- HIV Research and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Chemokine receptors and signaling
- HIV/AIDS Research and Interventions
- HIV-related health complications and treatments
- Mosquito-borne diseases and control
- Herpesvirus Infections and Treatments
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Birth, Development, and Health
- Cytomegalovirus and herpesvirus research
- Multiple Sclerosis Research Studies
- Inflammasome and immune disorders
- Genetic Associations and Epidemiology
- interferon and immune responses
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- Epigenetics and DNA Methylation
- RNA Interference and Gene Delivery
- Infectious Encephalopathies and Encephalitis
- Cell Adhesion Molecules Research
- Virus-based gene therapy research
- Glycosylation and Glycoproteins Research
- Viral Infections and Vectors
University of Alberta
2016-2025
Cork University Hospital
2025
Great Ormond Street Hospital
2017-2023
University College London
2014-2023
University of Calgary
2007-2023
Alberta Hip and Knee Clinic
2001-2023
Vancouver Infectious Diseases Centre
2023
Alberta Health Services
2010-2023
Women and Children’s Health Research Institute
2016-2022
South Australian Health and Medical Research Institute
2016-2022
Several members of the chemokine receptor family have been shown to function in association with CD4 permit HIV-1 entry and infection. However, mechanism by which these molecules serve as CD4-associated cofactors is unclear. In present report, we show that one member this family, termed Fusin/CXCR4, able an alternative for some isolates HIV-2 absence CD4. This conclusion supported finding (1) CD4-independent infection viruses inhibited anti-Fusin monoclonal antibody, (2) Fusin expression...
Chemokines provide directional cues for leukocyte migration and activation that are essential normal leukocytic trafficking host responses during processes such as inflammation, infection, cancer. Recently we reported matrix metalloproteinases (MMPs) modulate the activity of CC chemokine monocyte chemoattractant protein-3 by selective proteolysis to release N-terminal tetrapeptide. Here report processing, also at position 4-5, CXC chemokines stromal cell-derived factor (SDF)-1alpha beta...
Activated monocytes release a number of substances, including inflammatory cytokines and eicosanoids, that are highly toxic to cells the central nervous system. Because monocytic infiltration system closely correlates with HIV-1-associated dementia, it has been suggested monocyte-derived toxins mediate damage. In present study, we show HIV-1 transactivator protein Tat significantly increases astrocytic expression monocyte chemoattractant protein-1 (MCP-1). Astrocytic β-chemokines, which...
Chemokines are 8-10 kDa proteins involved in the control of leukocyte trafficking and activation. In free solution, chemokines monomers at physiologic concentrations, although many multimerize higher concentrations. Cell surface heparan sulfate may sequester chemokines, increasing their local concentrations facilitating binding to receptors expressed on leukocytes. competitive assays using immobilized heparin, a 2-3-fold increase bound radiolabeled chemokine was seen with unlabeled nanomolar...
The chemokine thymus and activation-regulated (TARC; CCL17) is displayed by cutaneous (but not intestinal) venules, thought to trigger vascular arrest of circulating skin homing memory T cells, which uniformly express the TARC receptor CC (CCR)4. Cutaneous cell–attracting (CTACK; CCL27), expressed keratinocytes, also attracts hypothesized assist in lymphocyte recruitment as well. Here we show that chronic inflammation induces CD4 cells expressing E-selectin binding activity (a marker cells)...
Kaposi's sarcoma-associated herpesvirus encodes a chemokine called vMIP-II. This protein displayed broader spectrum of receptor activities than any mammalian as it bound with high affinity to number both CC and CXC receptors. Binding vMIP-II, however, was not associated the normal, rapid mobilization calcium from intracellular stores; instead, blocked induced by endogenous chemokines. In freshly isolated human monocytes virally encoded vMIP-II acted potent efficient antagonist chemotaxis...
Significance The pore-forming protein gasdermin D (GSDMD) was recently identified as the principal executioner of pyroptosis (“fiery death”), a type proinflammatory programmed cell death driven by inflammasomes. Caspase-1 cleaves GSDMD, but whether this process contributes to neuroinflammation is unknown. Here, we report evidence GSDMD-mediated primary mechanism inflammatory demyelination in central nervous system during multiple sclerosis (MS), debilitating and incurable demyelinating...
Abstract The pathogenesis of the dementia associated with human immunodeficieny virus (HIV) infection is unclear, but has been postulated to be due indirect effects HIV including local production cytokines. To determine which cytokines are produced in nervous system and identify correlations dementia, cytokine messenger RNA expression was analyzed by reverse transcriptase‐polymerase chain reaction brains from 24 HIV‐ infected patients without 9 uninfected control subjects. Levels tumor...
Dendritic cells (DC) are migratory that exhibit complex trafficking properties in vivo. The present study was designed to characterize receptor expression and responsiveness chemoattractants of human DC obtained from PBMC by culture with granulocyte/macrophage-CSF IL-13. expressed appreciable levels the CCR1, CCR2, CCR5 receptors for CC chemokines chemokine CXCR1, CXCR2, CXCR4. increased intracellular free calcium migrated response MCP-3, MCP-4, RANTES, MIP-1alpha, MIP-1beta, MIP-5/HCC2 CXC...
Summary: HIV dementia has an annual incidence of 7% after AIDS development and eventually affects 20% all HIV-infected persons. Accurate early diagnosis can lead to optimized therapeutic management decisions. The purpose this study was design a valid instrument identify dementia. Five groups totalling 152 outpatients were evaluated: HIV-seronegative (SN) (n = 34); asymptomatic HIV-seropositive (ASX) 38); AIDS, nondemented (AIDS) 53); mildly demented (Dm) 39); severely (Ds) 7). None had CNS...
<h3>Importance</h3> Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits observationally associated with weight, but the causal nature these associations is uncertain. <h3>Objective</h3> To test for genetic evidence body mass index (BMI) related weight. <h3>Design, Setting, Participants</h3> Mendelian randomization whether BMI potentially causally offspring Data from 30 487 in 18 studies were analyzed....
Abstract Currently there are multiple teacher education reform policies being proposed, piloted, and debated at a variety of levels by various interest groups, stakeholders, policy-makers. Along with an unprecedented sense urgency about these important goals, what most U.S. reforms have in common is increased accountability. Using discourse approach to policy analysis, which we label "the politics policy," this article analyzes three complicated evolving contemporary accountability...
Human immunodeficiency virus type 1(HIV-1) infects and activates innate immune cells in the brain resulting inflammation neuronal death with accompanying neurological deficits. Induction of inflammasomes causes cleavage release IL-1β IL-18, representing pathogenic processes that underlie inflammatory diseases although their contribution HIV-associated disease is unknown. Investigation inflammasome-associated genes revealed IL-1β, IL-18 caspase-1 were induced brains HIV-infected persons...