Our laboratory investigates the biological chemistry and signaling pathways of nitric oxide by using biochemical and molecular methodologies in partnership with mass spectroscopy-based approaches. We uncovered that selective modification of cysteine residue by nitric oxide to generate S-nitrosocysteine regulates the function of enzymes participating in metabolism and mitochondrial bioenergetics. Current efforts are centered on uncovering the importance of S-nitrosocysteine in the regulation of B-oxidation of fatty acids and in the coordination of liver responses to metabolic deprivation or overloading. Another project investigates the utility of pharmacological agents that restore nitric oxide signaling to treat long-chain fatty acid oxidation disorders.
We are also generating inventories of cellular proteomes and secretomes of the mouse brain. These inventories are used to create 3D-functional landscapes of the mouse brain extracellular space and to identify astrocyte secreted proteins that influence neuronal development and neuronal demise. Other studies explore the role of nitric oxide and nitric-oxide mediated protein S-nitrosylation in the neuronastrocyte metabolism of glutamate.
Education and Training
Experimental Pathology - New York Medical College, Valhalla, NY
Titles and Academic Titles
Research Professor of Pediatrics and Pharmacology, Perelman School of Medicine at the University of Pennsylvania
Departments and Services
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. 6:rs1-7,2013.
Martinez M, Cuker A, Mills A, Lightfoot R, Fan Y, Tang "VB, Hazen SL, Ischiropoulos H. Nitrated fibrinogen is a biomarker of oxidative stress in venous thromboembolism. Free Radic Biol Med. 53:230-236,2012. PMC3392413.
Malleus K and Ischiropoulos H, Regional deficiencies in chaperone-mediated autophagy underlie a-synuclein aggregation and neurodegeneration. Neurobiol. Dis. 46:732-744,2012. PMC335297.
Thomson L, Tenopoulou M, Lightfoot R, Tsika E, Parastatidis I, Martinez M, Greco TM; Doulias P-T, Wu Y, Tang WHW, Hazen SL, Ischiropoulos H. Immunoglobulins against tyrosine nitrated epitopes in coronary artery disease. Circulation 126:2392-2401, 2012. PMC3501999.
Editorial and Academic Positions
2009-2013, Editorial board, Journal of Biological Chemistry
2009-present, Associate editor, Free Radical Biology and Medicine
2005-2009, Editorial Advisory Panel, Biochemical Journal
2005-2009, Current Respiratory Medicine Reviews
2003-present, Faculty Chemical Biology Section, Faculty 1000
2009-2013, Research Institute Faculty Advisory Committee on Compliance, The Children's Hospital of Philadelphia
2007-present, Deputy Chair, Research Institute-Cores Committee, The Children's Hospital of Philadelphia
2006-present, Director of Neonatology Research, The Children's Hospital of Philadelphia Research Institute
Patient Experience Ratings
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