A5061258100- Organ Transplantation Techniques and Outcomes
- Renal Transplantation Outcomes and Treatments
- Organ Donation and Transplantation
- Cell Adhesion Molecules Research
- Chemokine receptors and signaling
- Axon Guidance and Neuronal Signaling
- Liver Disease and Transplantation
- Immune Response and Inflammation
- Apelin-related biomedical research
- Angiogenesis and VEGF in Cancer
- Renal Diseases and Glomerulopathies
- Diversity and Career in Medicine
- Transplantation: Methods and Outcomes
- Pediatric Urology and Nephrology Studies
- Phagocytosis and Immune Regulation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- S100 Proteins and Annexins
- Metabolism and Genetic Disorders
- Ion Transport and Channel Regulation
- Immune cells in cancer
- Systemic Lupus Erythematosus Research
- Glycosylation and Glycoproteins Research
- Caveolin-1 and cellular processes
- Monoclonal and Polyclonal Antibodies Research
- Neuropeptides and Animal Physiology
Hospital for Sick Children
2016-2025
University of Toronto
2016-2025
Great Ormond Street Hospital
2021-2024
University College London
2021-2024
SickKids Foundation
2005-2024
University Health Network
2013-2023
Duke University
1997-2022
Canada Research Chairs
2020-2022
Toronto General Hospital
2016-2021
University of New Brunswick
2021
Leukocyte migration into sites of inflammation involves multiple molecular interactions between leukocytes and vascular endothelial cells, mediating sequential leukocyte capture, rolling, firm adhesion. In this study, we tested the role fractalkine (FKN), a transmembrane mucin-chemokine hybrid molecule expressed on activated endothelium, its receptor (CX3CR1) in adhesion, activation under physiologic flow conditions. Immobilized FKN fusion proteins captured resting peripheral blood...
Background— Cardiac consequences of obesity include inflammation, hypertrophy, and compromised energy metabolism. Glucagon-like peptide-1 is an incretin hormone capable cytoprotective actions that reduces inflammation endoplasmic reticulum stress in other tissues. Here we examine the cardiac effects glucagon-like analog liraglutide a model obesity, independent changes body weight. Methods Results— C57Bl6 mice were placed on 45% high-fat diet (HFD) or regular chow diet. Mice HFD developed...
Hypothermic preservation is known to cause renal graft injury, especially in donation after circulatory death (DCD) kidney transplantation. We investigated the impact of cold storage (SCS) versus short periods normothermic ex vivo perfusion (NEVKP) SCS prolonged, continuous NEVKP with near avoidance on function Following 30 min warm ischemia, kidneys were removed from 30-kg Yorkshire pigs and preserved for 16 h (A) SCS, (B) 15 + 1 NEVKP, (C) 8 (D) NEVKP. After contralateral resection, grafts...
Background. Normothermic ex vivo kidney perfusion (NEVKP) has shown promising results for preservation, assessment, and reconditioning of allografts in preclinical studies. Here, we report the first North American safety feasibility study deceased donor kidneys grafts transplanted following preservation with NEVKP. Methods. Outcomes 13 human that received 1 to 3 h NEVKP after being transported an anoxic hypothermic machine device were compared a matched control group 26 preserved alone....
Abstract The hallmark of acute allograft rejection is infiltration the inflamed graft by circulating leukocytes. We studied role fractalkine (FKN) and its receptor, CX3CR1, in rejection. FKN expression was negligible nonrejecting cardiac isografts but significantly enhanced rejecting allografts. At early time points, particularly prominent on vascular tissues endothelium. As progressed, further increased, with anti-FKN staining seen around vessels myocytes. To determine capacity endothelial...
Kidney transplantation is an optimal therapy for pediatric patients with end-stage kidney disease. This pilot study sought to examine multidimensional QOL outcomes after transplant using VAQOL and General Health, the PedsQL 4.0, End Stage Renal Disease Module, Impact on Family Module. Sample included 12 adolescents aged 13-18 yr their parent; three children eight six parents of two seven yr. All were 73 months post transplant. The median age at was 9.3 time since 3.2 mean 7.7/10 (child...
Hemolytic uremic syndrome (HUS) is a potentially life-threatening condition. It often occurs after gastrointestinal infection with E. coli O157:H7, which produces Shiga toxins (Stx) that cause hemolytic anemia, thrombocytopenia, and renal injury. Stx-mediated changes in endothelial phenotype have been linked to the pathogenesis of HUS. Here we report our studies investigating Stx-induced gene expression their contribution Stx function by inactivating host ribosomes but can also alter at...
Normothermic ex vivo kidney perfusion (NEVKP) represents a novel approach for graft preservation and functional improvement in transplantation. We investigated whether NEVKP also allows quality assessment before Kidneys from 30-kg pigs were recovered model of heart-beating donation (group A) after 30 minutes B) or 60 C) (n = 5/group) warm ischemia. After 8 hours NEVKP, contralateral kidneys resected, grafts autotransplanted, the followed 3 days. transplantation, renal function measured based...
