Research in my laboratory centers on uncovering the molecular and cellular mechanisms that contribute to organ dysfunction following pulmonary injury. A key focus is the interplay between cellular signaling pathways and the processes of injury and repair in critical lung cell types, including epithelial cells, endothelial cells, and alveolar macrophages. Through a range of experimental models, we examine how acute insults and chronic stressors impact cellular resilience and function. We are particularly interested in how genetic predisposition, aging, and environmental exposures shape the lung's metabolic capacity to adapt and recover from injury. As a practicing physician, my goal is to translate these insights into clinical practice by identifying the molecular drivers of diseases such as pulmonary fibrosis and acute respiratory distress syndrome, ultimately leading to the development of more effective therapies for these severe lung conditions
Summer Research
Contact
- Professor of Medicine
- CEO, Jane & Leonard Korman Respiratory Institute
- Division Chief, Pulmonary, Allergy & Critical Care Medicine
1020 Locust Street
Room 368
Philadelphia, PA 19107
Summer Research
Pulmonary Fibrosis is a metabolic disorder of the lung
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that causes progressive scarring of the lung and usually leads to death within a few years of diagnosis. One major risk factor for the development of IPF is advanced age and this believed to contribute to disease by comprising the ability of lung epithelial cells to regenerate after injury. In my lab, we study how aging affects the ability of the lung epithelium to metabolically adapt to pulmonary insults. We and others have shown that the aging epithelium does not properly divert nutrients/energy to areas of the cell in greatest need after injury, leading to persistent cellular damage that ultimately drives cells toward either an apoptotic or cellular senescence phenotype. Studies in my lab aim to understand how young cells metabolically adapt to injury so as to better understand how aging compromises these responses. Our hope is that by better understanding responses in young cells we can develop novel treatment approaches for age-related diseases like IPF.
Antifibrotic therapies for the treatment of pulmonary fibrosis
Pulmonary fibrosis is not a single disease but rather a group of conditions that cause scarring of the lung. Because collagen I-rich fibrils comprise the majority of all pulmonary scars, we are testing whether blocking a key step in type collagen I production is effective in limiting the progression of scar tissue in pulmonary fibrosis. The novel biological that is being tested was developed by Dr. Fertala at Thomas Jefferson University and works by blocking one of the earliest steps in the formation of collagen fibrils. Our pilot and published data indicate that this antibody not only binds to its intended target in the lung but also exhibits limited side effects. In ongoing studies, we are applying this antibody to the treatment pulmonary fibrosis using several animal models of disease and we are testing whether this therapy works synergistically with other clinically-relevant benchmark drugs. Because the target we have identified is identical in mice and humans, this therapy has real potential to help patients.