Pathogenic fungal infection and host immunity （Changbin Chen）
Pathogenic fungi are a significant clinical problem because of immunosuppression (due to HIV infection or immunosuppressive drugs) and antibiotic use. Our understanding of pathogenic mechanisms underlying fungal disease trails those of bacteria and viruses, primarily because fungi tend to be more challenging to manipulate experimentally. The diploid yeast Candida albicans is a normal commensal of humans but in patients with deficient immune systems, this pathogen behaves as an aggressive pathogen, attacking virtually any organ system, and leading to death as high as 40%. However, genetic programs, especially the determinants that are required for C. albicans infection in different stages, including commensalism and transition from commensalism to parasitism, are largely unknown.
Our laboratory aims to dissect molecular mechanisms of virulence and commensalism during C. albicans infection, and to understand how host immune systems act during C. albicans transitions from being a commensal to being a pathogen. Current research is mainly focusing on the following directions:
1. Role of a unique iron regulatory circuit in C. albicans commensalism and virulence. Our work is focusing on how three transcription regulators (Sfu1, Sef1 and Hap43) in the circuit participate in C. albicans commensal growth and disease development, as well as how host immune systems respond under either high iron or low iron environment.
2. Functional analyses of determinants important for C. albicans commensalism. This study includes: 1) a metagenomic screen for mutants with altered fitness in mouse gut, and 2) gene regulatory networks involving with the identified commensal factors.
3. Interaction between C. albicans and host immunity. Our early study identified a family of secreted, host immunity-related C. albicans proteins required for fungal virulence. We hypothesize that this family proteins may secrete into the host cells and mimic host homolog proteins to subvert the host innate immune system. In addition, we established a mouse gut commensal model to study how host immune systems respond to transitions of C. albicans from being a commensal to being a pathogen.