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Dyann Fergus Wirth, Ph.D.

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Biography
Massachusetts Institute of TechnologyPh.D.1978
University of Wisconsin , MadisonB.A.
1972 - 1973
Fellow
1973 - 1978
Predoctoral Fellowship
1982
Award in Molecular Parasitology
1985 - 1990
Award in Molecular Parasitology
1995
Bailey K. Ashford Award
1995
Bailey K. Ashford Award
1998 - 1999
President
2004
Member
2010
Fellow
2015
Joseph Augustin LePrince Medal
2016
Faculty Mentoring Award
2016
Fellow
2018
Lifetime Achievement Award

Overview
Protozoan parasites remain major causes of disease in developing countries throughout the world, yet little is known about the biology or molecular biology of these organisms. The long term goal of this work is to understand basic molecular mechanisms in protozoan parasites with the goal of discovering and applying parasite specific interventions.

The approach my laboratory has taken is to develop methods for molecular genetic manipulation of protozoan parasites in order to begin functional analysis of genes important for parasite virulence, with an emphasis of mechanisms of drug resistance in parasites. Drug resistance poses a particularly difficult problem in developing countries where newer chemotherapeutic agents are often unavailable or too expensive for routine use. Drug resistance is particularly acute in malaria where resistant parasites have spread throughout the endemic world.

Recent evidence from my laboratory and from several other groups worldwide has suggested that a major mechanism of drug resistance in protozoan parasites may be through the expression of a P-glycoprotein type molecule encoded by a multi-drug resistance gene. Genes related to mammalian multi-drug resistance genes have been identified in several protozoan parasites and overexpression of these genes is associated with drug resistance. The immediate goal of the research is to test the hypothesis that these mdr-like genes are indeed the cause of drug resistance in protozoan parasites. This work has been initiated in the Leishmania parasite where my laboratory has previously developed a transfection system, and thus the role of the Leishmania enriettii mdr-like genes can be directly tested.

In parallel, my laboratory has recently developed an analogous transfection system for the malaria parasite. By analyzing these two protozoan systems in parallel, one where the molecular tools are readily available and the other in which drug resistant parasites represent a major and immediate threat to world health, I hope both to understand the mechanism of drug resistance in protozoan parasites and to use this information to develop new approaches to either preventing or reversing drug resistance in these organisms.

Executive Assistant: Jessica Gard, jgard@hsph.harvard.edu

Research
The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. R01AI143723 (MAZITSCHEK, RALPH) Apr 1, 2020 - Mar 31, 2025
    NIH/NIAID
    Proline homeostasis: a novel mediator of drug tolerance in Plasmodium falciparum
    Role: Co-Principal Investigator
  2. R01AI099105 (WIRTH, DYANN F) Apr 5, 2013 - Mar 31, 2017
    NIH/NIAID
    Novel Genetic Mechanism of Artemisinin Resistance for Malaria
    Role: Co-Principal Investigator
  3. R01AI093716 (WIRTH, DYANN F) Jul 6, 2012 - Jun 30, 2021
    NIH/NIAID
    Targeting the Mitochondrion of P. falciparum
    Role: Principal Investigator
  4. R56AI082589 (WIRTH, DYANN F) Sep 25, 2009 - Aug 31, 2012
    NIH/NIAID
    Molecular Biomarkers for Malaria
    Role: Principal Investigator
  5. R01AI075080 (WIRTH, DYANN F) Jul 21, 2009 - Jun 30, 2012
    NIH/NIAID
    Genome Surveillance for drug resistant malaria
    Role: Principal Investigator

Bibliographic
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
  1. Dewasurendra RL, Baniecki ML, Schaffner S, Siriwardena Y, Moon J, Doshi R, Gunawardena S, Daniels RF, Neafsey D, Volkman S, Chandrasekharan NV, Wirth DF, Karunaweera ND. Use of a Plasmodium vivax genetic barcode for genomic surveillance and parasite tracking in Sri Lanka. Malar J. 2020 Sep 21; 19(1):342. PMID: 32958025.
