A5062546176- T-cell and B-cell Immunology
- Down syndrome and intellectual disability research
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Genetics and Neurodevelopmental Disorders
- Mast cells and histamine
- Immunotherapy and Immune Responses
- Platelet Disorders and Treatments
- Protein Kinase Regulation and GTPase Signaling
- Immune Response and Inflammation
- Congenital heart defects research
- Monoclonal and Polyclonal Antibodies Research
- Genomic variations and chromosomal abnormalities
- NF-κB Signaling Pathways
- Alzheimer's disease research and treatments
- Cell death mechanisms and regulation
- Epigenetics and DNA Methylation
- Genomics and Rare Diseases
- Chronic Lymphocytic Leukemia Research
- Glycosylation and Glycoproteins Research
- Immunodeficiency and Autoimmune Disorders
- Cell Image Analysis Techniques
- Fungal Infections and Studies
- Ubiquitin and proteasome pathways
- Prenatal Screening and Diagnostics
The Francis Crick Institute
2016-2025
Imperial College London
2015-2022
Imperial Valley College
2016-2020
University College London
2005-2018
King's College London
2018
Neurogen Brain & Spine Institute
2017
Medical Research Council
1983-2014
Morpho (United States)
2010
Max Planck Institute for Molecular Biomedicine
2010
Pyrogenesis (Canada)
2010
The parathyroid hormone-related peptide (PTHrP) gene was disrupted in murine embryonic stem cells by homologous recombination, and the null allele introduced into mouse germ line. Mice homozygous for PTHrP mutation died postnatally, probably from asphyxia, exhibited widespread abnormalities of endochondral bone development. Histological examination revealed a diminution chondrocyte proliferation, associated with premature maturation chondrocytes accelerated formation. Analysis earlier...
Abstract Lymphocyte activation gene-3 (LAG-3) is a CD4-related transmembrane protein expressed by regulatory T cells that binds MHC II on APCs. It shown in this study during Treg:DC interactions, LAG-3 engagement with class inhibits DC activation. cross-linking agonistic Abs induces an ITAM-mediated inhibitory signaling pathway, involving FcγRγ and ERK-mediated recruitment of SHP-1 suppresses dendritic cell maturation immunostimulatory capacity. These data reveal novel pathway DCs triggered...
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...
Aneuploidies are common chromosomal defects that result in growth and developmental deficits high levels of lethality humans. To gain insight into the biology aneuploidies, we manipulated mouse embryonic stem cells generated a trans-species aneuploid line stably transmits freely segregating, almost complete human chromosome 21 (Hsa21). This "transchromosomic" line, Tc1, is model trisomy 21, which manifests as Down syndrome (DS) humans, has phenotypic alterations behavior, synaptic...
Innate immune cells detect pathogens via pattern recognition receptors (PRRs), which signal for initiation of responses to infection. Studies with Dectin-1, a PRR fungi, have defined novel innate signaling pathway involving Syk kinase and the adaptor CARD9, is critical inducing Th17 fungal We show that another C-type lectin, Dectin-2, also signals contributes dendritic cell (DC) activation by particles. Unlike Dectin-2 couples indirectly, through association FcRgamma chain. In model Candida...
Lymphatic vessels develop from specialized endothelial cells in preexisting blood vessels, but the molecular signals that regulate this separation are unknown. Here we identify a failure to separate emerging lymphatic mice lacking hematopoietic signaling protein SLP-76 or Syk. Blood-lymphatic connections lead embryonic hemorrhage and arteriovenous shunting. Expression of slp-76 could not be detected cells, blood-filled lymphatics also arose wild-type reconstituted with SLP-76-deficient bone...
Recognition of microbial components by germ-line encoded pattern recognition receptors (PRR) initiates immune responses to infectious agents. We and others have proposed that pairs or sets PRR mediate host immunity. One such pair comprises the fungal beta-glucan receptor, Dectin-1, which collaborates through an undefined mechanism with Toll-like receptor 2 (TLR2) induce optimal cytokine in macrophages. show here Dectin-1 signaling spleen tyrosine kinase (Syk) pathway is required for this...
Homologous sets of transcription factors direct conserved tissue-specific gene expression, yet factor-binding events diverge rapidly between closely related species. We used hepatocytes from an aneuploid mouse strain carrying human chromosome 21 to determine, on a chromosomal scale, whether interspecies differences in transcriptional regulation are primarily directed by genetic sequence or nuclear environment. Virtually all locations, landmarks initiation, and the resulting expression...
Setting the tempo for development Many animals display similarities in their organization (body axis, organ systems, and so on). However, they can vastly different life spans thus must accommodate developmental time scales. Two studies now compare human mouse (see Perspective by Iwata Vanderhaeghen). Matsuda et al. studied mechanism which segmentation clock displays an oscillation period of 5 to 6 hours, whereas is 2 3 hours. They found that biochemical reactions, including protein...
<ns4:p>In this article, we first present a summary of the general assumptions about Down syndrome (DS) still to be found in literature. We go on show how new research has modified these assumptions, pointing wide range individual differences at every level description. argue that, context significant increases DS life expectancy, focus trisomy 21 all levels—genetic, cellular, neural, cognitive, behavioral, and environmental—constitutes one best approaches for understanding genotype/phenotype...