Barry Stripp, PhD
With annual treatment costs estimated in the billions, lung disease is the third leading cause of death in the United States. The mission in the Lung Program at the Cedars-Sinai Regenerative Medicine Institute is to use lung stem cells to identify critical determinants of lung epithelial maintenance, renewal and remodeling that can lead to more effective therapies for lung diseases.
The Lung Program focuses on fibroproliferative lung diseases — idiopathic pulmonary fibrosis (IPF) and bronchiolitis obliterans syndrome (BOS). For these lung diseases, the mechanism of disease inhalation and progression are poorly understood, and prognosis is poor due to the lack of effective treatment options. End-stage IPF and BOS are characterized by dysfunctional epithelium, coupled with expansion of underlying mesenchyme and deposition of extra cellular matrix leading to respiratory failure.
The Lung Program, based in the lab of Barry Stripp, PhD, is collaborating with Paul Noble, MD, chair of the Department of Medicine; Clive Svendsen, PhD, director of the Regenerative Medicine Institute; and Moshe Arditi, MD, director of Pediatric Infectious Diseases.
The research team is currently testing the hypothesis that epithelial progenitors receive environmental and intracellular signals that are essential for normal homeostasis and injury repair, and that these cells are dysregulated in lung disease. The hypothesis is being tested in three specific ways:
- Define signals between epithelial progenitors and stromal cells that direct epithelial maintenance and repair in normal homeostasis and disease.
- Determine how intrinsic regulatory mechanisms that normally direct the fate of postnatal airway epithelial progenitors are reprogrammed in disease to assume inappropriate cell fates that lead to tissue remodeling.
- Establish efficient methods for differentiation of human iPSCs into either bronchiolar or alveolar progenitors for patient-specific drug screens and cell therapy applications.
Our hope is that discoveries and model systems established in this collaborative research will be broadly applicable to other distal airway diseases such as the spectrum of disorders seen in severe chronic obstructive pulmonary disease (COPD), cystic fibrosis and lung cancer.
Cross section of a conducting airway from a mouse lung outlining some of the different cells that make up the normal lung.
Overall view of the lung with alveolar
Lineage tracing of airway epithelial progenitor cells with Trp53 loss-of-function using a multicolored Confetti reporter to follow cellular responses to ionizing radiation.