Impact of the Circadian Clock and Age on Anti-viral Responses that Contribute to Asthma

Principal Investigator(s):

Jeffrey Haspel, M.D., Ph.D. - Medicine

Status: Active

Center(s): Center for Pediatric Pulmonary Disease

Award Mechanism: Interdisciplinary Research Initiative

Project Period: 2/1/2016 - 1/31/2020

Total Amount: $450,000

Project Summary:

Project Summary
Asthma is a common childhood disease whose symptoms are strongly tied to time. The severity of asthma varies strongly by season, by the age of the child, and most intriguingly, by the time of day, such that many children experience their worst symptoms in the middle of the night. The latter suggests that the circadian clock, a collection of genes that produce circadian rhythms, is connected to asthma. A specific circadian clock gene called bmal1 may impact asthma by regulating the lung’s response to common respiratory viruses. Using mouse models, cell culture systems, and patient observations, this project aims to elucidate a novel antiviral program in the lung connected to circadian rhythms and child maturation, which could be pharmacologically targeted and also modified by behavioral changes.

Specific aims

·   Determine how the circadian clock gene bmal1 regulates the severity of respiratory viral illness and subsequent asthmatic lung disease in mice.

·   Determine how age modifies the impact of bmal1 on lung antiviral responses and asthma-like airway disease in mice.

·   Examine circadian function in asthmatic children with a prior history of severe respiratory viral illness.

Potential impact on child health
These findings could be translated into novel strategies to reduce severe respiratory infections and asthma development in children.

Eugene Agapov, M.D., Ph.D., Michael Holtzman M.D., Ph.D., Amjad Horani, M.D., Caroline Horner M.D., and Kenneth Schechtman Ph.D.