Positions

Overview

  • My research focuses on the mechanisms by which biological systems harness the generation of reactive species to modulate cell signaling pathways and maintain physiological homeostasis. My group is particularly interested in elucidating the mechanisms that result in the formation of electrophilic species in vivo. Electrophiles can regulate enzymatic and transcription factor function via covalent modification of reactive cysteine residues. In this regard, our overarching hypothesis is that the endogenous generation of electrophilic species in vivo is a conserved mechanism for maintaining physiological homeostasis and regulating inflammatory responses. Enabled by collaboration with basic and clinical scientists, we have studied the effects of endogenous electrophiles in pathological conditions such as sickle cell disease, acute and chronic renal injury, as well as cardiac arrest, both at the pre-clinical and clinical level. Finally, and in line with extensive expertise at the Center for Free Radical Biology, I maintain a keen interest in general redox biochemistry as well as in nitric oxide and metallo-protein biology.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2022 Immunomodulatory actions of a kynurenine-derived endogenous electrophileScience Advances.  8:eabm9138. 2022
    2021 Endogenous generation of nitro-fatty acid hybrids having dual nitrate ester (RONO2) and nitroalkene (RNO2) substituentsRedox Biology.  41. 2021
    2021 Xanthine Oxidase Drives Hemolysis and Vascular Malfunction in Sickle Cell DiseaseArteriosclerosis, Thrombosis and Vascular Biology.  769-782. 2021
    2020 Nitro-fatty acids as activators of hSIRT6 deacetylase activityJournal of Biological Chemistry.  295:18355-18366. 2020
    2020 Corrigendum to “Endogenous formation of novel nitro-nitrate species as intermediates of fatty acid nitration” [Free Radic. Biol. Med. 145(1) (2019) S22] (Free Radical Biology and Medicine (2019) 145(S1), (S0891584919317861) (10.1016/j.freeradbiomed.2020.01.180))Free Radical Biology and Medicine.  152:867. 2020
    2020 Nitrite elicits divergent NO-dependent signaling that associates with outcome in out of hospital cardiac arrest: Nitrite-derived signals correlate with OHCA outcomeRedox Biology.  32. 2020
    2020 Hemopexin deficiency promotes acute kidney injury in sickle cell diseaseBlood.  135:1044-1048. 2020
    2020 Nrf2 activation protects against lithium-induced nephrogenic diabetes insipidusJCI insight.  5. 2020
    2019 Smooth muscle cytochrome b5 reductase 3 deficiency accelerates pulmonary hypertension development in sickle cell miceBlood Advances.  3:4104-4116. 2019
    2019 Electrophiles modulate glutathione reductase activity via alkylation and upregulation of glutathione biosynthesisRedox Biology.  21. 2019
    2019 Electrophilic fatty acid nitroalkenes are systemically transported and distributed upon esterification to complex lipidsJournal of Lipid Research.  60:388-399. 2019
    2019 Hemoglobin alters vitamin carrier uptake and Vitamin D metabolism in proximal tubule cells: Implications for sickle cell diseaseAmerican Journal of Physiology: Cell Physiology.  317:C993-C1000. 2019
    2018 Nitro-fatty acids: New drug candidates for chronic inflammatory and fibrotic diseasesNitric Oxide: Biology and Chemistry.  79:31-37. 2018
    2018 In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammationRedox Biology.  15:522-531. 2018
    2017 Evaluation of 10-Nitro Oleic Acid Bio-Elimination in Rats and HumansScientific Reports.  7. 2017
    2017 The chemical basis of thiol addition to nitro-conjugated linoleic acid, a protective cell-signaling lipidJournal of Biological Chemistry.  292:1145-1159. 2017
    2016 Novel Roles for Peroxynitrite in Angiotensin II and CaMKII SignalingScientific Reports.  6. 2016
    2015 Nitrite and nitrate-dependent generation of anti-inflammatory fatty acid nitroalkenesFree Radical Biology and Medicine.  89:333-341. 2015
    2015 Convergence of biological nitration and nitrosation via symmetrical nitrous anhydrideNature Chemical Biology.  11:504-510. 2015
    2014 Olives and olive oil are sources of electrophilic fatty acid nitroalkenesPLoS One.  9. 2014
    2013 Modulation of nitro-fatty acid signaling prostaglandin reductase-1 is a nitroalkene reductaseJournal of Biological Chemistry.  288:25626-25637. 2013
    2013 Characterization and quantification of endogenous fatty acid nitroalkene metabolites in human urineJournal of Lipid Research.  54:1998-2009. 2013
    2013 Antioxidant functions for the hemoglobin β93 cysteine residue in erythrocytes and in the vascular compartment in vivoFree Radical Biology and Medicine.  55:119-129. 2013
    2012 Conjugated linoleic acid is a preferential substrate for fatty acid nitrationJournal of Biological Chemistry.  287:44071-44082. 2012
    2011 Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapyFree Radical Biology and Medicine.  51:805-812. 2011
    2011 Effects of T- and R-state stabilization on deoxyhemoglobin-nitrite reactions and stimulation of nitric oxide signalingNitric Oxide: Biology and Chemistry.  25:59-69. 2011
    2011 Acyloxy nitroso compounds as nitroxyl (HNO) donors: Kinetics, reactions with thiols, and vasodilation propertiesJournal of Medicinal Chemistry.  54:1059-1070. 2011
    2009 Sodium nitrite therapy attenuates the hypertensive effects of HBOC-201 via nitrite reductionBiochemical Journal.  422:423-432. 2009
    2009 A mitochondria-targeted S-nitrosothiol modulates respiration, nitrosates thiols, and protects against ischemia-reperfusion injuryProceedings of the National Academy of Sciences of USA.  106:10764-10769. 2009
    2009 Regulation of nitrite transport in red blood cells by hemoglobin oxygen fractional saturationAmerican Journal of Physiology: Heart and Circulatory Physiology.  296. 2009
    2008 SNO-hemoglobin is not essential for red blood cell-dependent hypoxic vasodilationNature Medicine.  14:773-777. 2008
    2007 Membrane "lens" effect: Focusing The Formation of Reactive Nitrogen Oxides from the .NO/O2 reactionChemical Research in Toxicology.  20:709-714. 2007
    2003 Reactions of manganese porphyrins with peroxynitrite and carbonate radical anionJournal of Biological Chemistry.  278:27432-27438. 2003

    Chapter

    Year Title Altmetric
    2011 Biochemistry of Storage of Red Blood Cells.  231-241. 2011
    2009 Nitric Oxide Regulation in Redox Signaling.  271-291. 2009

    Research Overview

  • • Formation, metabolism and signaling actions of endogenous electrophiles. Examples: Nitrated Fatty Acids, Kynurenine-derived electrophiles.
    • Redox biochemistry: Nitric oxide, reactive oxygen species, thiol and metalloprotein reactivity.
    • Preclinical development of electrophiles for oxidative and inflammatory organ injury.
    • Sickle Cell Disease, Acute and Chronic Renal Dysfunctions, Cardiac Arrest.
  • Education And Training

  • Doctor of Philosophy in Cell / Cellular and Molecular Biology, University of Alabama at Birmingham 2010
  • Full Name

  • Dario Vitturi Iglesias