Human fungal pathogens are major threat to public health, causing substantial disease with rising antifungal resistance. Our long term goal is to identify mechanisms of virulence and drug resistance that can be used to guide and refine treatment decisions. We utilize genomic approaches to study the evolution of human fungal pathogenic species, taking comparative, population genomic, and microevolutionary approaches to identify genes and variants associated with important phenotypes and to characterize how genome structure evolves.
| Blader I, Goodrum F, Imperiale MJ, Casadevall A, Arias CA, Baumler A, Burnham C-AD, Cuomo CA, Detweiler CS, Forrest GN, Gilbert JA, Lovett S, Maloy S, McAdam A, Newton I, Reguera G, O'Toole GA, Schloss PD, Shade A, Whiteley M. "A call for the United States to continue investing in science." mSphere, vol. 10, no. 3, 2025, pp. e0012825. |
| Mackey AI, Fillinger RJ, Hendricks PS, Thomson GJ, Cuomo CA, Bennett RJ, Anderson MZ. "Aneuploidy confers a unique transcriptional and phenotypic profile to Candida albicans." Nature Communications, vol. 16, no. 1, 2025, pp. 3287. |
| Case NT, Gurr SJ, Fisher MC, Blehert DS, Boone C, Casadevall A, Chowdhary A, Cuomo CA, Currie CR, Denning DW, Ene IV, Fritz-Laylin LK, Gerstein AC, Gow NAR, Gusa A, Iliev ID, James TY, Jin H, Kahmann R, Klein BS, Kronstad JW, Ost KS, Peay KG, Shapiro RS, Sheppard DC, Shlezinger N, Stajich JE, Stukenbrock EH, Taylor JW, Wright GD, Cowen LE, Heitman J, Segre JA. "Fungal impacts on Earth's ecosystems." Nature, vol. 638, no. 8049, 2025, pp. 49-57. |
| Rybak JM, Xie J, Martin-Vicente A, Guruceaga X, Thorn HI, Nywening AV, Ge W, Souza ACO, Shetty AC, McCracken C, Bruno VM, Parker JE, Kelly SL, Snell HM, Cuomo CA, Rogers PD, Fortwendel JR. "A secondary mechanism of action for triazole antifungals in Aspergillus fumigatus mediated by hmg1." Nature Communications, vol. 15, no. 1, 2024, pp. 3642. |
| Carolus H, Sofras D, Boccarella G, Sephton-Clark P, Biriukov V, Cauldron NC, Lobo Romero C, Vergauwen R, Yazdani S, Pierson S, Jacobs S, Vandecruys P, Wijnants S, Meis JF, Gabaldón T, van den Berg P, Rybak JM, Cuomo CA, Van Dijck P. "Acquired amphotericin B resistance leads to fitness trade-offs that can be mitigated by compensatory evolution in Candida auris." Nature Microbiology, vol. 9, no. 12, 2024, pp. 3304-3320. |
| Bergin S, Doorley LA, Rybak JM, Wolfe KH, Butler G, Cuomo CA, Rogers PD. "Analysis of clinical Candida parapsilosis isolates reveals copy number variation in key fluconazole resistance genes." Antimicrobial Agents and Chemotherapy, vol. 68, no. 6, 2024, pp. e0161923. |
| Coelho MA, David-Palma M, Shea T, Bowers K, McGinley-Smith S, Mohammad AW, Gnirke A, Yurkov AM, Nowrousian M, Sun S, Cuomo CA, Heitman J. "Comparative genomics of the closely related fungal genera Cryptococcus and Kwoniella reveals karyotype dynamics and suggests evolutionary mechanisms of pathogenesis." PLoS biology, vol. 22, no. 6, 2024, pp. e3002682. |
| Liao Y, Gao IH, Kusakabe T, Lin WY, Grier A, Pan X, Morzhanaeva O, Shea TP, Yano H, Karo-Atar D, Olsen KA, Oh JH, Vandegrift KJ, King IL, Cuomo CA, Artis D, Rehermann B, Lipman N, Iliev ID. "Fungal symbiont transmitted by free-living mice promotes type 2 immunity." vol. 636, no. 8043, 2024, pp. 697-704. |
