A5007124437- Phagocytosis and Immune Regulation
- Cellular transport and secretion
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Lipid Membrane Structure and Behavior
- Immune Response and Inflammation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- SARS-CoV-2 detection and testing
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- T-cell and B-cell Immunology
- Biosensors and Analytical Detection
- Autophagy in Disease and Therapy
- Neuroinflammation and Neurodegeneration Mechanisms
- Erythrocyte Function and Pathophysiology
- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Complement system in diseases
- Advanced biosensing and bioanalysis techniques
- CAR-T cell therapy research
- Sphingolipid Metabolism and Signaling
- Calcium signaling and nucleotide metabolism
- Cholesterol and Lipid Metabolism
- Advanced Fluorescence Microscopy Techniques
- Mosquito-borne diseases and control
University of Calgary
2021-2024
Ontario Brain Institute
2023-2024
The Francis Crick Institute
2018-2023
Hospital for Sick Children
2013-2023
University College London Hospitals NHS Foundation Trust
2020
University College London
2020
National Hospital for Neurology and Neurosurgery
2020
University of Florida
2010-2012
Macrophages respond to changes in environmental stimuli by assuming distinct functional phenotypes, a phenomenon referred as macrophage polarization. We generated classically (M1) and alternatively (M2) polarized macrophages--two extremes of the polarization spectrum--to compare properties their phagosomes. Specifically, we analyzed regulation luminal pH after particle engulfment. The phagosomes M1 macrophages had similar buffering power proton (equivalent) leakage permeability but...
Abstract Macropinocytosis can be induced in several cell types by stimulation with growth factors. In selected types, notably macrophages and dendritic cells, macropinocytosis occurs constitutively, supporting the uptake of antigens for subsequent presentation. Despite their different mode initiation contrasting physiological roles, it is tacitly assumed that both are mechanistically identical. We report constitutive stringently calcium dependent, while stimulus-induced not. Extracellular...
Macrophages and dendritic cells exposed to lipopolysaccharide (LPS) convert their lysosomes from small, punctate organelles into a network of tubules. Tubular have been implicated in phagosome maturation, retention fluid phase, antigen presentation. There is growing appreciation that act as sensors stress the metabolic state cell through kinase mTOR. Here we show LPS stimulates mTOR required for LPS-induced lysosome tubulation secretion major histocompatibility complex II macrophages cells....
T-cell immunoglobulin mucin protein 4 (TIM4), a phosphatidylserine (PtdSer)-binding receptor, mediates the phagocytosis of apoptotic cells. How TIM4 exerts its function is unclear, and conflicting data have emerged. To define mode action TIM4, we used two distinct but complementary approaches: 1) compared bone marrow-derived macrophages from wild-type TIM4(-/-) mice, 2) heterologously expressed in epithelioid AD293 cells, which rendered them competent for engulfment PtdSer-bearing targets....
Cross-presentation of antigens from dead tumor cells by type 1 conventional dendritic (cDC1s) is thought to underlie priming anti-cancer CD8
Human mesenchymal stem/stromal cells (MSCs) have been reported to produce an M2-like, alternatively activated phenotype in macrophages. In addition, MSCs mediate effective bacterial clearance pre-clinical sepsis models. Thus, a paradoxical antimicrobial and anti-inflammatory response that is not understood. Here, we studied the phenotypic functional of monocyte-derived human macrophages MSC exposure vitro . induced two distinct, coexistent phenotypes: M2-like (generally elongated morphology,...
ABSTRACT Aspergillus fumigatus , an opportunistic fungal pathogen, spreads in the environment by releasing numerous conidia that are capable of reaching small alveolar airways mammalian hosts. In otherwise healthy individuals, macrophages responsible for rapidly phagocytosing and eliminating these conidia, effectively curbing their germination consequent invasion pulmonary tissue. However, under some circumstances, fungus evades phagocyte-mediated immunity persists respiratory tree. Here, we...
Macropinocytosis mediates the uptake of antigens and nutrients that dictate regulation cell growth by mechanistic target rapamycin complex 1 (mTORC1). Because these functions differ in proinflammatory anti-inflammatory macrophages, we compared macropinocytic ability two extreme polarization states. We found macrophages perform vigorous macropinocytosis constitutively, while cells are virtually inactive. The total cellular content Rho-family GTPases was higher cells, but this disparity failed...
Conventional dendritic cells (cDCs) generate protective cytotoxic T lymphocyte (CTL) responses against extracellular pathogens and tumors. This is achieved through a process known as cross-presentation (XP), and, despite its biological importance, the mechanism(s) driving XP remains unclear. Here, we show that cDC-specific pore-forming protein called apolipoprotein L 7C (APOL7C) up-regulated in response to innate immune stimuli recruited phagosomes. Association of APOL7C with phagosomes led...
Parasitophorous vacuoles (PV) that harbour Leishmania parasites acquire some characteristics from fusion with host cell vesicles. Recent studies have shown PVs and display resident endoplasmic reticulum (ER) molecules. We investigated the importance of ER molecules to PV biology by assessing consequence blocking vesicles originate early secretory pathway. This was achieved targeting N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) mediate In presence dominant negative...
Excessive uptake of oxidized low-density lipoproteins (oxLDL) by macrophages is a fundamental characteristic atherosclerosis. However, signals regulating the engagement these ligands remain elusive. Using single-molecule imaging, we discovered mechanism whereby chemokine signaling enhanced binding oxLDL to scavenger receptor, CD36. By activating Rap1-GTPase, chemokines promoted integrin-mediated adhesion substratum. As result, cells exhibited pronounced remodeling cortical actin cytoskeleton...
<ns4:p>The ongoing pandemic of SARS-CoV-2 calls for rapid and cost-effective methods to accurately identify infected individuals. The vast majority patient samples is assessed viral RNA presence by RT-qPCR. Our biomedical research institute, in collaboration between partner hospitals an accredited clinical diagnostic laboratory, established a testing pipeline that has reported on more than 252,000 RT-qPCR results since its commencement at the beginning April 2020. However, due demand...
<ns4:p>The ongoing pandemic of SARS-CoV-2 calls for rapid and cost-effective methods to accurately identify infected individuals. The vast majority patient samples is assessed viral RNA presence by RT-qPCR. Our biomedical research institute, in collaboration between partner hospitals an accredited clinical diagnostic laboratory, established a testing pipeline that has reported on more than 252,000 RT-qPCR results since its commencement at the beginning April 2020. However, due demand...