A5037158345- Immune Cell Function and Interaction
- Immune cells in cancer
- T-cell and B-cell Immunology
- Protein Tyrosine Phosphatases
- Cancer Immunotherapy and Biomarkers
- Cytokine Signaling Pathways and Interactions
- IL-33, ST2, and ILC Pathways
- Galectins and Cancer Biology
- Chemokine receptors and signaling
- Monoclonal and Polyclonal Antibodies Research
- Cancer Genomics and Diagnostics
- Glycosylation and Glycoproteins Research
- Immunodeficiency and Autoimmune Disorders
- Immunotherapy and Immune Responses
- Protein Kinase Regulation and GTPase Signaling
- Cell Adhesion Molecules Research
- Atherosclerosis and Cardiovascular Diseases
- Endoplasmic Reticulum Stress and Disease
- RNA Interference and Gene Delivery
- RNA modifications and cancer
- Cancer Cells and Metastasis
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Inflammasome and immune disorders
- Asthma and respiratory diseases
University of British Columbia
2012-2024
BC Cancer Agency
2013
University of Michigan
2013
Ludwig Cancer Research
2001-2012
McGill University Health Centre
2009
McGill University
2009
Ludwig Cancer Research
2009
The Royal Melbourne Hospital
2001-2007
Walter and Eliza Hall Institute of Medical Research
2004
Cooperative Research Centre for Tissue Growth and Repair
2004
The intraerythrocytic parasite Plasmodium—the causative agent of malaria—produces an inorganic crystal called hemozoin (Hz) during the heme detoxification process, which is released into circulation erythrocyte lysis. Hz rapidly ingested by phagocytes and induces production several pro-inflammatory mediators such as interleukin-1β (IL-1β). However, mechanism regulating recognition IL-1β maturation has not been identified. Here, we show that production. Using knockout mice, showed Hz-induced...
The type III transforming growth factor β (TGFβ) receptor (TβRIII) binds both TGFβ and inhibin with high affinity modulates the association of these ligands their signaling receptors. However, significance TβRIII in vivo is not known. In this study, we have sought to determine role during development. We identified predominant expression sites ΤβRIII mRNA as liver heart midgestation disrupted murine gene by homologous recombination. Beginning at embryonic day 13.5, mice mutations developed...
A role for Lyn kinase as a positive regulator of immunoglobulin (Ig)E-dependent allergy has long been accepted. Contrary to this belief, was found have an important negative the allergic response. This became apparent from hyperresponsive degranulation lyn−/− bone marrow–derived mast cells, which is driven by hyperactivation Fyn that occurs, in part, through loss regulation COOH-terminal Src (Csk) and adaptor, Csk-binding protein. phenotype recapitulated vivo young mice showed enhanced...
The intracellular domain of human protein tyrosine phosphatase beta (HPTP beta) (44 kDa) was expressed in bacteria, purified using epitope 'tagging' immunoaffinity chromatography, and characterized with respect to kinetic profile, substrate specificity potential modulators enzyme activity. A chromogenic assay based on the Malachite Green method employed for detection inorganic phosphate (Pi) released from phosphopeptides by HPTP beta. This assay, modified so as improve its sensitivity,...
Genetic ablation of the Lyn tyrosine kinase has revealed unique inhibitory roles in B lymphocyte signaling. We now report consequences sustained activation vivo using a targeted gain-of-function mutation (Lynup/up mice). Lynup/up mice have reduced numbers conventional lymphocytes, down-regulated surface immunoglobulin M and costimulatory molecules, elevated B1a cells. cells are characterized by constitutive phosphorylation negative regulators cell antigen receptor (BCR) signaling including...
The roles of protein-tyrosine phosphatases (PTPs) in processes such as cell growth and adhesion are poorly understood. To explore the ability specific PTPs to regulate signaling pathways initiated by stimulation factor receptors, we expressed receptor-like PTP, PTPα, A431 epidermoid carcinoma cells. These cells express high levels epidermal (EGF) receptor proliferate response autocrine production transforming factor-α. Conversely, EGF <i>in vitro</i> leads inhibition triggers rapid...
Vascular endothelial growth factor (VEGF)-D is a secreted glycoprotein that induces angiogenesis and lymphangiogenesis. It consists of central domain, containing binding sites for VEGF receptor-2 (VEGFR-2) VEGFR-3, N- C-terminal propeptides. from the cell as homodimers full-length form can be proteolytically processed to remove was recently shown, using adenoviral gene delivery, fully VEGF-D in vivo, whereas does not. To better understand these observations, we monitored effect processing on...
