A5082507956- Inflammatory Bowel Disease
- IL-33, ST2, and ILC Pathways
- Microscopic Colitis
- Psoriasis: Treatment and Pathogenesis
- Immune Response and Inflammation
- Parasites and Host Interactions
- Computational Drug Discovery Methods
- Whipple's Disease and Interleukins
- Parasite Biology and Host Interactions
- Cytokine Signaling Pathways and Interactions
- Eosinophilic Esophagitis
- Tuberculosis Research and Epidemiology
- Microbial Natural Products and Biosynthesis
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Hemoglobinopathies and Related Disorders
- Allergic Rhinitis and Sensitization
- Mosquito-borne diseases and control
- Malaria Research and Control
- Gene Regulatory Network Analysis
- Mycobacterium research and diagnosis
- Protein Structure and Dynamics
- Sepsis Diagnosis and Treatment
- Biofuel production and bioconversion
- Infectious Diseases and Tuberculosis
Guy's and St Thomas' NHS Foundation Trust
2018-2025
King's College London
2018-2025
National Institute for Health Research
2017-2025
University of Southampton
2024-2025
Superior University
2024
University of Sargodha
2024
Southampton General Hospital
2024
Cancer Research UK
2024
National Health Service
2018-2022
Guy's Hospital
2018-2022
Abstract Biomphalaria snails are instrumental in transmission of the human blood fluke Schistosoma mansoni . With World Health Organization's goal to eliminate schistosomiasis as a global health problem by 2025, there is now renewed emphasis on snail control. Here, we characterize genome glabrata, lophotrochozoan protostome, and provide timely important information biology. We describe aspects phero-perception, stress responses, immune function regulation gene expression that support...
Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 123), non-COVID-19 ICU sepsis 25) and healthy controls 30). Severe acute respiratory syndrome 2 (SARS-CoV-2) RNA was detected plasma or serum (RNAemia) of when neutralizing antibody response low. RNAemia is associated higher 28-day mortality (hazard ratio [HR], 1.84 [95% CI, 1.22-2.77] adjusted for...
The function of interleukin-22 (IL-22) in intestinal barrier homeostasis remains controversial. Here, we map the transcriptional landscape regulated by IL-22 human colonic epithelial organoids and evaluate biological, functional clinical significance mediated pathways ulcerative colitis (UC). We show that pro-inflammatory are involved microbial recognition, cancer immune cell chemotaxis; most prominently those involving CXCR2
Penetration of skin, migration through tissues and establishment long-lived intravascular partners require Schistosoma parasites to successfully manipulate definitive host defences. While previous studies larval schistosomula have postulated a function for excreted/secreted (E/S) products in initiating these host-modulatory events, the role extracellular vesicles (EVs) has yet be considered. Here, using preparatory ultracentrifugation as well methodologies globally analyse both proteins...
Abstract Three CYP6Z genes are linked to a major pyrethroid resistance locus in the mosquito Anopheles gambiae . We have expressed CYP6Z2 Escherichia coli and produced structural model order examine its role detoxification. E. membranes co‐expressing An. P450 reductase (AgCPR) catalysed dealkylation of benzyloxyresorufin with kinetic parameters K m = 0.13 µM; cat 1.5 min ‐1 The IC 50 values wide range compounds were measured. Pyrethroids cypermethrin permethrin low values, but not...
BackgroundBlood transcriptomic signatures for diagnosis of tuberculosis have shown promise in case-control studies, but none been prospectively designed or validated adults presenting with the full clinical spectrum suspected tuberculosis, including extrapulmonary and common differential diagnoses that clinically resemble tuberculosis. We aimed to evaluate diagnostic accuracy patients routine practice.MethodsThe Validation New Technologies Diagnostic Evaluation Tuberculosis (VANTDET) study...
Background The debilitating human disease schistosomiasis is caused by infection with schistosome parasites that maintain a complex lifecycle alternating between definitive (human) and intermediate (snail) hosts. While much known about how the host responds to infection, there comparably less information available describing snail's response infection. Methodology/Principle findings Here, using recently revealed sequencing of Biomphalaria glabrata genome, we provide evidence predicted core...
