Zania Stamataki

Zania Stamataki
University of Birmingham · School of Immunity and Infection

PhD

About

102
Publications
12,413
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3,268
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Introduction
I am a Royal Society Dorothy Hodgkin Fellow at the University of Birmingham, interested in the study of lymphocyte-hepatocyte interactions in chronic inflammation. Lab website: www.stamatakilab.com University profile page: http://goo.gl/wNcyPI @ZaniaStamataki
Additional affiliations
January 2006 - December 2012
University of Birmingham

Publications

Publications (102)
Article
Full-text available
Background The systemic inflammatory response post-SARS-CoV-2 infection increases pro-inflammatory cytokine production, multi-organ damage, and mortality rates. Mast cells (MC) modulate thrombo-inflammatory disease progression ( e.g. , deep vein thrombosis) and the inflammatory response post-infection. Objective To enhance our understanding of the...
Article
The recent increase in unexplained acute hepatitis in children in 2022 has focused attention on acute paediatric liver disease. We discuss emerging evidence and leading causal hypotheses in context with potential long-term effects of the COVID-19 pandemic for young children.
Preprint
The engagement of the SARS-CoV-2 spike protein with ACE2 is a critical step for viral entry to human cells and accordingly blocking this interaction is a major determinant of the efficacy of monoclonal antibody therapeutics and vaccine-elicited serum antibodies. The emergence of SARS-CoV-2 variants necessitates the development of adaptable assays t...
Article
Aims Thrombotic complications and vasculopathy have been extensively associated with severe COVID-19 infection; however, the mechanisms inducing endotheliitis and the disruption of endothelial integrity in the microcirculation are poorly understood. We hypothesized that within the vessel wall, pericytes preferentially take up viral particles and me...
Article
Full-text available
Background: Patients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity. Objectives: To determine the immunogenicity of the third primary SARS-Co...
Article
Full-text available
Background Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood. Objectives COVID-19 in patients with antibody deficiency (COV-AD) is a multi-site UK study that aims to determine the immune respon...
Preprint
Background Patients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity. Objectives To determine the immunogenicity of the third primary SARS-CoV-2 i...
Article
Full-text available
The COVID-19 pandemic has demonstrated the real need for mechanisms to control the spread of airborne respiratory pathogens. Thus, preventing the spread of disease from pathogens has come to the forefront of the public consciousness. This has brought an increasing demand for novel technologies to prioritise clean air. In this study we report on the...
Preprint
Full-text available
Background Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood. Objectives COVID in patients with antibody deficiency (COV-AD) is a multi-site United Kingdom study that aims to determine the immu...
Article
Full-text available
Hepatitis C virus (HCV) is highly variable and transmits through infected blood to establish a chronic liver infection in the majority of patients. Our knowledge on the infectivity of clinical HCV strains is hampered by the lack of in vitro cell culture systems that support efficient viral replication. We and others have reported that HCV can assoc...
Article
Full-text available
Objective Tissue-resident memory T cells (T RM ) are vital immune sentinels that provide protective immunity. While hepatic CD8 ⁺ T RM have been well described, little is known about the location, phenotype and function of CD4 ⁺ T RM . Design We used multiparametric flow cytometry, histological assessment and novel human tissue coculture systems t...
Article
Full-text available
B lymphocytes are multitasking cells that direct the immune response by producing pro- or anti-inflammatory cytokines, by presenting processed antigen for T cell activation and co-stimulation, and by turning into antibody-secreting cells. These functions are important to control infection in the liver but can also exacerbate tissue damage and fibro...
Article
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The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has caused a significant number of fatalities and worldwide disruption. To identify drugs to repurpose to treat SARS-CoV-2 infections, we established a screen to measure the dimerization of angiotensin-converting enzyme 2 (ACE2), the primary receptor for the virus. This scree...
Article
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A Correction to this paper has been published: https://doi.org/10.1007/s10875-021-01029-z
Article
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Airborne pathogens pose high risks in terms of both contraction and transmission within the respiratory pathways, particularly the nasal region. However, there is little in the way of adequate intervention that can protect an individual or prevent further spread. This study reports on a nasal formulation with the capacity to combat such challenges,...
Article
Full-text available
The untranslated regions (UTRs) of viral genomes contain a variety of conserved yet dynamic structures crucial for viral replication, providing drug targets for the development of broad spectrum anti‐virals. We combine RNA analysis with Molecular Dynamics simulations to build the first 3D models of the structure and dynamics of key regions of the 5...
Article
