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.
Experimental Pathology - New York Medical College, Valhalla, NY
Researcher
Research Professor of Pediatrics and Pharmacology, Perelman School of Medicine at the University of Pennsylvania
Human Placental Transcriptome Reveals Critical Alterations in Inflammation and Energy Metabolism with Fetal Sex Differences in Spontaneous Preterm Birth. Lien YC, Zhang Z, Cheng Y, Polyak E, Sillers L, Falk MJ, Ischiropoulos H, Parry S, Simmons RA. Int J Mol Sci. 2021 Jul 23;22(15):7899. doi: 10.3390/ijms22157899. PMID: 34360662 Free PMC article.
Ramick MG, Kirkman DL, Stock JM, Muth BJ, Farquhar WB, Chirinos JA, Doulias PT, Ischiropoulos H, Edwards DG. The effect of dietary nitrate on exercise capacity in chronic kidney disease: a randomized controlled pilot study. Nitric Oxide. 2021 Jan 1;106:17-23. doi: 10.1016/j.niox.2020.10.002. Epub 2020 Oct 17.PMID: 33080411
Mishra V, Re DB, Le Verche V, Alvarez MJ, Vasciaveo A, Jacquier A, Doulias PT, Greco TM, Nizzardo M, Papadimitriou D, Nagata T, Rinchetti P, Perez-Torres EJ, Politi KA, Ikiz B, Clare K, Than ME, Corti S, Ischiropoulos H, Lotti F, Califano A, Przedborski S. Systematic elucidation of neuron-astrocyte interaction in models of amyotrophic lateral sclerosis using multi-modal integrated bioinformatics workflow. Nat Commun. 2020 Nov 4;11(1):5579. doi: 10.1038/s41467-020-19177-y.PMID: 33149111 Free PMC article.
Umanah GKE, Ghasemi M, Yin X, Chang M, Kim JW, Zhang J, Ma E, Scarffe LA, Lee YI, Chen R, Tangella K, McNamara A, Abalde-Atristain L, Dar MA, Bennett S, Cortes M, Andrabi SA, Doulias PT, Ischiropoulos H, Dawson TM, Dawson VL. AMPA Receptor Surface Expression Is Regulated by S-Nitrosylation of Thorase and Transnitrosylation of NSF. Cell Rep. 2020 Nov 3;33(5):108329. doi: 10.1016/j.celrep.2020.108329.PMID: 33147468 Free PMC article.
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.
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