A5014274785- Platelet Disorders and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- Protease and Inhibitor Mechanisms
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Heme Oxygenase-1 and Carbon Monoxide
- Peptidase Inhibition and Analysis
- Blood properties and coagulation
- Antiplatelet Therapy and Cardiovascular Diseases
- Nitric Oxide and Endothelin Effects
- Neonatal Health and Biochemistry
- Hemophilia Treatment and Research
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Venous Thromboembolism Diagnosis and Management
- Cancer-related molecular mechanisms research
- Hemoglobin structure and function
- Lipid metabolism and disorders
- Signaling Pathways in Disease
- Cell Adhesion Molecules Research
- Receptor Mechanisms and Signaling
- Advanced Proteomics Techniques and Applications
- Blood groups and transfusion
- Renin-Angiotensin System Studies
- Protein Kinase Regulation and GTPase Signaling
Stony Brook University
2015-2025
Stony Brook School
2022
State University of New York
2004-2018
Stony Brook University Hospital
2007-2017
Northport VA Medical Center
2003-2013
University of British Columbia
2013
Princeton University
2011
Brigham and Women's Hospital
2010
Case Western Reserve University
2010
University of California, San Francisco
2010
It has been proposed that tissue inhibitor of metalloproteinase-2 (TIMP-2), in stoichiometric concentrations, serves as an intermediate progelatinase A activation by binding to activated membrane type 1-matrix metalloproteinase 1 (MT1-MMP) on the plasma membrane. An MT1-MMP-independent cell surface receptor for TIMP-2 also postulated. To clarify binding, we have performed <sup>125</sup>I-TIMP-2 studies transfected COS-1 cells and endothelial cells. Specific receptors were identified with...
Production of vascular endothelial growth factor (VEGF) by cancer cells at invasive and metastatic sites is an important aspect tumor angiogenesis. Although known primarily as a mitogen permeability (VPF) for cells, VEGF/VPF has been proposed to induce the expression procoagulant factors in cells. In this study, we have explored ramifications VEGF induction tissue (TF) human umbilical vein (HUVECs) subsequent activation progelatinase A. Within 3 hr incubation with VEGF/VPF, accelerate TF...
Co-transfectQcccQP CHO
Abstract Cellular mechanisms responsible for the termination of ET‐1 signal are poorly understood. In order to examine hypothesis that nitric oxide serves as a physiological brake ET‐ 1 signaling, Chinese hamster ovary (CHO) cells stably transfected with ET A receptor cDNA (CHO‐ET) were studied. CHO‐ET responded robust [Ca 2+ ], transients and developed long‐lasting homologous desensitization. Donors (NO), 3‐morpholino‐sydnonimine HCl(SIN‐1), or sodium nitroprusside (SNP) reduced amplitude...
Proteolytically cleaved receptors, typified by the functional thrombin receptor (TR), represent a novel class of receptors that mediate signaling events coupling to G proteins. Northern blot analysis completed with human proteinase activated receptor-2 (PAR-2) cDNA as probe demonstrated approximately 3.5kb PAR-2 transcript in total cellular RNA from umbilical vein endothelial cells (HUVEC). Microspectrofluorimetry using Fura2-loaded HUVEC dose-dependent elevation intracellular calcium...
Cell migration is a critical determinant of cancer metastasis, and better understanding the genes involved will lead to identification novel targets aimed at preventing dissemination. KIAA1199 has been shown be upregulated in human cancers, yet its role progression was hitherto unknown.Clinical relevance assessed by examining expression specimens. In vitro vivo studies were employed determine function progression. Cellular localization microscopically determined. SNAP-tag pull-down assays...
Biliverdin IXβ reductase (BLVRB) is an NADPH-dependent enzyme previously implicated in a redox-regulated mechanism of thrombopoiesis distinct from the thrombopoietin (TPO)/c-MPL axis. Here, we apply computational modeling to inform molecule design, followed by de novo syntheses and screening unique small molecules retaining capacity for selective BLVRB inhibition as novel platelet-enhancing strategy. Two classes are identified, NMR spectroscopy co-crystallization studies confirm binding...
Angiogenesis requires degradation of vascular basement membrane prior to migration and proliferation endothelial cells; proteinases are essential ingredients in this process. Because thrombin's multiple effects on endothelium, we have examined its role matrix metalloproteinase activation using human umbilical vein cells. Gelatin zymography conditioned media revealed a prominent 72-kDa progelatinase A band. Addition alpha-thrombin cells resulted the generation 64 62 kDa gelatinolytic bands...
Endothelin (ET) synthesis is enhanced at sites of ischemia or in injured vessels. The purpose this study was to explore the possibility autocrine stimulation endothelial cell migration by members endothelin family. Experiments with microvascular transmigration a Boyden chemotactic apparatus showed that endothelins 1 and 3, as well selective agonist ETB receptor IRL-1620, equipotently stimulated migration. Endothelial unaffected blockade ETA receptor, but it inhibited antagonism. Based on our...
