A5079372457- Retinal Diseases and Treatments
- Retinopathy of Prematurity Studies
- Retinal Development and Disorders
- Neonatal Respiratory Health Research
- Cancer-related gene regulation
- Retinal and Optic Conditions
- CAR-T cell therapy research
- Immune cells in cancer
- Angiogenesis and VEGF in Cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Blood Coagulation and Thrombosis Mechanisms
- Receptor Mechanisms and Signaling
- Neonatal and fetal brain pathology
- Nitric Oxide and Endothelin Effects
- Retinal Imaging and Analysis
- Mitochondrial Function and Pathology
- Axon Guidance and Neuronal Signaling
- Pregnancy and preeclampsia studies
- Retinoids in leukemia and cellular processes
- Sirtuins and Resveratrol in Medicine
- Pancreatic function and diabetes
- Virus-based gene therapy research
- Glaucoma and retinal disorders
- Cytokine Signaling Pathways and Interactions
- Autophagy in Disease and Therapy
Centre Hospitalier Universitaire Sainte-Justine
2016-2025
Université de Montréal
2016-2025
McGill University
2014-2023
McGill University and Génome Québec Innovation Centre
2023
Hôpital Maisonneuve-Rosemont
2013-2022
Laboratoire Excell
2018
Boston Children's Hospital
2011-2015
Lund University
2015
University of Gothenburg
2014-2015
National Eye Institute
2015
In developed countries, the leading causes of blindness such as diabetic retinopathy are characterized by disorganized vasculature that can become fibrotic. Although many pathological vessels often naturally regress and spare sight-threatening complications, underlying mechanisms remain unknown. Here, we used orthogonal approaches in human patients with proliferative a mouse model ischemic retinopathies to identify an unconventional role for neutrophils vascular remodeling during late-stage...
Age-related macular degeneration is a prevalent neuroinflammatory condition and major cause of blindness driven by genetic environmental factors such as obesity. In diseases aging, modifiable can be compounded over the life span. We report that diet-induced obesity earlier in triggers persistent reprogramming innate immune system, lasting long after normalization metabolic abnormalities. Stearic acid, acting through Toll-like receptor 4 (TLR4), sufficient to remodel chromatin landscapes...
Proinflammatory cytokines contribute to the development of retinal vasculopathies. However, role these factors and mechanisms by which they elicit their effects in retina are not known. We investigated whether activated microglia during early stages ischemic retinopathy produces excessive interleukin-1β (IL-1β), elicits microvascular degeneration directly but rather triggering release proapoptotic/repulsive factor semaphorin-3A (Sema3A) from neurons.Sprague Dawley rats subjected induced...
Angiogenesis of the microvasculature is central to etiology many diseases including proliferative retinopathy, age-related macular degeneration and cancer. A mouse model microvascular angiogenesis would be very valuable enable access a wide range genetically manipulated tissues that closely approximate small blood vessel growth in vivo. Vascular endothelial cells cultured vitro are widely used, however, isolating pure vascular murine technically challenging. explant robust, quantitative can...
Abstract Preterm birth (PTB) is commonly accompanied by in utero fetal inflammation, and existing tocolytic drugs do not target inflammatory injury. Of the candidate proinflammatory mediators, IL-1 appears central sufficient to trigger loss. Therefore, we elucidated effects of antenatal exposure on postnatal development investigated two receptor antagonists, competitive inhibitor anakinra (Kineret) a potent noncompetitive 101.10, for efficacy blocking actions. Antenatal IL-1β induced Tnfa,...
Significance Diabetic retinopathy is a major cause of blindness in the working population. The most common visual impairment diabetic patients macular edema (DME). Roughly 40% with DME respond poorly to anti-VEGF therapies, which are standard care. Here we provide mechanistic insight for critical role NOTCH1 signaling compromising endothelial junction integrity during diabetes. Besides activating canonical transcriptional pathways, find that also provokes disruption junctions via...
G-protein-coupled receptors (GPCRs) are virtually involved in every physiological process. However, mechanisms for their ability to regulate a vast array of different processes remain elusive. An unconventional functional modality could at least part account such diverse involvements but has yet be explored. We found HCAR1, multifunctional lactate GPCR, localize the nucleus and therein capable initiating location-biased signaling notably nuclear-ERK AKT. discovered that nuclear HCAR1...
Glioblastoma contains a rare population of self-renewing brain tumor stem cells (BTSCs) which are endowed with properties to proliferate, spur the growth new tumors, and at same time, evade ionizing radiation (IR) chemotherapy. However, drivers BTSC resistance therapy remain unknown. The cytokine receptor for oncostatin M (OSMR) regulates proliferation glioblastoma tumorigenesis. Here, we report our discovery mitochondrial OSMR that confers IR via regulation oxidative phosphorylation,...
Abstract The roles of nitric oxide (NO) and endothelial NO synthase (eNOS) in the regulation angiogenesis are well documented. However, involvement eNOS sprouting tip-cells at vascular front during remains poorly defined. In this study, we show that downregulation markedly inhibits VEGF-stimulated migration cells but increases their polarization, as evidenced by reorientation Golgi migrating monolayers fewer filopodia on tip ends sprouts cell spheroids. effect inhibition EC polarization was...
Pathological neovascularization in age-related macular degeneration (nvAMD) drives the principal cause of blindness elderly. While there is a robust genetic association between genes innate immunity and AMD, genome-to-phenome relationships are low, suggesting critical contribution environmental triggers disease. Possible insight comes from observation that past history infection with pathogens such as Chlamydia pneumoniae, or other systemic inflammation, can predispose to nvAMD later life....
Abstract It has been postulated that intracellular binding sites for platelet-activating factor (PAF) contribute to proinflammatory responses PAF. Isolated nuclei from porcine cerebral microvascular endothelial cells (PCECs) produced PAF-molecular species in response H2O2. Using FACS analysis, we demonstrated the expression of PAF receptors on cell and nuclear surfaces PCECs. Confocal microscopy studies performed PCECs, Chinese hamster ovary stably overexpressing receptors, isolated PCECs...
Purpose.: Retinopathy of prematurity (ROP) is a major cause visual handicap in the pediatric population. To date, this disorder thought to stem from deficient retinal vascularization. Intriguingly, functional electrophysiological studies patients with mild or moderate ROP and oxygen-induced retinopathy (OIR) model rats reveal central photoreceptor disruption that overlies modest vessel loss; paucity vasculature occurs predominantly at periphery. Given choroidal circulation source oxygen...
Obesity gives rise to metabolic complications by mechanisms that are poorly understood. Although chronic inflammatory signaling in adipose tissue is typically associated with deficiencies linked excessive weight gain, we identified a subset of neuropilin-1 (NRP1)-expressing myeloid cells accumulate and protect against obesity syndrome. Ablation NRP1 macrophages compromised lipid uptake these cells, which reduced substrates for fatty acid β-oxidation shifted energy metabolism toward more...
Abstract Zonula occludens-1 (ZO-1) is involved in the regulation of cell-cell junctions between endothelial cells (ECs). Here we identify ZO-1 protein interactome and uncover interactions with RNA-binding proteins that are part stress granules (SGs). Downregulation increased SG formation response to protected ECs from cellular insults. The uncovered an association Y-box binding 1 (YB-1), a constituent SGs. Arsenite treatment decreased interaction YB-1, drove assembly. YB-1 expression...