Bench-to-bedside asthma research to study potential biomarker

In a previous prostate cancer study, Yaping Tu, Ph.D., a cancer biologist and associate professor of pharmacology at Creighton University School of Medicine, studied a mouse model that was missing a specific gene, called RGS2; he believed the deleted gene would lead to prostate cancer in the animals. Though the tumors failed to develop, Tu noticed the mice had trouble breathing and were less active, similar to asthma patients. With the help of Creighton's renowned allergy and asthma researcher Thomas Casale, M.D., professor of medicine and microbiology and immunology and Chief of the Division of Allergy and Immunology, Tu soon determined the animals suffered from airway hyperresponsiveness, or a twitchiness of the airways -- a cardinal feature of asthma.

"This finding piqued our interest and made us wonder if there was a connection to human patients with asthma," says Tu. "In a small study, we were able to confirm that RGS2 is downregulated in a high percentage of patients with asthma, confirming the possibility that this may be a target for a novel gene therapy in asthma patients."

Now with a $1.44 million, four-year NIH grant, Tu and collaborators Casale and Peter Abel, Ph.D., professor of pharmacology at Creighton University School of Medicine, will take a bench-to-bedside approach to explore how the gene works in the development of airway hyperresponsiveness and whether it can be used as a diagnostic marker for asthma. Finally, the collaborators will work to develop a therapeutic approach to restore gene function, with the hope of one day applying the research to human trials.

Asthma currently affects more than 25 million Americans. There is not one cause; different patients have different triggers. The one shared trait, however, is airway hypperresponsiveness possibly related to the change to RGS2.

"Our current treatment options are similar to a lock-and-key," Casale explains. "Each drug on the market is the key to unlock and treat a different symptom or pathway important in causing asthma -- and we still haven't found all of the keys. We still have a lot of work to do, but our findings suggest that therapy targeting RGS2 gene expression might just be the master key to managing a critical component of asthma as a whole."