Judith Smith, M.D., Ph.D.

Genes and environmental factors, such as early infection with respiratory viruses, increase the risk for childhood asthma. Studies in animals and people have increasingly implicated a gene called ORMDL3 in asthma development. Gene variants that increase ORMDL3 increase asthma risk. In addition, stimulation of human blood cells with rhinovirus, an asthma trigger, increases production of ORMDL3. We have found that decreasing levels of ORMDL3 diminishes rhinovirus replication in the epithelial cells lining the airways. We will study how the gene regulates viral asthma triggers. We will determine which function of ORMDL3 controls rhinovirus replication using drugs and genetic approaches. This research will lead to therapies targeting ORMDL3 in asthma.

Update:

Children who wheeze in response to rhinovirus (common cold virus) during their first three years of life, and who have specific genetic variants at the 17q21 chromosomal region, have a very high likelihood of developing asthma. Currently, the connections between 17q21 genetic variants, rhinovirus infection, and wheezing are not clear. We have found one of the 17q21 genes, called ORMDL3, is required for optimal replication of rhinovirus in human epithelial cells. Our results suggest ORMDL3 may prove a good therapeutic target: decreasing ORMDL3 activity to sufficiently low levels could decrease rhinovirus burden and thus rhinovirus-dependent illnesses including asthma exacerbations. Future work will build on these findings by exploring rhinovirus replication and gene expression in 17q21 genotyped epithelial cells.

Funded in partnership with the American Academy of Allergy, Asthma & Immunology