Figure : 3D reconstruction of immunofluorescent confocal image of a 300 micron thick mouse lung. Distinct cell compartments in the adult mouse lung alveolar epithelial cells (WHITE), interstitial fibroblasts (GREEN) and vascular fibroblasts (RED).
Perl Lab
Perl Research Lab
Our research focuses on alveolar fibroblasts during septation and bronchiolar fibrosis after epithelial injury. Our projects strive to understand the cellular and molecular mechanisms related to the pathology of lung diseases, like bronchopulmonary dysplasia (BPD), emphysema, chronic obstructive pulmonary disease (COPD) and bronchiolitis obliterans (BOS). We use state of the art transgenic mouse models to provide novel and innovative tools to enable studies of complex molecular pathways and lineage relationships, in lung development and diseases. Jenna Green established immunofluorescence staining protocols for adult mouse lung that allow 3d high resolution confocal imaging. Our histological approach is complemented by sophisticated flow cytometry to identify subpopulations of pulmonary fibroblasts, which was established by Leiling Chen, PhD. We have two major focuses in the lab:
- Role of
myofibroblast differentiation during alveolar septation: Arrest of alveolarization in
infants with BPD and loss of alveolar surface area in patients with COPD, pose
enormous public health burdens. Transgenic mice offer unique opportunities to
explore cellular and molecular mechanisms of compensatory lung growth that
might be useful in the future to increase the limited potential of adaptive
growth in human lungs. Our long-term goal is to identify the signaling pathways
that regulate the formation of new alveolar septae. We identified a critical
role for the interstitial myofibroblast in alveolar regeneration and are
currently funded by the NIH to study neo-alveolarization during compensatory
lung regrowth. We are in the course of 1) identifying roles of lung resident
fibroblast populations, 2) identifying genes that regulate fibroblast differentiation
and 3) determining the key pathways that are involved in alveolar regeneration.
- Epithelial injury results in airway fibrosis and allograft rejection: Bronchiolitis obliterans is a fatal lung syndrome responsible for graft failure in most lung transplant recipients. BOS is characterized by loss of epithelial integrity and airway fibrosis. The long-term goal of this project is to identify epithelial-mesenchymal interactions that facilitate proper lung repair and prevention of airway wall fibrosis. My laboratory has developed a conditional transgenic mouse model to induce diphtheria toxin mediated cell death specifically in bronchiolar Clara cells. We are using this mouse model to study 1) bronchiolar stem cells, 2) molecular mechanisms responsible for bronchiolar regeneration after acute injury and 3) airway wall fibrosis after chronic injury. Our recent studies demonstrated that excessive Clara cell depletion results in neutrophil and dendritic cell recruitment and subsequent chronic lung inflammation. In collaboration with Drs. Gelman and Huang from Washington University in St Louis we are currently investigating how established lung allografts undergo graft rejection after Clara cell injury. In collaboration with Drs. Klepetko and Aigner from the Medical University in Vienna we are investigating how ex vivo lung perfusion ameliorates graft function and decreases primary graft dysfunction in human lung transplant patients.
Alveolar Regeneration
Read about our work to find out what cellular and molecular mechanisms are important to regrow lung.
Read More About Alveolar Regeneration
Bronchiolar Injury and Repair
We are working to better understand the pathogenesis of the loss of epithelial integrity and subsequent peribronchiolar fibrosis to help improve therapies for lung disorders.
Read More About Bronchiolar Injury Repair
Conditional Mouse Technology
Dr. Perl was seminal in establishing the conditional mouse technology to regulate gene activation and in activation in the lung epithelium using the tetracycline inducible gene regulation.
Read More About Conditional Mouse Technology
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