Weaver Lab

  • Regulation of Alveolar Lipid Homeostasis

    Type II epithelial cells synthesize pulmonary surfactant, a lipid-rich mixture that is stored in highly specialized secretory granules called lamellar bodies. Surfactant is secreted into the alveolar airspaces where it plays a critical role in stabilizing the gas exchange surface: 

    • Too little surfactant results in alveolar collapse, impaired gas exchange and respiratory distress syndrome, the leading cause of morbidity and mortality in premature infants. 
    • Accumulation of surfactant in the airspaces impairs gas exchange by displacing air from the alveoli, leading to a debilitating disease called alveolar proteinosis. 

    Surfactant secretion must therefore be balanced by surfactant turnover to maintain an appropriate alveolar pool size (homeostasis). Alveolar surfactant can be degraded by macrophages, internalized by type II cells for recycling to lamellar bodies and resecretion, or degraded in lysosomes of type II cells. 

    Identification of the molecular pathway by which the type II cell “senses” alveolar surfactant  pool size and subsequently adjusts surfactant synthesis, secretion, recycling and / or degradation to maintain homeostasis is the major focus of this project. 

    We have recently identified several novel proteins involved in surfactant phospholipid transport / sensing and are currently generating knockout mice to analyze their function(s).

  • Lab Publications

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    2011

    Ridsdale R, Na CL, Xu Y, Greis KD, Weaver TE. Comparative Proteomic Analysis of Lung Lamellar Bodies and Lysosome-Related Organelles. PLoS ONE. 6:e16482. 2011.

    2010

    Perez-Gil J, Weaver TE. Pulmonary surfactant pathophysiology: current models and open questions. Physiology (Bethesda). 25:132-141. 2010.

    Other Significant Publications


 
  • Type 2 cell diagram.

    click to enlarge

    Type 2 cell diagram.