ADAM33 gene and environment interactions in developing lungs and their involvement in the early life origin of asthma

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Asthma is a common disease affecting both adults and children. It causes wheeziness, chesttightness and cough and is often triggered by exposure to allergens (eg. dust or animal fur). As aresult, the airways contract too much and too easily, limiting airflow into the lung. Asthma tends torun in families suggesting there are ‘asthma’ genes. ADAM33 is such a gene where small changeshave been found in people with asthma and in young children at risk of asthma. It is found inspecialized airway ‘smooth muscle’ cells (ASMCs) that cause airway ‘twitchiness’ in asthma and it isreleased in fluid that is present in the airways of asthmatic patients. In baby lungs, I have foundthat ADAM33 occurs in stem cells that give rise to ASMCs. Therefore, the objectives of my researchare to study the role of ADAM33 in airway development and to understand whether release ofADAM33 can give rise to abnormal ASMC development that might lead to asthma. I will alsoinvestigate whether, and how maternal allergy, a factor that predisposes babies for asthma, affectsADAM33 in ASMC. These studies should help devise new treatments for asthma close to the origin ofthe disease.