Grant: Operating Grant

Asthma affects up to three hundred thousand Canadians. In spite of significant advances in the field of symptom management, a proportion of asthmatics are refractory to current interventions and no cure is available for this lifelong disease. A class of molecules (sphingolipids) have recently emerged as important modulators of immunity, with therapeutic potential demonstrated in clinical trials for immune-related diseases like multiple sclerosis. Recently, synthetic analogs of these molecules were shown to prevent the development of experimental asthma. This new class of drugs affects the function of many actors involved in asthma pathogenesis. As a consequence, we currently ignore exactly how these new modulators act to alleviate experimental asthma. This research program is dedicated to further define the beneficial effects and mechanisms of action of these analogs and of their targets. To do so, we will combine the use new pharmacological agents, asthmatic human cell cultures as well as murine models of asthma, and genetically-modified mice. Classical and cutting edge analytical methods of immunology, molecular biology, biochemistry and physiology will be employed to integrate how this new class of molecules modulates sub-cellular, cellular, tissular and functional characteristics of the disease. The results of this program will improve our knowledge of novel modulators of asthma and ameliorate our general comprehension of the disease with possibility of rapid application for treatment since sphingosine analogs are currently approved for human use.