Fibrosis is the result of dysregulated tissue regeneration and characterized by excessive accumulation matrix proteins that become detrimental to function. In Crohn's disease, this manifests itself as recurrent gastrointestinal strictures for which there no effective therapy beyond surgical intervention. Using a model infection-induced chronic gut inflammation, we show Rora-deficient mice are protected from fibrosis; infected intestinal tissues display diminished pathology, attenuated...
To identify the physiological role of Hck, a functionally redundant member Src family tyrosine kinases expressed in myelomonocytic cells, we generated Hck(F/F) "knock-in" mice which carry targeted (Y) to phenylalanine (F) substitution COOH-terminal, negative regulatory Y(499)-residue Hck protein. Unlike their Hck(-/-) "loss-of-function" counterparts, "gain-of-function" spontaneously acquired lung pathology characterized by extensive eosinophilic and mononuclear cell infiltration within...
The Lyn tyrosine kinase plays essential inhibitory signaling roles within hematopoietic cells by recruiting phosphatases such as SH2-domain containing phosphatase-1 (SHP-1), SHP-2, and 5'-inositol phosphatase (SHIP-1) to the plasma membrane in response specific stimuli. Lyn-deficient mice display a collection of defects, including autoimmune disease result autoantibody production, perturbations myelopoiesis that ultimately lead splenomegaly myeloid neoplasia. In this study, we demonstrate...
The src homology 2 (SH2) domain containing protein-tyrosine-phosphatase SH-PTP2, was over-expressed in Escherichia coli for a kinetic study employing set of synthetic 13- to 14-mer phosphopeptide substrates. full-length SH-PTP2 protein, as well truncated form, lacking the two amino terminus SH2 domains (SH-PTP2(delta SH2)), exhibited Michaelis-Menten kinetics, and demonstrated striking substrate preferences on phosphopeptides having sequences based sites intracellular protein tyrosine...
Abstract The etiology of asthma, a chronic inflammatory disorder the airways, remains obscure, although T cells appear to be central disease mediators. Lyn tyrosine kinase has been implicated as both facilitator and inhibitor signaling pathways that play role in allergic inflammation, its asthma is unclear because not expressed cells. We show present study Lyn−/− mice develop severe, persistent asthma-like syndrome with lung eosinophilia, mast cell hyperdegranulation, intensified...
The intraerythrocytic parasite Plasmodium-the causative agent of malaria-produces an inorganic crystal called hemozoin (Hz) during the heme detoxification process, which is released into circulation erythrocyte lysis.Hz rapidly ingested by phagocytes and induces production several pro-inflammatory mediators such as interleukin-1b (IL-1b).However, mechanism regulating Hz recognition IL-1b maturation has not been identified.Here, we show that production.Using knockout mice, showed Hz-induced...
Abstract Cancer is associated with immune dysfunction characterized by the presence of proinflammatory and immunosuppressive cells factors that contribute to tumor growth progression. Here we show mammary defects in hematopoiesis, leading myeloproliferative-like disease (leukemoid reaction), anemia, disruption bone marrow stem/progenitor compartment. The included impaired erythropoiesis, leukocytosis, loss early progenitor marrow, splenic extramedullary hematopoiesis. We established an vitro...
Abstract We describe a simple, fast, sensitive, and nonisotopic bioanalytical technique for the detection of tyrosine‐phosphorylated peptides determination sites protein tyrosine phosphorylation. The employs phosphatase micro enzyme reactor coupled on‐line to either capillary electrophoresis or liquid chromatography electrospray ionization mass spectrometry instruments. was constructed by immobilizing genetically engineered, metabolically biotinylated human β onto inner surface small piece...
Monocytes are key effectors of the mononuclear phagocyte system, playing critical roles in regulating tissue homeostasis and coordinating inflammatory reactions, including those involved chronic diseases such as atherosclerosis. have traditionally been divided into 2 major subsets termed conventional monocytes patrolling (pMo) but recent systems immunology approaches identified marked heterogeneity within these cells, much what regulates monocyte population remains unknown. We others...
The Lyn tyrosine kinase is a unique member of the Src family non-receptor protein kinases whose principal role to regulate signals through inhibitory receptors thereby promoting signal attenuation. renowned for its in B cell antigen receptor and FcεRI signaling; however, it becoming increasingly apparent that also functions transduction from growth factor including GM-CSF, IL-3, IL-5, SCF, erythropoietin, CSF-1, G-CSF, thrombopoietin Flt3 ligand. Numerous studies have implicated...
Insight into the regulation of actions protein‐tyrosine kinases will be greatly facilitated by full characterization family phosphatases. A search for novel phosphatases resulted in isolation a cDNA, termed HLPR, encoding member human receptor‐like phosphatases: its cDNA sequence predicts protein 793 amino acids (unglycosylated M r , 87500) and includes 121 residue extracellular domain, single transmembrane segment, two tandem intra‐cytoplasmic catalytic domains. The HLPR gene is located on...