Scholars@Duke
Sheng Sun

Sheng Sun

Associate Research Professor in Molecular Genetics and Microbiology
Molecular Genetics and Microbiology
sheng.sun@duke.edu
213 Research Drive, CARL Building Room 320, Duke University Medical Center, Durham, NC 27710

Scholarly Works - Journal articles

Meiosis-specific genes play roles in ploidy reduction in Cryptococcus neoformans titan cells.

Journal article Proc Natl Acad Sci U S A · June 2, 2026 Cryptococcus neoformans is a fungal pathogen of humans that causes life-threatening meningoencephalitis. During infection, enlarged, polyploid titan cells are produced that promote persistence in the host, in part by resisting phagocytosis; under stress co ... Full text Link to item Cite

Systematic Profiling of Essential Fungal Transcription Factors Uncovers Ezt1 as a Central Pathobiological and Morphogenic Regulator in Cryptococcus neoformans.

Journal article bioRxiv · May 5, 2026 Cryptococcus neoformans is a global fungal pathogen that causes fatal cryptococcosis, underscoring the urgent need for novel therapeutics given the limitations of current antifungals. Here, we systematically investigate essential transcription factors (TFs ... Full text Link to item Cite

Dissecting the homeodomain MAT locus and engineering novel tripolar and bipolar mating systems in Cryptococcus amylolentus.

Journal article mBio · April 8, 2026 Sex in fungi is governed by the mating-type (MAT) locus, which exists as a bipolar, pseudobipolar, or tetrapolar system. The significance and impact of MAT on sexual reproduction, however, remain understudied. Furthermore, the evolution of fungal MAT loci ... Full text Link to item Cite

Homeodomain protein Sxi1α independently controls cell-cell fusion and gene expression during sexual reproduction in Cryptococcus deneoformans.

Journal article PLoS Genet · March 2026 Sex-specific homeodomain (HD) proteins are key regulators of cell identity and sexual development in fungi, typically functioning as heterodimers to govern transcription. In the human fungal pathogens Cryptococcus neoformans and Cryptococcus deneoformans, ... Full text Link to item Cite

Butyrolactol A enhances caspofungin efficacy via flippase inhibition in drug-resistant fungi.

Journal article Cell · January 22, 2026 Fungal infections cause millions of deaths annually and are challenging to treat due to limited therapeutic options and rising resistance. Cryptococci are intrinsically resistant to the latest generation of antifungals, echinocandins, while Candida auris, ... Full text Link to item Cite

Genomic evidence for a-α heterothallic and α-α unisexual mating and recombination in an environmental Cryptococcus deneoformans population.

Journal article PLoS Genet · December 2025 Cryptococcus deneoformans is a human fungal pathogen capable of both a-α and α-α mating and sexual reproduction in laboratory settings. However, the extent of a-α and α-α sexual reproductions in natural populations remain unexplored. Here we analyzed the w ... Full text Link to item Cite

Unisexual reproduction in the global human fungal pathogen Cryptococcus neoformans.

Journal article Proc Natl Acad Sci U S A · October 21, 2025 The human fungal pathogen Cryptococcus species complex (encompassing Cryptococcus neoformans, Cryptococcus deneoformans, and the Cryptococcus gattii species complexes) exhibits diversity in sexual reproduction, including α-a mating, pseudosexual reproducti ... Full text Link to item Cite

The complex evolution and genomic dynamics of mating-type loci in Cryptococcus and Kwoniella.

Journal article PLoS Biol · October 2025 Sexual reproduction in basidiomycete fungi is governed by MAT loci (P/R and HD), which exhibit remarkable evolutionary plasticity, characterized by expansions, rearrangements, and gene losses often associated with mating system transitions. The sister gene ... Full text Link to item Cite

Meiosis-specific genes play roles in ploidy reduction in Cryptococcus neoformans titan cells.

Journal article bioRxiv · September 18, 2025 Cryptococcus neoformans is a fungal pathogen of humans that causes life-threatening meningoencephalitis. During infection, enlarged, polyploid titan cells are produced that promote survival, evade immune cells, and generate diverse progeny. These titan cel ... Full text Link to item Cite

Fungal sexual reproduction and mating-type loci.

Journal article Curr Biol · June 9, 2025 Sexual reproduction is a hallmark of eukaryotes, generating diversity and variation through recombination and allele segregation, thereby facilitating natural selection. Unlike animals and plants, fungi do not have conventional male and female sexes but in ... Full text Open Access Link to item Cite

STRIPAK complex defects result in pseudosexual reproduction in Cryptococcus neoformans.

