Pulmonary Biology

  • Lung Morphogenesis

    Lung dysfunction at birth can occur due to prematurity or a number of congenital problems. Since perinatal death is most frequently associated with lung dysfunction, many of the groups in our division study the molecular and cellular mechanisms and processes that regulate lung development (morphogenesis). Lung morphogenesis occurs both prenatally and postnatally and is typically divided into five phases (see figure 1), with the final alveolar phase occurring principally after birth in humans and rodents. Our groups work on the pathways regulating each specific developmental phase, as well as the different cellular and structural processes distinct to each phase. As well as these important development pathways, lung maturation is crucial as it prepares the lung for birth, when the lung must very rapidly function as the gas exchange organ for the body. Prior to birth the fetus receives oxygen via the mother’s placenta. Surfactant is critical for lung function at birth, reducing air-liquid tension and allowing for lung expansion. Our division has a long history in understanding the role of different surfactant components and surfactant biology and regulation. For more information on these and the other developmental processes listed below, visit the faculty lab websites and biosketches below.

    Lung morphogenesis studies in the Division of Pulmonary Biology include:

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    + Early Lung Specification and Morphogenesis

    Early Lung Specification and Morphogenesis.

    Detection of E-cadherin by immunofluorescent staining shows epithelial cells & branching in early lung morphogenesis. (Picture courtesy of the Shannon laboratory.)

    Vrushank Davé, PhD: Transcriptional/signal networks in lung development and cancer

    Vladimir Kalinichenko, MD, PhD: Fox proteins in lung development and carcinogenesis

    Alan Kenny, MD, PhD: Molecular mechanisms early respiratory and gut development

    Anne-Karina Perl, PhD: Lung repair processes and progenitor cells in lung development

    John Shannon, PhD: Lung morphogenesis and differentiation, and FGFs

    Susan Wert, PhD: Histopathology of abnormal lung development, injury / repair  and human surfactant dysfunctions / mutations.

    Jeffrey Whitsett, MD: Lung transcriptional control, epithelial patterning and differentiation

    Yan Xu, PhD: Bioinformatics, systems biology of lung development and disease

    + Epithelial Cell Patterning and Differentiation

    Epithelial Cell Patterning and Differentiation.Immunostaining for pro-surfactant protein C (black) identifies type II epithelial cells in the distal saccules of developing lung of a transgenic mouse at E17.0.


    Vrushank Davé, PhD: Transcriptional/signal networks in lung development and cancer

    Stephan Glasser, PhD: SP-C in innate defense, interstitial lung disease and injury

    Machiko Ikegami, MD, PhD: Lung development and C/EBPα

    Vladimir Kalinichenko, MD, PhD: Fox proteins in lung development and carcinogenesis

    Thomas Korfhagen, MD, PhD: Surfactant proteins, lung infection, inflammation, and injury/repair

    Anne-Karina Perl, PhD: Lung repair processes and progenitor cells in lung development

    John Shannon, PhD: Lung morphogenesis and differentiation, and FGFs

    Susan Wert, PhD: Histopathology of abnormal lung development, injury / repair  and human surfactant dysfunctions / mutations.

    Jeffrey Whitsett, MD: Lung transcriptional control, epithelial patterning and differentiation

    Yan Xu, PhD: Bioinformatics, systems biology of lung development and disease

    + Epithelial-to-Mesenchymal Signaling Mechanisms

    Epithelial-to-Mesenchymal Signaling Mechanisms.Vascular morphogenesis in the developing lung is regulated by a complex system of epithelial-to-mesenchymal signaling mechanisms. Picture shows X-gal staining of lungs form Tie2-Lac Z mice at E12, which detects the endothelial plexus, a primitive vascular network that is forming alongside the developing airways. (Picture courtesy of Dr. Bridges in the Shannon laboratory.)

    James Greenberg, MD: Lung vascular, lymphatic, airway development and role of VEGF

    Vladimir Kalinichenko, MD, PhD: Fox proteins in lung development and carcinogenesis

    Timothy Le Cras, PhD: Lung development, pathogenesis of lung remodeling

    John Shannon, PhD: Lung morphogenesis and differentiation, and FGFs

    Jeffrey Whitsett, MD: Lung transcriptional control, epithelial patterning and differentiation

    + Vascular Development

    Vascular Development.Arteriogram shows complex system of branches that develops in the lung to supply blood for oxygenation to the distal airspaces (alveoli). (Picture courtesy of the Le Cras laboratory.)

