A5052314402- Parasites and Host Interactions
- Immunodeficiency and Autoimmune Disorders
- IL-33, ST2, and ILC Pathways
- Immune cells in cancer
- Parasite Biology and Host Interactions
- Inflammatory Bowel Disease
- Helminth infection and control
- Helicobacter pylori-related gastroenterology studies
- Immune Response and Inflammation
- Parasitic infections in humans and animals
- Blood disorders and treatments
- Cell Adhesion Molecules Research
- Reproductive System and Pregnancy
- Digestive system and related health
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Gut microbiota and health
- Influenza Virus Research Studies
- Liver Diseases and Immunity
- Abdominal vascular conditions and treatments
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune responses and vaccinations
- Barrier Structure and Function Studies
- Congenital gastrointestinal and neural anomalies
- melanin and skin pigmentation
AstraZeneca (Sweden)
2023
SickKids Foundation
2018-2021
Hospital for Sick Children
2017-2020
University of Calgary
2010-2020
University of Toronto
2018-2020
Institute of Infection and Immunity
2010
Canadian Society of Intestinal Research
2010
Australian National University
1981
Macrophages are important innate immune cells that associated with two distinct phenotypes: a pro-inflammatory (or classically activated) subset prototypic macrophage functions such as inflammatory cytokine production and bactericidal activity, an anti-inflammatory alternatively activated (AAM)) linked wound healing tissue repair processes. In this study, we examined the effect of interlukein-6 on human murine polarization. The results indicate despite being commonly implicated in...
Abstract Human actin-related protein 2/3 complex (Arp2/3), required for actin filament branching, has two ARPC1 component isoforms, with ARPC1B prominently expressed in blood cells. Here we show a child microthrombocytopenia, eosinophilia and inflammatory disease, homozygous frameshift mutation (p.Val91Trpfs*30). Platelet lysates reveal no greatly reduced Arp2/3 complex. Missense mutations are identified an unrelated patient similar symptoms deficiency. ARPC1B-deficient platelets...
Human IL-4 macrophages promote epithelial wound recovery and suppress colitis, supporting their use as a cell therapy for IBD.
Background & AimsMutations in the tetratricopeptide repeat domain 7A gene (TTC7A) cause intestinal epithelial and immune defects. Patients can become deficient develop apoptotic enterocolitis, multiple atresia, recurrent stenosis. The disease patients with TTC7A deficiency is severe untreatable, it recurs despite resection or allogeneic hematopoietic stem cell transplant. We screened drugs for those that prevent apoptosis of cells tested their effects an animal model disease.MethodsWe...
Helminth parasites provoke multicellular immune responses in their hosts that can suppress concomitant disease. The gut lumen-dwelling tapeworm Hymenolepis diminuta, unlike other assessed as helminth therapy, causes no host tissue damage while potently suppressing murine colitis. With the goal of harnessing immunomodulatory capacity infection with H. we putative generation anti-colitic regulatory B cells following diminuta infection. Splenic CD19(+) isolated from mice infected 7 [HdBc(7(d))]...
Alternatively activated macrophages (AAMs) (or M2a) can inhibit colitis but may also be associated with fibrosis. Thus, by using the dinitrobenzene sulfonic (DNBS) murine model of colitis, this study aimed to determine whether 1) bone marrow (BM)-derived AAMs could reduce 2) any anticolitic effect BM-AAMs was IL-10 dependent, and 3) repeated AAM treatments remained effective were fibrosis in gut or other tissues. Balb/c mice received (10 6 intraperitoneally) from wild-type (WT) −/− 48 h...
Infection with helminth parasites and treatment worm extracts can suppress inflammatory disease, including colitis. Postulating that dendritic cells (DCs) participated in the suppression of inflammation seeking to move beyond use helminths per se, we tested ability Hymenolepis diminuta antigen-pulsed DCs colitis as a novel cell-based immunotherapy. Bone marrow derived pulsed H. antigen (HD-DCs), or PBS-, BSA-, LPS-DCs controls, were transferred into wild-type (WT), interleukin-10 (IL-10)...
