Anesthesiology

The Lee Laboratory

Dr. Lee

Extracellular vesicles (EV) released into the plasma during severe acute lung injury (ALI) from pneumonia and/or following sepsis play a significant role in the early inflammatory response in the injured alveolus. We previously found that EVs released into the plasma during severe Escherichia coli bacterial pneumonia (“E.coli EV”) itself decreased alveolar fluid clearance rate and increased lung protein permeability, leading to pulmonary edema, when instilled intravenously into a naive perfused human lung.

While studying the biological effects of these EVs in the development of ALI, we recently found that incubation of E.coli EVs with lipopolysaccharide increased intra-vesicular leukotriene (LT) B4 levels and was associated with increased antimicrobial activity in macrophages when incubated with the EVs; LTB4 is a potent neutrophil chemoattractant and stimulus for phagocytosis. This potential function of plasma EVs, to migrate easily and traffic into the injured alveolus due to its nanometer size and enhance the anti-microbial activity of target cells, may be an early biological response to ALI prior to the migration of professional phagocytes. Plasma EVs, especially microvesicles which contain numerous cell surface receptors, can be stimulated by LPS to deliver vesicles with increased LTB4 content to combat the infection.

The primary focus of the laboratory is to enhance this biological response further by stimulation of EVs, targeting specific receptors on the EVs.

The laboratory is supported by funding from the National Institute of Health.

About the Principal Investigator

Dr. Lee is a physician-scientist whose primary area of expertise is in the role of extracellular vesicles (EV) in the pathogenesis of lung injury from severe bacterial pneumonia.  A major focus of the laboratory is to modify plasma EVs, by targeting receptors on the EVs, in hopes of developing a novel therapy for acute respiratory distress syndrome, a major clinical sequalae of pneumonia and sepsis.  Dr. Lee is a frequent reviewer for both national and international grant agencies.  He is currently a permanent member of the NIH Surgery, Anesthesiology and Trauma study section.

Opportunities

We are always interested in visiting scholars and students (undergraduate, graduate, postdoctoral scholars) joining the laboratory.  Please inquire about opportunities at [email protected]. 

Representative Research Publications

1.

Zhu, YY, Feng, XM, Abbott, J, Fang, X, Hao, Q, Monsel, A, Qu, JM, Matthay, M, and Lee, JW. Human mesenchymal stem cell microvesicles for treatment of E.coli endotoxin induced acute lung injury in mice. Stem Cells 32(1):116-25, 2014.

2.

Monsel, A, Zhu, YG, Gennai, S, Hao, Q, Hu, S, Rouby, JJ, Rosenzwajg, M, Matthay, MA, Lee, JW. Microvesicles Derived from Human Bone Marrow Mesenchymal Stem Cells Improve Survival in E.coli Pneumonia-induced Acute Lung Injury in Mice and Enhance Monocyte Phagocytosis of Bacteria. AJRCCM 192(3):324-36, 2015. 

3.

Fernandez-Bustamante, A, Frendl, G, Sprung, J, Kor, D, Subramaniam, B, Martinez Ruiz, R, Lee, JW, Henderson, W, Moss, A, Mehdiratta, N, Colwell, MM, Bartels, K, Kolodzie, K, Vidal Melo, M; The Perioperative Research Network (PRN) investigators. Multicenter prospective evaluation of postoperative pulmonary complications in non-cardiothoracic surgical patients with severe systemic disease.  JAMA Surgery 152(2):157-166, 2017.

4.

Park, J, Kim, S, Lim, H, Liu, A, Hu, S, Lee JH, Zhuo, H, Hao, Q, Matthay, MA, Lee, JW. Therapeutic Effects of Human Bone Marrow Derived Mesenchymal Stem Cell Microvesicles in an Ex Vivo Perfused Human Lung Injured with Severe E.coli Pneumonia.  Thorax 74(1):43-50, 2019. 

5.

Liu, A, Park, JH, Zhang, X, Sugita, S, Naito, N, Lee, JH, Kato, H, Hao, Q, Matthay, MA, Lee, JW.  Therapeutic Effects of Hyaluronic Acid in Bacterial Pneumonia In the Ex Vivo Perfused Human Lungs. AJRCCM 200(10):1234-1245, 2019.