The goals of the proposed research are to study the characteristics and regulation of active and passive water and solute transport across the normal and abnormal pulmonary alveolar epithelial barrier. We will study the transport properties of two preparations of isolated alveolar epithelium. These preparations will be used to determine transport pathways of solutes and water, measure alveolar epithelial transport properties under various physiological and pathological conditions, and determine the role of the integrity of lung epithelial barriers on the mechanisms of pathogenesis and resolution of alveolar pulmonary edema. The overall premise of these studies is that information about the characteristics and regulation of the transport of water and solutes across alveolar epithelium per se will lead to further insight not only into the basic functions of this tissue, but also into the importance of such transport properties in the generation and removal of alveolar fluid. The investigations will follow the two-pronged approach of utilizing harvested mammalian alveolar epithelial cells in primary culture and the hollow lungs of amphibians. Monolayers of mammalian Type II cells will be studied on both porous and nonporous surfaces, and amphibian lungs will be studied as sacs and flat sheets. Specific studies of the passive transport properties of these two preparations will include determination of passive non-electrolyte fluxes (including permeabilities and reflection coefficients), water fluxes due to hydrostatic and/or osmotic pressure gradients, pathways for transport across alveolar epithelium, and the effects on transport of physicochemical parameters such as temperature and pH. Active transport studies will include measurements of bioelectric properties (including spontaneous potential differences, tissue resistance and short circuit current), active ion fluxes, water movements due to active solute transport, and the effects of certain hormones and drugs (including, for example, theophylline and ADH). It is anticipated that our studies will provide information on the characteristics and regulation of active and passive solute and water transport of the alveolar epithelial barrier. These data should help us understand mammalian alveolar epithelial transport properties, in normal and abnormal lungs, and their roles in the prevention, formation, and resolution of alveolar pulmonary edema in vivo.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Weill Medical College of Cornell University
Schools of Medicine
New York
United States
Zip Code
Zhou, Beiyun; Liu, Yixin; Kahn, Michael et al. (2012) Interactions between ?-catenin and transforming growth factor-? signaling pathways mediate epithelial-mesenchymal transition and are dependent on the transcriptional co-activator cAMP-response element-binding protein (CREB)-binding protein (CBP). J Biol Chem 287:7026-38
Zhou, Beiyun; Buckley, Stephen T; Patel, Vipul et al. (2012) Troglitazone attenuates TGF-ýý1-induced EMT in alveolar epithelial cells via a PPARýý-independent mechanism. PLoS One 7:e38827
Yacobi, Nazanin R; Fazllolahi, Farnoosh; Kim, Yong Ho et al. (2011) Nanomaterial interactions with and trafficking across the lung alveolar epithelial barrier: implications for health effects of air-pollution particles. Air Qual Atmos Health 4:65-78
Fazlollahi, Farnoosh; Sipos, Arnold; Kim, Yong Ho et al. (2011) Translocation of PEGylated quantum dots across rat alveolar epithelial cell monolayers. Int J Nanomedicine 6:2849-57
Zhong, Qian; Zhou, Beiyun; Ann, David K et al. (2011) Role of endoplasmic reticulum stress in epithelial-mesenchymal transition of alveolar epithelial cells: effects of misfolded surfactant protein. Am J Respir Cell Mol Biol 45:498-509
Kim, Yong Ho; Fazlollahi, Farnoosh; Kennedy, Ian M et al. (2010) Alveolar epithelial cell injury due to zinc oxide nanoparticle exposure. Am J Respir Crit Care Med 182:1398-409
Yacobi, Nazanin R; Malmstadt, Noah; Fazlollahi, Farnoosh et al. (2010) Mechanisms of alveolar epithelial translocation of a defined population of nanoparticles. Am J Respir Cell Mol Biol 42:604-14
Flodby, Per; Borok, Zea; Banfalvi, Agnes et al. (2010) Directed expression of Cre in alveolar epithelial type 1 cells. Am J Respir Cell Mol Biol 43:173-8
Demaio, Lucas; Tseng, Wanru; Balverde, Zerlinde et al. (2009) Characterization of mouse alveolar epithelial cell monolayers. Am J Physiol Lung Cell Mol Physiol 296:L1051-8
Borok, Zea; Crandall, Edward D (2009) More life for a ""terminal"" cell. Am J Physiol Lung Cell Mol Physiol 297:L1042-4

Showing the most recent 10 out of 90 publications