Recently acquired and remotely latent Mycobacterium tuberculosis infection (LTBI) are clinically indistinguishable, yet recent acquisition of is the greatest risk factor for progression to in immunocompetent individuals. We aimed evaluate ability cellular immune signatures that differ between active LTBI distinguish recently from LTBI.Fifty-nine individuals were recruited: 20 had tuberculosis, 19 LTBI, LTBI. The proportion mycobacteria-specific CD4+ T cells secreting tumor necrosis α (TNF-α)...
Interactions between the epithelium and immune system are critical in pathogenesis of inflammatory bowel disease (IBD). In this study, we mapped transcriptional landscape human colonic epithelial organoids response to different cytokines responsible for mediating canonical mucosal responses. By profiling transcriptome treated with interferon gamma, interleukin-13, -17A, tumor necrosis factor alpha next-generation sequencing, unveil shared distinct regulation patterns function by cytokines....
Organoid-based models of murine and human innate lymphoid cell precursor (ILCP) maturation are presented. First, intestinal pulmonary organoids harnessed to demonstrate that the epithelial niche is sufficient drive tissue-specific all (ILC) groups in parallel, without requiring subset-specific cytokine supplementation. Then, more complex induced pluripotent stem (hiPSC)-based gut lung organoid used cells recapitulate ILC from a stringent systemic ILCP population, but only when...
Pancreatic ductal adenocarcinoma (PDAC) is insidious, with only 15-20% of those diagnosed suitable for surgical resection as it either too advanced and has invaded local structures or already spread to distant sites. The associated tumor microenvironment provides a protective shield which limits the efficacy chemotherapeutic agents, but also impairs delivery nutrients required PDAC cells. To compensate this, metabolic adaptions occur provide alternative sources fuel. aim this study explore...
Sepsis is one of the major causes human morbidity and results in a considerable number deaths each year. Lipopolysaccharide-induced sepsis has been associated with TLR4 signalling pathway which collaboration JAK/STAT regulate endotoxemia inflammation. However, during our immune system cannot maintain balance cytokine levels multiple organ damage eventual death. Different opinions have made previous studies about expression patterns role proinflammatory cytokines that attracted attention...
Friend of GATA1 (FOG-1) is an essential transcriptional co-factor the master erythroid transcription factor GATA1. The knockout Zfpm1 gene, coding for FOG-1, results in early embryonic lethality due to anemia mice, similar lethal phenotype Gata1 gene knockout. However, a detailed molecular analysis erythropoiesis presently incomplete. To this end, we used CRISPR/Cas9 mouse erythroleukemic (MEL) cells. Phenotypic characterization DMSO-induced terminal differentiation showed that MEL cells did...
The discrete modeling formalism of René Thomas is a well known approach for the and analysis Biological Regulatory Networks (BRNs). This uses set parameters which reflect dynamics BRN under study. These are initially unknown but may be deduced from appropriately chosen observed BRN. model can further enriched by using checking tool HyTech along with delay parameters. paves way to accurately analyse make predictions about critical trajectories lead normal or diseased response. In this paper,...
Infusions of the plant Picrasma excelsa, known as Jamaican bitterwood tea, are commonly consumed to lower blood sugar levels in diabetics who already on prescription medicines. We therefore investigated inhibition properties this tea against a panel cytochrome P450 (CYP) enzymes, which primarily responsible for metabolism majority drugs market. The two major ingredients, quassin and neoquassin, were then isolated used further characterization. Inhibition activities heterologously expressed...
Abstract Innate lymphoid cells are central to the regulation of immunity at mucosal barrier sites, with group 2 innate (ILC2s) being particularly important in type immunity. In this study, we demonstrate that microRNA(miR)-142 plays a critical, cell-intrinsic role homeostasis and function ILC2s. Mice deficient for miR-142 expression an ILC2 progenitor–biased development bone marrow, along peripheral ILC2s these display greatly altered phenotype based on surface marker expression....
IgE to peanut often occurs in the absence of allergy. Detection allergen component specific (sIgE) has improved diagnosis and birthed molecular arrays, which sensitization multiple components can be measured simultaneously.To improve diagnostic utility serology for allergy, by mapping interactions sIgE functional characteristics.A cohort 100 children was studied, with a 60-children employed external validation. Levels total IgE, peanut, were using singleplex ImmunoCAP multiplex immuno...