The mold Aspergillus fumigatus causes a severe often fatal pneumonia in patients with abnormal immune system. This mold can also colonize the airways of patients with underlying lung disease and leads to a worsening of their underlying condition. Current antifungal drugs have been disappointing in preventing and treating both of these diseases. Our research program is aimed at understanding how this organism causes human disease in order to develop new therapies. In the past 4 years we have identified a new molecule, galactosaminogalactan, produced by Aspergillus that is required for the organism to attach to lung cells and cause disease and inflammation. In addition, we have found that a type of white blood cell, the mast cell, actually worsens the outcome of Aspergillus colonization and promotes infection. In the coming period we will explore the mechanisms by which both of these factors favour the development of disease. In addition, we will develop and test new therapies that target galactosaminogalactan or the mast cell during invasive infection and colonization. We believe that these therapies will prove effective additions to the currently available antifungal drugs and can lead to better survival and improved outcomes in these conditions.