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Eduardo R. Lazarowski, PhD

Professor

Specialty Areas:

Nucleotide actions in the lung, purinergic receptors, mechanisms of nucleotide release, extracellular nucleotides as biomarkers of chronic lung diseases.

Chronology:

BS in Clinical Chemistry, University of Buenos Aires, 1975; MS in Biochemistry, University of Buenos Aires; 1978. PhD in Biochemistry, University of Buenos Aires, 1989; Visiting fellow to The Welcome Research Laboratories, Molecular/Cell Biology. NC USA, 1986-1990; Post-doctoral fellow, Department of Medicine, University of North Carolina, Chapel Hill, NC; Research Associate, Cystic Fibrosis Center and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 1994-1998; Research Assistant Professor of Medicine, Department of Medicine, University of North Carolina, Chapel Hill, NC, 1998-2004; Research Associate Professor, Department of Medicine, University of North Carolina, Chapel Hill, NC, 2004-2019; Research Professor, Department of Medicine, University of North Carolina, Chapel Hill, NC, 2019-present.

Research Focus:

Extracellular nucleotides activate purinergic receptors on airway epithelial cells, promoting mucociliary clearance activities that remove foreign particles and pathogens from the lung. Nucleotides also are potent pro-inflammatory signaling molecules acting on purinergic receptors expressed on immune/inflammatory cells. Dr. Lazarowski’s research is focused on understanding the molecular basis and pathophysiological consequences of nucleotide release in the lung. Dr. Lazarowski has identified conductive and vesicular mechanisms involved in the release of nucleotides and studies are in progress to assess the contribution of these mechanisms to the regulation of mucous hydration and inflammation in chronic lung diseases, including COPD and cystic fibrosis (CF). Studies also are underway to Identifying nucleotide distribution patterns associated with these and other chronic lung diseases and to assess the impact of tobacco smoke on airway surface liquid nucleotide homeostasis.

Selected Bibliography:

  1. Kong X, Bennett WC, Jania CM, Chason KD, German Z, Adouli J, Budney SD, Oby BT, van Heusden C, Lazarowski ER, Jaspers I, Randell SH, Hedgespeth BA, Cruse G, Hua X, Schworer SA, Smith GJ, Kelada SN, Tilley SL. Identification of an ATP/P2X7/mast cell pathway mediating ozone-induced bronchial hyperresponsiveness. JCI Insight. 2021 Nov 8;6(21):e140207. doi: 10.1172/jci.insight.140207. PMID: 34546976. PMCID: PMC8663556.
  2. van Heusden C, Grubb BR, Button B, Lazarowski ER. Airway Epithelial Nucleotide Release Contributes to Mucociliary Clearance. Life (Basel). 2021 May 11;11(5):430. doi: 10.3390/life11050430. PMID: 34064654; PMCID: PMC8151306.
  3. Lazarowski ER, Boucher RC. Purinergic receptors in airway hydration. Biochem Pharmacol. 2021 May;187:114387. doi: 10.1016/j.bcp.2020.114387. PMID: 33358825. PMCID: PMC8096650.
  4. Kirby BS, Sparks MA, Lazarowski ER, Lopez Domowicz DA, Zhu H, McMahon TJ. Pannexin 1 Channels Control the Hemodynamic Response to Hypoxia by Regulating O2-Sensitive Extracellular ATP in Blood. Am J Physiol Heart Circ Physiol. 2021 Mar 1;320(3):H1055-H1065. doi: 10.1152/ajpheart.00651.2020. PMID: 33449849. PMCID: PMC7988759.
  5. Battistone MA, Mendelsohn AC, Spallanzani RG, Allegretti AS, Liberman RN, Sesma J, Kalim S, Wall SM, Bonventre JV, Lazarowski ER, Brown D, Breton S. Pro-inflammatory P2Y14 receptor inhibition protects against ischemic acute kidney injury in mice. J Clin Invest. 2020 Jul 1;130(7):3734-3749. doi: 10.1172/JCI134791. PMID: 32287042. PMCID: PMC7324186.
  6. van Heusden C, Button B, Anderson WH, Ceppe A, Morton LC, O’Neal WK, Dang H, Alexis NE, Donaldson SH, Stephan H, Boucher RC, Lazarowski ER. Inhibition of ATP hydrolysis restores airway surface liquid production in cystic fibrosis airway epithelia. Am J Physiol Lung Cell Mol Physiol. 2020 Feb 1;318(2):L356-L365. doi: 10.1152/ajplung.00449.2019. PMID: 31800264. PMCID: PMC7052677.
  7. Clapp PW, Lavrich KS, van Heusden C, Lazarowski ER, Carson JL, Jaspers I. Cinnamaldehyde in Flavored E-Cigarette Liquids Temporarily Suppresses Bronchial Epithelial Cell Ciliary Motility by Dysregulation of Mitochondrial Function. Am J Physiol Lung Cell Mol Physiol. 2019 Mar 1;316(3):L470-L486. doi: 10.1152/ajplung.00304.2018. PMID: 30604630. PMCID: PMC6459291.
  8. Henderson AG, Anderson WH, Ceppe A, Coakley RD, Button B, Alexis NE, Peden DB, Lazarowski ER, Davis CW, Fuller F, Almond M, Qaqish B, Kesimer M, Boucher RC. Mucus hydration in subjects with stable chronic bronchitis: A comparison of spontaneous and induced sputum. COPD. 2018 Dec;15(6):572-580. doi: 10.1080/15412555.2019.1566892. PMID: 30712400. PMCID: PMC6428611.
  9. Müller T, Fay S, Vieira RP, Karmouty-Quintana H, Cicko S, Ayata CK, Zissel G, Goldmann T, Lungarella G, Ferrari D, Di Virgilio F, Robaye B, Boeynaems JM, Lazarowski ER, Blackburn MR, Idzko M. P2Y6 receptor activation promotes inflammation and tissue remodeling in pulmonary fibrosis. Front Immunol. 2017 Aug 22;8:1028. doi: 10.3389/fimmu.2017.01028. PMID: 28878780. PMCID: PMC5572280.
  10. Sesma JI, Weitzer CD, Livraghi-Butrico A, Dang H, Donaldson D, Alexis NE, Jacobson KA, Harden TK, Lazarowski ER. UDP-glucose promotes neutrophil recruitment in the lung. Purinergic Signal. 2016 Dec;12(4):627-35. PMID: 27421735; PMCID: PMC5124001.
  11. Anderson WH, Coakley RD, Button B, Henderson AG, Zeman KL, Alexis NE, Peden DB, Lazarowski ER, Davis CW, Bailey S, Fuller F, Almond M, Qaqish B, Bordonali E, Rubinstein M, Bennett WD, Kesimer M, Boucher RC. The relationship of mucus concentration (hydration) to mucus osmotic pressure and transport in chronic bronchitis. Am J Respir Crit Care Med. 2015 Jul 15;192(2):182-90. doi: 10.1164/rccm.201412-2230OC. PMID: 25909230; PMCID: PMC4532825.
  12. Lazarowski ER, Harden TK. UDP-sugars as extracellular signaling molecules: Cellular and physiologic consequences of P2Y14 receptor activation. Mol Pharmacol. 2015 Jul;88(1):151-60. doi: 10.1124/mol.115.098756. Review. PMID: 25829059; PMCID: PMC4468635.
  13. Okada SF, Ribeiro CM, Sesma JI, Seminario-Vidal L, Abdullah LH, van Heusden C, Lazarowski ER, Boucher RC. Inflammation promotes airway epithelial ATP release via calcium-dependent vesicular pathways. Am J Respir Cell Mol Biol. 2013 Nov;49(5):814-20. doi: 10.1165/rcmb.2012-0493OC. PMID: 23763446; PMCID: PMC3931099.
  14. Barrett MO, Sesma JI, Ball CB, Jayasekara PS, Jacobson KA, Lazarowski ER, Harden TK. A selective high-affinity antagonist of the P2Y14 receptor inhibits UDP-glucose-stimulated chemotaxis of human neutrophils. Mol Pharmacol. 2013 Jul;84(1):41-9. doi: 10.1124/mol.113.085654. PMID: 23592514; PMCID: PMC3684828.
  15. Sesma JI, Kreda SM, Okada SF, van Heusden C, Moussa L, Jones LC, O’Neal WK, Togawa N, Hiasa M, Moriyama Y, Lazarowski ER. Vesicular nucleotide transporter regulates the nucleotide content in airway epithelial mucin granules. Am J Physiol Cell Physiol. 2013 May 15;304(10):C976-84. doi: 10.1152/ajpcell.00371.2012. Erratum in: Am J Physiol Cell Physiol. 2014 Feb 15;306(4):C415. PMID: 23467297; PMCID: PMC3651637.
  16. Lazarowski ER. Vesicular and conductive mechanisms of nucleotide release. Purinergic Signal. 2012 Sep;8(3):359-73. doi: 10.1007/s11302-012-9304-9. Review. PMID: 22528679; PMCID: PMC3360093.
  17. Sesma JI, Kreda SM, Steinckwich-Besancon N, Dang H, García-Mata R, Harden TK, Lazarowski ER. The UDP-sugar-sensing P2Y(14) receptor promotes Rho-mediated signaling and chemotaxis in human neutrophils. Am J Physiol Cell Physiol. 2012 Sep 1;303(5):C490-8. doi: 10.1152/ajpcell.00138.2012. PMID: 22673622; PMCID: PMC3468347.
  18. Seminario-Vidal L, Okada SF, Sesma JI, Kreda SM, van Heusden CA, Zhu Y, Jones LC, O’Neal WK, Penuela S, Laird DW, Boucher RC, Lazarowski ER. Rho signaling regulates pannexin 1-mediated ATP release from airway epithelia. J Biol Chem. 2011 Jul 29;286(30):26277-86. doi: 10.1074/jbc.M111.260562. PMID: 21606493; PMCID: PMC3143590.
  19. Chekeni FB, Elliott MR, Sandilos JK, Walk SF, Kinchen JM, Lazarowski ER, Armstrong AJ, Penuela S, Laird DW, Salvesen GS, Isakson BE, Bayliss DA, Ravichandran KS. Pannexin 1 channels mediate ‘find-me’ signal release and membrane permeability during apoptosis. Nature. 2010 Oct 14;467(7317):863-7. doi: 10.1038/nature09413. PMID: 20944749; PMCID: PMC3006164.
  20. Kreda SM, Seminario-Vidal L, van Heusden CA, O’Neal W, Jones L, Boucher RC, Lazarowski ER. Receptor-promoted exocytosis of airway epithelial mucin granules containing a spectrum of adenine nucleotides. J Physiol. 2010 Jun 15;588(Pt 12):2255-67. doi: 10.1113/jphysiol.2009.186643. PMID: 20421285; PMCID: PMC2911224.
Eduardo Lazarowski