| Kelly M, Cuomo CA, Beukema W, Carranza S, Erens J, Foubert M, Li Z, Lötters S, Schulz V, Steinfartz S, Van Praet S, Veith M, Pasmans F, Martel A. "High phenotypic diversity correlated with genomic variation across the European Batrachochytrium salamandrivorans epizootic." PLoS pathogens, vol. 20, no. 10, 2024, pp. e1012579. |
| Cauldron NC, Shea T, Cuomo CA. "Improved genome assembly of Candida auris strain B8441 and annotation of B11205." Microbiology resource announcements, vol. 13, no. 10, 2024, pp. e0051224. |
| Stott KE, Mohabir JT, Bowers K, Tenor JL, Toffaletti DL, Unsworth J, Jimenez-Valverde A, Ahmadu A, Moyo M, Gondwe E, Chimang'anga W, Chasweka M, Lawrence DS, Jarvis JN, Harrison T, Hope W, Lalloo DG, Mwandumba HC, Perfect JR, Cuomo CA, AMBITION Study Group. "Integration of genomic and pharmacokinetic data to predict clinical outcomes in HIV-associated cryptococcal meningitis." mBio, vol. 15, no. 10, 2024, pp. e0159224. |
| Després PC, Shapiro RS, Cuomo CA. "New approaches to tackle a rising problem: Large-scale methods to study antifungal resistance." PLoS pathogens, vol. 20, no. 9, 2024, pp. e1012478. |
| Li X, Muñoz JF, Gade L, Argimon S, Bougnoux ME, Bowers JR, Chow NA, Cuesta I, Farrer RA, Maufrais C, Monroy-Nieto J, Pradhan D, Uehling J, Vu D, Yeats CA, Aanensen DM, d'Enfert C, Engelthaler DM, Eyre DW, Fisher MC, Hagen F, Meyer W, Singh G, Alastruey-Izquierdo A, Litvintseva AP, Cuomo CA. "Comparing genomic variant identification protocols for Candida auris." Microbial genomics, vol. 9, no. 4, 2023. |
| Sephton-Clark P, Temfack E, Tenor JL, Toffaletti DL, Loyse A, Molloy SF, Perfect JR, Bicanic T, Harrison TS, Lortholary O, Kouanfack C, Cuomo CA. "Genetic diversity and microevolution in clinical Cryptococcus isolates from Cameroon." Med Mycol, vol. 61, no. 12, 2023. |
| Shea T, Mohabir JT, Kurbessoian T, Berdy B, Fontaine J, Gnirke A, Livny J, Stajich JE, Cuomo CA. "Genome Sequence of Lichtheimia ornata, an Emerging Opportunistic Mucorales Pathogen." Microbiology resource announcements, vol. 12, no. 7, 2023, pp. e0033823. |
| Martinez-Zurita A, Cuomo CA. "Genome-Wide Identification of Variants Associated with Antifungal Drug Resistance." Methods in Molecular Biology, vol. 2658, 2023, pp. 81-103. |
| Sephton-Clark P, Nguyen T, Hoa NT, Ashton P, van Doorn HR, Ly VT, Le T, Cuomo CA. "Impact of pathogen genetics on clinical phenotypes in a population of Talaromyces marneffei from Vietnam." Genetics, vol. 224, no. 4, 2023. |
| Chowdhary A, Gupta N, Wurster S, Kumar R, Mohabir JT, Tatavarthy S, Mittal V, Rani P, Barman P, Sachdeva N, Singh A, Sharma B, Jiang Y, Cuomo CA, Kontoyiannis DP. "Multimodal analysis of the COVID-19-associated mucormycosis outbreak in Delhi, India indicates the convergence of clinical and environmental risk factors." Mycoses, vol. 66, no. 6, 2023, pp. 515-526. |
| Cuomo CA. "Opening Up Editorial Boards." Microbiology spectrum, vol. 11, no. 1, 2023, pp. e0493722. |
| Sephton-Clark P, McConnell SA, Grossman N, Baker RP, Dragotakes Q, Fan Y, Fu MS, Gerbig G, Greengo S, Hardwick JM, Kulkarni M, Levitz SM, Nosanchuk JD, Shoham S, Smith DFQ, Stempinski P, Timp W, Wear MP, Cuomo CA, Casadevall A. "Similar evolutionary trajectories in an environmental Cryptococcus neoformans isolate after human and murine infection." Proceedings of the National Academy of Sciences, vol. 120, no. 2, 2023, pp. e2217111120. |
