A5035525689- Malaria Research and Control
- Mosquito-borne diseases and control
- Nitric Oxide and Endothelin Effects
- Trypanosoma species research and implications
- Cellular transport and secretion
- Complement system in diseases
- CRISPR and Genetic Engineering
- Estrogen and related hormone effects
- Heat shock proteins research
- HIV Research and Treatment
- Phagocytosis and Immune Regulation
- Neuroinflammation and Neurodegeneration Mechanisms
- Signaling Pathways in Disease
- Immunotherapy and Immune Responses
- ATP Synthase and ATPases Research
- Animal Genetics and Reproduction
- Eicosanoids and Hypertension Pharmacology
- Genomics and Chromatin Dynamics
- Invertebrate Immune Response Mechanisms
- Microbial infections and disease research
- Vector-borne infectious diseases
- Immune cells in cancer
- Peroxisome Proliferator-Activated Receptors
- Extracellular vesicles in disease
- Immune Cell Function and Interaction
University of Hertfordshire
2023-2024
Wellcome Sanger Institute
2014-2024
École Pratique des Hautes Études
2002-2015
Université de Bourgogne
2005-2015
Simón Bolívar University
1992-2007
University of Cambridge
1995-2006
Inserm
2002-2005
Fondation pour la Recherche Médicale
2002
University of Liverpool
2000
Physiological Society
1995
HSP27 is an ATP-independent chaperone that confers protection against apoptosis through various mechanisms, including a direct interaction with cytochrome c. Here we show overexpression in cell types enhances the degradation of ubiquitinated proteins by 26S proteasome response to stressful stimuli, such as etoposide or tumor necrosis factor alpha (TNF-alpha). We demonstrate binds polyubiquitin chains and vitro vivo. The ubiquitin-proteasome pathway involved activation transcription NF-kappaB...
Heterozygous somatic mutations affecting the spliceosome gene SF3B1 drive age-related clonal hematopoiesis, myelodysplastic syndromes (MDS) and other neoplasms. To study their role in such disorders, we generated knock-in mice with hematopoietic-specific expression of Sf3b1-K700E, commonest type mutation MDS. Sf3b1K700E/+ animals had impaired erythropoiesis progressive anemia without ringed sideroblasts, as well reduced hematopoietic stem cell numbers host-repopulating fitness. understand...
Spiradenoma and cylindroma are distinctive skin adnexal tumors with sweat gland differentiation potential for malignant transformation aggressive behaviour. We present the genomic analysis of 75 samples from 57 representative patients including 15 cylindromas, 17 spiradenomas, 2 cylindroma-spiradenoma hybrid tumors, 24 low- high-grade spiradenocarcinoma cases, together morphologically benign precursor regions these cancers. reveal somatic or germline alterations CYLD gene in 15/15...
Abstract As malaria control programmes concentrate their efforts towards elimination a better understanding of transmission patterns at fine spatial resolution units becomes necessary. Defining that consider heterogeneity, human movement and migration will help to set up achievable milestones guide the creation efficient operational administrative units. Using combination genetic epidemiological data we defined unit as area contributing 95% cases diagnosed catchment facility located in town...
Coordinated regulation of gene expression is a hallmark the Plasmodium falciparum asexual blood-stage development cycle. We report that carbon catabolite repressor protein 4 (CCR4)-associated factor 1 (CAF1) critical in regulating more than 1,000 genes during malaria parasites' intraerythrocytic stages, especially egress and invasion proteins. CAF1 knockout results mistimed expression, aberrant accumulation localization proteins involved parasite egress, new host cells, leading to premature...
Plasmodium falciparum secretes extracellular vesicles (PfEVs) that contain parasite-derived RNA. However, the significance of secreted RNA remains unexplored. Here, we compare and intracellular from asexual cultures six P. lines. We find secretion via is not only periodic throughout intraerythrocytic developmental cycle but also highly conserved across isolates. further demonstrate phases are discernibly shifted compared to those within secreting whole parasite. Finally, transcripts genes...
Chromogranin A (CgA) may be critical for secretory granule biogenesis in sympathoadrenal cells. We found that silencing the expression of CgA reduced number granules normal cells (PC12), and we therefore questioned whether a discrete domain might promote formation regulated pathway variant (A35C) devoid such phenotype. The granule-forming activity series human domains labeled with hemagglutinin epitope, green fluorescent protein, or embryonic alkaline phosphatase was assessed A35C by...
