Christina Cuomo
· Viatris Professor of Molecular Microbiology and ImmunologyBrown University · Immunology and Infectious Diseases
Active 1994–2024
About
Christina Cuomo is the Viatris Professor of Molecular Microbiology and Immunology at Brown University. Her research focuses on human fungal pathogens, which pose a significant threat to public health due to their capacity to cause disease and develop rising antifungal resistance. Her long-term goal is to identify mechanisms of virulence and drug resistance to improve treatment decisions. Cuomo utilizes genomic approaches to study the evolution of human fungal pathogenic species, employing comparative, population genomic, and microevolutionary methods to identify genes and variants associated with important phenotypes and to understand how genome structure evolves. Her work encompasses studying various fungal species such as Candida and Cryptococcus neoformans, with a particular emphasis on microbial drug resistance, genomics, and molecular diagnostics. Cuomo's contributions include advancing genome assembly techniques, analyzing genetic diversity and microevolution in clinical isolates, and exploring the molecular and genetic basis of antifungal resistance. Her research provides critical insights into fungal pathogenicity, resistance mechanisms, and the evolutionary dynamics of fungi affecting human health.
Research topics
- Biology
- Genetics
- Evolutionary biology
- Computational biology
- Microbiology
- Computer Science
- Medicine
- Environmental planning
- Environmental ethics
- Ecology
- Botany
- Geography
Selected publications
Diploid-dominant life cycles characterize the early evolution of Fungi
Proceedings of the National Academy of Sciences · 2022 · 80 citations
- Biology
- Evolutionary biology
- Genetics
Most of the described species in kingdom Fungi are contained in two phyla, the Ascomycota and the Basidiomycota (subkingdom Dikarya). As a result, our understanding of the biology of the kingdom is heavily influenced by traits observed in Dikarya, such as aerial spore dispersal and life cycles dominated by mitosis of haploid nuclei. We now appreciate that Fungi comprises numerous phylum-level lineages in addition to those of Dikarya, but the phylogeny and genetic characteristics of most of these lineages are poorly understood due to limited genome sampling. Here, we addressed major evolutionary trends in the non-Dikarya fungi by phylogenomic analysis of 69 newly generated draft genome sequences of the zoosporic (flagellated) lineages of true fungi. Our phylogeny indicated five lineages of zoosporic fungi and placed Blastocladiomycota, which has an alternation of haploid and diploid generations, as branching closer to the Dikarya than to the Chytridiomyceta. Our estimates of heterozygosity based on genome sequence data indicate that the zoosporic lineages plus the Zoopagomycota are frequently characterized by diploid-dominant life cycles. We mapped additional traits, such as ancestral cell-cycle regulators, cell-membrane- and cell-wall-associated genes, and the use of the amino acid selenocysteine on the phylogeny and found that these ancestral traits that are shared with Metazoa have been subject to extensive parallel loss across zoosporic lineages. Together, our results indicate a gradual transition in the genetics and cell biology of fungi from their ancestor and caution against assuming that traits measured in Dikarya are typical of other fungal lineages.
Genome Medicine · 2022 · 42 citations
- Biology
- Genetics
- Computational biology
BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) are an urgent global health threat. Inferring the dynamics of local CRE dissemination is currently limited by our inability to confidently trace the spread of resistance determinants to unrelated bacterial hosts. Whole-genome sequence comparison is useful for identifying CRE clonal transmission and outbreaks, but high-frequency horizontal gene transfer (HGT) of carbapenem resistance genes and subsequent genome rearrangement complicate tracing the local persistence and mobilization of these genes across organisms. METHODS: To overcome this limitation, we developed a new approach to identify recent HGT of large, near-identical plasmid segments across species boundaries, which also allowed us to overcome technical challenges with genome assembly. We applied this to complete and near-complete genome assemblies to examine the local spread of CRE in a systematic, prospective collection of all CRE, as well as time- and species-matched carbapenem-susceptible Enterobacterales, isolated from patients from four US hospitals over nearly 5 years. RESULTS: Our CRE collection comprised a diverse range of species, lineages, and carbapenem resistance mechanisms, many of which were encoded on a variety of promiscuous plasmid types. We found and quantified rearrangement, persistence, and repeated transfer of plasmid segments, including those harboring carbapenemases, between organisms over multiple years. Some plasmid segments were found to be strongly associated with specific locales, thus representing geographic signatures that make it possible to trace recent and localized HGT events. Functional analysis of these signatures revealed genes commonly found in plasmids of nosocomial pathogens, such as functions required for plasmid retention and spread, as well survival against a variety of antibiotic and antiseptics common to the hospital environment. CONCLUSIONS: Collectively, the framework we developed provides a clearer, high-resolution picture of the epidemiology of antibiotic resistance importation, spread, and persistence in patients and healthcare networks.