| Matzko ME, Sephton-Clark PCS, Young EL, Jhaveri TA, Martinsen MA, Mojica E, Boykin R, Pierce VM, Cuomo CA, Bhattacharyya RP. "A novel rRNA hybridization-based approach to rapid, accurate Candida identification directly from blood culture." Med Mycol, vol. 60, no. 9, 2022. |
| Voorhies M, Cohen S, Shea TP, Petrus S, Muñoz JF, Poplawski S, Goldman WE, Michael TP, Cuomo CA, Sil A, Beyhan S. "Chromosome-Level Genome Assembly of a Human Fungal Pathogen Reveals Synteny among Geographically Distinct Species." mBio, vol. 13, no. 1, 2022, pp. e0257421. |
| Alanio A, Snell HM, Cordier C, Desnos-Olivier M, Dellière S, Aissaoui N, Sturny-Leclère A, Da Silva E, Eblé C, Rouveau M, Thégat M, Zebiche W, Lafaurie M, Denis B, Touratier S, Benyamina M, Dudoignon E, Hamane S, Cuomo CA, Dépret F. "First Patient-to-Patient Intrahospital Transmission of Clade I Candida auris in France Revealed after a Two-Month Incubation Period." Microbiology spectrum, vol. 10, no. 5, 2022, pp. e0183322. |
| Shea TP, Cuomo CA. "Generating Complete Genome Assemblies of Candida auris." Methods in Molecular Biology, vol. 2517, 2022, pp. 205-214. |
| Sephton-Clark P, Tenor JL, Toffaletti DL, Meyers N, Giamberardino C, Molloy SF, Palmucci JR, Chan A, Chikaonda T, Heyderman R, Hosseinipour M, Kalata N, Kanyama C, Kukacha C, Lupiya D, Mwandumba HC, Harrison T, Bicanic T, Perfect JR, Cuomo CA. "Genomic Variation across a Clinical Cryptococcus Population Linked to Disease Outcome." mBio, vol. 13, no. 6, 2022, pp. e0262622. |
| Salamzade R, Manson AL, Walker BJ, Brennan-Krohn T, Worby CJ, Ma P, He LL, Shea TP, Qu J, Chapman SB, Howe W, Young SK, Wurster JI, Delaney ML, Kanjilal S, Onderdonk AB, Bittencourt CE, Gussin GM, Kim D, Peterson EM, Ferraro MJ, Hooper DC, Shenoy ES, Cuomo CA, Cosimi LA, Huang SS, Kirby JE, Pierce VM, Bhattacharyya RP, Earl AM. "Inter-species geographic signatures for tracing horizontal gene transfer and long-term persistence of carbapenem resistance." Genome medicine, vol. 14, no. 1, 2022, pp. 37. |
| Rybak JM, Barker KS, Muñoz JF, Parker JE, Ahmad S, Mokaddas E, Abdullah A, Elhagracy RS, Kelly SL, Cuomo CA, Rogers PD. "In vivo emergence of high-level resistance during treatment reveals the first identified mechanism of amphotericin B resistance in Candida auris." Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, vol. 28, no. 6, 2022, pp. 838-843. |
| Bagal UR, Phan J, Welsh RM, Misas E, Wagner D, Gade L, Litvintseva AP, Cuomo CA, Chow NA. "MycoSNP: A Portable Workflow for Performing Whole-Genome Sequencing Analysis of Candida auris." Methods in Molecular Biology, vol. 2517, 2022, pp. 215-228. |
| Helmstetter N, Chybowska AD, Delaney C, Da Silva Dantas A, Gifford H, Wacker T, Munro C, Warris A, Jones B, Cuomo CA, Wilson D, Ramage G, Farrer RA. "Population genetics and microevolution of clinical Candida glabrata reveals recombinant sequence types and hyper-variation within mitochondrial genomes, virulence genes, and drug targets." Genetics, vol. 221, no. 1, 2022. |