Nitric oxide (NO) produced by inducible nitric-oxide synthase (NOSII) is mainly regulated at the transcriptional level nuclear factor-κB (NF-κB). In present study, we further analyzed role of NF-κB in vivo regulation NOSII gene comparing two clones isolated from EMT-6 mouse mammary cancer cell line. response to interleukin (IL)-1β or lipopolysaccharide (LPS), clone J (EMT-6J) cells produce 3-fold more NO than H (EMT-6H) cells, an effect correlated with enhanced activation EMT-6J cells....
There is considerable interest in determining the conditions leading to enhanced inducible nitric oxide synthase (iNOS) gene expression and (NO) biosynthesis. Using vivo footprinting, we demonstrate that heat shock of murine macrophages concurrent with lipopolysaccharide (LPS) treatment stimulated changes guanine methylation sensitivity at ?898/9, a putative partial element (HSE) -893/4, site bordering an E-box, within iNOS enhancer, suggesting occupation by transcription factors these...
Electrical excitability in neurons depends on the expression and activity of voltage-gated sodium channels neuronal plasma membrane. The ion-conducting α-subunit channel is associated with auxiliary β-subunits which there are four known types. In present study, we describe first detailed structure/function analysis β3-subunit. We correlate effect point mutations deletions β3 functional properties its membrane-targeting behaviour. show that extracellular domain influences gating properties,...
Abstract The rat PC12 variant cell line, A35C, lacks regulated secretory organelles due to a selective transcriptional block. Hence, A35C may provide clues about the mechanisms that underlie control of neurosecretion. We used mRNA microarray profiling examine gene expression in A35C. Genes for proteins were down‐regulated, while other membrane trafficking pathways unaffected. A subset genes repressed contain binding sites neuronal repressor, RE1‐silencing transcription factor (REST), and...
Oct-1 (POU2f1) and Oct-2 (POU2f2) are members of the POU family transcription factors. They recognize same DNA sequence but fulfil distinct functions: is ubiquitous regulates a variety genes while restricted to B-cells neurones. Here we examine interplay regulatory mechanisms these factors control inducible nitric oxide synthase (iNOS, NOS2). Using two breast cancer cell lines as comparative model, found that MCF-7 express iNOS upon cytokine stimulation MDA-MB-231 do not. present in both...
The human inducible nitric oxide synthase (iNOS or NOSII) gene is regulated through an extended and complex promoter. In this study, the transcriptional regulation of NOSII investigated in colon cell line HCT-8R. Stimulation with a cytokine mix (interferon-gamma, interleukin 1-beta, tumor necrosis factor alpha) induces mRNA accumulation, as well promoter activity these cells. Several random deletions were performed within proximal 7 kb promoter, which led to identification region, whose...
Invasion of human erythrocytes is essential for Plasmodium falciparum parasite survival and pathogenesis, also a complex phenotype. While some later steps in invasion appear to be invariant essential, the earlier recognition are controlled by series redundant, only partially understood, receptor-ligand interactions. Reverse genetic analysis laboratory adapted strains has identified multiple genes that when deleted can alter invasion, but how relative contributions each gene translate...
Abstract The recurrent emergence of drug resistance in Plasmodium falciparum increases the urgency to genetically validate mechanisms and identify new targets. Reverse genetics have facilitated genome-scale knockout screens berghei Toxoplasma gondii , which pooled transfections multiple vectors were critical increasing scale throughput. These approaches not yet been implemented human malaria species such as P. knowlesi part because extent can be performed these remains evaluated. Here we use...
The impact of cerebral malaria on the transcriptional profiles tissues is difficult to study using noninvasive approaches. We isolated plasma extracellular vesicles (EVs) from patients with and community controls sequenced their mRNA content. Deconvolution analysis revealed that EVs are enriched in transcripts brain origin. ordered based EV-transcriptional cross-sectionally collected samples inferred disease trajectory while healthy as a starting point. found neuronal decreased trajectory,...
Malaria antibody detection is valuable in providing retrospective confirmation of an attack malaria. Blood bank screening another area were malaria serology potentially useful. In the present study, we tested presence antibodies to Plasmodium falciparum sera from blood donors non-endemic and malaria-endemic areas Venezuela. Sera 1,000 by indirect immunofluorescent (IFA) assay IgG-ELISA for using a synchronized vitro-cultured Venezuelan isolate P. as antigen source. A selected group positive...