A5029103579- Galectins and Cancer Biology
- Glycosylation and Glycoproteins Research
- Legionella and Acanthamoeba research
- Heme Oxygenase-1 and Carbon Monoxide
- Ocular Surface and Contact Lens
- Signaling Pathways in Disease
- Wnt/β-catenin signaling in development and cancer
- Glaucoma and retinal disorders
- Macrophage Migration Inhibitory Factor
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Proteoglycans and glycosaminoglycans research
- Ocular Infections and Treatments
- Connexins and lens biology
- Corneal Surgery and Treatments
- Carbohydrate Chemistry and Synthesis
- Vibrio bacteria research studies
- Invertebrate Immune Response Mechanisms
- Lymphatic System and Diseases
- Polysaccharides and Plant Cell Walls
- Wound Healing and Treatments
- Biomarkers in Disease Mechanisms
- Amoebic Infections and Treatments
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Bacterial biofilms and quorum sensing
- Protein Tyrosine Phosphatases
Tufts University
2012-2023
Inner Mongolia People's Hospital
2015
Ophthalmology Associates (United States)
2010
Eye Center
2001-2009
University of California, Davis
2003
Smith-Kettlewell Eye Research Institute
2003
Tufts Medical Center
1988-1999
Boston University
1988
Recent studies have shown that a carbohydrate-binding protein, galectin-3, is novel pro-angiogenic molecule. The mechanism by which galectin-3 promotes angiogenesis remains unknown. We demonstrate here mediator of vascular endothelial growth factor (VEGF)- and basic fibroblast (bFGF)-mediated angiogenic response. Angiogenesis assays revealed inhibitors, β-lactose dominant-negative reduce VEGF- bFGF-mediated in vitro response reduced knockdown cells Gal3−/− animals. Integrin αvβ3 was...
Maintenance of an intact mucosal barrier is critical to preventing damage and infection wet-surfaced epithelia. The mechanism defense has been the subject much investigation, there evidence now implicating O-glycosylated mucins on epithelial cell surface. Here we investigate a new role for carbohydrate-binding protein galectin-3 in stabilizing barriers through its interaction with apical glycocalyx. Using surface eye as model system, found that colocalized two distinct membrane-associated...
Angiogenesis is heavily influenced by VEGF-A and its family of receptors, particularly VEGF receptor 2 (VEGF-R2). Like most cell surface proteins, VEGF-R2 glycosylated, although the function with respect to glycosylation pattern poorly characterized. Galectin-3, a glycan binding protein, interacts EGF TGFβ retaining them on plasma membrane altering their signal transduction. Because glycosylated both galectin-3 are involved angiogenesis, we hypothesized that binds modulates transduction as...
Abstract Lymphangiogenesis plays a pivotal role in diverse pathological conditions. Here, we demonstrate that carbohydrate-binding protein, galectin-8, promotes lymphangiogenesis. Galectin-8 is markedly upregulated inflamed human and mouse corneas, galectin-8 inhibitors reduce inflammatory In the model of corneal allogeneic transplantation, galectin-8-induced lymphangiogenesis associated with an increased rate graft rejection. Further, murine herpes simplex virus keratitis, pathology are...
Disorders of wound healing characterized by impaired or delayed re-epithelialization are a serious medical problem. These conditions affect many tissues, painful, and difficult to treat. In this study, using cornea as model, we demonstrate for the first time importance carbohydrate-binding proteins galectins-3 -7 in wounds. two different models corneal healing, wounds was significantly slower galectin-3-deficient (gal3<sup>−/−</sup>) mice compared with wild-type (gal3<sup>+/+</sup>) mice....
Recent studies have shown that galectin-3 (Gal-3; also known as LGALS3), a beta-galactoside-binding lectin, promotes cell migration during re-epithelialization of corneal wounds. The goal this study was to characterize the molecular mechanism by which Gal-3 stimulates migration. We demonstrate here exogenous Gal-3, but not Gal-1 or Gal-8, scattering and formation lamellipodia in human epithelial cells beta-lactose-inhibitable manner. alpha3beta1 integrin identified major Gal-3-binding...
Dynamic modulation of the physical contacts between neighboring cells is integral to epithelial processes such as tissue repair and cancer dissemination. Induction matrix metalloproteinase activity contributes disassembly intercellular junctions degradation extracellular matrix, thus mitigating constraint cell movement. Using cornea a model, we show here that carbohydrate-binding protein, galectin-3, promotes cell-cell detachment redistribution tight junction protein occludin via its...
Purpose: Corneal neovascularization and scarring commonly lead to significant vision loss. This study was designed determine whether a small-molecule inhibitor of galectin-3 can inhibit both corneal angiogenesis fibrosis in experimental mouse models. Methods: Animal models silver nitrate cautery alkaline burn were used induce fibrosis, respectively. Corneas treated with the inhibitor, 33DFTG, or vehicle alone processed for whole-mount immunofluorescence staining Western blot analysis...
Acanthamoeba keratitis is a vision-threatening infection caused by pathogenic species of the genus Acanthamoeba. Although not all spp. can cause keratitis, it important to differentiate and isolates from nonpathogens. Since extracellular proteases may play role in ocular pathology, we used colorimetric, cytopathic, zymographic assays assess protease activity nonpathogenic Colorimetric assays, using azo-linked protein as substrate, showed Acanthamoeba-conditioned medium differentiated...