| Case NT, Berman J, Blehert DS, Cramer RA, Cuomo C, Currie CR, Ene IV, Fisher MC, Fritz-Laylin LK, Gerstein AC, Glass NL, Gow NAR, Gurr SJ, Hittinger CT, Hohl TM, Iliev ID, James TY, Jin H, Klein BS, Kronstad JW, Lorch JM, McGovern V, Mitchell AP, Segre JA, Shapiro RS, Sheppard DC, Sil A, Stajich JE, Stukenbrock EE, Taylor JW, Thompson D, Wright GD, Heitman J, Cowen LE. "The future of fungi: threats and opportunities." G3 (Bethesda, Md.), vol. 12, no. 11, 2022. |
| Gow NAR, Johnson C, Berman J, Coste AT, Cuomo CA, Perlin DS, Bicanic T, Harrison TS, Wiederhold N, Bromley M, Chiller T, Edgar K. "The importance of antimicrobial resistance in medical mycology." Nature Communications, vol. 13, no. 1, 2022, pp. 5352. |
| Rybak JM, Cuomo CA, Rogers PD. "The molecular and genetic basis of antifungal resistance in the emerging fungal pathogen Candida auris." Current opinion in microbiology, vol. 70, 2022, pp. 102208. |
| Gröhs Ferrareze PA, Maufrais C, Silva Araujo Streit R, Priest SJ, Cuomo CA, Heitman J, Staats CC, Janbon G. "Application of an optimized annotation pipeline to the Cryptococcus deuterogattii genome reveals dynamic primary metabolic gene clusters and genomic impact of RNAi loss." G3 (Bethesda, Md.), vol. 11, no. 2, 2021. |
| Chung M, Bruno VM, Rasko DA, Cuomo CA, Muñoz JF, Livny J, Shetty AC, Mahurkar A, Dunning Hotopp JC. "Best practices on the differential expression analysis of multi-species RNA-seq." Genome Biology, vol. 22, no. 1, 2021, pp. 121. |
| Schwartz IS, Muñoz JF, Kenyon CR, Govender NP, McTaggart L, Maphanga TG, Richardson S, Becker P, Cuomo CA, McEwen JG, Sigler L. "Blastomycosis in Africa and the Middle East: A Comprehensive Review of Reported Cases and Reanalysis of Historical Isolates Based on Molecular Data." Clinical Infectious Diseases, vol. 73, no. 7, 2021, pp. e1560-e1569. |
| Muñoz JF, Welsh RM, Shea T, Batra D, Gade L, Howard D, Rowe LA, Meis JF, Litvintseva AP, Cuomo CA. "Clade-specific chromosomal rearrangements and loss of subtelomeric adhesins in Candida auris." Genetics, vol. 218, no. 1, 2021. |
| Beekman CN, Cuomo CA, Bennett RJ, Ene IV. "Comparative genomics of white and opaque cell states supports an epigenetic mechanism of phenotypic switching in Candida albicans." G3 (Bethesda, Md.), vol. 11, no. 2, 2021. |
| Kelly M, Pasmans F, Muñoz JF, Shea TP, Carranza S, Cuomo CA, Martel A. "Diversity, multifaceted evolution, and facultative saprotrophism in the European Batrachochytrium salamandrivorans epidemic." Nature Communications, vol. 12, no. 1, 2021, pp. 6688. |
| Yu CH, Sephton-Clark P, Tenor JL, Toffaletti DL, Giamberardino C, Haverkamp M, Cuomo CA, Perfect JR. "Gene Expression of Diverse Cryptococcus Isolates during Infection of the Human Central Nervous System." mBio, vol. 12, no. 6, 2021, pp. e0231321. |
| Farrer RA, Borman AM, Inkster T, Fisher MC, Johnson EM, Cuomo CA. "Genomic epidemiology of a Cryptococcus neoformans case cluster in Glasgow, Scotland, 2018." Microbial genomics, vol. 7, no. 3, 2021. |
| Cissé OH, Ma L, Dekker JP, Khil PP, Youn JH, Brenchley JM, Blair R, Pahar B, Chabé M, Van Rompay KKA, Keesler R, Sukura A, Hirsch V, Kutty G, Liu Y, Peng L, Chen J, Song J, Weissenbacher-Lang C, Xu J, Upham NS, Stajich JE, Cuomo CA, Cushion MT, Kovacs JA. "Genomic insights into the host specific adaptation of the Pneumocystis genus." Communications biology, vol. 4, no. 1, 2021, pp. 305. |
