Ph.D. Defense by Anthony O. Awojoodu

Event Details
  • Date/Time:
    • Friday October 31, 2014
      2:00 pm - 4:00 pm
  • Location: Room 1103, Whitaker Building
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Summaries

Summary Sentence: Sphingolipid Dysregulation in Erythrocytes During Sickle Cell Disease Contributes to Pro-Inflammatory Microparticle Generation and Subsequent Inflammatory Cell Activation

Full Summary: No summary paragraph submitted.

Anthony O. Awojoodu
BME Ph.D. Defense Presentation
Date: Friday, October 31, 2014
Time: 2:00 pm
Location: Room 1103, Whitaker Building


Committee:
Advisor: Dr. Edward A. Botchwey (BME - Georgia Tech)
Dr. Manu O. Platt (BME - Georgia Tech)
Dr. Greg Gibson (Biology – Georgia Tech)
Dr. Gilda Barabino (School of Engineering – City College of New York)
Dr. Shayn M. Peirce-Cottler (BME – University of Virginia)

Title: Sphingolipid Dysregulation in Erythrocytes During Sickle Cell Disease Contributes to Pro-Inflammatory Microparticle Generation and Subsequent Inflammatory Cell Activation

Abstract:
Sickle cell disease is a hereditary blood disorder caused by a point mutation in the gene encoding hemoglobin. This mutation causes hemoglobin molecules to polymerize during de-oxygenation of erythrocytes producing to rod-shaped polymers that bend and distort the red blood cell membrane, making it more rigid and “sickled”. This sickling causes red blood cells to lose their flexibility and ability to navigate small capillaries and also enhances the production of pro-inflammatory membrane-derived microparticles, leading to chronic inflammation and many complications such as peripheral artery disease, stroke, myocardial infarction, vasculitis and even death. Sphingolipids are a class of lipids containing a backbone of sphingoid bases and are integral components of erythrocyte and microparticle membranes. Many of these lipids are known to mediate biological processes, but their expression, distribution and orientation in erythrocytes during sickle cell disease has never been explored. Sphingomyelin, the most abundant sphingolipid in the red blood cell membrane is hydrolyzed by sphingomyelinase to produce ceramide, which has been shown to alter membrane dynamics and enhance microvessel formation. Additionally, ceramide can be further metabolized to form sphingosine and sphingosine 1-phosphate, which is a bioactive ligand for 5 known G-protein coupled receptors present on most blood and vascular cells that modulates cell motility, proliferation, migration and phenotype. Prior to this work, it was not understood how sphingolipid metabolism contributes to vascular inflammation in sickle cell disease. Together, this body of work has elucidated key enzymatic and lipidomic alterations in sphingolipid metabolism (i.e. the activation of acid sphingomyelinase on red blood cells) that result in the production of sphingolipid-rich erythrocyte-derived microparticles, which enhance inflammatory cell activation. Our work has elucidated novel pharmacological targets to reduce microparticle generation and subsequent vascular inflammation in sickle cell disease.

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Keywords
BME, PhD Defense; graduate students
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  • Created By: Danielle Ramirez
  • Workflow Status: Published
  • Created On: Oct 17, 2014 - 10:19am
  • Last Updated: Oct 7, 2016 - 10:09pm