A5014643963- Phagocytosis and Immune Regulation
- Acute Kidney Injury Research
- Renal Transplantation Outcomes and Treatments
- Cancer, Hypoxia, and Metabolism
- Organ Donation and Transplantation
- Chronic Kidney Disease and Diabetes
- Renal cell carcinoma treatment
- Organ Transplantation Techniques and Outcomes
- Renal and Vascular Pathologies
- Dialysis and Renal Disease Management
- Diabetes and associated disorders
- Renal and related cancers
- T-cell and B-cell Immunology
- Cancer Research and Treatments
- Advanced MRI Techniques and Applications
- Cancer-related Molecular Pathways
- Cardiac Imaging and Diagnostics
- GDF15 and Related Biomarkers
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Erythrocyte Function and Pathophysiology
- Nutrition and Health in Aging
- Cardiovascular Function and Risk Factors
- Mitochondrial Function and Pathology
- Frailty in Older Adults
Western University
2014-2024
London Health Sciences Centre
2014-2024
Lawson Health Research Institute
2014-2024
University of Ottawa
2003-2023
American Association For Cancer Research
2023
Hôpital Maisonneuve-Rosemont
2021
McGill University
2021
Centre Hospitalier de l’Université de Montréal
2021
Hôpital du Sacré-Cœur de Montréal
2021
Université de Montréal
2021
Following injury, the clearance of apoptotic and necrotic cells is necessary for mitigation resolution inflammation tissue repair. In addition to macrophages, which are traditionally assigned this task, neighboring epithelial in affected postulated contribute process. Kidney injury molecule-1 (KIM-1 or TIM-1) an immunoglobulin superfamily cell-surface protein not expressed by myeloid lineage but highly upregulated on surface injured kidney cells. Here we demonstrate that assumed attributes...
Loss of skeletal muscle is an important determinant survival in patients with cancer-induced weight loss. The effect the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) on reduction body loss and protein degradation MAC16 model has been compared that eicosapentaenoic acid (EPA), a recognized inhibitor degradation. HMB was found to attenuate development at dose greater than 0.125 g/kg accompanied by small tumor growth rate. When EPA used suboptimal level (0.6 g/kg) combination...
Overexpression of the EGF receptor (EGFR) is a recurrent theme in human cancer and thought to cause aggressive phenotypes resistance standard therapy. There has, thus, been concerted effort identifying EGFR gene mutations explain misregulation expression as well differential sensitivity anti-EGFR drugs. However, such genetic alterations have proven be rare occurrences most types cancer, suggesting existence more general physiological trigger for aberrant expression. Here, we provide evidence...
Bi-allelic-inactivating mutations of the VHL tumor suppressor gene are found in majority clear cell renal carcinomas (VHL-/- RCC). VHL-/- RCC cells overproduce hypoxia-inducible genes as a consequence constitutive, oxygen-independent activation hypoxia inducible factor (HIF). While HIF explains highly vascularized nature loss lesions, relative role oncogenesis and growth control remains unknown. Here, we report that plays central promoting unregulated by activating transforming factor-α...
Background Ischemia-reperfusion injury (IRI) is a major risk factor for chronic renal failure. Here, we characterize the different modes of programmed cell death in tubular and microvascular compartments during various stages IRI-induced AKI, their relative importance to fibrogenesis.Methods We performed unilateral artery clamping 30 minutes contralateral nephrectomy wild-type mice (C57BL/6) or caspase-3-/- mice.Results Compared with counterparts, early stage AKI had high urine cystatin C...
Ischemia-reperfusion injury is unavoidable during organ transplantation. Prolonged ischemia-reperfusion detrimental to short-term and long-term graft function survival. H2S a recently characterized, endogenously produced gaseous molecule with important physiological roles that has been shown be cytoprotective tissue injury. The current study aimed determine whether could mitigate cold renal in the clinically relevant context of allogeneic transplantation.Following bilateral native...
<h3>BACKGROUND:</h3> Patients receiving in-centre hemodialysis are at high risk of exposure to SARS-CoV-2 and death if infected. One dose the BNT162b2 vaccine is efficacious in general population, but responses patients uncertain. <h3>METHODS:</h3> We obtained serial plasma from health care worker controls before after vaccination with 1 mRNA vaccine, as well convalescent who survived COVID-19. measured anti–receptor binding domain (RBD) immunoglobulin G (IgG) levels stratified groups by...
