Division of Intramural Research
Pulmonary Critical Care Medicine Branch

Stewart J. Levine
M.D., State University of New York at Stony Brook, 1983

Pulmonary-Critical Care Medicine Branch
National Heart, Lung, and Blood Institute 
National Institutes of Health
Division of Intramural Research
10 Center Drive, Room 6D03
Bethesda, Maryland 20892-1590
Phone Number: 301-402-1448
Fax Number: 301-496-2363
Email: levines@nhlbi.nih.gov 

Research Interest(s):

Airway Inflammation
Asthma
Cytokines and Cytokine Receptors
Molecular & Cellular Biology
Immunology
Proteases
Pulmonary / Respiratory Diseases

Research Description:

Regulation of Airway Inflammation in Asthma

Our research focuses on the regulation of airway inflammation in patients with asthma. In particular, we are interested in cytokine receptor shedding as a mechanism by which pro-inflammatory events in the airway can be attenuated. We have identified a novel aminopeptidase regulator of tumor necrosis factor receptor shedding, that we have named ARTS-1, which promotes the release of soluble TNFR1 from airway epithelial cells. We are currently utilizing proteomic and cellular biological approaches to characterize the function of ARTS-1 and its ability to regulate innate immune responses via the modulation of cytokine receptor shedding. We are also interested in identifying novel mechanisms by which airway inflammation can be inhibited in patients with asthma and are conducting a clinical trial aimed at investigating whether TNF antagonism, utilizing a soluble TNF receptor, is efficacious for the treatment of asthma. We are also investigating whether novel polymorphisms exist in proteases that regulate cytokine receptor shedding in patients with asthma. Through these research efforts, our goal is to identify novel mechanisms by which airway inflammatory events can be down-regulated.

Selected Publications:

Cui X, Hawari F, Alsaaty S, Lawrence M, Combs CA, Geng W, Rouhani FN, Miskinis D, Levine SJ. Identification of ARTS-1 as a novel TNFR1 binding protein that promotes TNFR1 ectodomain shedding. J Clin Invest 2002; 110: 515-526.

Levine SJ. Fas-Mediated Alveolar Epithelial Cell Apoptosis in Acute Lung Injury: Friend or Foe? Critical Care Medicine 2002; 30 (7): 1667-1668.

Levine SJ. NF-ΚB: A Key Signaling Pathway in Asthma. In: Gutkin S, Finkel T, editors. Signal Transduction and Disease. John Wiley and Sons. In press.

Russian DA, Levine SJ. Pneumocystis carinii pneumonia in patients without HIV infection. Am J Med Sci 2001;321(1):56-65. PubMed

Nanavaty U, Goldstein AD, Levine SJ. Polymorphisms in candidate asthma genes. Am J Med Sci 2001;321(1):11-6. PubMed

Last updated August 29, 2002

Principal Investigators

• Joel Moss
• Martha Vaughan
• Vincent Manganiello
• Bernadette Gochuico
• Stewart Levine