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Environmental Genetics Group

Genetic Susceptibility in Lung Disease

Steven Kleeberger, Ph.D.
Steven Kleeberger, Ph.D.
Principal Investigator

Tel (919) 541-3540
Fax (919) 541-4133
P.O. Box 12233
Mail Drop D2-01
Research Triangle Park, North Carolina 27709
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Research Summary

The Environmental Genetics Group uses state-of-the-art methods in inhalation toxicology, pulmonary physiology and molecular genetics to study the role of genetics background as a susceptibility factor in environmental lung disease.

Epidemiological studies have associated exposures to outdoor and indoor pollutants with increased morbidity and mortality in urban cities throughout the U.S. and other industrialized countries.  Because of the potential impact that pollutants may have on public health, identification of the intrinsic and extrinsic factors that influence susceptibility to the pulmonary response(s) to exposures is an important issue. 

Research approach used by the Environmental Genetics Group

The Environmental Genetics Group has identified quantitative trait loci (QTL) for susceptibility to the inflammatory responses to ozone, sulfate-associated particles and hyperoxia.  Candidate genes for the QTLs have been identified, and functional analyses have confirmed important roles for each.  The group believes that investigation of the mechanisms of genetic susceptibility will have important implications for understanding the pathogenesis of environmental lung diseases.  Applying in vivo and in vitro findings in translational investigations to human populations have provided unique insight into disease mechanisms. 

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Major areas of research:

Current projects:

  • Utilizing proven positional cloning techniques to identify the gene or genes that determine differential susceptibility to O3-induced pulmonary inflammation and injury in inbred mice and search for homologues in the human genome.
  • Determining the mechanisms through which Nrf2 confers differential susceptibility to oxidant-induced lung injury in inbred mice.
  • Identifying the mode of inheritance of susceptibility to the cardiopulmonary response to inhaled particles in the mouse, and identifying and mapping the susceptibility genes.
  • Investigating the role of innate immunity genes and oxidant stress genes in susceptibility to viral infection, with particular emphasis on respiratory syncytial virus (RSV). 
  • Using translational approaches to determine the importance of a gene by environment interaction in the pathogenesis of lung disease, including acute respiratory distress syndrome (ARDS), bronchopulmonary dysplasia (BPD), asthma and coal worker's pneumoconiosis (CWP).

Steven R. Kleeberger, Ph.D., head of the Environmental Genetics Group, earned his A.B. in zoology at Miami University in Oxford, Ohio, and his Ph.D. in ecology and environmental physiology at Kent State University in Kent, Ohio. He holds several Adjunct Professorships: Environmental Health Sciences, Johns Hopkins University; Medicine, Duke University; Pediatrics and Curriculum in Toxicology, University of North Carolina at Chapel Hill. He has published over 110 peer-reviewed articles in leading biomedical journals as well as two dozen book chapters and invited reviews. Kleeberger was a professor of environmental health sciences at the Johns Hopkins Bloomberg School of Public Health before joining NIEHS in 2002. He is a reviewer for over 20 journals, and he has held a number of editorial board positions, including ones on Pharmacogenetics and The American Journal of Respiratory and Critical Care Medicine.  He has given over 90 invited lectures in the United States, Europe, Asia and South America.  He has been president of the Inhalation Specialty Section of the Society of Toxicology, and has also served or currently serves on multiple study sections at the National Institutes of Health, international advisory committees on genetic susceptibility and the Clean Air Scientific Advisory Committee (CASAC) Review Panel.

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Last Reviewed: January 29, 2008