Faculty Focus
Ann Akeson, PhD, studies the vascular development of the lung. Extensive characterization of two cell lines immortalized from murine fetal lung mesenchyme has shown that these cells are endothelial-like and provide useful in vitro systems for analysis of lung vasculogenesis and angiogenesis. The cells have been successfully used to generate chimeric animals through introduction into mouse blastocysts thus generating a possible in vivo model for vascular development.
Cindy J. Bachurski, PhD:
- Gene therapy: Intratracheal administration of replication deficient adenoviral vectors cause acute and chronic cytopathic effects. In collaboration with Dr. Zsengellér and the Molecular Morphology Core, we have shown that intratracheal adenoviral vector instillation disrupts pulmonary surfactant protein homeostasis in both wild type and nu/nu Balb/c mice (Zsengeller et al, 1997).
- Transcriptional regulation: Surfactant protein-C was identified as the first lung-specific nuclear factor I (NFI) responsive gene. Four of five footprinted regions within 320 bp of the start of transcription of the mouse SP-C gene contain critical NFI half-sites required for basal promoter activity in MLE cells and NFI transactivation in HeLa cells (Bachurski et al, 1997).
Zissis C. Chroneos, PhD has current projects including cloning and biochemical identification of the surfactant protein A receptor; the role of the cystic fibrosis transmembrane regulator in the clearance of Pseudomonas aeruginosa; mechanisms of IL-4-mediated clearance of Pseudomonas aeruginaosa; bacterial-host interaction in transgenic animal models.
Stephan W. Glasser, PhD's laboratory completed analysis of SP-C gene constructs in the lungs of developing mice. Experiments were also completed that define a lung cell selective enhancer for the SP-C gene. Dr. Glasser is trying to identify transcription factors that regulate SP-C gene transcription. Dr. Glasser has also identified embryonic stem cells with a disrupted SP-C gene which will be used to generate SP-C deficient mice.
The laboratory of James M. Greenberg, MD, studies the development of the pulmonary mesenchyme, with a focus on the pulmonary vascularture. He has developed in vitro and in vivo models to study the development of the pulmonary vasculature and to identify the factors mediating its formation.
The current projects of Machiko Ikegami, MD, PhD, include surfactant metabolic in vivo using transgenic mice, immature lamb and adult rabbit; effect of ventilation style on surfactant metabolism in immature lung; and function of surfactant components.
In collaboration with Dr. Ikegami, Alan Jobe, MD, PhD, has established a laboratory to study lung maturation and lung function in preterm lambs. Dr. Jobe has continued studies of lung maturation in sheep with collaborators in Australia and studies of lung injury with collaborators in Texas. He has actively participated in the activities of the Pulmonary Biology Division to characterize surfactant function and homeostasis in transgenic mice.
Using transgenic mouse models, Thomas R. Korfhagen, MD, PhD, completed studies demonstrating that SP-A is part of the innate immunity in vivo enhancing clearance of certain bacterial pathogens, streptococci, pseudomonas, and hemophilus from the lung. SP-D in vivo modulates clearance of phospholipid from the lung. Transforming growth factor-( protects the lung from ultrafine particle injury by reducing inflammation. Taken together, these studies identify molecular mechanisms protecting the lung from injury.
During the past year, the laboratory of Ward R. Rice, MD, PhD continued to examine signal transduction pathways regulating Type II cell growth and differentiation. Transgenic mice were generated in which GM-CSF signaling in Type II cells was disrupted and are currently being characterized.
The work of Timothy E. Weaver, PhD, focuses on the study of structure and function of SP-B with particular emphasis on intracellular processing and trafficking.
One of the major research efforts of Susan E. Wert, PhD, involves immunohistochemical analysis of human biopsy and autopsy material related to a variety of neonatal pulmonary diseases, such as respiratory distress syndrome (RDS), pulmonary alveolar proteinosis (PAP), hyaline membrane disease (HMD), bronchopulmonary dysplasia (BPD), acinar dysplasia, interstitial lung disease, and congenital cystic adenomatoid malformation (CCAM). To date, 15 novel mutations in the SP-B gene have been identified, indicating that there is a greater degree of allelic heterogeneity than previously appreciated (manuscript in preparation).
The research of Cong Yan, PhD, focuses on the function of retinoic acid receptor in morphogenesis and differentiation of the respiratory epithelium.
The work of Barbara B. Warner, MD, focuses to the adaptive responses of the lung to hyperoxic induced injury in neonates.
Jeffrey A. Whitsett, MD, continues to define signaling mechanisms controlling lung morphogenesis, differentiation and surfactant function in the developing lung. Gene targeted studies have helped elucidate the roles of GMCSF, CCSP, SP-A, SP-B and SP-D in lung function.
The major focus of Jon Wispe, MD, (LINK) is now clinical activities at Cincinnati Children's and Mercy Hospital Anderson. In the lab, he is completing the study of the effect of increased (SP-C:Mn-SOD) and decreased (Mn-SOD+/-) MnSOD on the development of chronic neonatal oxygen injury.
