Harry Ischiropoulos, Ph.D

faculty photo
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 Research Expertise

RESEARCH INTERESTS
Biological chemistry of nitric oxide in cardiovascular diseases and thrombosis. Oxidative processes in protein aggregation and neurodegeneration. Non-invasive, mass spectrometry-based discovery and validation of disease biomarkers.

KEY WORDS
Biological chemistry of nitric oxide; oxidative processes and stress; protein aggregation and neurodegeneration; post-translational protein modifications.

RESEARCH TECHNIQUES
Biochemical analysis of post-translational modifications; liquid chromatography-mass spectrometry; proteomics; nitric oxide detection; cell model systems of neuronal injury.

RESEARCH SUMMARY
We investigate the biological chemistry and molecular mechanisms of nitric oxide signaling. Nitric oxide is a free radical that mediates blood flow and many other physiological responses within every major organ system.

Currently mass spectrometry-based proteomic data in conjunction with structure-function analysis explore the biochemical and biophysical specificity of two nitric oxide-mediated post-translational modifications cysteine S-nitrosation and tyrosine nitration. Studies explore the consequences of these modifications on protein function in metabolic processes and mitochondrial bioenergetics.

We are also generating inventories of mouse brain proteomes, phosphoproteomes, S-nitrosoproteomes and secretomes. These inventories are used to create 3D-functional landscapes of the mouse brain extracellular space and to identify signaling pathways that influence neuron physiology and neurodegeneration.

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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