Faculty and Research
Heitman Lab Members
Soo Chan Lee, PhD
320 CARL Building
Box 3546 DUMC
Durham, N.C. 27710
Associate Faculty Member of F1000
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.
- Lee, Soo Chan* and Heitman, J. 2014. Sex in the Mucoralean fungi. Mycoses. In press.
* Corresponding author.
- Lee, Soo Chan*, Sun, S*., and Heitman, J. 2014. Unseen sex in ancient virgin fungi. New Phytologist. 201:3-5. [Article]
* Co-first authors.
- Lee, Soo Chan, Li, A., Calo, S., and Heitman, J. 2013. Calcineurin plays key roles in the dimorphic transition and virulence in the human pathogenic zygomycete Mucor circinelloides. PLoS Pathogens. 9: e1003625. [Article]
- Lee, Soo Chan, Ristaino, J., and Heitman, J. 2012. Parallels in intercellular communication in oomycete and fungl pathogens of plants and humans. PLoS Pathogens. 12:e1003028. Pearls Review. [Article]
- Lee, Soo Chan, Phadke, S., Sun, S., and Heitman, J. 2012. Pseudohyphal growth of Cryptococcus neoformans is a reversible dimorphic transition in response to ammonium that requires the Amt1/2 ammonium permeases. Eukaryotic Cell. 11:1391-1398. [Article]
- Lee, Soo Chan and Heitman, J. 2012. Function of Cryptococcus neoformans KAR7 (SEC66) in karyogamy during unisexual and opposite-sex mating in. Eukaryotic Cell. 11:783-794. [Article]
- Bastidas, R. J., Shertz, C. A., Soo Chan Lee, Heitman, J., and Cardenas, M. E. 2012. Rapamycin exerts antifungal activity in vitro and in vivo in Mucor circinelloides via FKBP12 dependent inhibition of TOR. Eukaryotic Cell. 11:270-281. [Article]
- Wang, X., Li, W., Sun, S., Kozubowski, L., Lee, Soo Chan, Feretzaki, M., Heitman, J. 2012. Know your enemy: how to build and vanquish a global fungal scourge. Mycopathologia. 173:295-301. [Article]
- Li, C. H., Cervantes, M., Springer, D. J., Ruiz-Vazquez, R. M., Torres-Martinez, S. R., Heitman, J.*, and Lee, Soo Chan*. 2011. Sporangiospore size dimorphism is linked to virulence of Mucor circinelloides species subcomplex. PLoS Pathogens. 7:e1002086. [Article]
* co-corresponding authors
- evaluated by the Faculty of 1000
- cover image
- Gryganskyi, A. P., Lee, Soo Chan, Litvintseva, A. P., Smith, M. E., Bonito, G., Porter, G. M., Anishchenko, I. M., Heitman, J., Vilgalys, R. 2010. Structure, function, and phylogeny of the mating locus in the Rhizopus oryzae complex. PLoS ONE. 5: e15273. [Article]
- Lee, Soo Chan, Corradi, N., Doan, S., Dietrich, F. S., Keeling, P. J., and Heitman, J. 2010. Evolution of the sex-related locus and genomic features shared in microsporidia and fungi. PLoS ONE. 5: e10539. [Article]
- Lee, Soo Chan, Ni, M., Li, W., Shertz, C., and Heitman, J. 2010. The evolution of sex: a perspective from the fungal kingdom. Microbiology and Molecular Biology Reviews. 74: 298-340. [Article]
- Lee, Soo Chan, Louis M. Weiss, and Joseph Heitman. 2009. Generation of genetic diversity in microsporidia via sexual reproduction and horizontal gene transfer. Communicative & Integrative Biology. 2:5, 414-417. [Article]
- Kozubowski, L*, Lee, Soo Chan*, and Heitman, J. 2009. Signaling pathways in the pathogenesis of Cryptococcus. Cellular Microbiology. 11:370-380. [Article]
- Lee, Soo Chan, Corradi, N., Byrnes, E. J., Torres-Martinez, S., Dietrich, F. S., Keeling, P. J., and Heitman, J. 2008. Microsporidia evolved from ancestral sexual fungi. Current Biology. 18:1675-1679. [Article]
This paper was highlighted and commented on in:
- Surridge, C. 2008. Sex and the parasitic fungi. Nature Reviews Microbiology. 6:873.
- Dyer, P. 2008. Microsporidia sex – a missing link to fungi. Current Biology. 18: R1012-
- Lee, Soo Chan and Shaw, B.D. 2008. ArfB links protein lipidation and endocytosis to polarized growth of Aspergillus nidulans. Communicative & Integrative Biology. 1:51-52. [Article]
- Lee, Soo Chan, Schmidtke, S.N., Dangott, L. J., and Shaw, B.D. 2008. Aspergillus nidulans ArfB plays a role in endocytosis and polarized growth. Eukaryotic Cell.7:1278-1288. [Article]
- Lee, Soo Chan and Shaw, B.D. 2008. Localization and function of ADP ribosylation factor A in Aspergillus nidulans. FEMS Microbiology Letter. 283:216-222. [Article]
- Lee, Soo Chan and Shaw, B.D. 2007. A novel interaction between N-myristoylation and the 26S proteasome during cell morphogenesis. Molecular Microbiology. 63: 1054-1068. [Article]
- Lee, S. J., Lee, Soo Chan, Choi, S. H., Chung, M. K, Rhie, H. G., and Lee, Ho Sa. 2001. Effect of ArsA, arsenite-specific ATPase, on inhibition of cell division in Escherichia coli. Journal of Microbiology and Biotechnology. 11: 825-830. [Article]
- Mendoza, L., Vilela, R., Volz, K., Ibrahim, A., Voigt, K., and Soo Chan Lee*. A book chapter: Human fungal pathogens of Mucorales and Entomorphthorales in the book “Human Fungal Pathogens”. Cold Spring Harbor Laboratory. In press * Leading and senior author
- Lee, Soo Chan, Heitman, J., and Ironside, J. A book chapter: Sex in the microsporidia in the book “Microsporidia: Pathogens of Opportunity”. Wiley Press. In press.
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