A5090087970- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
- Autophagy in Disease and Therapy
- Toxin Mechanisms and Immunotoxins
- Photoreceptor and optogenetics research
- Oral microbiology and periodontitis research
- Streptococcal Infections and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Cell Adhesion Molecules Research
- Peroxisome Proliferator-Activated Receptors
- Cholesterol and Lipid Metabolism
- Calcium signaling and nucleotide metabolism
- Glaucoma and retinal disorders
- Retinoids in leukemia and cellular processes
- Immune Response and Inflammation
- Bacterial Genetics and Biotechnology
- bioluminescence and chemiluminescence research
- Oral and Maxillofacial Pathology
- Neuroscience and Neuropharmacology Research
- Connexins and lens biology
- Bacteriophages and microbial interactions
- Erythrocyte Function and Pathophysiology
- Receptor Mechanisms and Signaling
University of Pennsylvania
2016-2025
California University of Pennsylvania
2016-2023
Philadelphia University
2021
University of Connecticut
2007
West Virginia University
2007
Cancer Genetics (United States)
2007
University of Maryland, Baltimore
2006
Laboratoire de Biochimie
2005
Thomas Jefferson University
2005
Stratford University
1996-2002
Purpose of review: Alkaline phosphatase is an important component in hard tissue formation, highly expressed mineralized cells. It appropriate to review the current status this enzyme. Recent findings: The mechanism with which enzyme carries out its function not completely understood, but it appears act both increase local concentration inorganic phosphate, a mineralization promoter, and decrease extracellular pyrophosphate, inhibitor mineral formation. localized outside plasma membrane...
Lysosomal enzymes function optimally in acidic environments, and elevation of lysosomal pH can impede their ability to degrade material delivered lysosomes through autophagy or phagocytosis. We hypothesize that abnormal is a key aspect diseases accumulation restoring will improve cell function. The propensity nanoparticles end up the lysosome makes them an ideal method delivering drugs lysosomes. This study asked whether could traffic lysosomes, lower enhance degradation by cultured human...
Daily, the retinal pigment epithelium (RPE) ingests a bolus of lipid and protein in form phagocytized photoreceptor outer segments (OS). The RPE, like liver, expresses enzymes required for fatty acid oxidation ketogenesis. This suggests that these pathways play role disposal lipids from ingested OS, as well providing mechanism recycling metabolic intermediates back to retina. In this study, we examined whether OS phagocytosis was linked We found increased levels β-hydroxybutyrate (β-HB)...
The retina is one of the most metabolically active tissues in body and utilizes glucose to produce energy intermediates required for daily renewal photoreceptor cell outer segments. Glucose transporter 1 (GLUT1) facilitates transport across blood retinal barrier (BRB) formed by pigment epithelium (RPE) inner BRB endothelium. We used conditional knockout mice study impact reducing RPE on Müller glial cells. Transgenic expressing Cre recombinase under control Bestrophin1 ( Best1) promoter were...
Rhodopsin, a prototypical G protein receptor, is found both in the plasma membrane and discs of bovine rod outer segments. The ability each these membranes to activate phosphodiesterase upon stimulation by light presence GTP cGMP was investigated. showed little or no activity when compared with disc membranes. contains approximately 28 mol% cholesterol 8 mol % discs. Upon oxidation at least 70 cholestenone, approached that initiated When 50:50 mixture rhodopsin tested for activity, results...
Abstract The Actinobacillus actinomycetemcomitans cytolethal distending toxin (Cdt) is a potent immunotoxin that induces G2 arrest in human lymphocytes. We now show the CdtB subunit exhibits phosphatidylinositol (PI)-3,4,5-triphosphate phosphatase activity. Breakdown product analysis indicates hydrolyzes PI-3,4,5-P3 to PI-3,4-P2 and therefore functions manner similar 5-phosphatases. Conserved amino acids critical catalysis this family of enzymes were mutated cdtB gene. mutant proteins...
Oxidative stress has been implicated in the pathogenesis of age-related macular degeneration, leading cause blindness older adults, with retinal pigment epithelium (RPE) cells playing a key role. To better understand cytotoxic mechanisms underlying oxidative stress, we used cell culture and mouse models iron overload, as can catalyze reactive oxygen species formation RPE. Iron-loading cultured induced pluripotent stem cell-derived RPE increased lysosomal abundance, impaired proteolysis...
