DEVELOPMENT AND CONTROL OF PULMONARY ALVEOLAR STABILITY

Summary

Principal Investigator: Samuel Hawgood
Abstract: DESCRIPTION (provided by applicant): This application proposes to continue multidisciplinary studies of development, control and disorders of the pulmonary parenchyma. The objectives of the proposal are to examine some of the mechanisms involved in the formation and stabilization of the pulmonary parenchyma during development and post-natal life, and in states of health and disease. By stabilization we mean the integrated physiochemical and biological processes that develop and maintain alveolar architecture in an optimal state for pulmonary gas exchange. As in our past studies we emphasize investigations of alveolar epithelial development, functions of the lung surfactant system, and alveolar disease processes leading to infection and inflammation. The broad goals of the three inter-related projects proposed are: Project 1: Structure and function of surfactant proteins. To study the relationship between the structure of the surfactant proteins, specifically SP-D, and their functions in regulating the immune milieu of the alveolus. Project 2: Expression and role of CEACAM6 in the alveolus. To investigate the role of carcinoembryonic antigen-6 in alveolar innate immune defense, surfactant function, and epithelial response to acute lung injury. Project 3: Alveolar epithelial cell fates: mapping and regulation. To study alveolar epithelial cell lineages during development and regeneration and to elucidate novel regulatory molecules important to the process of alveolar epithelial differentiation. The overall purpose of these studies is to deepen our understanding of the processes underlying lung parenchymal stability and to contribute to new concepts and treatments for lung diseases associated with disorders of alveolar stability, growth, maturation, and repair after injury.
Funding Period: 1997-07-01 - 2015-12-31
more information: NIH RePORT

Top Publications

  1. ncbi Congenital diaphragmatic hernia prevents absorption of distal air space fluid in late-gestation rat fetuses
    Hans G Folkesson
    Dept of Physiology and Pharmacology, Northeastern Ohio Universities College of Medicine, 4209 State Route 44, PO Box 95, Rootstown, OH 44272 0095, USA
    Am J Physiol Lung Cell Mol Physiol 290:L478-84. 2006
  2. pmc Distribution and surfactant association of carcinoembryonic cell adhesion molecule 6 in human lung
    Cheryl Chapin
    Department of Pediatrics, University of California San Francisco, San Francisco, California, USA
    Am J Physiol Lung Cell Mol Physiol 302:L216-25. 2012
  3. pmc A small-molecule smoothened agonist prevents glucocorticoid-induced neonatal cerebellar injury
    Vivi M Heine
    Division of Neonatology, Department of Pediatrics, University of California, San Francisco UCSF, San Francisco, CA 94143, USA
    Sci Transl Med 3:105ra104. 2011
  4. pmc HTII-280, a biomarker specific to the apical plasma membrane of human lung alveolar type II cells
    Robert F Gonzalez
    Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94118, USA
    J Histochem Cytochem 58:891-901. 2010
  5. pmc Rat alveolar type I cells proliferate, express OCT-4, and exhibit phenotypic plasticity in vitro
    Robert F Gonzalez
    Cardiovascular Research Institute, University of California San Francisco, 94118, USA
    Am J Physiol Lung Cell Mol Physiol 297:L1045-55. 2009
  6. pmc Characteristics of Cl- uptake in rat alveolar type I cells
    Meshell Johnson
    Department of Medicine, University of California, San Francisco, 3333 California St, Suite 150, Box 1245, San Francisco, CA 94118, USA
    Am J Physiol Lung Cell Mol Physiol 297:L816-27. 2009
  7. pmc Clearance of Pseudomonas aeruginosa from a healthy ocular surface involves surfactant protein D and is compromised by bacterial elastase in a murine null-infection model
    James J Mun
    School of Optometry, University of California, Berkeley, CA 94720 2020, USA
    Infect Immun 77:2392-8. 2009
  8. ncbi Expression of surfactant protein D in human corneal epithelial cells is upregulated by Pseudomonas aeruginosa
    Minjian Ni
    School of Optometry, University of California, Berkeley, CA 94720, USA
    FEMS Immunol Med Microbiol 54:177-84. 2008
  9. pmc Directed expression of transgenes to alveolar type I cells in the mouse
    Jeff N Vanderbilt
    Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94118, USA
    Am J Respir Cell Mol Biol 39:253-62. 2008
  10. ncbi Alveolar epithelial transport in the adult lung
    Leland G Dobbs
    Department of Medicine, University of California San Francisco, San Francisco, CA 94118, USA
    Respir Physiol Neurobiol 159:283-300. 2007

