Harry Ischiropoulos, Ph.D
Research Professor of Pediatrics
Department: Pediatrics
Graduate Group Affiliations
Contact information
Suite 416 Abramson Research Center
Room 417
Philadelphia, PA 19104
Room 417
Philadelphia, PA 19104
Office: 215-590-5320
Fax: 215-590-4267
Fax: 215-590-4267
Email:
ischirop@mail.med.upenn.edu
ischirop@mail.med.upenn.edu
Publications
Links
Search PubMed for articles
Neuroscience graduate group faculty webpage.
Pharmacological Sciences graduate group faculty webpage.
Search PubMed for articles
Neuroscience graduate group faculty webpage.
Pharmacological Sciences graduate group faculty webpage.
Education:
B.S. (Chemistry)
Wagner College, 1984.
M.S. (Pathology)
New York Medical College, 1987.
Ph.D. (Experimental Pathology)
New York Medical College, 1990.
Permanent linkB.S. (Chemistry)
Wagner College, 1984.
M.S. (Pathology)
New York Medical College, 1987.
Ph.D. (Experimental Pathology)
New York Medical College, 1990.
Description of Research Expertise
RESEARCH INTERESTSBiological 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 also explore the consequences of these modifications on protein function.
In addition, we are evaluating the usefulness of tracking specific nitric oxide-modified and oxidized proteins in human diseases (e.g., respiratory distress syndromes of neonates and adults, vascular disorders and neurodegenerative disorders). Our goal is to determine if they can be used as predictors of disease development, disease outcome or as surrogate markers for determining the efficacy of therapeutic interventions. Finally, we are exploring the use of protein tyrosine nitration to heighten immune responses and to augment the function of proteins in the coagulation cascade.
Selected Publications
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.
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.
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.
Martinez-Vicente Marta, Talloczy Zsolt, Kaushik Susmita, Massey Ashish C, Mazzulli Joseph, Mosharov Eugene V, Hodara Roberto, Fredenburg Ross, Wu Du-Chu, Follenzi Antonia, Dauer William, Przedborski Serge, Ischiropoulos Harry, Lansbury Peter T, Sulzer David, Cuervo Ana Maria: Dopamine-modified alpha-synuclein blocks chaperone-mediated autophagy. J Clin Invest 118(2): 777-788, Feb 2008.
Parastatidis Ioannis, Thomson Leonor, Fries Diana M, Moore Ryan E, Tohyama Junichiro, Fu Xiaoming, Hazen Stanley L, Heijnen Harry F G, Dennehy Michelle K, Liebler Daniel C, Rader Daniel J, Ischiropoulos Harry: Increased protein nitration burden in the atherosclerotic lesions and plasma of apolipoprotein A-I deficient mice. Circ Res 101(4): 368-376, Aug 2007.
Szabó C, Ischiropoulos H, Radi R: Peroxynitrite: biochemistry, pathophysiology and development of therapeutics. Nat Rev. Drug Discovery 6(8): 662-680, Aug 2007.