Full-text available
The untranslated regions (UTRs) of viral genomes contain a variety of conserved yet dynamic structures crucial for viral replication, providing drug targets for the development of broad spectrum anti‐virals. We combine RNA analysis with Molecular Dynamics simulations to build the first 3D models of the structure and dynamics of key regions of the 5...
Preprint
Full-text available
Objective Thrombotic complications and vasculopathy have been extensively associated with severe COVID-19 infection, however the mechanisms by which endotheliitis is induced remain poorly understood. Here we investigate vascular permeability in the context of SARS-CoV-2-mediated endotheliitis in patient samples and a vascular organoid model. Metho...
Article
Full-text available
Persistent liver inflammation can lead to cirrhosis, which associates with significant morbidity and mortality worldwide. There are no curative treatments beyond transplantation, followed by long-term immunosuppression. The global burden of end stage liver disease has been increasing and there is a shortage of donor organs, therefore new therapies...
Preprint
Full-text available
The untranslated regions (UTRs) of viral genomes contain a variety of conserved yet dynamic structures crucial for viral replication, providing drug targets for the development of broad spectrum anti-virals. We combine in vitro RNA analysis with Molecular Dynamics simulations to build the first 3D models of the structure and dynamics of key regions...
Article
Full-text available
Blockade of PD-1/PD-L1 interactions is proving an exciting, durable therapeutic modality in a range of cancers whereby T cells are released from checkpoint inhibition to revive their inherent anti-tumour activity. Here we have studied various ways to model ex vivo T cell function in order to compare the impact of the clinically utilised anti-PD-1 a...
Preprint
Full-text available
The SARS-CoV-2 pandemic has caused a significant number of fatalities and worldwide disruption. To identify drugs to repurpose to treat SARS-CoV-2 infections, we established a screen to measure dimerization of ACE2, the primary receptor for the virus. This screen identified fenofibric acid, the active metabolite of fenofibrate. Fenofibric acid also...
Article
Full-text available
Significance The glycosylation of proteins is a major protein modification that occurs extensively in eukaryotes. Glycosidases in the secretory pathway that trim N-linked glycans play key roles in protein quality control and in the specific modifications leading to mature glycoproteins. Inhibition of glucosidases in the secretory pathway is a prove...
Preprint
Full-text available
Airborne pathogens pose high risks in terms of both contraction and transmission within the respiratory pathways, in particular the nasal region. Although knowledge of airborne transmission has long been known, there is little in the way of adequate intervention that can protect the individual, or even prevent further spread. This study focuses on...
Conference Paper
Prolonged exposure to antigens can lead to a state of reduced T cell responsiveness termed exhaustion. Restoring T cell functions from this state of reduced functionality by, for example, blockade of inhibitory immune checkpoints is now an established therapeutic modality with lasting impact on survival for some patients. Modelling human T cell exh...
Preprint
Full-text available
Background & Aims Tissue-resident memory T cells (T RM ) are important immune sentinels that provide efficient in situ immunity. Liver-resident CD8 ⁺ T RM have been previously described, and contribute to viral control in persistent hepatotropic infections. However, little is known regarding liver CD4 ⁺ T RM cells. Here we profiled resident and non...
Article
The COVID-19 pandemic is an unprecedented healthcare emergency causing mortality and illness across the world. Although primarily affecting the lungs, the SARS-CoV-2 virus also affects the cardiovascular system. In addition to cardiac effects, e.g. myocarditis, arrhythmias, and myocardial damage, the vasculature is affected in COVID-19, both direct...
Preprint
Full-text available
Hepatitis C virus (HCV) is highly variable and transmits through infected blood to establish a chronic liver infection in the majority of patients. Our knowledge of the infectivity of clinical HCV strains is hampered by the lack of in vitro cell culture systems that support efficient viral replication. We previously reported that laboratory strains...
Preprint
Full-text available
Mammalian protein N - linked glycosylation is critical for glycoprotein folding, quality control, trafficking, recognition and function. N - linked glycans are synthesized from Glc 3 Man 9 GlcNAc 2 precursors that are trimmed and modified in the endoplasmic reticulum (ER) and Golgi apparatus by glycoside hydrolases and glycosyltransferases. Endo-α-...
Article
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The liver is our largest internal organ and it plays major roles in drug detoxification and immunity, where the ingestion of extracellular material through phagocytosis is a critical pathway. Phagocytosis is the deliberate endocytosis of large particles, microbes, dead cells or cell debris and can lead to cell-in-cell structures. Various types of c...
Conference Paper
Background and Aims. Regulatory T cells (Treg) dampen inflammation and they are increased in the liver compared to blood, contributing to a tolerising environment. The swift neutralisation of Treg cells is important to enable immune effector functions to combat infection, but the mode of this is not understood. We noted that hepatocytes preferentia...
