asthma exacerbations. Patients with severe (SA) have interferon impaired responses, but underlying mechanisms unknown. Antiviral responses been mostly investigated transcriptionally, post-transcriptional regulation poorly understood. Nonsense mediated decay (NMD) is an RNA pathway that modulates ~10% transcriptome and other positive strand viruses. <b>Aim:</b> To determine role NMD in RV pathophysiology its possible...
<b>Background:</b> Asthma is the most common chronic inflammatory disease of airways, with ~4% patients requiring maximum therapy including biologics. Glucocorticoids remain as mainstay treatment in asthma, but little known about their genome-wide effects epithelium or post-transcriptional responses. <b>Aim:</b> To determine role RNA binding proteins (RBPs) ZFP36L1 and ZFP36L2 bronchial glucocorticoid responses asthma. <b>Results:</b> Employing Frac-seq (subcellular fractionation RNA-seq)...
<b>Background:</b> Asthma is the most common chronic inflammatory disease of airways. Patients with asthma show interferon-deficient responses to rhinovirus (RV), frequent trigger exacerbations. The mechanisms underlying impaired antiviral immunity are inadequately understood. <b>Aim:</b> To determine role mRNA decay factors in RV pathophysiology and immunity asthma. <b>Methods:</b> We applied Frac-seq (subcellular fractionation RNA-seq) primary bronchial epithelial cells (BECs)...