Nature Communications · 2020 · 69 citations
- Microbiology
- Biology
- Genetics
Candida auris is an emerging fungal pathogen that exhibits resistance to multiple drugs, including the most commonly prescribed antifungal, fluconazole. Here, we use a combinatorial screening approach to identify a bis-benzodioxolylindolinone (azoffluxin) that synergizes with fluconazole against C. auris. Azoffluxin enhances fluconazole activity through the inhibition of efflux pump Cdr1, thus increasing intracellular fluconazole levels. This activity is conserved across most C. auris clades, with the exception of clade III. Azoffluxin also inhibits efflux in highly azole-resistant strains of Candida albicans, another human fungal pathogen, increasing their susceptibility to fluconazole. Furthermore, azoffluxin enhances fluconazole activity in mice infected with C. auris, reducing fungal burden. Our findings suggest that pharmacologically targeting Cdr1 in combination with azoles may be an effective strategy to control infection caused by azole-resistant isolates of C. auris.
Threats Posed by the Fungal Kingdom to Humans, Wildlife, and Agriculture
mBio · 2020 · 526 citations
- Environmental ethics
- Geography
- Biology
The fungal kingdom includes at least 6 million eukaryotic species and is remarkable with respect to its profound impact on global health, biodiversity, ecology, agriculture, manufacturing, and biomedical research. Approximately 625 fungal species have been reported to infect vertebrates, 200 of which can be human associated, either as commensals and members of our microbiome or as pathogens that cause infectious diseases. These organisms pose a growing threat to human health with the global increase in the incidence of invasive fungal infections, prevalence of fungal allergy, and the evolution of fungal pathogens resistant to some or all current classes of antifungals. More broadly, there has been an unprecedented and worldwide emergence of fungal pathogens affecting animal and plant biodiversity. Approximately 8,000 species of fungi and Oomycetes are associated with plant disease. Indeed, across agriculture, such fungal diseases of plants include new devastating epidemics of trees and jeopardize food security worldwide by causing epidemics in staple and commodity crops that feed billions. Further, ingestion of mycotoxins contributes to ill health and causes cancer. Coordinated international research efforts, enhanced technology translation, and greater policy outreach by scientists are needed to more fully understand the biology and drivers that underlie the emergence of fungal diseases and to mitigate against their impacts. Here, we focus on poignant examples of emerging fungal threats in each of three areas: human health, wildlife biodiversity, and food security.
Phytopathology · 2020 · 207 citations
- Biology
- Evolutionary biology
- Botany
, as it remains the best scientific, nomenclatural, and practical taxonomic option available.
mBio · 2020 · 437 citations
Senior authorCorresponding- Computer Science
- Biology
- Evolutionary biology
clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology.
Recent grants
Frequent coauthors
- 80 shared
Joseph Heitman
Duke University Hospital
- 60 shared
Bruce W. Birren
- 52 shared
Evan Mauceli
Complete Genomics (United States)
- 51 shared
Alexandre Alanio
Assistance Publique – Hôpitaux de Paris
- 51 shared
Li‐Jun Ma
University of Massachusetts Amherst
- 51 shared
Harold Kistler
University of Minnesota
- 47 shared
Rhys A. Farrer
University of Exeter
- 44 shared
José F. Muñoz
Broad Institute
Education
PhD/Genetics
Harvard University
AB/Biology
Bryn Mawr College
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