    James Greenberg, MD: Lung vascular, lymphatic, airway development and role of VEGF

    Vladimir Kalinichenko, MD, PhD: Fox proteins in lung development and carcinogenesis

    Timothy Le Cras, PhD: Lung development, pathogenesis of lung remodeling

    Jeffrey Whitsett, MD: Lung transcriptional control, epithelial patterning and differentiation

    + Alveolar Morphogenesis

    Alveolar Morphogenesis.Picture shows elastin fibers (black) in the walls of alveoli and at the tips of secondary septae in the lung. The correct deposition of elastin fibers is critical for alveologenesis and alveolar structure. Alveoli are the functional site of gas exchange in the lung and form the large surface area of the lung needed for gas exchange. (Picture courtesy of the Le Cras laboratory.)

    Timothy Le Cras, PhD: Lung development, pathogenesis of lung remodeling

    Anne-Karina Perl, PhD: Lung repair processes and progenitor cells in lung development

    John Shannon, PhD: Lung morphogenesis and differentiation, and FGFs

    Susan Wert, PhD: Histopathology of abnormal lung development, injury / repair  and human surfactant dysfunctions / mutations.

    Jeffrey Whitsett, MD: Lung transcriptional control, epithelial patterning and differentiation

    + Surfactant Regulation and Biology

    Surfactant Regulation and Biology.Electron micrograph shows that surfactant in the airspace is present in multiple forms including lamellar body, tubular myelin and small lipid vesicles. (Picture courtesy of the Ikegami laboratory.



    Stephan Glasser, PhD: SP-C in innate defense, interstitial lung disease and injury

    Machiko Ikegami, MD, PhD: Surfactant metabolism and function

    Paul Kingma, MD, PhD: SP-D in neonatal sepsis, RDS, innate immune system, neonatal infection

    Thomas Korfhagen, MD, PhD: Surfactant proteins, lung infection, inflammation, and injury/repair

    Ward Rice, MD, PhD: Molecular and cellular mechanisms regulating surfactant processing

    John Shannon, PhD: Lung morphogenesis and differentiation, and FGFs

    Timothy Weaver, PhD: Cytoprotective pathways, epithelium adaptation to stress, surfactant

    Susan Wert, PhD: Histopathology of abnormal lung development, injury / repair  and human surfactant dysfunctions / mutations.

    Jeffrey Whitsett, MD: Lung transcriptional control, epithelial patterning and differentiation

    Yan Xu, PhD: Bioinformatics, systems biology of lung development and disease

    + Lung Specific Gene Regulation and Transcription Factors

    Lung Specific Gene Regulation and Transcription Factors.Double immunofluorescent staining shows a transcription factor (pink) in the nucleus of endothelial cells (green) of a primitive developing vessel in the fetal mouse lung E13.0.  Nuclei were labeled with DAPI (blue) and the developing epithelium is on the right of the picture. (Picture courtesy of the Le Cras and Whitsett laboratories.)

    Vrushank Davé, PhD: Transcriptional/signal networks in lung development and cancer

    Stephan Glasser, PhD: SP-C in innate defense, interstitial lung disease and injury

    Machiko Ikegami, MD, PhD: Transcriptional control of surfactant maturation

    Vladimir Kalinichenko, MD, PhD: Fox proteins in lung development and carcinogenesis

    Anne-Karina Perl, PhD: Lung repair processes and progenitor cells in lung development

    John Shannon, PhD: Lung morphogenesis and differentiation, and FGFs

    Susan Wert, PhD: Histopathology of abnormal lung development, injury / repair  and human surfactant dysfunctions / mutations.

    Jeffrey Whitsett, MD: Lung transcriptional control, epithelial patterning and differentiation

    Kathryn Wikenheiser-Brokamp, MD, PhD: Epithelial cell growth regulation, pathways in lung cancer

    Yan Xu, PhD: Bioinformatics, systems biology of lung development and disease

    + Lung Progenitor / Stem Cells

    Lung Progenitor / Stem Cells. Fluorescent staining detects cells, which have originated from a common progenitor source, populating the tracheal rings. (Picture courtesy of the Perl and Whitsett laboratories.)

    Timothy Le Cras, PhD: Lung development, pathogenesis of lung remodeling

    Anne-Karina Perl, PhD: Lung repair processes and progenitor cells in lung development

    John Shannon, PhD: Lung morphogenesis and differentiation, and FGFs

    Susan Wert, PhD: Histopathology of abnormal lung development, injury / repair  and human surfactant dysfunctions / mutations.

    Jeffrey Whitsett, MD: Lung transcriptional control, epithelial patterning and differentiation

    Kathryn Wikenheiser-Brokamp, MD, PhD: Epithelial cell growth regulation, pathways in lung cancer

    Yan Xu, PhD: Bioinformatics, systems biology of lung development and disease


 
  • Lung development phases: human and mouse.

    Click for larger image.

    Lung development phases: human and mouse.

    The developmental stages of lung morphogenesis are shown for human and mouse. The schematic primarily depicts airway morphogenesis.