Faculty and Research
Heitman Lab Members
315 CARL Building
Box 3546 DUMC
Durham, N.C. 27710
I recently received my PhD from Duke University where I was a graduate student in the University Program In Genetics and Genomics. As a graduate student in the Heitman lab, my research was focused on unisexual reproduction of the human fungal pathogen Cryptococcus neoformans. Our studies revealed that unisexual reproduction generates de novo phenotypic and genotypic diversity in clonal populations, including SNPs, chromosomal translocations, and aneuploidy. Our studies suggest that unisexual reproduction may be an evolutionary strategy to enable genotypic plasticity and facilitate rapid adaptation to novel environments in the absence of compatible mating partner. Unisexual reproduction is tightly regulated by the conserved pheromone-signaling cascade. However the downstream targets of the pathway are largely unknown. We applied an insertional mutagenesis via Agrobacterium tumefaciens transkingdom DNA delivery to genetically dissect unisexual reproduction. We identified three key regulators of sexual reproduction; Spo11 and Ubc5 that are essential for sporulation, and Znf3 which is required for hyphal development during unisexual and bisexual reproduction. Surprisingly, Znf3 participates in transposon silencing during unisexual reproduction and may serve as a link between RNAi silencing and sexual development.
Currently, I am interested in characterizing the role of Znf3 in sex- and mitotic-induced silencing (SIS and MIS) in Cryptococcus lineages. These ongoing studies provide novel insights on the RNAi mechanism employed by this pathogen as a genome defense against transposable elements.
Feretzaki M, Heitman J. Unisexual reproduction drives evolution of eukaryotic microbial pathogens. PLoS Pathog. 2013 9(10): e1003674.
Billmyre RB, Calo S, Feretzaki M, Wang X, Heitman J. RNAi function, diversity, and loss in the fungal kingdom. Chromosome Res. 2013 Dec;21(6-7):561-72.
Ni M*, Feretzaki M*, Li W, Floyd-Averette A, Mieczkowski P, Dietrich FS, Heitman J. Unisexual and heterosexual meiotic reproduction generate aneuploidy and phenotypic diversity de novo in the yeast Cryptococcus neoformans. PLoS Biol. 2013 Sep;11(9):e1001653. (* Denotes equal contribution) – Featured in Live Science, Duke Today, and highlighted in Nature Reviews Microbiology.
Feretzaki M, Heitman J. Genetic circuits that govern opposite- and same-sex mating in Cryptococcus neoformans. PLoS Genet. 2013 Aug;9(8):e1003688 -Featured on F1000.
Phadke SS*, Feretzaki M*, Heitman J. Unisexual reproduction enhances fungal competitiveness by promoting habitat exploration via hyphal growth and sporulation. Eukaryot Cell. 2013 Aug;12(8):1155-9. (* Denotes equal contribution).
Wang X, Li W, Sun S, Kozubowski L, Lee SC, Feretzaki M, Heitman J. Know Your Enemy: How to Build and Vanquish a Global Fungal Scourge. Mycopathologia. 2012 Jun;173(5-6):295-301.
Ni M, Feretzaki M, Sun S, Wang X, Heitman J. Sex in Fungi. Annu Rev Genet. 2011;45:405-30.
Lin X, Jackson J, Feretzaki M, Xue C, Heitman J. Transcription factors Mat2 and Znf2 operate circuits orchestrating opposite and same-sex mating in Cryptococcus neoformans. PLoS Genetics, 2010 May 13;6(5):e1000953.
Oyarzo MP, Medeiros LJ, Atwell C, Feretzaki M, Wang S, Drakos E, Amin HM, Rassidakis GZ. C-FLIP Confers resistance to Fas-mediated apoptosis in anaplastic large cell lymphoma. Blood. 2006 Mar 15;107(6):2544-7.
Rassidakis GZ, Feretzaki M, Atwell C, Grammatikakis I, Lin Q, Lai R, Claret FX, Medeiros LJ, Amin HM. Inhibition of Akt increases p27Kip1 levels and induces cell cycle arrest in anaplastic large cell lymphoma. Blood. 2005 Jan 15;105(2):827-9.
Amin HM, Medeiros LJ, Ma Y, Feretzaki M, Das P, Leventaki V, Rassidakis GZ, O'Connor SL, McDonnell TJ, Lai R. Inhibition of JAK3 induces apoptosis and decreases anaplastic lymphoma kinase activity in anaplastic large cell lymphoma. Oncogene. 2003 Aug 21;22(35):5399-407.
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