    Citations:    
  2. Daniels RF, Schaffner SF, Dieye Y, Dieng G, Hainsworth M, Fall FB, Diouf CN, Ndiop M, Cisse M, Gueye AB, Sarr O, Guinot P, Deme AB, Bei AK, Sy M, Thwing J, MacInnis B, Earle D, Guinovart C, Sene D, Hartl DL, Ndiaye D, Steketee RW, Wirth DF, Volkman SK. Genetic evidence for imported malaria and local transmission in Richard Toll, Senegal. Malar J. 2020 Aug 03; 19(1):276. PMID: 32746830.
    Citations:    
  3. Daniels RF, Schaffner SF, Bennett A, Porter TR, Yukich JO, Mulube C, Mambwe B, Mwenda MC, Chishimba S, Bridges DJ, Moonga H, Hamainza B, Chizema Kawesha E, Miller JM, Steketee RW, Wirth DF, Eisele TP, Hartl DL, Volkman SK. Evidence for Reduced Malaria Parasite Population after Application of Population-Level Antimalarial Drug Strategies in Southern Province, Zambia. Am J Trop Med Hyg. 2020 Aug; 103(2_Suppl):66-73. PMID: 32618255.
    Citations:    
  4. McPhillie M, Zhou Y, El Bissati K, Dubey J, Lorenzi H, Capper M, Lukens AK, Hickman M, Muench S, Verma SK, Weber CR, Wheeler K, Gordon J, Sanders J, Moulton H, Wang K, Kim TK, He Y, Santos T, Woods S, Lee P, Donkin D, Kim E, Fraczek L, Lykins J, Esaa F, Alibana-Clouser F, Dovgin S, Weiss L, Brasseur G, Wirth D, Kent M, Hood L, Meunieur B, Roberts CW, Hasnain SS, Antonyuk SV, Fishwick C, McLeod R. Author Correction: New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections. Sci Rep. 2020 Mar 23; 10(1):5512. PMID: 32251362.
    Citations:    
  5. Meibalan E, Barry A, Gibbins MP, Awandu S, Meerstein-Kessel L, Achcar F, Bopp S, Moxon C, Diarra A, Debe S, Ouédraogo N, Barry-Some I, Badoum E, Fagnima T, Lanke K, Gonçalves BP, Bradley J, Wirth D, Drakeley C, Guelbeogo WM, Tiono AB, Marti M, Bousema T. P. falciparum gametocyte density and infectivity in peripheral blood and skin tissue of naturally infected parasite carriers in Burkina Faso. J Infect Dis. 2019 Dec 26. PMID: 31875909.
    Citations:    
  6. Mandt REK, Lafuente-Monasterio MJ, Sakata-Kato T, Luth MR, Segura D, Pablos-Tanarro A, Viera S, Magan N, Ottilie S, Winzeler EA, Lukens AK, Gamo FJ, Wirth DF. In vitro selection predicts malaria parasite resistance to dihydroorotate dehydrogenase inhibitors in a mouse infection model. Sci Transl Med. 2019 12 04; 11(521). PMID: 31801884.
    Citations:    
  7. Chen AJ, Huang KC, Bopp S, Summers R, Dong P, Huang Y, Zong C, Wirth D, Cheng JX. Quantitative imaging of intraerythrocytic hemozoin by transient absorption microscopy. J Biomed Opt. 2019 12; 25(1):1-11. PMID: 31849205.
    Citations:    
  8. Diédhiou CK, Moussa RA, Bei AK, Daniels R, Papa Mze N, Ndiaye D, Faye N, Wirth D, Amambua-Ngwa A, Mboup S, Ahouidi AD. Temporal changes in Plasmodium falciparum reticulocyte binding protein homolog 2b (PfRh2b) in Senegal and The Gambia. Malar J. 2019 Jul 16; 18(1):239. PMID: 31311552.
    Citations:    
  9. Early AM, Daniels RF, Farrell TM, Grimsby J, Volkman SK, Wirth DF, MacInnis BL, Neafsey DE. Detection of low-density Plasmodium falciparum infections using amplicon deep sequencing. Malar J. 2019 Jul 01; 18(1):219. PMID: 31262308.
