Publications
173 results found
Progatzky F, Dallman MJ, Lo Celso C, 2013, From seeing to believing: labelling strategies for <i>in vivo</i> cell-tracking experiments, INTERFACE FOCUS, Vol: 3, ISSN: 2042-8898
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- Citations: 181
Taylor HB, Liepe J, Barthen C, et al., 2012, P38 and JNK have opposing effects on persistence of in vivo leukocyte migration in zebrafish, Immunology and Cell Biology, Vol: 91, Pages: 60-69, ISSN: 1440-1711
The recruitment and migration of macrophages and neutrophils is an important process during the early stages of the innate immune system in response to acute injury. Transgenic pu.1:EGFP zebrafish permit the acquisition of leukocyte migration trajectories during inflammation. Currently, these high-quality live-imaging data are mainly analysed using general statistics, for example, cell velocity. Here, we present a spatio-temporal analysis of the cell dynamics using transition matrices, which provide information of the type of cell migration. We find evidence that leukocytes exhibit types of migratory behaviour, which differ from previously described random walk processes. Dimethyl sulfoxide treatment decreased the level of persistence at early time points after wounding and ablated temporal dependencies observed in untreated embryos. We then use pharmacological inhibition of p38 and c-Jun N-terminal kinase mitogen-activated protein kinases to determine their effects on in vivo leukocyte migration patterns and discuss how they modify the characteristics of the cell migration process. In particular, we find that their respective inhibition leads to decreased and increased levels of persistent motion in leukocytes following wounding. This example shows the high level of information content, which can be gained from live-imaging data if appropriate statistical tools are used.
Le Friec G, Sheppard D, Whiteman P, et al., 2012, The CD46-Jagged1 interaction is critical for human T(H)1 immunity, Nature Immunology, Vol: 13, Pages: 1213-1221, ISSN: 1529-2908
CD46 is a complement regulator with important roles related to the immune response. CD46 functions as a pathogen receptor and is a potent costimulator for the induction of interferon-γ (IFN-γ)-secreting effector T helper type 1 (TH1) cells and their subsequent switch into interleukin 10 (IL-10)-producing regulatory T cells. Here we identified the Notch family member Jagged1 as a physiological ligand for CD46. Furthermore, we found that CD46 regulated the expression of Notch receptors and ligands during T cell activation and that disturbance of the CD46-Notch crosstalk impeded induction of IFN-γ and switching to IL-10. Notably, CD4+ T cells from CD46-deficient patients and patients with hypomorphic mutations in the gene encoding Jagged1 (Alagille syndrome) failed to mount appropriate TH1 responses in vitro and in vivo, which suggested that CD46-Jagged1 crosstalk is responsible for the recurrent infections in subpopulations of these patients.
Le Friec G, Shamoun S, Couzi L, et al., 2012, Jagged1 is a CD46 ligand and disturbance in CD46/Jagged 1 interaction leads to abnormal Th1 function and infections in humans, European Congress of Immunology, Publisher: WILEY-BLACKWELL, Pages: 8-8, ISSN: 0019-2805
Progatzky F, Taylor H, Bugeon L, et al., 2012, The role of Nfil3 in zebrafish hematopoiesis, DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY, Vol: 38, Pages: 187-192, ISSN: 0145-305X
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- Citations: 4
Gentle ME, Rose A, Bugeon L, et al., 2012, Noncanonical Notch Signaling Modulates Cytokine Responses of Dendritic Cells to Inflammatory Stimuli, JOURNAL OF IMMUNOLOGY, Vol: 189, Pages: 1274-1284, ISSN: 0022-1767
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- Citations: 38
Rose A, Kay E, Wren BW, et al., 2012, The Campylobacter jejuni NCTC11168 capsule prevents excessive cytokine production by dendritic cells, MEDICAL MICROBIOLOGY AND IMMUNOLOGY, Vol: 201, Pages: 137-144, ISSN: 0300-8584
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- Citations: 21
Chen L, McGinty J, Taylor HB, et al., 2012, Incorporation of an experimentally determined MTF for spatial frequency filtering and deconvolution during optical projection tomography reconstruction, OPTICS EXPRESS, Vol: 20, Pages: 7323-7337, ISSN: 1094-4087
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- Citations: 15
Chen L, McGinty J, Taylor HB, et al., 2012, Improved OPT reconstructions based on the MTF and extension to FLIM-OPT
We demonstrate the improved reconstruction of OPT datasets by incorporating the measured MTF in the reconstruction process. We also extend OPT to FLIM-OPT and demonstrate its use for imaging live zebrafish embryos displaying autofluorescence. © 2012 OSA.
