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CMB/UPGG Graduate Student (2010)
320 CARL Building
Box 3546 DUMC
Durham, N.C. 27710
I am a fifth year graduate student from the University Program in Genetic and Genomics. I entered Duke in 2010 through the Cell and Molecular Biology (CMB) program. After my undergraduate work at the University of Maryland, I spent a year as a post-baccalaureate fellow at the National Cancer Institute in Bethesda.
Fungal pathogens, like Cryptococcus neoformans, typically cause disease in immunocompromised patients. These patients often include HIV/AIDS individuals as well as patients undergoing immunosuppressive therapy, such as transplant recipients. In contrast, the closely related pathogen Cryptococcus gattii shows a different host tropism than C. neoformans. Two of the C. gattii species, VGIII and VGIV, retain the proclivity for infecting immunocompromised hosts, but the other two, VGI and VGII, tend to infect otherwise healthy individuals. Notably, the VGII subtype is responsible for an ongoing and expanding outbreak, originating from the Vancouver Island area of the Pacific Northwest and spreading into both the continental United States and Canada.
Genomes for prototypical strains of VGI and VGII have both been sequenced recently and the outbreak strains of VGII have been found to lack most of the canonical components of the RNAi pathway in comparison with VGI and the Cryptococcus neoformans genomes. While RNAi is a feature of the last common Eukaryotic ancestor, RNAi loss has occurred multiple times throughout fungi, including S. cerevisiae and the plant pathogen Ustilago maydis, and other eukaryotic pathogens such as the leishmanias and malaria. Studying C. gattii may allow us to understand the importance, or lack thereof, of RNAi to an emerging pathogen expanding into a new and previously inhospitable environment.
In addition, I am interested in the genetic and evolutionary basis of the development of the C. gattii outbreak in the Pacific Northwest. The recent availability of cheap, high-throughput genome sequencing has allowed us to begin asking questions about this outbreak that were previously untenable. I have found evidence of multiple independent introductions of the different clonal lineages responsible for the Pacific Northwest outbreak, but also of ancestral recombination that may have contributed to the generation of the predecessors to these recent clonal outbreak clusters. In addition I found evidence for the involvement of microevolution mediated by a hypermutator mutation in the major component of the outbreak. I continue to explore the role of hypermutators in the evolution of virulence.
Sun S, Billmyre RB, Mieczokowski P, Heitman J (2014) Unisexual reproduction drives meiotic recombination and phenotypic and karyotypic plasticity in Cryptococcus neoformans. PLOS Genetics. DOI: 10.1371/journal.pgen.1004849
Fu C, Sun S, Billmyre RB, Roach KC, Heitman J (2014) Unisexual versus bisexual mating in Cryptococcus neoformans: Consequences and biological impacts. Fungal Genetics and Biology, (14)00143-1.
Billmyre RB, Croll D, Li W, Mieczkowski P, Carter D, Cuomo CA, Kronstad JW, Heitman J (2014). Highly recombinant VGII Cryptococcus gattii population develops clonal outbreak clusters through both sexual macroevolution and asexual microevolution. mBio, 5(4), e01494-14.
Springer DJ, Billmyre RB, Filler E, Voelz K, Pursall R, Mieczkowski P, Larsen R, Dietrich F, May R, Filler S, Heitman J (2014). Cryptococcus gattii VGIII isolates causing infections in HIV/AIDS patients in Southern California: Identification of the local environmental source as arboreal. PLOS Pathogens, 10(8), e1004285.
Lee SC, Billmyre RB, Li A, Carson S, Sykes SM, Huh EY, Mieczkowski P, Ko D, Cuomo CA, Heitman J (2014). Analysis of a foodborne fungal pathogen outbreak: virulence and genome of a Mucor circinelloides isolate from yogurt. mBio, 5(4), e01390-14.
Janbon G, Ormerod KL, Paulet D, Byrnes EJ, Yadav V, Chatterjee G, Mullapudi N, Hon C, Billmyre RB, Brunel F, Bahn YS, Chen W, Chen Y, Chow EWL, Coppee JY, Floyd-Averette A, Gaillardin C, Gerik KJ, Goldberg J, Gonzalez-Hilarion S, Gujja S, Hamlin JL, Hsueh YP, Ianiri G, Jones S, Kodira CD, Kozubowski L, Lam W, Marra M, Mesner LD, Mieczkowski P, Moyrand F, Nielsen K, Proux C, Rossignol T, Schein JE, Sun S, Wollschlaeger C, Wood IA, Zeng Q, Neuveglise C, Newlon C, Perfect JR, Lodge JK, Idnurm A, Stajich JE, Kronstad JW, Sanyal K, Heitman J, Fraser JA, Cuomo CA, Dietrich FS (2014). Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation. PLOS Genetics, 10(4), e1004261.
Billmyre RB, Calo S, Feretzaki M, Wang X, Heitman J (2013) RNAi function, diversity, and loss in the fungal kingdom. Chromosome Research 21(6-7).
Calo S, Billmyre RB, Heitman J (2013) Generators of phenotypic diversity in the evolution of pathogenic microorganisms. PLOS Pathogens 9(3): e1003181. doi:10.1371/journal.ppat.1003181
Springer DJ, Phadke S, Billmyre RB, Heitman J (2012) Cryptococcus gattii, no longer an accidental pathogen? Current Fungal Infection Reports 6(4).
Zou Y, Pisciotta J, Billmyre RB, Baskakov IV. (2009). Photosynthetic microbial fuel cells with positive light response. Biotechnology and Bioengineering, 104(5).