Soo Chan Lee, PhD

Research Track Faculty
Assistant Research Professor
Associate Faculty Member of F1000

Soo Chan Lee Assistant Research Professor 320 CARL Building
Box 3546 DUMC
Durham, N.C. 27710
Phone: 919.684.3036
Fax: 919.684.2790
soochan.lee@duke.edu

 

research • biography • publications

I trained with Dr. Brian Shaw at Texas A&M University as a PhD student. I was primarily interested in how Aspergillus nidulans, a filamentous fungus, establishes and maintains hyphal polarity. In this study, I investigated the role of protein lipidation, especially N-myristoylation, in the polarized growth of the fungus. After receiving my PhD in December 2007 from Texas A&M University, I relocated to Durham, NC, to join the Heitman laboratory as a post-doctoral fellow. Currently, my research is focused on understanding the sexual development of three different groups of human pathogenic of fungi: Cryptococcus neoformans, a basidiomycete, Mucor circinelloides, a zygomycete, and Encephalitozoon cuniculi, a microsporidian.

I am studying the sex locus of the zygomycetes, a basal fungal lineage. Following the identification of the sex locus in Phycomyces blakesleeanus, a zygomycete (Idnurm et al. 2008. Nature), I found that the sex locus is conserved in other zygomycete species. The sex locus forms a syntenic gene cluster encoding with a triose phosphate transferase, HMG domain protein, and RNA helicase genes. The HMG domain proteins (SexP and SexM in plus and minus strain, respectively) are a key transcription factor defining sexual identity in zygomycetes (as in humans), and I am investigating the role of this protein during zygomycete mating. I discovered that microsporidia share a syntenic sex locus with zygomycetes. To test the hypothesis that microsporidia may have an extant sexual cycle, I am working with several E. cuniculi isolates cultured in RK13 (rabbit kidney) cell lines to test whether I can observe a bona fide sexual cycle.

Second, I have expanded my expertise in zygomycetes to investigate virulence and pathogenicity. As part of this line of investigation, I found that spore size is a virulence factor in Mucor, where larger spores are more virulent than smaller spores. Key findings of my study include a difference in the interactions of large and small spores with macrophages. Large spores germinate inside macrophages, whereas smaller spores remain dormant inside macrophages. My study also found that zygomycetes can cause three different types of macrophage cell death: 1) macrophage cell lysis caused by zygomycete germination, 2) death of macrophages that have phagocytosed spores, and 3) death of bystander macrophages. I am working to establish which type of cell death is involved in these interactions (apoptosis or pyroptosis).

Third, I am interested in genetics of dimorphism and its role in pathogenesis in Mucor. Mucor typically grows as hyphae, but yeast growth is observed under low oxygen/high CO2 conditions. I have found that the calcineurin inhibitor FK506 inhibits hyphal growth and drives multi-budded yeast growth. I disrupted the calcineurin B regulatory subunit gene (cnbR) and the cnbR mutants without calcineurin activity exhibit only yeast growth, providing compelling evidence that calcineurin governs dimorphic transition. Interestingly the yeast-locked strains are significantly less virulent than wild-type, indicating hyphal growth may be a virulence attribute in this fungus.

In the study of C. neoformans, I am also interested in the genetics and roles of yeast-pseudohypha transition of C. neoformans. Pathogenic cryptococcinormally proliferate as unicellular budding yeast during vegetative growth or during infection of animal hosts. However, when co-cultured with amoeba, a natural predator in soils, C. neoformans cells form pseudohyphae. While yeast C. neoformans cells are engulfed by amoeba, pseudohyphal C. neoformans cells are free from amoeba and were either not engulfed or have escaped. C. neoformans also forms atypical pseudohyphae during host infection; pseudohyphal growth has been observed in infected host tissues. These observations may imply that C. neoformans forms pseudohyphae as a survival strategy to escape from natural predators or host defenses. I revealed that nitrogen-limiting conditions trigger pseudohyphal growth of C. neoformans. I also found that two ammonium permease genes, AMT1 and AMT2, are required for pseudohyphal growth of C. neoformans. Wild-type and amt1 or amt2 single mutants are capable of forming pseudohyphae, whereas amt1 amt2 double mutants fail to form pseudohyphae under nitrogen-limited conditions.

I am interested in nuclear dynamics during opposite- and same-sex mating of C. neoformans and I investigated the roles of karyogamy genes during these processes. In this project, I identified five karyogamy (KAR) gene orthologs using a BLAST search with the Saccharomyces cerevisiae KAR genes: CnKAR2, CnKAR3, CnKAR4, CnKAR7, and CnKAR8. I found that kar7 mutants display significant defects in hyphal growth and basidiospore chain formation in both opposite- and same-sex mating.

I served as a TA in the Molecular Mycology Course (2009) at the Marine Biology Lab, Woods Hole, MA. and have been supported by the Molecular Mycology and Pathogenesis Training Program (T32-AI52080) from the NIH.