Liepe J, Taylor H, Barnes CP, et al., 2012, Calibrating spatio-temporal models of leukocyte dynamics against <i>in vivo</i> live-imaging data using approximate Bayesian computation, INTEGRATIVE BIOLOGY, Vol: 4, Pages: 335-345, ISSN: 1757-9694
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- Citations: 30
Antkowiak M, Torres-Mapa ML, McGinty J, et al., 2012, Towards gene therapy based on femtosecond optical transfection, BIOPHOTONICS: PHOTONIC SOLUTIONS FOR BETTER HEALTH CARE III, Vol: 8427, ISSN: 0277-786X
Bugeon L, Taylor HB, Progatzky F, et al., 2011, The NOTCH pathway contributes to cell fate decision in myelopoiesis, HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, Vol: 96, Pages: 1753-1760, ISSN: 0390-6078
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- Citations: 12
Le Friec G, Bugeon L, Dallman M, et al., 2011, Crosstalk between complement and notch systems is required for normal function and regulation of Th1 responses, Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL, Pages: 67-67, ISSN: 0019-2805
Silk D, Kirk PDW, Barnes CP, et al., 2011, Designing attractive models via automated identification of chaotic and oscillatory dynamical regimes, NATURE COMMUNICATIONS, Vol: 2, ISSN: 2041-1723
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- Citations: 23
Lara R, Mauri F, Gray C, et al., 2011, An siRNA screen identifies RSK1 as a key regulator of lung cancer metastasis., Oncogene, Vol: 30, Pages: 3513-3521
We performed a kinome-wide siRNA screen and identified 70 kinases altering cell migration in A549 lung cancer cells. In particular, ribosomal S6 kinase 1 (RSK1) silencing increased, whereas RSK2 and RSK4 downregulation inhibited cell motility. In a secondary collagen-based three-dimensional invasion screen, 38 of our hits cross-validated, including RSK1 and RSK4. In two further lung cancer cell lines, RSK1 but not RSK4 silencing showed identical modulation of cell motility. We therefore selected RSK1 for further investigation. Bioinformatic analysis followed by co-immunoprecipitation-based validation revealed that the actin regulators VASP and Mena interact with RSK1. Moreover, RSK1 phosphorylated VASP on T278, a site regulating its binding to actin. In addition, silencing of RSK1 enhanced the metastatic potential of these cells in vivo using a zebrafish model. Finally, we investigated the relevance of this finding in human lung cancer samples. In isogenically matched tissue, RSK1 was reduced in metastatic versus primary lung cancer lesions. Moreover, patients with RSK1-negative lung tumours showed increased number of metastases. Our results suggest that the findings of our high-throughput in vitro screen can reliably identify relevant clinical targets and as a proof of principle, RSK1 may provide a biomarker for metastasis in lung cancer patients
Lara R, Mauri FA, Taylor H, et al., 2011, An siRNA screen identifies RSK1 as a key modulator of lung cancer metastasis, ONCOGENE, Vol: 30, Pages: 3513-3521, ISSN: 0950-9232
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- Citations: 73
Pridgeon C, Bugeon L, Donnelly L, et al., 2011, Regulation of IL-17 in chronic inflammation in the human lung., Clin Sci (Lond), Vol: 120, Pages: 515-524
The regulation of human Th17 cell effector function by Treg cells (regulatory T-cells) is poorly understood. In the present study, we report that human Treg (CD4(+)CD25(+)) cells inhibit the proliferative response of Th17 cells but not their capacity to secrete IL (interleukin)-17. However, they could inhibit proliferation and cytokine production by Th1 and Th2 cells as determined by IFN-γ (interferon-γ) and IL-5 biosynthesis. Currently, as there is interest in the role of IL-17-producing cells and Treg cells in chronic inflammatory diseases in humans, we investigated the presence of CD4(+)CD25(+) T-cells and IL-17 in inflammation in the human lung. Transcripts for IL-17 were expressed in mononuclear cells and purified T-cells from lung tissue of patients with chronic pulmonary inflammation and, when activated, these cells secrete soluble protein. The T-cell-specific transcription factors RORCv2 (retinoic acid-related orphan receptor Cv2; for Th17) and FOXP3 (forkhead box P3; for Treg cells) were enriched in the T-cell fraction of lung mononuclear cells. Retrospective stratification of the patient cohort into those with COPD (chronic obstructive pulmonary disease) and non-COPD lung disease revealed no difference in the expression of IL-17 and IL-23 receptor between the groups. We observed that CD4(+)CD25(+) T-cells were present in comparable numbers in COPD and non-COPD lung tissue and with no correlation between the presence of CD4(+)CD25(+) T-cells and IL-17-producing cells. These results suggest that IL-17-expressing cells are present in chronically inflamed lung tissue, but there is no evidence to support this is due to the recruitment or expansion of Treg cells.
