Harry Ischiropoulos, Ph.D.
Philadelphia, PA 19104
Wagner College, 1984.
New York Medical College, 1987.
Ph.D. (Experimental Pathology)
New York Medical College, 1990.
Description of Research ExpertiseRESEARCH INTERESTS
Biological chemistry of nitric oxide in cardiovascular and neuronal systems. Oxidative processes in protein aggregation and neurodegeneration. Non-invasive, mass spectrometry-based discovery and validation of disease biomarkers.
Biological chemistry of nitric oxide; oxidative processes and stress; protein aggregation and neurodegeneration; post-translational protein modifications.
Biochemical analysis of post-translational modifications; liquid chromatography-mass spectrometry; proteomics; nitric oxide detection; cell model systems of neuronal injury.
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 PublicationsDoulias PT, Tenopoulou M, Greene JL, Raju K, Ischiropoulos H: Nitric oxide regulates mitochondrial fatty acid metabolism through reversible protein S-nitrosylation. Sci Signal 6(256): rs1, Jan 2013.
Thomson L, Tenopoulou M, Lightfoot R, Tsika E, Parastatidis I, Martinez M, Greco TM, Doulias PT, Wu Y, Tang WHW, Hazen SL, Ischiropoulos H: Immunoglobulins against tyrosine-nitrated epitopes in coronary artery disease. Circulation 126(20): 2392-2401, 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 E, Moysidou M, Guo J, Cushman M, Gannon P, Sandaltzopoulos R, Giasson BI, Krainc D, Ischiropoulos H, Mazzulli JR: Distinct region-specific alpha-synuclein oligomers in A53T transgenic mice: implications for neurodegeneration. J Neurosci 30(9): 3409-3418, Mar 2010.
Parastatidis I, Thomson L, Burke A, Chernysh I, Nagaswami C, Visser J, Stamer S, Liebler DC, Koliakos G, Heijnen HFG, Fitzgerald GA, Weisel JW, Ischiropoulos H: Fibrinogen beta-chain tyrosine nitration is a prothrombotic risk factor. J Biol Chem 283(49): 33846-33853, Dec 2008.