A5074839791- Immune cells in cancer
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Inflammatory Bowel Disease
- Immunodeficiency and Autoimmune Disorders
- Cytokine Signaling Pathways and Interactions
- Phagocytosis and Immune Regulation
- Diet and metabolism studies
- T-cell and B-cell Immunology
- Gut microbiota and health
- Acute Myeloid Leukemia Research
- Mast cells and histamine
- Cancer, Lipids, and Metabolism
- Chronic Lymphocytic Leukemia Research
- Helicobacter pylori-related gastroenterology studies
- PI3K/AKT/mTOR signaling in cancer
- Cancer, Hypoxia, and Metabolism
- Sphingolipid Metabolism and Signaling
- Renal Diseases and Glomerulopathies
- Endoplasmic Reticulum Stress and Disease
- Eosinophilic Esophagitis
- Protein Tyrosine Phosphatases
- Digestive system and related health
- Liver physiology and pathology
- Monoclonal and Polyclonal Antibodies Research
University of British Columbia
2016-2025
British Columbia Children's Hospital
2012-2024
University of British Columbia Hospital
2018-2020
The Kids Research Institute Australia
2019
The University of Western Australia
2019
Child and Family Research Institute
2010-2016
BC Cancer Agency
2003-2011
National Human Genome Research Institute
2011
Terry Fox Research Institute
2005-2009
Sahlgrenska University Hospital
2006
Macrophages infected with Mycobacterium tuberculosis undergo increased rates of apoptosis. Important objectives are to define the microbial factors that cause apoptosis, mechanisms involved and impact on infection. The 19-kDa M. glycolipoprotein (p19) is both cell wall-associated secreted a candidate virulence factor. We investigated potential recombinant, His-tagged p19 lacking secretion/acylation signal induce macrophage TUNEL assay annexin V binding membrane phosphatidylserine were used...
Abstract Mcl-1 protein expression was found to be up-regulated during infection with virulent Mycobacterium tuberculosis strain H37Rv. induction in THP-1 cells optimal at a multiplicity of 0.8–1.2 bacilli per macrophage and independent opsonin coating the bacteria. elevated as early 4 h, peaked 5.8-fold above control 24 remained 48 h after infection. In cells, mMcl-1 mRNA induced by live H37Rv but not attenuated M. H37Ra, heat-killed H37Rv, or latex beads. monocyte-derived macrophages...
We investigated the basis for induction of monocyte antimycobacterial activity by 1α,25-dihydroxyvitamin D<sub>3</sub> (D<sub>3</sub>). As expected, incubation <i>Mycobacterium tuberculosis-</i>infected THP-1 cells or human peripheral blood, monocyte-derived macrophages with hormone resulted in activity. This effect was significantly abrogated pretreatment either phosphatidylinositol 3-kinase (PI 3-K) inhibitors, wortmannin LY294002, antisense oligonucleotides to p110 subunit PI 3-Kα. Cells...
Since cancer cells depend on glucose more than normal cells, we compared the effects of low carbohydrate (CHO) diets to a Western diet growth rate tumors in mice. To avoid caloric restriction-induced effects, designed CHO isocaloric with by increasing protein rather fat levels because reported tumor-promoting high and immune-stimulating protein. We found that both murine human carcinomas grew slower mice containing amylose characterized relatively There was no weight difference between...
1α,25-dihydroxyvitamin D3 (D3) promotes the maturation of myeloid cells and surface expressions CD14 CD11b, markers cell differentiation in response to D3. To examine how these responses are regulated, THP-1 were grown serum-free medium incubated with This was associated rapid transient increases phosphatidylinositol 3-kinase (PI 3-kinase) activity. Furthermore, induction expression abrogated by (a) PI inhibitors LY294002 wortmannin; (b) antisense oligonucleotides mRNA for p110 catalytic...
Abstract There is a great deal of interest in determining what regulates the generation classically activated (M1) vs alternatively (M2) macrophages (Mφs) because opposing effects that these two Mφ subsets have on tumor progression. We show herein IL-3 and, to lesser extent, GM-CSF skew murine progenitors toward an M2 phenotype, especially absence SHIP. Specifically, addition cytokines, with or without M-CSF, adherence- lineage-depleted (Lin−) SHIP−/− bone marrow (BM) cells induces high...
Macrophages are critical players in the innate immune response to infectious challenge or injury, initiating and directing acquired response. Macrophage dysfunction can lead an inability mount appropriate as such, has been implicated many disease processes, including inflammatory bowel diseases. display polarized phenotypes that broadly divided into two categories. Classically activated macrophages, by stimulation with IFNγ LPS, play essential role bacterial whereas alternatively IL-4 IL-13,...
Abstract Alternatively activated macrophages are critical in host defense against parasites and protective inflammatory bowel disease, but contribute to pathology asthma solid tumors. The mechanisms underlying alternative activation of only partially understood little is known about their amenability manipulation pathophysiological conditions. Herein, we demonstrate that Src homology 2‐domain‐containing inositol‐5′‐phosphatase (SHIP)‐deficient murine more sensitive IL‐4‐mediated skewing an...
ABSTRACT mφ are heterogeneous in their functions, and although it is clear that inflammatory contribute to inflammation IBDs, multiple lines of evidence suggest M2a may offer protection during intestinal inflammation. In vivo SHIP-deficient mouse so mice provide a unique genetic model mφ. Based on this, this study tested the hypothesis SHIP-deficient, protect from The objectives were compare susceptibility SHIP+/+ SHIP−/− littermates with DSS-induced determine whether was mφ-mediated could...
Inflammatory bowel disease, encompassing both ulcerative colitis and Crohn's is characterized by chronic, relapsing-remitting gastrointestinal inflammation of unknown etiology. SHIP deficient mice develop fully penetrant, spontaneous ileitis at 6 weeks age, thus offer a tractable model disease-like inflammation. Since disruptions to the microbiome are implicated in pathogenesis we conducted 16S rRNA gene survey ileum, cecum, colon, stool contents SHIP+/+ SHIP−/− mice. We predicted that...
Maintaining an appropriate balance between subsets of CD4(+) Th and T regulatory cells (Tregs) is critical to maintain immune homeostasis prevent autoimmunity. Through a common requirement for TGF-beta, the development peripherally induced Tregs intimately linked that Th17 cells, with resulting lineages depending on presence proinflammatory cytokines such as IL-6. Currently very little known about molecular signaling pathways control vs cells. Reduced activity PI3K pathway required...
Interleukin-1β (IL-1β) production is impaired in cord blood monocytes. However, the mechanism underlying this developmental attenuation remains unclear. Here, we analyzed extent of variability within Toll-like receptor (TLR)/NLRP3 inflammasome pathways human neonates. We show that immature low CD14 expressing/CD16(pos) monocytes predominate before 33 weeks gestation, and these cells lack pro-IL-1β precursor protein upon LPS stimulation. In contrast, high levels are produced expressing...