In Brief Background Donation after circulatory death (DCD) is current clinical practice to increase the donor pool. Deleterious effects on renal graft function are described for hypothermic preservation. Therefore, research focuses investigating alternative preservation techniques, such as normothermic perfusion. Methods We compared continuous pressure-controlled ex vivo kidney perfusion (NEVKP) with static cold storage (SCS) in a porcine model of DCD autotransplantation. After 30 minutes...
Better preservation strategies for the storage of donation after circulatory death grafts are essential to improve graft function and increase kidney donor pool. We compared continuous normothermic ex vivo perfusion (NEVKP) with hypothermic anoxic machine (HAMP) static cold (SCS) in a porcine autotransplantation model.Porcine kidneys were exposed 30 minutes warm ischemia then reimplanted following either 16 hours SCS, HAMP (LifePort 1.0), or NEVKP before (n = 5 per group). The contralateral...
Hypothermic kidney storage causes preservation injury and is poorly tolerated by renal grafts. We investigated whether static cold (SCS) can be safely replaced with a novel technique of pressure-controlled normothermic ex vivo perfusion (NEVKP) in heart-beating donor transplantation.Right kidneys were removed from 30 kg Yorkshire pigs model donation either preserved histidine-tryptophan-ketoglutarate solution for 8 hours (n = 5), or subjected to NEVKP 5) followed heterotopic...
In inflammatory diseases, circulating neutrophils are recruited to sites of injury. Attractant signals provided by many different chemotactic molecules, such that blockade one may not prevent neutrophil recruitment effectively. The Slit family secreted proteins and their transmembrane receptor, Robo, repel axonal migration during CNS development. Emerging evidence shows inhibiting the activation Rho-family GTPases, Slit2/Robo also inhibit other cell types toward a variety factors in vitro...
Neutrophils recruited to the postischemic kidney contribute pathogenesis of ischemia-reperfusion injury (IRI), which is most common cause renal failure among hospitalized patients. The Slit family secreted proteins inhibits chemotaxis leukocytes by preventing activation Rho-family GTPases, suggesting that members this might modulate recruitment neutrophils and resulting IRI. Here, in static microfluidic shear assays, Slit2 inhibited multiple steps required for infiltration into tissue....
Abstract Macropinocytosis is essential for myeloid cells to survey their environment and growth of RAS-transformed cancer cells. Several factors inflammatory stimuli are known induce macropinocytosis, but its endogenous inhibitors have remained elusive. Stimulation Roundabout receptors by Slit ligands inhibits directional migration many cell types, including immune We report that SLIT2 macropinocytosis in vitro vivo inducing cytoskeletal changes macrophages. In mice, attenuates the uptake...
Abstract Macrophages are important mediators of immune responses with critical roles in the recognition and clearance pathogens, as well resolution inflammation wound healing. The neuronal guidance cue SLIT2 has been widely studied for its effects on cell functions, most notably directional migration. Recently, shown to directly enhance bacterial killing by macrophages, but inflammatory activation macrophages less known. Using RNA sequencing analysis, quantitative polymerase chain reaction,...
Neutrophils are involved in the inflammatory responses during atherosclerosis. Human neutrophil peptides (HNPs) released from activated neutrophils exert immune modulating properties. We hypothesized that HNPs play an important role neutrophil-mediated cardiovascular atherosclerosis.We examined of endothelial-leukocyte interaction, platelet activation, and foam cell formation vitro vivo. demonstrated stimulation human coronary artery endothelial cells with clinically relevant concentrations...
Normothermic ex vivo kidney perfusion (NEVKP) demonstrated superior results compared to hypothermic storage in donation after circulatory death (DCD) transplantation. It is unknown whether an optimal time exists following allow for the recovery of renal grafts from cold ischemic injury. In a porcine model DCD autotransplantation, impact initial static (SCS) (8 h) followed by various periods NEVKP was investigated: group A, 8 hSCS only (control); B, + 1 hNEVKP (brief NEVKP); C, (intermediate...
Kidney transplantation has become a well-established treatment option for patients with end-stage renal failure. The persisting organ shortage remains serious problem. Therefore, the acceptance criteria donors have been extended leading to usage of marginal kidney grafts. These organs tolerate cold storage poorly resulting in increased preservation injury and higher rates delayed graft function. To overcome limitations storage, extensive research is focused on alternative normothermic...
Metabolism of arachidonic acid by the cyclo-oxygenase (COX) pathway generates a family prostanoid mediators. Nonsteroidal anti-inflammatory drugs (NSAIDs) act inhibiting COX, thereby reducing synthesis. The efficacy these agents in inflammation suggests dominant proinflammatory role for COX pathway. However, actions metabolites are complex, and certain prostanoids, such as PGE(2), some circumstances actually inhibit immune inflammatory responses. In studies, we examine hypothesis that NSAIDs...
Vascular injury and atherothrombosis involve vessel infiltration by inflammatory leukocytes, migration of medial vascular smooth muscle cells to the intimal layer, ultimately acute thrombosis. A strategy simultaneously target these pathological processes has yet be identified. The secreted protein, Slit2, its transmembrane receptor, Robo-1, repel neuronal in developing central nervous system. More recently, it been appreciated that Slit2 impairs chemotaxis leukocytes toward diverse...