A5076944041- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Signaling Pathways in Disease
- CAR-T cell therapy research
- Cytokine Signaling Pathways and Interactions
- Galectins and Cancer Biology
- Immunotherapy and Immune Responses
- Platelet Disorders and Treatments
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- Mast cells and histamine
- Glycosylation and Glycoproteins Research
- Protein Kinase Regulation and GTPase Signaling
- Protein Tyrosine Phosphatases
- Asthma and respiratory diseases
- PI3K/AKT/mTOR signaling in cancer
- Cancer Immunotherapy and Biomarkers
- Blood disorders and treatments
- Immunodeficiency and Autoimmune Disorders
- Ubiquitin and proteasome pathways
- NF-κB Signaling Pathways
- Cell death mechanisms and regulation
- Receptor Mechanisms and Signaling
- Blood properties and coagulation
Cancer Research Institute
2008-2024
University of Pennsylvania
2009-2024
Cornell University
2013-2024
Weill Cornell Medicine
2017-2024
UPMC Hillman Cancer Center
2001-2013
Abramson Center for Jewish Life
2000-2012
Cancer Research Institute of the Slovak Academy of Sciences
2001-2011
Cancer Research Center
2010-2011
Health Affairs
2011
Center for Rheumatology
2008
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...
The leukocyte-specific adapter molecule SLP-76 (Src homology 2 domain–containing leukocyte protein of 76 kilodaltons) is rapidly phosphorylated on tyrosine residues after receptor ligation in several hematopoietically derived cell types. Mice made deficient for expression contained no peripheral T cells as a result an early block thymopoiesis. Macrophage and natural killer compartments were intact SLP-76–deficient mice, despite these lineages wild-type mice. Thus, the required normal...
Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are 2 similar diseases characterized by a cytokine storm, overwhelming inflammation, multiorgan dysfunction, death. Animal models of HLH suggest that disease is driven IFN-γ produced CD8⁺ lymphocytes stimulated persistent antigen exposure. In these patients with "primary" HLH, the persists due to genetic defects, resulting in ineffective cytotoxic responses T cells poor pathogen clearance. However, infectious...
Stimulation of the T-cell antigen receptor (TCR), which itself is not a protein-tyrosine kinase (PTK), activates PTK and phospholipase C (PLC). Using human leukemic line Jurkat normal peripheral blood lymphocytes, we demonstrate that stimulation TCR specifically induces recovery PLC activity in eluates from anti-phosphotyrosine immunoprecipitates. muscarinic receptor, subtype 1, when expressed through guanine nucleotide binding protein but does induce Western blot analysis reveals PLC-gamma...
CD45, a hematopoietic cell-specific surface antigen, has recently been shown to be protein tyrosine phosphatase. Expression of CD45 is essential for the T-cell antigen receptor couple with phosphatidylinositol second messenger pathway and antigen-mediated proliferation T lymphocytes. In this report we describe CD45-deficient mutant human leukemia line Jurkat. expression required activation receptor-associated kinase as well pathway. Additionally, stimulation lymphocytes by way accessory...
The activation of protein tyrosine kinases is a critical event in T cell antigen receptor (TCR)-mediated signaling. One substrate the TCR-activated kinase pathway 76-kDa (pp76) that associates with adaptor Grb2. In this report we describe purification pp76 and molecular cloning its cDNA, which encodes novel 533-amino acid single carboxyl-terminal Src homology 2 (SH2) domain. Although no recognizable motifs related to tyrosine, serine/threonine, or lipid domains are present predicted amino...
SLAP-130/Fyb (SLP-76–associated phosphoprotein or Fyn-binding protein; also known as Fyb/Slap) is a hematopoietic-specific adapter, which associates with and modulates function of SH2-containing leukocyte 76 kilodaltons (SLP-76). T cells from mice lacking show markedly impaired proliferation following CD3 engagement. In addition, the cell receptor (TCR) in mutant fails to enhance integrin-dependent adhesion. Although TCR-induced actin polymerization normal, TCR-stimulated clustering integrin...
Ligation of the multimeric T-cell antigen receptor complex (TCR) triggers a pleiotropic cellular activation response that includes lymphokine secretion, cell-cycle progression, and ultimately, proliferation. The earliest detectable biochemical event triggered by TCR cross-linkage is tyrosine phosphorylation specific intracellular proteins, which, in turn, propagate receptor-mediated signals into cytoplasm nucleus. In this study, we have examined effects pervanadate, powerful inhibitor...
Abstract Although previous studies have investigated the role of IL-27/WSX-1 interactions in regulation Th1 responses, little is known about their regulating Th2-type responses. Studies presented this work identify a direct for negative type 2 responses independent effects on 1 cytokines. WSX-1−/− mice infected with gastrointestinal helminth Trichuris muris displayed accelerated expulsion parasites and development exaggerated goblet cell hyperplasia mastocytosis gut due to increased...
Dystroglycan is a novel laminin receptor that links the extracellular matrix and sarcolemma in skeletal muscle. The dystroglycan complex containing alpha- beta-dystroglycan also serves as an agrin muscle, where it may regulate agrin-induced acetylcholine clustering at neuromuscular junction. beta-Dystroglycan has now been expressed vitro shown to directly interact with Grb2, adapter protein involved signal transduction cytoskeletal organization. Protein binding assays two Grb2 mutants,...
Activation of lymphocytes through their antigen receptors leads to mobilization intracellular Ca2+ ions. This process requires expression SLP adaptors and involves phosphorylation phospholipase C-γ isoforms by the Tec-related protein tyrosine kinase Btk in B cells Itk T cells. The SH2 domain is essential for mutations this lead X-linked agammaglobulinemia immuno deficiency humans. Here we show that, contrast domains from other signaling proteins, exhibit a restricted binding specificity....