Research Interests

• Membrane protein and phospholipid trafficking in lung epithelial cells
• Control of lung lipoprotein synthesis and secretion
• Lipid and protein oxidation in ischemia-reperfusion injury.

  
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  Description of Research

  Lung surfactant is a lipoprotein secretory product of alveolar epithelium that serves to stabilize lung alveoli during the respiratory cycle. Our studies are directed towards understanding regulation of the cellular processing of lung surfactant. Current projects include evaluation of granular pneumocyte receptors for surfactant-associated proteins; mechanisms for endocytosis of lung surfactant; coupling of endocytosis to secretion; and pathways for intracellular trafficking and degradation of internalized surfactant components. Major emphasis is directed toward study of the role and properties of a novel Ca++-independent phospholipase A2 that we have isolated from lung epithelium. Delineation of the pathways of surfactant metabolism will provide important information for understanding the respiratory distress syndrome including its treatment by the administration of exogenous surfactant. A second area of research is the study of mechanisms for lung injury associated with decreased organ bloodflow. Ischemia/reperfusion injury is evaluated using in vivo and isolated perfused rat lung models. Lipid peroxidation and protein oxidation under varying conditions of oxygenation are correlated with alterations of lung function and with anti-oxidant capacity of tissue. This program investigates mechanisms for initiation of oxygen-derived radical production, the roles of Fe++ and peroxynitrite as oxidants, the pathways for protein oxidation, and novel methods for treatment with anti-oxidants. A goal of these studies is to develop methods for prevention and treatment of ischemia-mediated lung injury.

  Recent Publications

  Dierick, J.F., Wenders, F., Chainiaux, F., Remacle, J., Fisher, A.B., and Toussaint, O. Retrovirally mediated overexpression of peroxiredoxin VI increases the survival of WI-38 human diploid fibroblasts exposed to cytotoxic doses of tert-utylhydroperoxide and UVB. Biogerontology. 4:125-131, 2003.

  Mo, Y., Feinstein, S.I., Manevich, Y., Zhang, Q., Lu, L., Ho, Y.S. and Fisher, A.B. 1-Cys peroxiredoxin knock-out mice express mRNA but not protein for a highly related intronless gene. FEBS Lett. 555:192-198, 2003.

  Milovanova, T., Manevich, Y., Haddad, A., Chatterjee, S., Moore, J.S. and Fisher, A.B. Endothelial cell proliferation associated with abrupt reduction in shear stress is dependent on reactive oxygen species. Antiox & Redox Signal. 6:245-258, 2004.

  Manevich, Y., Feinstein, S.I., and Fisher, A.B. Activation of the anti-oxidant enzyme 1 cys peroxiredoxin requires glutathionylation mediated by heterodimerization with pGST. Proc. Nat. Acad. Sci.. 101:3780-3785, 2004.

  Wang, Y., Manevich, Y., Feinstein, S.I., and Fisher, A.B. Adenovirus–mediated transfer of the 1-cys peroxiredoxin gene to mouse lung protects against hyperoxic injury. Am. J. Physiol (Lung Cell. Mol. Physiol.) 286:L1188-1193, 2004.

  Lab

  Lab personnel:

  Sed Ligula, Ph.D., Research Associate
  Felis Tempus Sed, Ph.D., Research Associate
  Pretium Vel, Ph.D., Postdoc
  Dignissim Eu, CAMB Student
  Donec Vulputate, Lab Manager

   

  last updated 10/2004