Type IIB von Willebrand Disease (vWD) is characterized by the selective loss of large Factor (vWF) multimers from plasma, presumably due to their increased reactivity with platelets and subsequent clearance circulation. Using PCR, one a panel four potential missense mutations was identified in each 14 patients studied 11 unrelated families. None these substitutions encountered normal DNAs. These changes all represent C----T transitions at CpG dinucleotides, proposed "hot spots" for mutation...
IQGAPs are multidomain scaffolding proteins that integrate Rho GTPase and Ca2+/calmodulin signals with cell adhesive cytoskeletal reorganizational events. Targeted disruption of the murine Iqgap2 gene resulted in age-dependent development apoptosis hepatocellular carcinoma (HCC), characterized by overexpression IQGAP1, loss membrane E-cadherin expression, cytoplasmic translocation (and activation) beta-catenin, a nuclear target cyclin D1. In normal hepatocytes, IQGAP2 was found to exist as...
AimsThe Raf-MEK1/2-ERK1/2 (ERK1/2—extracellular signal-regulated kinases 1/2) signalling cascade is crucial in triggering cardiac responses to different stress stimuli. Scaffold proteins are key elements coordinating molecules for their appropriate spatiotemporal activation. Here, we investigated the role of IQ motif-containing GTPase-activating protein 1 (IQGAP1), a scaffold ERK1/2 cascade, heart function and remodelling response pressure overload.
Proteolytically activated receptors (PARs) represent an emerging subset of seven transmembrane G protein-coupled that mediate cell activation events by receptor cleavage at distinct scissile bonds located within amino termini. Differential genomic blotting using a yeast artificial chromosome known to contain the PAR-1 and PAR-2 genes identified PAR-3 gene PAR cluster spanning ∼100 kilobases 5q13. The is relatively small (∼12 kilobases); and, like genes, it displays two-exon structure, with...
The restitution of epithelial integrity is accomplished in part by cell migration. Studying this process, we have found that nitric oxide (NO) release migrating BSC-1 cells displayed a biphasic response to the inflicted wounds; an initial transient NO followed delayed sustained elevation. Whereas constitutive endothelial synthase (NOS) did not show any spatial or temporal changes associated with wounding, inducible NOS became expressed 3 h after wounding and showed higher abundance at edges...
Membrane type matrix metalloproteinase 1 (MT-MMP1), a novel 63-kDa member of the family, is membrane-anchored enzyme and an activator for gelatinase A. In addition to its C-terminal hydrophobic transmembrane domain, MT-MMP1 has insertion 11 amino acids between propeptide catalytic domain encrypted with RRKR recognition motif paired basic acid cleaving enzyme, furin. this report, we investigated whether cleavage by Golgi-associated furin analogous similar activation mechanism observed...
Until recently, the lack of specific inhibitors various forms nitric oxide synthase (NOS) hampered a stringent evaluation role played by inducible NOS (iNOS) in cell damage. Phosphorothioate derivatives iNOS antisense and control sense or scrambled oligodeoxynucleotides (S-ODNs) were synthesized, their effect on epithelial viability was examined under oxidant stress. Exposure BSC-1 kidney tubular cells to H2O2 resulted elevation NO release, accompanied significant decrease population viable...
Activation of secreted latent matrix metalloproteinases (MMPs) is accompanied by cleavage the N-terminal propeptide, thereby liberating active zinc from binding to conserved cysteine in pro-domain. It has been assumed that an analogous mechanism responsible for activation membrane type 1 MMP (MT1-MMP). Using recombinant wild-type MT1-MMP cDNA and mutant cDNAs transfected into COS-1 cells lacking endogenous MT1-MMP, we have examined function propeptide domain MT1-MMP. was characterized...
Substrate degradation and cell migration are key steps in cancer metastasis. Membrane-type 1-matrix metalloproteinase (MT1-MMP) has been linked with these processes. Using the fluorescein isothiocyanate (FITC)-labeled fibronectin assay combined phagokinetic assay, structure-function relationships of MT1-MMP were studied. Our data indicate that initiates substrate enhances migration; occurs as a concurrent but independent event. recombinant DNA approaches, we demonstrated hemopexin-like...
Abstract To investigate the possible role of mast cells (MC) in regulating leukocyte adhesion to vascular endothelial (EC), microvascular and macrovascular EC were exposed activated MC or conditioned medium (MCCM). Expression intercellular molecules (ICAM‐1 VCAM‐1) on was monitored. Incubation human dermal (HDMEC) umbilical vein (HUVEC) with MCCM markedly increased ICAM‐1 VCAM‐1 surface expression, noted as éarly 4 hr. Maximal levels observed at 16 hr followed by a general decline over 48 A...