Invasive fungal infections are a major cause of death for the rapidly growing number of patients whose immune systems are compromised as a consequence of modern medical treatments. The incidence of invasive aspergillosis (IA), caused largely by the fungus Aspergillus fumigatus, has increased three-fold in the last decade. IA is a leading cause of infectious mortality in immunocompromised patients, with deaths attributable to IA increasing by 357% between 1980-1997. Despite the use of newer antifungal agents, current IA therapy has a dismal 40-50% treatment success rate. The devastating effects of IA have escalated to such a degree that the Infectious Diseases Society of America identified A. fumigatus as one of only six infectious pathogens (and the only fungal pathogen) for which a substantive treatment breakthrough is urgently needed.  

IA occurs in immunocompromised patients when A. fumigatus conidia (asexual spores) are inhaled and germinate into long tubular cells called hyphae, which are the critical growing and invading structures of A. fumigatus and are essential to establishing invasive disease. Our approach is that blocking or altering A. fumigatus hyphal growth can be used to prevent and treat IA. Recent findings demonstrate that a promising and untapped target, the calcineurin pathway, controls hyphal growth, tissue invasion, and virulence in A. fumigatus. We feel that manipulation of the A. fumigatus calcineurin pathway can halt invasive disease, synergize with antifungal therapies, and improve patient outcomes.

Our focus is on translational research designed to investigate and halt the pathogenesis and disease of Aspergillus fumigatus. The laboratory goal is to stop hyphal growth, and we are targeting the stress response pathways in A. fumigatus as a means to deciphering virulence factors and improving antifungal therapy outcomes. At present, the highlight is on the calcineurin signaling pathway in A. fumigatus, and we have shown some exciting results that clearly demonstrate the power of inhibiting calcineurin to stop hyphal growth.  

The lab uses numerous molecular biologic approaches, genomics through real-time PCR and microarrays, in vitro antifungal susceptibility testing, cell viability assays, and several different animal models all to reach our goal of deciphering and then stopping A. fumigatus pathogenesis.