Interleukin (IL)-22, an immune cell-derived cytokine whose receptor expression is restricted to non-immune cells (e.g. epithelial cells), can be anti-inflammatory and pro-inflammatory. Mice infected with the tapeworm Hymenolepis diminuta are protected from dinitrobenzene sulphonic acid (DNBS)-induced colitis. Here we assessed expulsion of H. diminuta, concomitant response outcome DNBS-induced colitis in wild-type (WT) IL-22 deficient mice (IL-22-/-) ± infection. Interleukin-22-/- had a...
Awareness of the immunological underpinnings host-parasite interactions may reveal immune signaling pathways that could be used to treat inflammatory disease in humans. Previously we showed infection with rat tapeworm, Hymenolepis diminuta, as a model helminth, or systemic delivery worm antigen (HdAg) significantly reduced severity dinitrobenzene sulfonic acid (DNBS)-induced colitis mice. Extending these analyses, intraperitoneal injection HdAg dose-dependently suppressed dextran sodium...
Interferon gamma (IFNγ) is an important regulatory cytokine that can exert a pro-inflammatory effect in the gut, where it has been shown to increase epithelial permeability via disruption of tight junctions. Here we investigated potential for IFNγ regulate adherens junction protein E-cadherin, mediator normal tissue function, using model T84 human colonic cell line. (10 ng/ml) stimulated increased internalization E-cadherin as assessed by immunofluorescence microscopy; was reversed when...
Immune cells exhibit low-level, constitutive signaling at rest (tonic signaling). Such tonic signals are required for fundamental processes, including the survival of B lymphocytes, but when they elevated by genetic or environmental causes, can lead to autoimmunity. Events that control ongoing signal transduction are, therefore, tightly regulated submembrane cytoskeletal polymers like F-actin. The actin-binding proteins underpin process, however, poorly described. By investigating patients...
The adoptive transfer of alternatively activated macrophages (AAMs) has proven to attenuate inflammation in multiple mouse models colitis; however, the effect cryopreservation on AAMs, ability previously frozen AAMs block dinitrobenzene sulfonic acid (DNBS) (Th1) and oxazolone (Th2) colitis their migration postinjection remains unknown. Here we have found that while reduced mRNA expression canonical markers interleukin (IL)-4-treated [M(IL-4)], this step did not translate protein or...
Macrophages play central roles in immunity as early effectors and modulating adaptive immune reponses; we implicated macrophages the anticolitic effect of infection with tapeworm Hymenolepis diminuta. Here, gene arrays revealed that H. diminuta antigen (HdAg) evoked a program murine distinct from elicited by IL-4. Further, HdAg suppressed LPS-evoked release TNF-α IL-1β via autocrine IL-10 signaling. In assessing ability treated vitro an extract [M(HdAg)] to affect disease, intravenous, but...
Abstract Very early onset inflammatory bowel disease (VEOIBD) denotes children with of IBD before six years age. A number monogenic disorders are associated VEOIBD including tetratricopeptide repeat domain 7A (TTC7A) deficiency. TTC7A-deficiency is characterized by apoptotic colitis in milder cases severe intestinal atresia and immunodeficiency complete loss protein. We used whole exome sequencing a patient presenting colonic apoptosis no identified known variants, to identify compound...
There is limited information on how indoor tanning promotes melanoma development. We investigated use in patients with melanomas sun-exposed skin and studied the clinicopathological molecular characteristics relation to exposure. Patients from a multidisciplinary clinic for cutaneous cancers completed standardized questionnaires risk factors as component of medical history at their initial consultations. For this study, we included December 2013 May 2015. The 114 who reported exposure were...
Background Awareness of the immunological basis host‐parasite interactions can reveal new approaches to cure and/or treat inflammatory disease. We have shown that mice infected with tapeworm Hymenolepis diminuta (Hd) or systemic delivery worm antigen (HdAg) developed significantly less severe dinitrobenzene sulphonic acid (DNBS)‐induced murine colitis. Aim In ongoing analyses this helminth‐mouse model system we assessed effect HdAg and adoptive transfer HdAg‐recruited peritoneal exudate...
Wnt/β-catenin signaling plays an important role in controlling lung epithelial cell homeostasis and fate commitment is dysregulated COPD with reduced Wnt activity. As it controls alveolar self-renewal, we performed a whole genome CRISPR screen to identify negative regulators of for potential regenerative therapies addressing emphysema. 152 hits were identified A549 cells (p<0.1 vs. neutral control), which then screened small airway pathway activation by β-catenin nuclear translocation...