A5031709180- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- RNA Research and Splicing
- RNA modifications and cancer
- Cell Adhesion Molecules Research
- Immunotherapy and Immune Responses
- RNA and protein synthesis mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Cancer-related molecular mechanisms research
- Immune Response and Inflammation
- Chronic Lymphocytic Leukemia Research
- PI3K/AKT/mTOR signaling in cancer
- Cytokine Signaling Pathways and Interactions
- Platelet Disorders and Treatments
- NF-κB Signaling Pathways
- Protein Kinase Regulation and GTPase Signaling
- interferon and immune responses
- MicroRNA in disease regulation
- Immunodeficiency and Autoimmune Disorders
- CAR-T cell therapy research
- Mast cells and histamine
- Immune cells in cancer
- Glycosylation and Glycoproteins Research
- RNA Interference and Gene Delivery
- RNA regulation and disease
Babraham Institute
2016-2025
University of Oxford
1997-2022
Scottish National Blood Transfusion Service
2012-2020
University of Cambridge
2007-2020
Goethe University Frankfurt
2020
National Trust for Scotland
2017
University College London
1963-2016
University of Edinburgh
2014
University of Sheffield
2013
Medical Research Council
2013
MicroRNAs are a class of small RNAs that increasingly being recognized as important regulators gene expression. Although hundreds microRNAs present in the mammalian genome, genetic studies addressing their physiological roles at an early stage. We have shown mice deficient for bic/microRNA-155 immunodeficient and display increased lung airway remodeling. demonstrate requirement function B T lymphocytes dendritic cells. Transcriptome analysis bic/microRNA-155-deficient CD4+ cells identified...
Abstract High levels of interleukin 6 (IL 6/B cell stimulatory factor‐2) were detected in synovial fluids from the joints patients with active rheumatoid arthritis (RA). The cells found freshly isolated fluid constitutively expressed IL6 mRNA. tissues obtained by joint biopsy also to produce vitro. Immunohistochemical analysis demonstrated that CD2 + T as well CD20 blastoid B IL6. data indicate is generated RA and its overproduction may explain local generalized symptoms RA, since can...
Receptors on macrophages for the Fc region of IgG (FcγR) mediate a number responses important host immunity. Signaling events necessary these are likely initiated by activation Src-family and Syk-family tyrosine kinases after FcγR cross-linking. Macrophages derived from Syk-deficient (Syk−) mice were defective in phagocytosis particles bound FcγRs, as well many FcγR-induced signaling events, including phosphorylation cellular substrates MAP kinases. In contrast, Syk− exhibited normal to...
Mice lacking the p110δ catalytic subunit of phosphatidylinositol 3-kinase have reduced numbers B1 and marginal zone B cells, levels serum immunoglobulins, respond poorly to immunization with type II thymus-independent antigen, are defective in their primary secondary responses thymus-dependent antigen. p110δ−/− cells proliferate response cell receptor (BCR) or CD40 signals vitro, fail activate protein kinase B, prone apoptosis. function is required for BCR-mediated calcium flux, activation...
Foxp3 is a transcription factor that essential for the normal development of regulatory T cells (Tregs). In absence microRNAs (miRNAs), Foxp3(+) Tregs develop but fail to maintain immune homeostasis, leading scurfy-like disease. Global analysis network genes regulated by has identified miRNA miR-155, which highly expressed in Tregs, as direct target Foxp3. this study we report miR-155-deficient mice have reduced numbers both thymus and periphery, due impaired development. However, found no...
Transforming growth factor-beta 1 (TGF-beta 1) is one of a family polypeptides involved in the regulation cell and differentiation. The effects human rTGF-beta on production IL-1 TNF by activated PBMC were studied. addition TGF-beta alone caused an increase levels mRNA for alpha, beta, TGF-alpha. This was due to increased transcription rather than enhanced stability. induced appropriate size as assessed Northern blotting. However, did not appear be translated into protein, inasmuch...
Abstract Granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), in addition to being a growth for granulocytes and macrophages, is an activator of cells the monocyte/macrophage lineage induces HLA class II expression cytokine synthesis these target cells. Macrophage activation are prominent features rheumatoid arthritis (RA) joints, but mechanism their stimulation not understood, since interferon‐y, major stimulus expression, usually detectable at protein level synovial cell culture...
Abstract The presence of neutrophils in the synovial joint patients with rheumatoid arthritis (RA) is thought to be due activity chemotactic factors released by activated cells joint. We have shown this report, for first time, abundance one such factor, interleukin 8 (IL 8), fluid both RA and other non‐RA diseases, spontaneous production IL8 mRNA culture. There was no correlation between levels protein, suggesting that similar neutrophil are also present exudate. In support concept neither...
Vav is a GTP/GDP exchange factor (GEF) for members of the Rho-family GTPases that rapidly tyrosine-phosphorylated after engagement T cell receptor (TCR), suggesting it may transduce signals from receptor. cells mice made Vav-deficient by gene targeting ( −/− ) fail to proliferate in response TCR stimulation because they secrete IL-2. We now show this due at least part failure initiate IL-2 transcription. Furthermore, we analyze TCR-proximal signaling pathways and despite normal activation...
The generation of high-affinity Abs is essential for immunity and requires collaboration between B T cells within germinal centers (GCs). By using novel mouse models with a conditional deletion the p110δ catalytic subunit PI3K pathway, we established that required in cells, but not GC reaction. We found formation follicular helper (T(FH)) to be critically dependent on cells. Furthermore, by deleting phosphatase tensin homolog deleted chromosome 10, which opposes activated positive...