Article
Full-text available
The liver is a front‐line immune tissue that plays a major role in the detection, capture and clearance of pathogens and foreign antigens entering the blood‐stream, especially from the gut. Our largest internal organ maintains this immune barrier in the face of constant exposure to external but harmless antigens through a highly specialised network...
Article
The 5-hydroxytryptamine (5-HT) (serotonin) 5-HT3 receptor represents a clinical target for antagonists to deliver symptomatic relief to patients with diarrhea-predominant irritable bowel syndrome (IBS-d) or carcinoid syndrome. Unfortunately, this pharmacological strategy can present side effects (e.g., severe constipation). The present study invest...
Article
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The glucagon-like peptide-1 receptor (GLP1R) is a class B G protein-coupled receptor (GPCR) involved in metabolism. Presently, its visualization is limited to genetic manipulation, antibody detection or the use of probes that stimulate receptor activation. Herein, we present LUXendin645, a far-red fluorescent GLP1R antagonistic peptide label. LUXen...
Article
Full-text available
CD4+ T cells play critical roles in directing immunity, both as T helper and as regulatory T (Treg) cells. Here, we demonstrate that hepatocytes can modulate T cell populations through engulfment of live CD4+ lymphocytes. We term this phenomenon enclysis to reflect the specific enclosure of CD4+ T cells in hepatocytes. Enclysis is selective for CD4...
Preprint
Full-text available
The glucagon-like peptide-1 receptor (GLP1R) is a class B G protein-coupled receptor (GPCR) involved in metabolism. Presently, its visualization is limited to genetic manipulation, antibody detection or the use of probes that stimulate receptor activation. Herein, we present LUXendin645, a far-red fluorescent GLP1R antagonistic peptide label. LUXen...
Article
Full-text available
Restoring antiviral immunity is a promising immunotherapeutic approach to the treatment of chronic hepatitis B virus (HBV) infection. Dendritic cells play a crucial role in triggering antiviral immunity. In this study, we identified immunodominant epitopes prevalent in CD8⁺ T cell responses. We characterized the hierarchy of HBV epitopes targeted b...
Article
Full-text available
Toxic substances and microbial or food-derived antigens continuously challenge the liver, which is tasked with their safe neutralization. This vital organ is also important for the removal of apoptotic immune cells during inflammation and has been previously described as a “graveyard” for dying lymphocytes. The clearance of apoptotic and necrotic c...
Article
Full-text available
Natural killer (NK) cells play a major role in anti-viral immunity as first line defense during hepatitis B infection, particularly in untreated patients whose T cells functions are profoundly impaired. Cytokine interferon (IFN)-γ and tumor necrosis factor (TNF)-α produced by NK cells are important anti-viral factors. However, there is lack of a qu...
Conference Paper
Introduction Acute liver failure (ALF) is characterised by overwhelming hepatocyte death and liver inflammation with massive infiltration of myeloid cells in necrotic areas. The mechanisms underlying resolution of acute hepatic inflammation are largely unknown. Here, we aimed to investigate the impact of Mer-Tyrosine-Kinase (MerTK) during ALF and a...
Article
Full-text available
Objective: Acute liver failure (ALF) is characterised by overwhelming hepatocyte death and liver inflammation with massive infiltration of myeloid cells in necrotic areas. The mechanisms underlying resolution of acute hepatic inflammation are largely unknown. Here, we aimed to investigate the impact of Mer tyrosine kinase (MerTK) during ALF and al...
Chapter
The liver is the largest internal organ and filters around 3 pints of blood per minute. This continuous flux of blood should not be confused with rapid egress of lymphocytes through the liver; this organ has intricate corridors of specialized sinusoidal spaces, ensuring that immune cells decelerate to shear flow rates, and providing ample opportuni...
Chapter
Lymphocyte recruitment to different organs, and even alternate anatomical regions within the same organ, is differentially regulated. Key combinations of adhesion molecules and chemokines govern compartmentalization, and these can change depending upon the nature and duration of tissue injury. We are interested in understanding lymphocyte recruitme...
Article
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Mutations in the hepatitis B virus (HBV) core promoter (CP) have been shown to be associated with hepatocellular carcinoma (HCC). The CP region overlaps HBV X gene, which activates AKT to regulate hepatocyte survival. However, the cooperation between these two cascades in HCC progression remains poorly understood. Here, we assayed virological facto...
Article
Human cytomegalovirus infection (HCMV) is associated with an increased morbidity after liver transplantation by facilitating allograft rejection and accelerating underlying hepatic inflammation. We hypothesized that human hepatic sinusoidal endothelial cells infected with HCMV possess the capacity to modulate allogeneic T cell recruitment and activ...
Article
Full-text available
The transmembrane domain proteins of the claudin superfamily are the major structural components of cellular tight junctions. One family member, claudin-1, also associates with tetraspanin CD81 as part of a receptor complex that is essential for hepatitis C virus (HCV) infection of the liver. To understand the molecular basis of claudin-1/CD81 asso...