DUKE MYCOLOGY RESEARCH UNIT
Faculty and Research

Heitman Lab Members

Ying-Lien Chen Post-Doctoral Fellow 315 CARL Building Box 3546 DUMC Durham, N.C. 27710 Phone: 919.684.2809 Fax: 919.684.5458 Email: yc87@notes.duke.edu

I received my PhD in Microbiology from the University of Tennessee (UT) in May 2009. In the fall of 2004, I began my studies at UT and joined Dr. Todd Reynolds’ lab to investigate the roles of phospholipid biosynthesis in Candida albicans virulence. My research showed that de novo biosynthesis of phosphatidylserine (PS) and phosphatidylethanolamine is essential for virulence, and due to the lack of mammalian homologs, PS synthase is a novel drug target. My studies also demonstrated that C. albicans has two equally effective mechanisms for obtaining inositol while in the host. It can either generate inositol de novo through Ino1p, or it can import it from the host through Itr1p. In August 2008, I attended the Molecular Mycology (MOMY) course at Woods Hole. Subsequently, in June 2009, I joined the Heitman lab to continue my interests in fungal pathogenesis. Here, I hope to unveil the roles of calcineurin in seven completely sequenced non-albicans Candida species. Further, my goal is to determine the roles of calcineurin in Cryptococcus gattii and identify the calcineurin downstream target(s) in Cryptococcus neoformans.

My current work shows that Candida species exhibit striking differences in response to the calcineurin inhibitors FK506 and CsA. In contrast to C. albicans, in which calcineurin is required for growth in serum but not at 37C, I find that FK506 and CsA block growth of Candida parapsilosis (2 of 3 isolates) and Lodderomyces elongisporus at 37C, as well as result in the inviability of Candida glabrata at 39C. This suggests calcineurin may play a more general role in promoting fungal growth under thermal stress. So far, I have successfully generated independent homozygous cna1/cna1, cnb1/cnb1, and crz1/crz1 mutants of C. dubliniensis; these calcineurin mutants are sensitive to SDS, calcium ions, and fluconazole, although crz1/crz1 mutants only have intermediate phenotypes. Interestingly, C. glabrata cna1 mutants are sensitive to high temperature, SDS, caspofungin, fluconazole, and lithium but not to calcium ions. Both the wax moth and mouse models used to assay fungal virulence for candidiasis are ongoing. These advances extend calcineurin inhibitor combination therapy with fluconazole or caspofungin to a broader emerging pathogenic Candida species.