Research Area: 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 mothers 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 of these and the other developmental processes listed below please visit the faculty lab websites and biosketches listed below.
Lung morphogenesis studies in the Division of Pulmonary Biology include:
| Early Lung Specification and Morphogenesis |
|
Detection of E-cadherin by immunofluroescent staining shows epithelial cells & branching in early lung morphogenesis. (Picture courtesy of the Shannon laboratory.) |
| Ann Akeson, PhD |
Lung vasculogenesis, endothelial lineage selection, and lymphatics |
| 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 |
Pathology developing lung, injury / repair and surfactant dysfunction |
| 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 |
|
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. |
| Cindy Bachurski, PhD |
Transcriptional control/interactions development and injury/repair |
| 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 |
Pathology developing lung, injury / repair and surfactant dysfunction |
| 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 |
|
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.) |
| Ann Akeson, PhD |
Lung vasculogenesis, endothelial lineage selection, and lymphatics |
| 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 |
|
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.) |
| Ann Akeson, PhD |
Lung vasculogenesis, endothelial lineage selection, and lymphatics |
| 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 |
|
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 |
Pathology developing lung, injury / repair and surfactant dysfunction |
| Jeffrey Whitsett, MD |
Lung transcriptional control, epithelial patterning and differentiation |
| 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.) |
| Cindy Bachurski, PhD |
Transcriptional control/interactions development and injury/repair |
| 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 |
Pathology developing lung, injury / repair and surfactant dysfunction |
| 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 |
|
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.) |
| Cindy Bachurski, PhD |
Transcriptional control/interactions development and injury/repair |
| 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 |
Pathology developing lung, injury / repair and surfactant dysfunction |
| 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 |
|
Fluorescent staining detects cells, which have originated from a common progenitor source, populating the tracheal rings. (Picture courtesy of the Perl and Whitsett laboratories.) |
| Cindy Bachurski, PhD |
Transcriptional control/interactions development and injury/repair |
| 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 |
Pathology developing lung, injury / repair and surfactant dysfunction |
| 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 |
| Innate Immune Defense Mechanisms |
| Henry Akinbi, MD |
Lung innate defense, including infection and inflammation |
| Stephan Glasser, PhD |
SP-C in innate defense, interstitial lung disease and injury |
| Machiko Ikegami, MD, PhD |
SP-D and SP-B in lung defense |
| Thomas Korfhagen, MD, PhD |
Surfactant proteins, lung infection, inflammation, and injury/repair |
| Bruce Trapnell, MD |
Regulation innate immunity, inflammation, GM-CSF in lung disease |
| Timothy Weaver, PhD |
Cytoprotective pathways, epithelium adaptation to stress, surfactant |
| Jeffrey Whitsett, MD |
Lung transcriptional control, epithelial patterning and differentiation |
| Yan Xu, PhD |
Bioinformatics, systems biology of lung development and disease |