    Citations:    
  10. Sharma AI, Demas AR, Hartl DL, Wirth DF. Reply to Velavan et al.: Polymorphisms of pfcoronin in natural populations: Implications for functional significance. Proc Natl Acad Sci U S A. 2019 06 25; 116(26):12613-12614. PMID: 31239364.
    Citations:    
  11. Dantzler KW, Ma S, Ngotho P, Stone WJR, Tao D, Rijpma S, De Niz M, Nilsson Bark SK, Jore MM, Raaijmakers TK, Early AM, Ubaida-Mohien C, Lemgruber L, Campo JJ, Teng AA, Le TQ, Walker CL, Hermand P, Deterre P, Davies DH, Felgner P, Morlais I, Wirth DF, Neafsey DE, Dinglasan RR, Laufer M, Huttenhower C, Seydel K, Taylor T, Bousema T, Marti M. Naturally acquired immunity against immature Plasmodium falciparum gametocytes. Sci Transl Med. 2019 06 05; 11(495). PMID: 31167926.
    Citations:    
  12. Fagbami L, Deik AA, Singh K, Santos SA, Herman JD, Bopp SE, Lukens AK, Clish CB, Wirth DF, Mazitschek R. The Adaptive Proline Response in P. falciparum Is Independent of PfeIK1 and eIF2a Signaling. ACS Infect Dis. 2019 04 12; 5(4):515-520. PMID: 30773881.
    Citations:    
  13. Bankole BE, Kayode AT, Nosamiefan IO, Eromon P, Baniecki ML, Daniels RF, Hamilton EJ, Durfee K, MacInnis B, Okafor H, Sowunmi A, Volkman SK, Sabeti P, Wirth D, Happi CT, Folarin OA. Characterization of Plasmodium falciparum structure in Nigeria with malaria SNPs barcode. Malar J. 2018 Dec 17; 17(1):472. PMID: 30558627.
    Citations:    Fields:    Translation:AnimalsCells
  14. Antonova-Koch Y, Meister S, Abraham M, Luth MR, Ottilie S, Lukens AK, Sakata-Kato T, Vanaerschot M, Owen E, Jado JC, Maher SP, Calla J, Plouffe D, Zhong Y, Chen K, Chaumeau V, Conway AJ, McNamara CW, Ibanez M, Gagaring K, Serrano FN, Eribez K, Taggard CM, Cheung AL, Lincoln C, Ambachew B, Rouillier M, Siegel D, Nosten F, Kyle DE, Gamo FJ, Zhou Y, Llinás M, Fidock DA, Wirth DF, Burrows J, Campo B, Winzeler EA. Open-source discovery of chemical leads for next-generation chemoprotective antimalarials. Science. 2018 12 07; 362(6419). PMID: 30523084.
    Citations:    Fields:    
  15. Demas AR, Sharma AI, Wong W, Early AM, Redmond S, Bopp S, Neafsey DE, Volkman SK, Hartl DL, Wirth DF. Mutations in Plasmodium falciparum actin-binding protein coronin confer reduced artemisinin susceptibility. Proc Natl Acad Sci U S A. 2018 12 11; 115(50):12799-12804. PMID: 30420498.
    Citations:    Fields:    Translation:HumansAnimalsCells
  16. Larsen EM, Chang CF, Sakata-Kato T, Arico JW, Lombardo VM, Wirth DF, Taylor RE. Conformation-guided analogue design identifies potential antimalarial compounds through inhibition of mitochondrial respiration. Org Biomol Chem. 2018 08 01; 16(30):5403-5406. PMID: 30009295.
    Citations:    Fields:    
  17. Redmond SN, MacInnis BM, Bopp S, Bei AK, Ndiaye D, Hartl DL, Wirth DF, Volkman SK, Neafsey DE. De Novo Mutations Resolve Disease Transmission Pathways in Clonal Malaria. Mol Biol Evol. 2018 07 01; 35(7):1678-1689. PMID: 29722884.
