Department of Medicine

Acute Lung Injury / ARDS

Program Description

The Acute Lung Injury / Adult Respiratory Distress Syndrome 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.

Dr. 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 erythrocytes and endothelial cells, and its regulation of neutrophilic lung inflammation.  The laboratory is currently investigating the role of Duffy antigen erythrocyte membrane protein in modulating transfusion related acute lung injury.  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.

Dr. McVerry's research interest has focused on the regional pathophysiology of acute lung injury, the role of endothelial barrier regulation in the evolution and treatment of acute lung injury, and the control of pulmonary vascular tone in both the normal and the injured lung.   In addition, Dr. McVerry has an interest on the regulation of insulin and glucose metabolism in critical illness, and its impact on the evolution and treatment of acute lung injury.

Dr. Ray's research program is focused in four areas:

1. 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.
2. The development of transgenic and knockout mice to model lung diseases. Lung disease processes involve complex interactions and regulation of expression of critical biomolecules. Lung inflammation is an important component of several lung diseases.  Chemokines (low molecular weight protein molecules involved in inflammatory cell migration to the tissue by forming a chemical gradient) and cytokines (low molecular weight proteins that regulate cellular functions) play important roles in the inflammatory processes.   Using inducible lung specific expression of key chemokines and cytokines Dr. Ray is developing murine models of human diseases. He has also initiated the development of lung specific conditional knock out mice. 
3. 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.
4. 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. Ray is a project leader on the Host Defense SCCOR.

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.