The focus of my research program is to decipher the molecular and cellular basis of immunity against Candida and Aspergillus species, major causative agents of invasive mycoses in patients with cancer.
We have developed fluorescence-based reporters of fungal physiology to examine the outcome of fungal cell-host cell interactions with single-encounter resolution at the portal of infection. Fluorescent Aspergillus reporter (FLARE) conidia (i.e., vegetative spores, the infectious fungal propagule) change their fluorescence properties when phagocytes inactivate fungal cells at the portal of infection (Figure 1). Using this bioreporter, we can measure fungal cell uptake and fungal cell killing by host leukocytes at single-encounter resolution in vivo.
This technique enables us to examine leukocyte effectors implicated in fungal uptake and killing, identify and functionally characterize the antifungal activities of neutrophils, monocytes, plasmacytoid dendritic cells, and epithelial cells, and to analyze fungal genetic circuits implicated in pathogenesis. A major goal of this research is to develop an integrated model of sterilizing barrier immunity against inhaled mold pathogens.