| Romsdahl J, Schultzhaus Z, Cuomo CA, Dong H, Abeyratne-Perera H, Hervey WJ 4th, Wang Z. "Phenotypic Characterization and Comparative Genomics of the Melanin-Producing Yeast Exophiala lecanii-corni Reveals a Distinct Stress Tolerance Profile and Reduced Ribosomal Genetic Content." Journal of fungi (Basel, Switzerland), vol. 7, no. 12, 2021. |
| Geiser DM, Al-Hatmi AMS, Aoki T, Arie T, Balmas V, Barnes I, Bergstrom GC, Bhattacharyya MK, Blomquist CL, Bowden RL, Brankovics B, Brown DW, Burgess LW, Bushley K, Busman M, Cano-Lira JF, Carrillo JD, Chang HX, Chen CY, Chen W, Chilvers M, Chulze S, Coleman JJ, Cuomo CA, de Beer ZW, de Hoog GS, Del Castillo-Múnera J, Del Ponte EM, Diéguez-Uribeondo J, Di Pietro A, Edel-Hermann V, Elmer WH, Epstein L, Eskalen A, Esposto MC, Everts KL, Fernández-Pavía SP, da Silva GF, Foroud NA, Fourie G, Frandsen RJN, Freeman S, Freitag M, Frenkel O, Fuller KK, Gagkaeva T, Gardiner DM, Glenn AE, Gold SE, Gordon TR, Gregory NF, Gryzenhout M, Guarro J, Gugino BK, Gutierrez S, Hammond-Kosack KE, Harris LJ, Homa M, Hong CF, Hornok L, Huang JW, Ilkit M, Jacobs A, Jacobs K, Jiang C, Jiménez-Gasco MDM, Kang S, Kasson MT, Kazan K, Kennell JC, Kim HS, Kistler HC, Kuldau GA, Kulik T, Kurzai O, Laraba I, Laurence MH, Lee T, Lee YW, Lee YH, Leslie JF, Liew ECY, Lofton LW, Logrieco AF, López-Berges MS, Luque AG, Lysøe E, Ma LJ, Marra RE, Martin FN, May SR, McCormick SP, McGee C, Meis JF, Migheli Q, Mohamed Nor NMI, Monod M, Moretti A, Mostert D, Mulè G, Munaut F, Munkvold GP, Nicholson P, Nucci M, O'Donnell K, Pasquali M, Pfenning LH, Prigitano A, Proctor RH, Ranque S, Rehner SA, Rep M, Rodríguez-Alvarado G, Rose LJ, Roth MG, Ruiz-Roldán C, Saleh AA, Salleh B, Sang H, Scandiani MM, Scauflaire J, Schmale DG 3rd, Short DPG, Šišić A, Smith JA, Smyth CW, Son H, Spahr E, Stajich JE, Steenkamp E, Steinberg C, Subramaniam R, Suga H, Summerell BA, Susca A, Swett CL, Toomajian C, Torres-Cruz TJ, Tortorano AM, Urban M, Vaillancourt LJ, Vallad GE, van der Lee TAJ, Vanderpool D, van Diepeningen AD, Vaughan MM, Venter E, Vermeulen M, Verweij PE, Viljoen A, Waalwijk C, Wallace EC, Walther G, Wang J, Ward TJ, Wickes BL, Wiederhold NP, Wingfield MJ, Wood AKM, Xu JR, Yang XB, Yli-Mattila T, Yun SH, Zakaria L, Zhang H, Zhang N, Zhang SX, Zhang X. "Phylogenomic Analysis of a 55.1-kb 19-Gene Dataset Resolves a Monophyletic Fusarium that Includes the Fusarium solani Species Complex." Phytopathology, vol. 111, no. 7, 2021, pp. 1064-1079. |
| Cuomo CA. "The Relaunch of Microbiology Spectrum." Microbiology spectrum, vol. 9, no. 1, 2021, pp. e0039621. |
The impact of fungal pathogens on global health is significant and increasing, yet current interventions are insufficient to meet this challenge. Genomic approaches provide the best opportunity to examine interactions between different fungal pathogens, their hosts, and associated microbial communities at large scale. My group will take multiple approaches to examine how genome variation of fungal pathogen populations contributes to virulence and host adaptation, understanding antifungal drug resistance, and applying genomic approaches to challenges such as the development of new diagnostics.
