{"id":79,"date":"2007-03-06T17:50:49","date_gmt":"2007-03-06T21:50:49","guid":{"rendered":"https:\/\/www.bumc.bu.edu\/cardiovascularproteomics\/clinical-projects\/project-10\/"},"modified":"2019-07-01T14:02:10","modified_gmt":"2019-07-01T18:02:10","slug":"project-10","status":"publish","type":"page","link":"https:\/\/www.bumc.bu.edu\/cardiovascularproteomics\/project-10\/","title":{"rendered":"Project 10"},"content":{"rendered":"

Interim update 2006<\/a>
\nInterim update 2005<\/a><\/p>\n

Proteomic Markers of Endothelial Damage and Oxidative Stress in Sickle Cell Disease<\/h3>\n

Endothelial activators are generated during sickle vasoocclusive episodes; moreover, oxidant damage to both the sickle erythrocyte and endothelium alters their membrane contents and changes their adhesive, metabolic and rheologic properties promoting adhesion and endothelial cell dysfunction. Aberrant endothelial cell proteins are expressed and oxidant radicals post-translationally modify proteins that promote further interaction of blood cells with the endothelium. Our aims are to:<\/p>\n

    \n
  1. Study oxidative damage in sickle red cell membrane and cytoplasmic proteins from patients with vasoocclusive sickle cell crisis. Key red cell enzymes (eg. G-6-PD, GSH peroxidase, SOD) and membrane and cytoskeletal proteins (eg. spectrin, ankyrin, Band 4.1, etc) will be studied for oxidative modification.<\/li>\n
  2. Detect modified proteins in human endothelial cells and plasma obtained from sickle patients at baseline or during acute vasoocclusive crisis. Microvascular endothelial cells will be cultured from skin biopsies of sickle cell patients. We will focus on oxidative modification to endothelial proteins (eg. eNOS, iNOS, GTP cyclohydrolase, guanylyl cyclase, heme oxygenase, SOD, catalase, and adhesion molecules (VCAM, ICAM, selectins).<\/li>\n
  3. Investigate oxidant stress in a transgenic sickle cell mouse model. Transgenic mice that express solely the HbS gene with three different concentrations of fetal Hb provide a spectrum of phenotypes. The expression of cellular proteins and oxidative post-translational modification of selected proteins will be determined during manipulation of vasoocclusive crisis in these mice using: NOS substrate (arginine), NOS cofactors (BH4), NOS inhibitors and inhaled NO, or antioxidants.<\/li>\n<\/ol>\n

    Researchers have used proteomic tools to study post-translational protein modifications in the plasma of patients with pulmonary hypertension of sickle cell disease. They created a repository of sickle cell disease samples and determined post-translational modifications in plasma from two sickle cell patients with pulmonary hypertension and two normal volunteers. Plasma was separated by use of albumin removal cartridges. MALDI-MS and LC-MS\/MS were performed for peptide analysis on the albumin-enriched samples. The albumin-depleted samples were analyzed by PF2D, followed by MALDI-MS. This work may help identify important pathophysiological features of sickle cell disease with prognostic, diagnostic and therapeutic implications. Abstracts have been presented at recent meetings:<\/p>\n

    CSCC 2006<\/a>
    \n    ASMS 2005 (Claire Dauly)<\/a><\/p>\n

    \n
    \n
    \"imageAdam Odhiambo<\/div>\n
    Elizabeth Klings, M.D.<\/a>, Assistant Professor, Boston University School of Medicine, studies the role of altered nitric oxide biology and oxidative stress in the pathogenesis of pulmonary vascular complications of sickle cell disease.
    \nAdam Odhiambo, senior research technician in the Pulmonary Center, is a graduate student pursuing his M.A. degree in graduate medical sciences at Boston University School of Medicine.<\/div>\n
    \"image
    \nElizabeth Klings<\/div>\n<\/div>\n

    <\/p>\n

    \n
    \"image
    \nHarrison Farber<\/div>\n
    Harrison Farber, M.D.<\/a>, Professor, Boston University School of Medicine
    \n    Martin Steinberg, M.D.<\/a>, Professor, Boston University School of Medicine and Director, Center of Excellence in Sickle Cell Disease<\/a><\/div>\n
    \"image
    \nMartin Steinberg<\/div>\n<\/div>\n<\/div>\n

    \"image
    \nSurinder Safaya<\/p>\n

    Click here to go to the BUSM Cardiovascular Proteomics Center’s Intranet<\/a> for “Proteomic Markers of Endothelial Damage and Oxidative Stress in Sickle Cell Disease” presentation.<\/p>\n","protected":false},"excerpt":{"rendered":"

    Interim update 2006 Interim update 2005 Proteomic Markers of Endothelial Damage and Oxidative Stress in Sickle Cell Disease Endothelial activators are generated during sickle vasoocclusive episodes; moreover, oxidant damage to both the sickle erythrocyte and endothelium alters their membrane contents and changes their adhesive, metabolic and rheologic properties promoting adhesion and endothelial cell dysfunction. Aberrant […]<\/p>\n","protected":false},"author":2,"featured_media":0,"parent":0,"menu_order":79,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/www.bumc.bu.edu\/cardiovascularproteomics\/wp-json\/wp\/v2\/pages\/79"}],"collection":[{"href":"https:\/\/www.bumc.bu.edu\/cardiovascularproteomics\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.bumc.bu.edu\/cardiovascularproteomics\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/cardiovascularproteomics\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/cardiovascularproteomics\/wp-json\/wp\/v2\/comments?post=79"}],"version-history":[{"count":11,"href":"https:\/\/www.bumc.bu.edu\/cardiovascularproteomics\/wp-json\/wp\/v2\/pages\/79\/revisions"}],"predecessor-version":[{"id":2683,"href":"https:\/\/www.bumc.bu.edu\/cardiovascularproteomics\/wp-json\/wp\/v2\/pages\/79\/revisions\/2683"}],"wp:attachment":[{"href":"https:\/\/www.bumc.bu.edu\/cardiovascularproteomics\/wp-json\/wp\/v2\/media?parent=79"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}