Journal article PLoS Genet · June 2025 STRIPAK is an evolutionarily conserved signaling complex that coordinates diverse cellular processes across fungi and animals. In the human fungal pathogen Cryptococcus neoformans, STRIPAK was recently shown to play critical roles in maintaining genome sta ... Full text Open Access Link to item Cite

Essential genes encoded by the mating-type locus of the human fungal pathogen Cryptococcus neoformans.

Journal article mBio · April 9, 2025 Fungal sexual reproduction is controlled by the mating-type (MAT) locus. In contrast to a majority of species in the phylum Basidiomycota that have tetrapolar mating-type systems, the opportunistic human pathogen Cryptococcus neoformans employs a bipolar m ... Full text Open Access Link to item Cite

Distinct evolutionary trajectories following loss of RNA interference in Cryptococcus neoformans.

Journal article Proc Natl Acad Sci U S A · November 19, 2024 While increased mutation rates typically have negative consequences in multicellular organisms, hypermutation can be advantageous for microbes adapting to the environment. Previously, we identified two hypermutator Cryptococcus neoformans clinical isolates ... Full text Link to item Cite

The Cryptococcus neoformans STRIPAK complex controls genome stability, sexual development, and virulence.

Journal article PLoS Pathog · November 2024 The eukaryotic serine/threonine protein phosphatase PP2A is a heterotrimeric enzyme composed of a scaffold A subunit, a regulatory B subunit, and a catalytic C subunit. Of the four known B subunits, the B"' subunit (known as striatin) interacts with the mu ... Full text Open Access Link to item Cite

Comparative genomics of the closely related fungal genera Cryptococcus and Kwoniella reveals karyotype dynamics and suggests evolutionary mechanisms of pathogenesis.

Journal article PLoS Biol · June 2024 In exploring the evolutionary trajectories of both pathogenesis and karyotype dynamics in fungi, we conducted a large-scale comparative genomic analysis spanning the Cryptococcus genus, encompassing both global human fungal pathogens and nonpathogenic spec ... Full text Open Access Link to item Cite

Calcineurin contributes to RNAi-mediated transgene silencing and small interfering RNA production in the human fungal pathogen Cryptococcus neoformans.

Journal article Genetics · March 6, 2024 Adaptation to external environmental challenges at the cellular level requires rapid responses and involves relay of information to the nucleus to drive key gene expression changes through downstream transcription factors. Here, we describe an alternative ... Full text Link to item Cite

On the evolution of variation in sexual reproduction through the prism of eukaryotic microbes.

Journal article Proc Natl Acad Sci U S A · March 7, 2023 Almost all eukaryotes undergo sexual reproduction to generate diversity and select for fitness in their population pools. Interestingly, the systems by which sex is defined are highly diverse and can even differ between evolutionarily closely related speci ... Full text Link to item Cite

Obligate sexual reproduction of a homothallic fungus closely related to the Cryptococcus pathogenic species complex.

Journal article Elife · June 17, 2022 eLife digest. Fungi are enigmatic organisms that flourish in soil, on decaying plants, or during infection of animals or plants. Growing in myriad forms, from single-celled yeast to multicellular molds and mushrooms, fungi have also evolved ... Full text Open Access Link to item Cite

Epistatic genetic interactions govern morphogenesis during sexual reproduction and infection in a global human fungal pathogen.

Journal article Proc Natl Acad Sci U S A · February 22, 2022 Cellular development is orchestrated by evolutionarily conserved signaling pathways, which are often pleiotropic and involve intra- and interpathway epistatic interactions that form intricate, complex regulatory networks. Cryptococcus species are a group o ... Full text Link to item Cite

Clonal evolution in serially passaged Cryptococcus neoformans × deneoformans hybrids reveals a heterogenous landscape of genomic change.

Journal article Genetics · January 4, 2022 Cryptococcus neoformans × deneoformans hybrids (also known as serotype AD hybrids) are basidiomycete yeasts that are common in a clinical setting. Like many hybrids, the AD hybrids are largely locked at the F1 stage and are mostly unable to undergo normal ... Full text Link to item Cite

Dynamic genome plasticity during unisexual reproduction in the human fungal pathogen Cryptococcus deneoformans.

