A5003034262- Tryptophan and brain disorders
- Stress Responses and Cortisol
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Bacterial Infections and Vaccines
- Long-Term Effects of COVID-19
- Helicobacter pylori-related gastroenterology studies
- Mental Health Research Topics
- Galectins and Cancer Biology
- Mindfulness and Compassion Interventions
- Healthcare Operations and Scheduling Optimization
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Alzheimer's disease research and treatments
- Machine Learning in Healthcare
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Intensive Care Unit Cognitive Disorders
- COVID-19 and Mental Health
- Escherichia coli research studies
- Functional Brain Connectivity Studies
- Extracellular vesicles in disease
- Hormonal Regulation and Hypertension
- Immunodeficiency and Autoimmune Disorders
- vaccines and immunoinformatics approaches
University of Cambridge
2016-2024
MRC Epidemiology Unit
2023-2024
Addenbrooke's Hospital
2020-2022
Cambridge School
2021
Hudson Institute of Medical Research
2014-2018
Leeds Teaching Hospitals NHS Trust
2017
Cambridge Hospital
2017
Cambridge University Hospitals NHS Foundation Trust
2016
Monash University
2010-2015
Monash Institute of Medical Research
2010-2014
The kinetics of the immune changes in COVID-19 across severity groups have not been rigorously assessed. Using immunophenotyping, RNA sequencing, and serum cytokine analysis, we analyzed serial samples from 207 SARS-CoV2-infected individuals with a range disease severities over 12 weeks symptom onset. An early robust bystander CD8+ T cell response, without systemic inflammation, characterized asymptomatic or mild disease. Hospitalized had delayed responses inflammation that was already...
Neuroinflammation and microglial activation are significant processes in Alzheimer's disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes with disease, experimental data demonstrated proliferation as a component of the neuropathology. In this study, we tested efficacy selective CSF1R inhibitor JNJ-40346527 (JNJ-527) P301S mouse tauopathy model. We first anti-proliferative effects JNJ-527 on microglia ME7 prion model, its impact inflammatory...
Gram-negative pathogens ubiquitously shed outer membrane vesicles (OMVs) that play a central role in initiating and regulating pathogenesis the host. Due to their highly inflammatory nature, OMVs are extensively being examined for mediating disease addition applications innovative vaccines. A key mechanism whereby mediate inflammation progression is dependent on ability enter host cells. Currently, of OMV size determining cellular entry protein composition remains unknown. In this study, we...
Abstract Persistent symptoms following SARS-CoV-2 infection are increasingly reported, although the drivers of post-acute sequelae (PASC) COVID-19 unclear. Here we assessed 214 individuals infected with SARS-CoV-2, varying disease severity, for one year from symptom onset to determine early correlates PASC. A multivariate signature detected beyond two weeks disease, encompassing unresolving inflammation, anemia, low serum iron, altered iron-homeostasis gene expression and emerging stress...
After infection of B cells, Epstein-Barr virus (EBV) engages host pathways that mediate cell proliferation and transformation, contributing to the propensity drive immune dysregulation lymphomagenesis. We found EBV protein EBNA2 initiates nicotinamide adenine dinucleotide (NAD) de novo biosynthesis by driving expression metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1) in infected cells. Virus-enforced NAD production sustained mitochondrial complex I activity, match adenosine...
Abstract The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome 2 (SARS-CoV-2) antiviral therapy. Here we report use remdesivir in a patient with COVID-19 and prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence complement activation robust T cell response, developed persistent SARS-CoV-2 pneumonitis, without progressing multi-organ involvement. This unusual clinical...
Background Hypothetically, psychotic disorders could be caused or conditioned by immunological mechanisms. If so, one might expect there to peripheral immune system phenotypes that are measurable in blood cells as biomarkers of states. Methods We used multi-parameter flow cytometry venous quantify and determine the activation state 73 cell subsets for 18 patients with chronic schizophrenia (17 treated clozapine), healthy volunteers matched age, sex, BMI smoking. multivariate methods (partial...
Multiple studies have established the importance of tol-pal gene cluster in bacterial cell membrane integrity and outer vesicle (OMV) formation Escherichia coli. In contrast, functions Tol-Pal proteins pathogenic organisms, including those Epsilonproteobacteria, remain poorly if at all defined. The aim this study was to characterize roles two key components system, TolB Pal, OMV bacterium, Helicobacter pylori.H. pylori ΔtolB, Δpal ΔtolBpal mutants, as well complemented strains, were...