Lara R, Mauri F, Taylor H, et al., 2011, IDENTIFICATION OF RSK1 AS A KEY MODULATOR OF LUNG CANCER METASTASIS, JOURNAL OF THORACIC ONCOLOGY, Vol: 6, Pages: S514-S515, ISSN: 1556-0864
McGinty J, Taylor HB, Chen L, et al., 2011, In vivo fluorescence lifetime optical projection tomography, Biomedical Optics Express, Vol: 2, Pages: 1340-1350, ISSN: 2156-7085
We demonstrate the application of fluorescence lifetime optical projection tomography (FLIM-OPT) to in vivo imaging of lysC:GFP transgenic zebrafish embryos (Danio rerio). This method has been applied to unambiguously distinguish between the fluorescent protein (GFP) signal in myeloid cells from background autofluorescence based on the fluorescence lifetime. The combination of FLIM, an inherently ratiometric method, in conjunction with OPT results in a quantitative 3-D tomographic technique that could be used as a robust method for in vivo biological and pharmaceutical research, for example as a readout of Förster resonance energy transfer based interactions.
Kumar S, Alibhai D, Margineanu A, et al., 2011, FLIM FRET technology for drug discovery: automated multiwell-plate high-content analysis, multiplexed readouts and application in situ, ChemPhysChem: a European journal of chemical physics and physical chemistry, Vol: 12, Pages: 609-626, ISSN: 1439-4235
A fluorescence lifetime imaging (FLIM) technology platform intendedto read out changes in Fçrster resonance energy transfer(FRET) efficiency is presented for the study of protein interactionsacross the drug-discovery pipeline. FLIM provides arobust, inherently ratiometric imaging modality for drug discoverythat could allow the same sensor constructs to betranslated from automated cell-based assays through smalltransparent organisms such as zebrafish to mammals. To thisend, an automated FLIM multiwell-plate reader is described forhigh content analysis of fixed and live cells, tomographic FLIMin zebrafish and FLIM FRET of live cells via confocal endomicroscopy.For cell-based assays, an exemplar application readingout protein aggregation using FLIM FRET is presented, andthe potential for multiple simultaneous FLIM (FRET) readoutsin microscopy is illustrated.
Le Friec G, Bugeon L, Dallman M, et al., 2010, CD46: just a Notch up your common complement regulator, Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL PUBLISHING, INC, Pages: 174-174, ISSN: 0019-2805
Le Friec G, Bugeon L, Dallman M, et al., 2010, CD46: Just a Notch up your common complement regulator, 23rd International National Complement Workshop, Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: 2229-2229, ISSN: 0161-5890
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- Citations: 3
Saric J, Li JV, Swann JR, et al., 2010, Integrated Cytokine and Metabolic Analysis of Pathological Responses to Parasite Exposure in Rodents, JOURNAL OF PROTEOME RESEARCH, Vol: 9, Pages: 2255-2264, ISSN: 1535-3893
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- Citations: 33
Turro E, Lewin A, Rose A, et al., 2010, MMBGX: a method for estimating expression at the isoform level and detecting differential splicing using whole-transcript Affymetrix arrays (vol 38, pg e4, 2010), NUCLEIC ACIDS RESEARCH, Vol: 38, Pages: 1413-1413, ISSN: 0305-1048
Turro E, Lewin A, Rose A, et al., 2010, MMBGX: a method for estimating expression at the isoform level and detecting differential splicing using whole-transcript Affymetrix arrays, NUCLEIC ACIDS RESEARCH, Vol: 38, ISSN: 0305-1048
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- Citations: 18
Mollet G, Ratelade J, Boyer O, et al., 2009, Podocin Inactivation in Mature Kidneys Causes Focal Segmental Glomerulosclerosis and Nephrotic Syndrome, JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol: 20, Pages: 2181-2189, ISSN: 1046-6673
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- Citations: 79
Bugeon L, Gardner LM, Rose A, et al., 2008, Cutting Edge: Notch Signaling Induces a Distinct Cytokine Profile in Dendritic Cells That Supports T Cell-Mediated Regulation and IL-2-Dependent IL-17 Production, JOURNAL OF IMMUNOLOGY, Vol: 181, Pages: 8189-8193, ISSN: 0022-1767
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- Citations: 32
Chen Y, Liu Y, Yuan Z, et al., 2007, Rosiglitazone suppresses cyclosporin-induced chronic transplant dysfunction and prolongs survival of rat cardiac allografts, TRANSPLANTATION, Vol: 83, Pages: 1602-1610, ISSN: 0041-1337
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- Citations: 7
Chen Y, Li X, Tian L, et al., 2007, Inhibition of sonic hedgehog signaling reduces chronic rejection and prolongs allograft survival in a rat orthotopic small bowel transplantation model, TRANSPLANTATION, Vol: 83, Pages: 1351-1357, ISSN: 0041-1337
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- Citations: 11
Chan VSF, Chau S-Y, Tian L, et al., 2006, Sonic hedgehog promotes CD4<SUP>+</SUP> T lymphocyte proliferation and modulates the expression of a subset of CD28-targeted genes, INTERNATIONAL IMMUNOLOGY, Vol: 18, Pages: 1627-1636, ISSN: 0953-8178
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- Citations: 16
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