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Harry Ischiropoulos, PhD
Research Professor of Pediatrics and Systems Pharmacology and Translational Therapeutics
Dr. Ischiropoulos's research objectives are to develop and test novel therapeutics for long-chain fatty acid oxidation (LCFA) disorders, a collection of inherited metabolic diseases that affect the heart, liver and muscle. A second area of interest is the resolution of the nitric oxide signaling pathways at the proteome level in the cardiovascular and neuronal systems.
Bio
Dr. Ischiropoulos's research objectives are to develop and test novel therapeutics for long-chain fatty acid oxidation (LCFA) disorders, a collection of inherited metabolic diseases that affect the heart, liver and muscle. A second area of interest is the resolution of the nitric oxide signaling pathways at the proteome level in the cardiovascular and neuronal systems.
Along with his colleagues, one of the current projects in Dr. Ischiropoulos’s lab involves synthesizing multifunctional hybrid molecules as potential therapeutics for LCFA oxidation disorders. He tests these molecules in fibroblasts from patients with mutations in carnitine palmitoyltransferase-2, very long chain acyl CoA dehydrogenase, and mitochondrial trifunctional protein.
He uses mass spectrometry-based proteomic technologies to identify and quantify the full spectrum of nitric oxide-induced post-translational modifications in the cardiovascular system, providing for the first time a system-level appreciation of nitric oxide signalling.
Education and Training
BS, Wagner College (Chemistry), 1984
PhD, New York Medical College (Experimental Pathology), 1990
Titles and Academic Titles
Gisela and Dennis Alter Research Professor in Pediatric Neonatology
Research Professor of Pediatrics and Systems Pharmacology and Translational Therapeutics
Professional Awards
Parker B. Francis Fellowship in Pulmonary Research, 1993-1996
Young Investigator Award, International Society for Free Radical Research, 1994
Young Investigator Award, Oxygen Society, 1995
Established Investigator, American Heart Association, 1996-2001
Academic Prize in Medicine, Bodossaki Foundation, Athens, Greece, 1998
Publication Highlights
PubMed:
Tenopoulou M, Doulias PT, Nakamoto K, Berrios K, Zura G, Li C, Faust M, Yakovishina V, Evans P, Tan L, Bennett MJ, Snyder NW, Quinn WJ 3rd, Baur JA, Atochin DN, Huang PL, Ischiropoulos H. Oral nitrite restores age-dependent phenotypes in eNOS-null mice. JCI Insight. 2018 Jan; 3(16):e122156. PMID: 30135317; PMCID: PMC6141175
Raju K, Doulias PT, Evans P, Krizman EN, Jackson JG, Horyn O, Daikhin Y, Nissim I, Yudkoff M, Nissim I, Sharp KA, Robinson MB, Ischiropoulos H. Regulation of brain glutamate metabolism by nitric oxide and S-nitrosylation. Sci Signal. 2015 Jan; 8:ra68. PMID:26152695, PMCID:PMC 4746709
Gould NS, Evans P, Martínez-Acedo P, Marino SM, Gladyshev VN, Carroll KS, Ischiropoulos H. Site-specific proteomic mapping identifies selectively modified regulatory cysteine residues in functionally distinct protein networks. Chem Biol. 2015 Jan; 22:965-75, 2015, PMID: 26165157 PMCID: PMC4515171
Doulias P-T. Tenopoulou M, Greene, JL, Raju, K and Ischiropoulos H. Nitric oxide regulates mitochondrial fatty acid metabolism through reversible protein S-nitrosylation. Sci. Signal. 2013 Jan; 6: rs1-7, 2013, PMID: 23281369, PMCID: PMC4010156
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. 2010 Jan; USA, 107:16958-16963, 2010. PMID: 20837516; PMCID: PMC2947911