Research Grants

  1. Gastointestinal Hormone Research Core Center
    Chung Owyang; Fiscal Year: 2013

Detail Information

Publications15

  1. ncbi Congenital diaphragmatic hernia prevents absorption of distal air space fluid in late-gestation rat fetuses
    Hans G Folkesson
    Dept of Physiology and Pharmacology, Northeastern Ohio Universities College of Medicine, 4209 State Route 44, PO Box 95, Rootstown, OH 44272 0095, USA
    Am J Physiol Lung Cell Mol Physiol 290:L478-84. 2006
    ....
  2. pmc Distribution and surfactant association of carcinoembryonic cell adhesion molecule 6 in human lung
    Cheryl Chapin
    Department of Pediatrics, University of California San Francisco, San Francisco, California, USA
    Am J Physiol Lung Cell Mol Physiol 302:L216-25. 2012
    ..Production appears to be upregulated during neonatal lung disease, perhaps related to roles of CEACAM6 in surfactant function, cell proliferation, and innate immune defense...
  3. pmc A small-molecule smoothened agonist prevents glucocorticoid-induced neonatal cerebellar injury
    Vivi M Heine
    Division of Neonatology, Department of Pediatrics, University of California, San Francisco UCSF, San Francisco, CA 94143, USA
    Sci Transl Med 3:105ra104. 2011
    ..These findings suggest that a small-molecule agonist of Smo has potential as a neuroprotective agent in neonates at risk for glucocorticoid-induced neonatal cerebellar injury...
  4. pmc HTII-280, a biomarker specific to the apical plasma membrane of human lung alveolar type II cells
    Robert F Gonzalez
    Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94118, USA
    J Histochem Cytochem 58:891-901. 2010
    ..HTII-280 is likely to be a useful morphological and biochemical marker of human TII cells that may help to advance our understanding of various lung pathological conditions, including the origin and development of various lung tumors...
  5. pmc Rat alveolar type I cells proliferate, express OCT-4, and exhibit phenotypic plasticity in vitro
    Robert F Gonzalez
    Cardiovascular Research Institute, University of California San Francisco, 94118, USA
    Am J Physiol Lung Cell Mol Physiol 297:L1045-55. 2009
    ..Together, the findings that TI cells proliferate and exhibit phenotypic plasticity in vitro raise the possibility that TI cells may have similar properties in vivo...
  6. pmc Characteristics of Cl- uptake in rat alveolar type I cells
    Meshell Johnson
    Department of Medicine, University of California, San Francisco, 3333 California St, Suite 150, Box 1245, San Francisco, CA 94118, USA
    Am J Physiol Lung Cell Mol Physiol 297:L816-27. 2009
    ....
  7. pmc Clearance of Pseudomonas aeruginosa from a healthy ocular surface involves surfactant protein D and is compromised by bacterial elastase in a murine null-infection model
    James J Mun
    School of Optometry, University of California, Berkeley, CA 94720 2020, USA
    Infect Immun 77:2392-8. 2009
    ..aeruginosa from the healthy ocular surface and that proteases can compromise that clearance. The data also suggest that SP-D degradation in vivo is a mechanism by which P. aeruginosa proteases could contribute to virulence...
  8. ncbi Expression of surfactant protein D in human corneal epithelial cells is upregulated by Pseudomonas aeruginosa
    Minjian Ni
    School of Optometry, University of California, Berkeley, CA 94720, USA
    FEMS Immunol Med Microbiol 54:177-84. 2008
    ..aeruginosa or its antigens, they can involve different regions of the same ligand. The data suggest that separate mechanisms may regulate SP-D secretion and production by human corneal epithelia...
  9. pmc Directed expression of transgenes to alveolar type I cells in the mouse
    Jeff N Vanderbilt
    Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94118, USA
    Am J Respir Cell Mol Biol 39:253-62. 2008
    ..Because their pulmonary expression is more restricted than endogenous mouse podoplanin, RTIbac derivatives should be useful for mouse type I cell-specific transgene delivery...
  10. ncbi Alveolar epithelial transport in the adult lung
    Leland G Dobbs
    Department of Medicine, University of California San Francisco, San Francisco, CA 94118, USA
    Respir Physiol Neurobiol 159:283-300. 2007
    ..We will highlight some of the unanswered questions, outline the similarities and differences in results obtained with different model systems, and describe some of the complex and interweaving regulatory networks...
  11. pmc N-linked glycosylation attenuates H3N2 influenza viruses
    David J Vigerust
    St Jude Children s Research Hospital, 332 N Lauderdale Street, Memphis, TN 38105 2794, USA
    J Virol 81:8593-600. 2007
    ..The continued exploration of interactions between highly glycosylated viruses and surfactant proteins may lead to an improved understanding of the biology within the lung and strategies for viral control...
  12. pmc Loss of bacterial diversity during antibiotic treatment of intubated patients colonized with Pseudomonas aeruginosa
    J L Flanagan
    Department of Anesthesia and Perioperative, University of California, San Francisco, CA, USA
    J Clin Microbiol 45:1954-62. 2007
    ....
  13. ncbi Ion transport in alveolar type I cells
    Meshell D Johnson
    Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA
    Mol Biosyst 3:178-86. 2007
    ..Various methods were employed to show that type I cells contained ENaC (HSC and NSC channels), CNG and K(+) channels, and CFTR, further necessitating a revision of the current theories of ion and fluid transport in the lung...
  14. pmc Surfactant proteins A and D enhance pulmonary clearance of Pseudomonas aeruginosa
    Eric Giannoni
    Department of Pediatrics, Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143 0110, USA
    Am J Respir Cell Mol Biol 34:704-10. 2006
    ..aeruginosa by stimulating phagocytosis by alveolar macrophages and by modulating the inflammatory response in the lungs. These findings also show that the functions of SP-A and SP-D are not completely redundant in vivo...
  15. pmc Isolation and culture of alveolar epithelial Type I and Type II cells from rat lungs
    Robert F Gonzalez
    The Cardiovascular Research Institute, University of California, San Francisco, CA, USA
    Methods Mol Biol 945:145-59. 2013
    ..This chapter provides information about methods for isolating and culturing both of these cell types from rat lungs...

Research Grants30

  1. Gastointestinal Hormone Research Core Center
    Chung Owyang; Fiscal Year: 2013
    ..abstract_text> ..