Penn Cardiovascular Institute

Penn Cardiovascular Institute Research Directory

faculty photo

Harry Ischiropoulos, Ph.D

Research Professor of Pediatrics
Department: Pediatrics

Contact information
Suite 416 Abramson Research Center
Room 417
Philadelphia, PA 19104
Office: 215-590-5320
Fax: 215-590-4267
Education:
B.S. (Chemistry)
Wagner College, 1984.
M.S. (Pathology)
New York Medical College, 1987.
Ph.D. (Experimental Pathology)
New York Medical College, 1990.
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Description of CVI Expertise

CVI Program Unit(s):
Lipid / Atherosclerosis / CAD / ACS / Prevention

CVI Research Description:
The major focus of one of our research projects is to identify, characterize and validate biomarkers for the assessment of cardiovascular diseases. By employing proteomicc approaches coupled with state-of-the art stable isotope dilution liquid chromatography/tandem mass spectrometry (LC/MS/MS) we are evaluating the utility of protein modifications as biomarkers of oxidative stress by correlating changes with the development and severity of cardiovascular disease in human populations with defined clinical risks.

Oxidative stress has been proposed as a major cause of vascular injury leading to the development of atherosclerosis. A consequence of oxidative stress is the formation of reactive nitrogen species that specifically modify tyrosine residues in proteins leading to the formation of the unusual amino acid nitrotyrosine. Nitrated proteins have been detected in atherosclerotic lesions and the levels of nitrated proteins in plasma may serve as independent risk association factor for coronary artery disease.

We have also identified several potential plasma protein candidate markers for coronary artery disease and currently we are evaluating in a large cohort of coronary disease patients one of these proteins, nitrated fibrinogen. Studies are also designed to provide insights into the molecular mechanisms of abnormal hemostatic regulation in human coronary heart disease by investigating the biochemical and biophysical alterations in fibrinogen that regulate critical pro- and anti-thrombotic functions of this protein.

Selected Publications

Doulias Paschalis-Thomas, Tenopoulou Margarita, Greene Jennifer L, Raju Karthik, Ischiropoulos Harry: Nitric oxide regulates mitochondrial fatty acid metabolism through reversible protein S-nitrosylation. Science signaling 6(256): rs1, Jan 2013.

Thomson Leonor, Tenopoulou Margarita, Lightfoot Richard, Tsika Epida, Parastatidis Ioannis, Martinez Marissa, Greco Todd M, Doulias Paschalis-Thomas, Wu Yuping, Tang W H Wilson, Hazen Stanley L, Ischiropoulos Harry: Immunoglobulins against tyrosine-nitrated epitopes in coronary artery disease. Circulation 126(20): 2392-401, Nov 2012.

Doulias PT, Greene JL, Greco TM, Tenopoulou M, Seeholzer SH, Dunbrack RL, Ischiropoulos H.: Structural profiling of endogenous S-nitrosocysteine residues reveals unique features that accommodate diverse mechanisms for protein S-nitrosylation. Proc Natl Acad Sci U S A. 107(39): 6958-6963, Sep 2010.

Greco TM, Seeholzer SH, Mak A, Spruce L, Ischiropoulos H: Quantitative mass spectrometry-based proteomics reveals the dynamic range of primary mouse astrocyte protein secretion. J Proteome Res 9(5): 2764-2774, May 2010.

Tsika Elpida, Moysidou Maria, Guo Jing, Cushman Mimi, Gannon Patrick, Sandaltzopoulos Raphael, Giasson Benoit I, Krainc Dimitri, Ischiropoulos Harry, Mazzulli Joseph R: Distinct region-specific alpha-synuclein oligomers in A53T transgenic mice: implications for neurodegeneration. J Neurosci 30(9): 3409-3418, Mar 2010.

Parastatidis Ioannis, Thomson Leonor, Burke Anne, Chernysh Irina, Nagaswami Chandrasekaran, Visser Jetze, Stamer Sheryl, Liebler Daniel C, Koliakos George, Heijnen Harry F G, Fitzgerald Garret A, Weisel John W, Ischiropoulos Harry: Fibrinogen beta-chain tyrosine nitration is a prothrombotic risk factor. The Journal of biological chemistry 283(49): 33846-53, Dec 2008.

Keene Sarah Dunn, Greco Todd M, Parastatidis Ioannis, Lee Seon-Hwa, Hughes Ethan G, Balice-Gordon Rita J, Speicher David W, Ischiropoulos Harry: Mass spectrometric and computational analysis of cytokine-induced alterations in the astrocyte secretome. Proteomics 9(3): 768-82, Feb 2009.

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Last updated: 03/19/2014
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