Abstract Lipid processing by the retinal pigment epithelium (RPE) is necessary to maintain health and function. Dysregulation of lipid homeostasis due normal aging or age‐related disease triggers accumulation within RPE, on Bruch's membrane (BrM), in subretinal space. In its role as a hub for trafficking into out neural retina, RPE packages significant amount droplets storage apolipoprotein B (APOB)‐containing lipoproteins (Blps) export. Microsomal triglyceride transfer protein (MTP),...
Hepes, 4-(2-hydroxyethyl)-l-piperazineethanesulfonic acid SUV, small unilamellar vesicles.
Actinobacillus actinomycetemcomitans produces a leukotoxin (Ltx) that kills leukocyte function-associated antigen-1 (LFA-1)-bearing cells from man, the Great Apes and Old World monkeys. The unique specificity of Ltx for beta2 integrin, LFA-1, suggests it is capable providing insight into pathogenic mechanisms other RTX toxins. Using Jurkat T cell line an LFA-1-deficient mutant (Jbeta2.7) as models, we found initial effect to elevate cytosolic Ca2+ [Ca2+]c, event independent Ltx/LFA-1...
Induction of cell cycle arrest in lymphocytes after exposure to the Aggregatibacter actinomycetemcomitans cytolethal distending toxin (Cdt) is dependent upon integrity lipid membrane microdomains. In this study we further demonstrate that association Cdt with lymphocyte plasma membranes binding cholesterol. Depletion cholesterol resulted reduced binding, whereas repletion cholesterol-depleted cells restored binding. We employed fluorescence resonance energy transfer and surface plasmon model...
Binding of the talin-1 FERM (4.1/ezrin/radixin/moesin) domain to β3 cytosolic tail causes activation integrin αIIbβ3. The also binds acidic phospholipids. Although much is known about interaction with integrins and lipids, relative contribution each regulation possible synergy between them remain be clarified. Here, we examined thermodynamic interplay binding phospholipid bilayers its sites in tail. We found that although both F0F1 F2F3 subdomains bind bilayers, full-length an affinity...
ABSTRACT The cytolethal distending toxin (Cdt) is produced from a number of bacteria capable causing infection and inflammatory disease. Our previous studies with Actinobacillus actinomycetemcomitans Cdt demonstrate not only that the active subunit functions as phosphatidylinositol-3,4,5-triphosphate (PIP3) phosphatase but also macrophages exposed to were stimulated produce proinflammatory cytokines. We now Cdt-induced response involves activation NLRP3 inflammasome. Specific inhibitors...
The Aggregatibactor actinomycetemcomitans cytolethal distending toxin (Cdt) induces G2 arrest and apoptosis in lymphocytes; these toxic effects are due to the active subunit, CdtB, which functions as a phosphatidylinositol-3,4,5-triphosphate (PIP3) phosphatase. We now extend our investigation demonstrate that Cdt is able perturb human macrophage function. THP-1- monocyte-derived macrophages were found not be susceptible Cdt-induced apoptosis. Nonetheless, was capable of binding perturbing...
Abstract Late-onset retinal degeneration (L-ORD) is an autosomal dominant disorder caused by a missense substitution in CTRP5 . Distinctive clinical features include sub-retinal pigment epithelium (RPE) deposits, choroidal neovascularization, and RPE atrophy. In induced pluripotent stem cells-derived from L-ORD patients (L-ORD-iRPE), we show that the pathogenic variant leads to reduced secretion. silico modeling suggests lower binding of mutant adiponectin receptor 1 (ADIPOR1). Downstream...
Photoreceptors consume glucose supplied by the choriocapillaris to support phototransduction and outer segment (OS) renewal. Reduced supply underlies photoreceptor cell death in inherited retinal degeneration age-related disease. We have previously shown that restricting transport into retina conditional deletion of Slc2a1 encoding GLUT1 resulted loss impaired OS However, neurons, glia, pigment epithelium play specialized, synergistic roles metabolite exchange, cell-specific map uptake...
Autophagy is a catabolic self-degradative pathway that promotes the degradation and recycling of intracellular material through lysosomal compartment. Although first believed to function in conditions nutritional stress, autophagy emerging as critical cellular pathway, involved variety physiological pathophysiological processes. dysregulation associated with an increasing number diseases, including ocular diseases. On one hand, mutations autophagy-related genes have been linked cataracts,...