    Citations:    Fields:    
  18. Schaffner SF, Taylor AR, Wong W, Wirth DF, Neafsey DE. hmmIBD: software to infer pairwise identity by descent between haploid genotypes. Malar J. 2018 May 15; 17(1):196. PMID: 29764422.
    Citations: 2     Fields:    Translation:Animals
  19. Obaldia N, Meibalan E, Sa JM, Ma S, Clark MA, Mejia P, Moraes Barros RR, Otero W, Ferreira MU, Mitchell JR, Milner DA, Huttenhower C, Wirth DF, Duraisingh MT, Wellems TE, Marti M. Bone Marrow Is a Major Parasite Reservoir in Plasmodium vivax Infection. mBio. 2018 05 08; 9(3). PMID: 29739900.
    Citations:    Fields:    Translation:HumansAnimals
  20. Grignard L, Gonçalves BP, Early AM, Daniels RF, Tiono AB, Guelbéogo WM, Ouédraogo A, van Veen EM, Lanke K, Diarra A, Nebie I, Sirima SB, Targett GA, Volkman SK, Neafsey DE, Wirth DF, Bousema T, Drakeley C. Transmission of molecularly undetectable circulating parasite clones leads to high infection complexity in mosquitoes post feeding. Int J Parasitol. 2018 07; 48(8):671-677. PMID: 29738740.
    Citations:    Fields:    
  21. Bopp S, Magistrado P, Wong W, Schaffner SF, Mukherjee A, Lim P, Dhorda M, Amaratunga C, Woodrow CJ, Ashley EA, White NJ, Dondorp AM, Fairhurst RM, Ariey F, Menard D, Wirth DF, Volkman SK. Plasmepsin II-III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum. Nat Commun. 2018 05 02; 9(1):1769. PMID: 29720620.
    Citations: 1     Fields:    Translation:HumansAnimals
  22. Early AM, Lievens M, MacInnis BL, Ockenhouse CF, Volkman SK, Adjei S, Agbenyega T, Ansong D, Gondi S, Greenwood B, Hamel M, Odero C, Otieno K, Otieno W, Owusu-Agyei S, Asante KP, Sorgho H, Tina L, Tinto H, Valea I, Wirth DF, Neafsey DE. Host-mediated selection impacts the diversity of Plasmodium falciparum antigens within infections. Nat Commun. 2018 04 11; 9(1):1381. PMID: 29643376.
    Citations:    Fields:    Translation:HumansAnimals
  23. Mukherjee A, Gagnon D, Wirth DF, Richard D. Inactivation of Plasmepsins 2 and 3 Sensitizes Plasmodium falciparum to the Antimalarial Drug Piperaquine. Antimicrob Agents Chemother. 2018 04; 62(4). PMID: 29439977.
    Citations: 1     Fields:    
  24. Bei AK, Niang M, Deme AB, Daniels RF, Sarr FD, Sokhna C, Talla C, Faye J, Diagne N, Doucoure S, Mboup S, Wirth DF, Tall A, Ndiaye D, Hartl DL, Volkman SK, Toure-Balde A. Dramatic Changes in Malaria Population Genetic Complexity in Dielmo and Ndiop, Senegal, Revealed Using Genomic Surveillance. J Infect Dis. 2018 01 30; 217(4):622-627. PMID: 29325146.
    Citations:    Fields:    
  25. Wirth DF, Casamitjana N, Tanner M, Reich MR. Global action for training in malaria elimination. Malar J. 2018 Jan 25; 17(1):51. PMID: 29370810.
    Citations: 1     Fields:    Translation:HumansAnimalsPHPublic Health
  26. Ross LS, Lafuente-Monasterio MJ, Sakata-Kato T, Mandt REK, Gamo FJ, Wirth DF, Lukens AK. Identification of Collateral Sensitivity to Dihydroorotate Dehydrogenase Inhibitors in Plasmodium falciparum. ACS Infect Dis. 2018 04 13; 4(4):508-515. PMID: 29336544.