Abstract The mRNA expression signatures associated with the ‘pro-inflammatory’ phenotype of depression, and differential depression subtypes effects antidepressants, are still unknown. We examined 130 depressed patients (58 treatment-resistant, 36 antidepressant-responsive currently untreated) 40 healthy controls from BIODEP study, used whole-blood qPCR to measure 16 candidate mRNAs, some never measured before: interleukin ( IL)-1-beta , IL-6 TNF-alpha macrophage inhibiting factor MIF ),...
There is increasing evidence for a subgroup of major depressive disorder (MDD) associated with heightened peripheral blood inflammatory markers. In this study, we aimed to understand the mechanistic brain-immune axis in inflammation-linked depression by investigating associations between functional connectivity (FC) brain networks and immune markers depression. Resting-state magnetic resonance imaging (fMRI) (C-reactive protein; CRP, interleukin-6; IL-6 cells) were collected on N = 46...
Abstract The biology driving individual patient responses to severe acute respiratory syndrome coronavirus 2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data and covering year after disease onset, from 215 infected individuals with differing severities. Our analyses revealed distinct ‘systemic recovery’ profiles, specific progression resolution of the inflammatory, immune cell, metabolic clinical responses. In...
Abstract Compelling evidence demonstrates that some individuals suffering from major depressive disorder (MDD) exhibit increased levels of inflammation. Most studies focus on inflammation-related proteins, such as serum or plasma C-reactive protein (CRP). However, the immune-related modifications associated with MDD may be not entirely captured by CRP alone. Analysing mRNA gene expression levels, we aimed to identify broader molecular phenotypes MDD. We examined 168 non-interventional,...
Sex hormones have biological effects on inflammation, and these might contribute to the sex-specific features of depression. C-reactive protein (CRP) is most widely used inflammatory biomarker consistent evidence shows a significant proportion (20–30 %) patients with major depressive disorder (MDD) CRP levels above 3 mg/L, threshold indicating at least low-grade inflammation. Here, we investigate interplay between sex in cross-sectional, observational Biomarkers Depression Study. We measured...
ABSTRACT Infection with Helicobacter pylori cag pathogenicity island ( PAI)-positive strains is associated more destructive tissue damage and an increased risk of severe disease. The PAI encodes a type IV secretion system (TFSS) that delivers the bacterial effector molecules CagA peptidoglycan into host cell cytoplasm, thereby inducing responses in cells. It was previously shown interactions between CagL, present on TFSS pilus, α 5 β 1 integrin were critical for translocation induction...
Prominent early features of COVID-19 include severe, often clinically silent, hypoxia and a pronounced reduction in B cells, the latter important defence against SARS-CoV-2. This presentation resembles phenotype mice with VHL-deficient which Hypoxia-Inducible Factors are constitutively active, suggesting might drive cell abnormalities COVID-19.
Abstract Psychological distress persisting for weeks or more promotes pro-inflammatory immune dysregulation, a risk factor range of chronic diseases. We have recently shown that mindfulness training reduces among university students. Here we present an exploratory trial to study dysregulation in cohort students who were exposed progressively greater stress as the exam period approached, and explore whether mitigated this dysregulation. Healthy University Cambridge randomised join 8-week...
The human pathogen Helicobacter pylori acquires cholesterol from membrane raft domains in eukaryotic cells, commonly known as "lipid rafts." Incorporation of this into the H. cell allows bacterium to avoid clearance by host immune system and resist effects antibiotics antimicrobial peptides. presence bacteria suggested that may have cholesterol-enriched within its membrane. Consistent with suggestion, we identified a hypothetical protein (HP0248) homology flotillin proteins normally found...
Clotting Factor V (FV) is primarily synthesized in the liver and when cleaved by thrombin forms pro-coagulant Va (FVa). Using whole blood RNAseq scRNAseq of peripheral mononuclear cells, we find that FV mRNA expressed leukocytes, identify neutrophils, monocytes, T regulatory cells as sources increased hospitalized patients with COVID-19. Proteomic analysis confirms circulating neutrophils severe COVID-19, immunofluorescence microscopy identifies lung-infiltrating leukocytes COVID-19 lung...