A5059673586- Sphingolipid Metabolism and Signaling
- Receptor Mechanisms and Signaling
- Circadian rhythm and melatonin
- Neonatal Respiratory Health Research
- Endoplasmic Reticulum Stress and Disease
- Angiogenesis and VEGF in Cancer
- Lipid Membrane Structure and Behavior
- Protein Kinase Regulation and GTPase Signaling
- Cholesterol and Lipid Metabolism
- Caveolin-1 and cellular processes
- Ion Transport and Channel Regulation
- Lymphatic System and Diseases
- Cell Adhesion Molecules Research
- Cellular transport and secretion
- Ion channel regulation and function
- Lipid metabolism and disorders
- Pharmacological Effects of Natural Compounds
- Computational Drug Discovery Methods
- Nitric Oxide and Endothelin Effects
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Inflammasome and immune disorders
- Neuropeptides and Animal Physiology
- Inflammatory mediators and NSAID effects
- Porphyrin and Phthalocyanine Chemistry
- Respiratory Support and Mechanisms
Harvard University
2017-2024
Boston Children's Hospital
2017-2024
Université de Sherbrooke
2011-2014
Université des Sciences de la Santé
2014
Cardiovascular diseases could be treated by chaperones that deliver the lipid mediator S1P promotes endothelial function.
Sphingosine 1-phosphate receptor-1 (S1PR1) is essential for embryonic vascular development and maturation. In the adult, it a key regulator of barrier function inflammatory processes. Its roles in tumor angiogenesis, growth, metastasis are not well understood. this paper, we show that S1PR1 expressed active vessels. Murine vessels lack endothelium (S1pr1 ECKO) excessive sprouting branching, decreased function, poor perfusion accompanied by loose attachment pericytes. Compound knockout S1pr1,...
Sphingosine 1-phosphate (S1P) and S1P receptors (S1PRs) regulate migration of lymphocytes out thymus to blood lymph nodes (LNs) efferent lymph, whereas their role in other tissue sites is not known. Here, we investigated the question how these molecules leukocyte from tissues through afferent lymphatics draining LNs (dLNs). S1P, but chemokines, selectively enhanced human murine CD4 T cell across lymphatic endothelial cells (LECs). S1PR1 S1PR4, LEC S1PR2, were required for LECs into vessels...
Sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) activate G protein–coupled receptors (GPCRs) to regulate biological processes. Using a genome-wide CRISPR/dCas9–based GPCR signaling screen, LPAR1 was identified as an inducer of S1PR1/β-arrestin coupling while suppressing Gαi signaling. S1pr1 Lpar1-positive lymphatic endothelial cells (LECs) lymph nodes exhibit constitutive signaling, which suppressed by antagonism. Pharmacological inhibition or genetic loss function Lpar1...
High-density lipoprotein (HDL) nanoparticles promote endothelial cell (EC) function and suppress inflammation, but their utility in treating EC dysfunction has not been fully explored. Here, we describe a fusion protein named ApoA1-ApoM (A1M) consisting of apolipoprotein A1 (ApoA1), the principal structural HDL that forms lipid nanoparticles, ApoM, chaperone for bioactive sphingosine 1-phosphate (S1P). A1M HDL-like particles, binds to S1P, is signaling competent. Molecular dynamics...
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease which leads to significant morbidity and mortality from respiratory failure. The two drugs currently approved for clinical use slow the rate of decline in lung function but have not been shown halt progression or reverse established fibrosis. Thus, new therapeutic targets are needed. Endothelial injury resultant vascular permeability critical components response tissue present patients with IPF. However, it remains unclear...
Export of newly synthesized G protein–coupled receptors (GPCRs) remains poorly characterized. We show in this paper that lipocalin-type prostaglandin D2 (PGD2) synthase (L-PGDS) interacts intracellularly with the GPCR DP1 an agonist-independent manner. L-PGDS promotes cell surface expression DP1, but not other GPCRs, HEK293 and HeLa cells, independent enzyme activity. In addition, formation a DP1–Hsp90 complex necessary for export to is dependent on interaction between C-terminal MEEVD...
We identified the WD-repeat-containing protein, WDR36, as an interacting partner of β isoform thromboxane A(2) receptor (TPβ) by yeast two-hybrid screening. demonstrated that WDR36 directly interacts with C-terminus and first intracellular loop TPβ in vitro GST-pulldown assays. The interaction a cellular context was observed co-immunoprecipitation, which positively affected stimulation. TPβ-WDR36 colocalization detected confocal microscopy at plasma membrane non-stimulated HEK293 cells but...
Previous reports by us and others demonstrated that G protein-coupled receptors interact functionally with Rab GTPases. Here, we show the β(2)-adrenergic receptor (β(2)AR) interacts geranylgeranyltransferase α-subunit (RGGTA). Confocal microscopy showed β(2)AR co-localizes RGGTA in intracellular compartments at plasma membrane. Site-directed mutagenesis revealed binds to L(339)L(340) motif C terminus known be involved transport of from endoplasmic reticulum cell surface. Modulation cellular...
Respiratory viral infections are frequent causes of acute respiratory distress syndrome (ARDS), a disabling condition with mortality up to 46%. The pulmonary endothelium plays an important role in the development ARDS as well pathogenesis fibrosis; however, therapeutic potential modulate endothelium-dependent signaling prevent deleterious consequences has not been explored. Here, we used clinically relevant influenza A virus infection model, endothelial cell–specific transgenic...
Hypolipidemic pharmacophoric moieties of statins, fibrates, ACAT inhibitors and beta-sitosterol analog series were identified by computational modeling, compared with the computed structure new potential glycyrrhetinic acid derivatives lipid-lowering drugs. Their electronic geometric domains, similar to those suggest a fibrate -like mechanism matching biochemical data. Keywords: acat inhibitors, molecular glycyrrhizin, glycyrrhiza glabra
Abstract Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) activate G protein-coupled receptors (GPCRs) to regulate key pathobiological processes. Here we report a novel lipid mediator GPCR cross-talk mechanism that modulates lymphatic endothelial junctional architecture in lymph nodes. LPAR1 was identified as an inducer of S1PR1/ ß-arrestin coupling from genome-wide CRISPR/ Cas9 transcriptional activation screen. induced S1PR1 recruitment while suppressing Gαi protein signaling....
Abstract Sphingosine 1-phosphate receptor-1 (S1PR1) is essential for embryonic vascular development and maturation. In the adult, it a key regulator of barrier function inflammatory processes. Its roles in tumor angiogenesis, growth metastasis are not well understood. this report, we show that S1PR1 expressed active vessels. Tumor vessels lack ( S1pr1 ECKO) excessive sprouting branching, decreased function, poor perfusion accompanied by loose attachment pericytes. Compound knockout , 2 3...
Abstract High-density lipoprotein (HDL) particles suppress inflammation-induced tissue injury via vascular and myeloid cell-dependent mechanisms. As such, HDL-associated bioactive lipids such as sphingosine 1-phosphate (S1P) prostacyclin (PGI 2 ) signal their respective G protein-coupled receptors on target cells to promote endothelial function platelet myeloid-dependent pathophysiology. Here we have constructed a fusion protein of apolipoprotein A1 (ApoA1) M (ApoM) (A1M) that forms HDL-like...