Eduardo Lazarowski, Ph.D.
Research Associate Professor

Degrees
    BS: 
    (1975) U.of Buenos Aires
    Argentina
   MS: 
    (1978) U. of Buenos Aires
    Argentina
   PhD: 
    (1989) U. of Buenos Aires
    Argentina
  Pre-Doctoral Fellowships: 
    (1980-82) Oncology
    Güemes Private Hospital
    Buenos Aires Argentina
    (1983-86) Immuno Pharm. Co.
    Buenos Aires Argentina
  Post-Doctoral Training: 
    (1986-990) Visiting Fellow
    Welcome Research Laboratories
    NC
    (1990-94) Post-doc Fellow
    U. of North Carolina
    Chapel Hill NC

    

Office:   7017 Thurston-Bowles
Phone:  919-966-7046
Fax:      919-966-5178
email:   Eduardo_Lazarowski@med.unc.edu

Research Summary:

Extracellular nucleotides and nucleosides regulate the mucociliary clearance (MCC) process that removes noxious materials from the airways. Nucleotide actions in the airways are mediated by several G protein-coupled purinergic receptors. Our lab has played a role in defining the contribution of P2Y2 , P2Y6 , and A2b receptors to MCC responses initiated by the release of ATP and UTP into the airway surface liquid (ASL) (Fig. 1) . Our research interest is to understand the molecular basis of nucleotide release in the airways, and hence, the mechanisms by which purinergic receptors control MCC activities. We have developed HPLC-based assays that accurately quantify sub-nanomolar levels of various nucleotide species. We have discovered that regulated release of ATP into ASL is accompanied by release of uridine nucleotides and UDP-sugars, i.e. UDP-glucose and UDP-galactose and e xperiments are underway to study the biology and the physiological implications of UDP-sugars in ASL. Since UDP-glucose and UDP-galactose are essential components of glycosylation reactions in the ER and Golgi apparatus, they may be released as residual cargo products of the secretory pathway (Fig. 2). We are carrying out studies to examine the role of elements within the secretory pathway, e.g., the Golgi UDP-Gal translocator UGT1 and the non-selective UDP-sugar transporter HFRC1, in both constitutive and regulated release of nucleotides.

Research Interests:

• Purinergic signaling
• P2Y­14 receptor biology
• UDP-sugar transporters
• Vesicular trafficking of nucleotides

Selected Recent Publications:

•  Okada, S.F., Nicholas, R.A., Kreda, S.M., Lazarowski, E.R., Boucher, R.C. Physiological regulation of ATP release at the apical surface of human airway epithelia. J. Biol. Chem (2006, in press).

•  Lazarowski, E. R . Regulated release of nucleotides and UDP-sugars from astrocytoma cells. In “Purinergic signaling in neuron-glia interactions”. Novartis Foundation Symposium No 276. Eds: Chadwick, D.J and Goode, J. Pg 73-90 (2006).

•  Erlinge D., Jan Harnek, van Heusden C., Olivecrona G., Jern S., and Lazarowski E . Uridine triphosphate (UTP) is released during cardiac ischemia. International Journal of Cardiology 100:427-33 (2005).

•  Lazarowski E. R ., Tarran R., Grubb B. R., van Heusden C., and Boucher R. C. Nucleotide release provides a mechanism for airway surface liquid homeostasis. J. Biol. Chem . 279 , 35551-35556 (2004).

•  Lazarowski E R., Boucher R. C. and Harden T. K. Mechanisms of release of nucleotides and integration of their action as P2X- and P2Y-receptor activating molecules. Mol. Pharmacol . 64, 785-795 (2003).

Lazarowski, E. R. Homolya, L. Boucher R. C. and Harden, T. K. Identification of an ecto-nucleoside diphosphokinase and its contribution to interconversion of P2 receptor agonists. J. Biol. Chem. 272: 20402-20407 (1997).

Clinical Contact         Phone: (919)966-2531 Fax: (919)966-7013 420 Burnett-Womack Bldg. CB# 7020 The Univ. of North Carolina Chapel Hill, NC 27599-7020

Research Contact        Phone: (919)966-1077 Fax: (919)966-7524 7011 Thurston-Bowles Bldg. CB# 7248 The Univ. of North Carolina Chapel Hill, NC 27599-7248