Objective Osteoarthritis (OA) exposes all joint tissues to physiologic stresses, increasing the need clear apoptotic cells from tissues, including synovium. We undertook this study assess burden of in synovial tissue patients with late‐stage knee OA and investigate whether impairs macrophage‐mediated clearance via efferocytosis. Methods Synovial was collected individuals healthy knees during arthroplasty. cell assessed by immunofluorescence for cleaved caspase 3. Efferocytosis Jurkat CD14+...
Background: Genetic causes of chronic diseases, once considered rare in adult-onset disease, now account for between 10 and 20% cases kidney disease (CKD). Confirming a genetic diagnosis can influence management; however, the utility testing older adults remains poorly understood, partly due to age-based restrictions on access. To better evaluate diagnostic yield clinical this population, we analyzed data from aged ≥50 years with CKD who were assessed specialized genetics clinic. Methods: We...
Type I diabetes and multiple sclerosis (MS) are distinct autoimmune diseases where T cells target either islet or CNS self-proteins. Unexpectedly, we found that autoreactive in diabetic patients, relatives with high risk, nonobese (NOD) mice, MS patients routinely classical as well autoantigens. The pathogenic potential of autoreactivity was testable NOD mice. Pertussis holotoxin, without additional Ags adjuvants, allowed development an mouse-specific, encephalitis variable...
Cellular pathways relay information through dynamic protein interactions. We have assessed the kinetic properties of murine double minute (MDM2) and von Hippel-Lindau (VHL) ubiquitin ligases in living cells under physiological conditions that alter stability their respective p53 hypoxia-inducible factor substrates. Photobleaching experiments reveal MDM2 VHL are highly mobile proteins settings where substrates efficiently degraded. The nucleolar architecture converts to a static state...
Tubulointerstitial injury plays an important role in the development and progression of chronic kidney disease (CKD). Kidney molecule (KIM)-1 is induced damaged proximal tubules both acute renal CKD. However, dynamics KIM-1 CKD effects expression on are unknown. Here, we aimed to determine associations between tubular levels, function, inflammation The relationships levels clinicopathological parameters were analyzed patients with progressive nonprogressive IgA nephropathy. was increased...
Abstract Malignancy is a manifestation of acquired defects in regulatory circuits that direct normal cell proliferation and homeostasis. Most these operate through autonomous pathways, whereas others potentially involve the neighboring microenvironment. We report metalloprotease ADAM17 plays pivotal role several tumor capabilities by mediating availability soluble transforming growth factor-α, an epidermal factor receptor (EGFR) ligand, thus establishment key autocrine signaling pathway....
Cardiovascular disease is a significant cause of morbidity and mortality in patients with end-stage renal (ESRD) kidney transplant (KT) patients. Compared left ventricular (LV) ejection fraction (LVEF), LV strain has emerged as an important marker function it less load dependent. We sought to evaluate changes using cardiovascular magnetic resonance imaging (CMR) ESRD who received KT, determine whether KT may improve function. conducted prospective multi-centre longitudinal study 79 (40 on...
Efficient clearance of apoptotic cells (efferocytosis) prevents inflammation and permits repair following tissue injury. Kidney injury molecule-1 (KIM-1) is a receptor for phosphatidylserine, an "eat-me" signal exposed on the surface that marks them phagocytic clearance. KIM-1 upregulated proximal tubule epithelial (PTECs) during ischemic acute kidney (AKI), enabling efferocytosis by surviving PTECs. spontaneously cleaved at its ectodomain region to generate soluble fragment serves sensitive...
Abstract Key Points Frailty prevalence varies for the Phenotype, a frailty index, and Clinical Scale in transplant candidates. Agreement between these measures determining status was variable, suggesting they measure different aspects of frailty. The index were associated with shorter time to death or waitlist withdrawal an unadjusted analysis. Background Comparisons assessment tools candidates are recognized priority area kidney transplantation. We compared using three established cohort...
Apoptosis is an essential mechanism for the maintenance of somatic tissues, and when dysregulated can lead to numerous pathological conditions. G proteins regulate apoptosis in addition other cellular functions, but roles specific signaling are not well characterized. Galpha12 stimulates protein phosphatase 2A (PP2A), a serine/threonine that modulates pathways, including apoptosis. Herein, we examined whether regulates epithelial cells. Inducible expression or constitutively active...