Mapping the basis of virulence and drug resistance in human fungal pathogens
Cryptococcus neoformans is a fungal pathogen of enormous clinical importance causing life-threatening meningoencephalitis. While Cryptococcus is an opportunistic pathogen, it is clear that some isolates are better adapted to infect humans, possibly due to interactions with other eukaryotes in the environment. Our genome-wide association studies of clinical compared to environmental isolates found that the top associated loci included many genes linked to virulence. Building on this work, my group is characterizing the genetic basis of virulence in clinical collections of C. neoformans using genomic and transcriptomic approaches. We aim to identify genes and pathways that are markers of aggressive isolates, which can be used to guide treatment and select new targets for intervention.
Genomic analysis of emerging drug resistance
Antifungal drug resistance in fungi is a rising threat to public health, with wider use of drugs in clinics and cross resistance to those used in agriculture and the appearance of multidrug-resistance species Candida auris raising serious concerns over available treatments. Our initial genomic analyses of C. auris demonstrated that this outbreak consisted of four geographically specific clades that appear to have emerged nearly simultaneously, and that each clade displayed different sets of mutations contributing to azole resistance. By combining genome-wide association, experimental evolution, and transcriptomic approaches, we seek to explain mechanisms of resistance to the other two major classes of antifungal drugs and to characterize the impact of these mutations on the fungal cell, to better understand how C. auris can tolerate becoming multidrug resistant. This project has supported open, collaborative platforms for genomic analysis, including cloud based pipelines, scripts, and workspaces to enable easy re-use of data and pipelines by the fungal research community.
Accelerating fungal diagnostics
Diagnosis of fungal infections in clinical microbiology laboratories is currently a time intensive process that can delay therapeutic decisions. We are adapting an RNA based single molecule detection method originally developed with bacterial species for both the identification of fungal species and typing of antifungal drug resistance. We have demonstrated that this phylogeny-informed rRNA-based strain identification (Phirst-ID) could detect Candida species directly from lysates of blood culture bottles with high specificity and sensitivity. This method was also able to correctly identify clinical cases of mixed Candida species infections. We are extending the approach to target all clinically relevant fungal species. In parallel, for species that display notable drug resistance, we are performing RNA-Seq of drug resistant and sensitive strains to identify markers that can be used to classify drug resistant strains. This is a flexible platform where fungal probes could be combined in a panel with bacterial probes, to allow for a pan-microbial diagnostic in a clinical microbiology setting.
1) NIH 1RO1 AI69066-01
3/6/2023-2/29/2028
Mapping the genomic and molecular mechanisms of antifungal resistance in the emerging fungal pathogen Candida auris
MPI with P. David Rogers (St Jude's Childrens Research Institute)
2) NIH 2U19 AI110818-11
4/1/2024-3/31/2029
Fungal genomics: population and systematic studies to map determinants of virulence, unique biology, and drug resistance
PI of Fungal project and Assistant Director of Broad Genomic Center for Infectious Disease (PIs Bruce Birren and Daniel Neafsey)
3) NIH 1R01 AI153405-01
7/1/2020-6/30/2025
Rapid fungal identification and antifungal susceptibility testing through quantitative, multiplexed RNA detection.
Collaboration with Roby Bhattacharyya (PI, Broad Institute)
| Year | Degree | Institution |
|---|---|---|
| 1996 | PhD | Harvard University |
| 1991 | AB | Bryn Mawr College |
| Visiting Scientist. Broad Institute, 2023- |
| BIOL 1525 - Pathogenomics: Analysis, interpretation and applications of microbial genomes |