<i>Acanthamoeba</i> keratitis is a vision-threatening corneal infection. The mannose-binding protein of<i>Acanthamoeba</i> thought to mediate adhesion of parasites host cells. We characterized the amoeba lectin with respect its carbohydrate binding properties and role in amoeba-induced cytopathic effect (CPE). Sugar inhibition assays revealed that has highest affinity for α-Man Man(α1–3)Man units. <i>In vitro</i> indicated mannose-based saccharides which inhibit epithelial cells were also...
Purpose : The ocular microenvironment is immunosuppressive and anti-inflammatory. Since various pigmented epithelia contribute to this microenvironment, we studied the relative capacities of pigment epithelial (PE) cells cultured from iris, ciliary body, retina mouse eyes suppress T-cell activation in vitro. Methods Pigment epithelium was for 14 days, then assayed capacity, directly or across transwell membranes, mixed lymphocyte reactions anti-CD3 stimulation T cells. Potential molecules...
Acanthamoeba keratitis is a sight-threatening corneal infection. In recent study, the saccharide mannose has been shown to inhibit binding of organisms epithelium cornea (L. D. Morton, G. L. McLaughlin, and H. E. Whiteley, Infect. Immun. 59:3819-3822, 1991). an attempt determine molecular mechanism by which acanthamoebae adhere surface cornea, present study was designed whether castellanii derived from infected human (i) binds mannose-containing glycoproteins (mannose-GPs) (ii) expresses one...
Acanthamoebae produce a painful, blinding infection of the cornea. The mannose-binding protein (MBP) Acanthamoeba is thought to play key role in pathogenesis by mediating adhesion parasites host cells. We describe here isolation and molecular cloning MBP. MBP was isolated chromatography on mannose affinity gel. Gel filtration experiments revealed that lectin ∼400-kDa constituted multiple 130-kDa subunits. Cloning sequencing indicated gene composed 6 exons 5 introns span 3.6 kb amoeba genome...
purpose. To determine whether the expression of Acanthamoeba mannose-binding protein (MBP) is associated with pathogenicity parasite in vitro. methods. Both active trophozoites and dormant cysts a pathogenic strain A. castellanii were analyzed for their ability to bind corneal epithelium, express MBP, produce cytopathic effect (CPE) on host cells. In addition, cell binding, CPE-inducing ability, MBP pattern four different isolates various degrees vitro analyzed. Binding assays performed...
Background Interaction of transmembrane mucins with the multivalent carbohydrate-binding protein galectin-3 is critical to maintaining integrity ocular surface epithelial glycocalyx. This study aimed determine whether disruption multimerization and insertion synthetic glycopolymers in plasma membrane could be used modulate glycocalyx barrier function corneal cells. Methodology/Principal Findings Abrogation biosynthesis multilayered cultures human cells using siRNA, null mice, resulted...
Galectins (Gals) have emerged as potent immunoregulatory molecules that control chronic inflammation through distinct mechanisms. Gal‐8, a tandem‐repeat type Gal with unique preference for α2,3‐sialylated glycans, is ubiquitously expressed, but little known about its role in T‐cell differentiation. Here we report Gal‐8 promotes the polyclonal differentiation of primary mouse regulatory T (Treg) cells vitro . We further show also facilitates antigen‐specific Treg cells, and polarized presence...
Abstract Objective The physiologic mechanisms involving growth factors, including PDGF‐BB, EGF, and TGF‐β1, as potent mediators of fibroblasts epithelial cells in corneal wound healing remain unknown. goal this study was to determine culture methods for equine keratocytes investigate how exogenous factors influence proliferation both cell types. Procedures Cell cultures were established from healthy corneas harvested horses immediately following euthanasia maintained using standard tissue...
purpose. To identify differentially expressed glycogenes in trabecular meshwork (TM) of eyes with primary open-angle glaucoma (POAG). methods. Total RNA was isolated from TM cadaveric derived donors diagnosed glaucomas different etiologies and normal control subjects. amplified hybridized to the GLYCOv2 oligonucleotide microarray that contains probes for carbohydrate-binding proteins, glycosyltransferases, other genes involved regulation glycosylation. Statistical analysis used between POAG...
Corneal infection with Pseudomonas aeruginosa leads to a severe immunoinflammatory lesion, often causing vision impairment and blindness. Although past studies have indicated critical role for CD4(+) T cells, particularly Th1 in corneal immunopathology, the relative contribution of recently discovered Th17 regulatory cells is undefined. In this study, we demonstrate that after P. infection, both infiltrate cornea increased representation cells. addition also migrate into during early as well...
Dry eye is a common disorder caused by inadequate hydration of the ocular surface that results in disruption barrier function. The homeostatic protein clusterin (CLU) prominent at fluid-tissue interfaces throughout body. CLU levels are reduced human inflammatory disorders manifest as severe dry eye, well preclinical mouse model for desiccating stress mimics eye. Using this model, we show here prevents and ameliorates remarkable sealing mechanism dependent on attainment critical all-or-none...