The Acute Lung Injury (ALI) / Adult Respiratory Distress Syndrome (ARDS) Research Program
Director: Janet S. Lee, MD
The Acute Lung Injury (ALI)/ Adult Respiratory Distress Syndrome (ARDS) Research Program is focused on the investigation of fundamental mechanisms in lung injury and repair. The program utilizes advanced tools in molecular, biochemical, and clinical investigation. Extensive collaborative interactions exist with the Departments of Surgery, Anesthesiology, Pathology, and Environmental Health. The primary program faculty includes Dr. Janet S. Lee, Dr. Bryan McVerry, Dr. Prabir Ray, and Dr. Michael Donahoe.
The mission of the ALI/ARDS Center is to synergize basic and translational discoveries that can lead to novel treatments for patients with severe acute lung injury. The ALI Center focuses on:
- identification of novel genetic, proteomic, and lipidomic markers of acute lung injury
- discovery of new and fundamentally basic mechanisms underlying the pathobiology of sepsis and acute lung injury in critically ill patients
- establishing a regional and highly synergistic network of investigation in ALI between the Divisions of Pulmonary Medicine at the University of Pittsburgh, the VAPHS, and the UPMC Department of Critical Care Medicine
- establishing trials with stem cell and immunomodulatory drugs for the treatment of lung injury
- leading cutting-edge clinical research initiatives to reverse lung injury associated with viral (e.g. influenzae) and bacterial pneumonia
Dr. Janet Lee’s research interest includes neutrophil-mediated lung inflammation and injury. Specifically, Dr. Lee’s laboratory investigates the role of chemokines, chemokine binding proteins and receptors in facilitating the process of lung inflammation. One primary focus of the laboratory is the Duffy antigen, a high affinity inflammatory chemokine binding protein expressed on red cells and endothelium, and its regulation of neutrophilic lung injury and inflammation. The laboratory is currently investigating the role of red cell transfusion in perpetuating thrombo-inflammatory injury in the susceptible host. Dr. Lee’s interest also includes how we examine systemic markers of inflammation in neutrophilic lung diseases such as acute lung injury and chronic obstructive pulmonary disease.
Red cell transfusion in Acute Lung Injury. Under normal conditions, the alveolar epithelium and endothelium provide a tight barrier function preventing the leakage of fluid, protein, and cells into the airspaces. Red cell transfusion may contribute to lung injury by amplifying innate immune activation signals in susceptible hosts to augment neutrophilic inflammation and promote injury. Stored red cells in transfusates may activate endothelium, provide chemokine signals, and microparticles with exposed phosphatidylserine on their surface that may facilitate hemostatic activation.
Dr. Bryan McVerry’s research interest has focused on the regional pathophysiology of acute lung injury and on pulmonary endothelial function in the acutely injured lung as it pertains to alveolar capillary barrier regulation and the control of pulmonary vascular tone.
Dr. Prabir Ray’s research program is focused in the following areas:
-Mechanism(s) of keratinocyte growth factor (KGF)-mediated protection of lung from oxidative injury. KGF plays an important role in the repair of lung alveolar epithelium after injury. Using an inducible transgenic approach and molecular biology techniques his group has identified signaling proteins involved in KGF receptor signaling. Currently he is studying signal transduction pathways involving these molecules and their role in the healing process after oxidative injury to the lung.
-Proteomic analysis of lung diseases. Hypothetically, almost all diseases are the result of imbalance in protein expression. Conceptually, a decrease in “good” protein levels and an increase in “bad” protein levels results in disease. Dr. Ray has initiated a project to establish a quantitative differential protein expression profile (proteome) of specific cell types isolated from normal lung and diseased lung and also from BAL. After identification of specific profiles and using molecular biology techniques, he will have a better understanding of disease processes. This will also help to develop differential diagnostic antibody chips for lung diseases.
-Role of dendritic cells in lung inflammation. The dendritic cell (DC) is an important cell in the immune system. It exerts its effects by diverse biochemical processes from antigen processing and presentation to cell migration by producing chemokines. Dr. Ray initiated studies on regulation of chemokine production by DC in Th1- and Th2 driven lung diseases.
Dr. Michael Donahoe is the Medical Director of the MICU and actively directing a broad range of projects focused on patient safety and care quality management in the ICU. He has conducted a broad range of clinical trials in ARDS, nutrition support, catheter management, and nosocomial infections. Collaborations exist with the Department of Critical Care Medicine and the School of Nursing.