Gisela and Dennis Alter Research Professor of Pediatrics and Pharmacology

417 Abramson Research Center
215-590-5320 ischirop@mail.med.upenn.edu

Research Interests:
The research efforts of my laboratory are focused on three areas:
1) Biological chemistry of nitric oxide in cardiovascular diseases and thrombosis. We employ proteomics to discover the complement of proteins modified post-transitionally by nitric oxide on cysteine and tyrosine residues. The functional consequences of these modifications on nitric oxide signaling in atherosclerosis and deep vein thrombosis are under investigation.

2) Oxidative processes in protein aggregation and neurodegeneration. We use cellular and mouse models to investigate the role of oxidative chemistry in the aggregation of a-synuclein and in neurodegeneration.

3) Functional proteomics to turn inventories of cellular secretomes to biological insights by defining secreted proteins that regulate neuron growth, differentiation and death.

Selected Publications:

Parastatidis, I., Thomson, L.M., Burke, A., Chernysh, I. Nagaswami, C., Visser, J., Stamer, S., Liebler, D.C., Koliakos, G., Heijnen, H.F.G., FitzGerald, G.A., Weisel, J.W., and Ischiropoulos (2008) H. Fibrinogen β-chain tyrosine nitration is a prothrombotic risk factor. J. Biol. Chem. Sep 25. [Epub ahead of print] PMID: 18818200.

Parastatidis, I., Thomson, L.M., Fries D.M., Moore, R.E., Tohyama, J., Fu, X., Hazen, S.L., Heijnen, H.F.G., Dennehy, M.K., Liebler, D.C., Rader, D.J. and Ischiropoulos, H. (2007) Increased protein nitration burden in the atherosclerotic lesions and plasma of apolipoprotein A-I deficient mice. Circ. Res. 101:368-76.

Greco, T.M., Hodara, R., Parastatidis, I., Heijnen, HFG, Dennehy, M.K., Liebler, D.C. and Ischiropoulos, H. (2006) Identification of S-nitrosylation motifs by site-specific mapping of the S-nitrosocysteine proteome in human vascular smooth muscle cells. Proc. Natl. Acad. Sci. USA, 103:7420-7425.

Mazzulli, J.R., Mishizen, A.J., Giasson, B.I., Lynch, D.R., Thomas, S.A., Akira Nakashima, A., Nagatsu, T., Ota, A., and Ischiropoulos, H. (2006) Cytosolic catechols inhibit alpha-synuclein aggregation and facilitate the formation of intracellular soluble oligomeric intermediates. J. Neurosci. 26:10068-10078.

Hodara, R., Norris, E.H., Giasson, B.I., Mishizen-Eberz, A.J., Lynch, D.R., Lee, V. M-Y. and Ischiropoulos, H. (2004) Functional consequences of α-synuclein tyrosine nitration: diminished binding to lipid vesicles and increased fibril formation. J. Biol. Chem. 279:47746-47753.