Journal article PLoS Genet · November 2021 Genome copy number variation occurs during each mitotic and meiotic cycle and it is crucial for organisms to maintain their natural ploidy. Defects in ploidy transitions can lead to chromosome instability, which is a hallmark of cancer. Ploidy in the haplo ... Full text Link to item Cite

Uniparental nuclear inheritance following bisexual mating in fungi.

Journal article Elife · August 2, 2021 Some remarkable animal species require an opposite-sex partner for their sexual development but discard the partner's genome before gamete formation, generating hemi-clonal progeny in a process called hybridogenesis. Here, we discovered a similar phenomeno ... Full text Link to item Cite

Correction to: The evolving species concepts used for yeasts: from phenotypes and genomes to speciation networks (Fungal Diversity, (2021), 109, 1, (27-55), 10.1007/s13225-021-00475-9)

Journal article Fungal Diversity · July 1, 2021 The name of the second author was incorrectly captured in the initial online publication, and due to an error at the proofs stage, several proof corrections had been left undone. The original online article has been corrected. ... Full text Cite

Factors enforcing the species boundary between the human pathogens Cryptococcus neoformans and Cryptococcus deneoformans.

Journal article PLoS Genet · January 2021 Hybridization has resulted in the origin and variation in extant species, and hybrids continue to arise despite pre- and post-zygotic barriers that limit their formation and evolutionary success. One important system that maintains species boundaries in pr ... Full text Link to item Cite

Pleiotropy and epistasis within and between signaling pathways defines the genetic architecture of fungal virulence.

Journal article PLoS Genet · January 2021 Cryptococcal disease is estimated to affect nearly a quarter of a million people annually. Environmental isolates of Cryptococcus deneoformans, which make up 15 to 30% of clinical infections in temperate climates such as Europe, vary in their pathogenicity ... Full text Link to item Cite

The evolving species concepts used for yeasts: from phenotypes and genomes to speciation networks.

Journal article Fungal Divers · 2021 Here we review how evolving species concepts have been applied to understand yeast diversity. Initially, a phenotypic species concept was utilized taking into consideration morphological aspects of colonies and cells, and growth profiles. Later the biologi ... Full text Link to item Cite

Microbe Profile: Cryptococcus neoformans species complex.

Journal article Microbiology (Reading) · September 2020 Cryptococcus neoformans is a lethal fungus disguised in a polysaccharide coat. It can remain dormant in the host for decades prior to reactivation, causing systemic cryptococcosis in humans and other mammals. Cryptococcus deploys a multitude of traits to a ... Full text Link to item Cite

Transposon mobilization in the human fungal pathogen Cryptococcus is mutagenic during infection and promotes drug resistance in vitro.

Journal article Proc Natl Acad Sci U S A · May 5, 2020 When transitioning from the environment, pathogenic microorganisms must adapt rapidly to survive in hostile host conditions. This is especially true for environmental fungi that cause opportunistic infections in immunocompromised patients since these micro ... Full text Link to item Cite

Centromere scission drives chromosome shuffling and reproductive isolation.

Journal article Proc Natl Acad Sci U S A · April 7, 2020 A fundamental characteristic of eukaryotic organisms is the generation of genetic variation via sexual reproduction. Conversely, significant large-scale genome structure variations could hamper sexual reproduction, causing reproductive isolation and promot ... Full text Link to item Cite

The Pheromone and Pheromone Receptor Mating-Type Locus Is Involved in Controlling Uniparental Mitochondrial Inheritance in Cryptococcus.

Journal article Genetics · March 2020 Mitochondria are inherited uniparentally during sexual reproduction in the majority of eukaryotic species studied, including humans, mice, and nematodes, as well as many fungal species. Mitochondrial uniparental inheritance (mito-UPI) could be beneficial i ... Full text Cite

Genetic and Genomic Analyses Reveal Boundaries between Species Closely Related to Cryptococcus Pathogens.

Journal article mBio · June 11, 2019 Speciation is a central mechanism of biological diversification. While speciation is well studied in plants and animals, in comparison, relatively little is known about speciation in fungi. One fungal model is the Cryptococcus genus, which is best known fo ... Full text Link to item Cite

Fungal genome and mating system transitions facilitated by chromosomal translocations involving intercentromeric recombination.

Journal article PLoS Biol · August 2017 Species within the human pathogenic Cryptococcus species complex are major threats to public health, causing approximately 1 million annual infections globally. Cryptococcus amylolentus is the most closely known related species of the pathogenic Cryptococc ... Full text Link to item Cite