    Citations:    Fields:    
  27. Cowell AN, Istvan ES, Lukens AK, Gomez-Lorenzo MG, Vanaerschot M, Sakata-Kato T, Flannery EL, Magistrado P, Owen E, Abraham M, LaMonte G, Painter HJ, Williams RM, Franco V, Linares M, Arriaga I, Bopp S, Corey VC, Gnädig NF, Coburn-Flynn O, Reimer C, Gupta P, Murithi JM, Moura PA, Fuchs O, Sasaki E, Kim SW, Teng CH, Wang LT, Akidil A, Adjalley S, Willis PA, Siegel D, Tanaseichuk O, Zhong Y, Zhou Y, Llinás M, Ottilie S, Gamo FJ, Lee MCS, Goldberg DE, Fidock DA, Wirth DF, Winzeler EA. Mapping the malaria parasite druggable genome by using in vitro evolution and chemogenomics. Science. 2018 01 12; 359(6372):191-199. PMID: 29326268.
    Citations: 7     Fields:    Translation:Animals
  28. Wong W, Wenger EA, Hartl DL, Wirth DF. Modeling the genetic relatedness of Plasmodium falciparum parasites following meiotic recombination and cotransmission. PLoS Comput Biol. 2018 01; 14(1):e1005923. PMID: 29315306.
    Citations:    Fields:    Translation:HumansAnimalsCells
  29. Rabinovich RN, Drakeley C, Djimde AA, Hall BF, Hay SI, Hemingway J, Kaslow DC, Noor A, Okumu F, Steketee R, Tanner M, Wells TNC, Whittaker MA, Winzeler EA, Wirth DF, Whitfield K, Alonso PL. malERA: An updated research agenda for malaria elimination and eradication. PLoS Med. 2017 Nov; 14(11):e1002456. PMID: 29190300.
    Citations: 12     Fields:    Translation:HumansAnimalsPHPublic Health
  30. Nilsson Bark SK, Ahmad R, Dantzler K, Lukens AK, De Niz M, Szucs MJ, Jin X, Cotton J, Hoffmann D, Bric-Furlong E, Oomen R, Parrington M, Milner D, Neafsey DE, Carr SA, Wirth DF, Marti M. Quantitative Proteomic Profiling Reveals Novel Plasmodium falciparum Surface Antigens and Possible Vaccine Candidates. Mol Cell Proteomics. 2018 01; 17(1):43-60. PMID: 29162636.
    Citations:    Fields:    Translation:AnimalsCells
  31. Brancucci NMB, Gerdt JP, Wang C, De Niz M, Philip N, Adapa SR, Zhang M, Hitz E, Niederwieser I, Boltryk SD, Laffitte MC, Clark MA, Grüring C, Ravel D, Blancke Soares A, Demas A, Bopp S, Rubio-Ruiz B, Conejo-Garcia A, Wirth DF, Gendaszewska-Darmach E, Duraisingh MT, Adams JH, Voss TS, Waters AP, Jiang RHY, Clardy J, Marti M. Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum. Cell. 2017 Dec 14; 171(7):1532-1544.e15. PMID: 29129376.
    Citations: 17     Fields:    Translation:HumansAnimals
  32. Gonçalves BP, Kapulu MC, Sawa P, Guelbéogo WM, Tiono AB, Grignard L, Stone W, Hellewell J, Lanke K, Bastiaens GJH, Bradley J, Nébié I, Ngoi JM, Oriango R, Mkabili D, Nyaurah M, Midega J, Wirth DF, Marsh K, Churcher TS, Bejon P, Sirima SB, Drakeley C, Bousema T. Examining the human infectious reservoir for Plasmodium falciparum malaria in areas of differing transmission intensity. Nat Commun. 2017 10 26; 8(1):1133. PMID: 29074880.
    Citations: 9     Fields:    Translation:HumansAnimalsPHPublic Health
  33. Mukherjee A, Bopp S, Magistrado P, Wong W, Daniels R, Demas A, Schaffner S, Amaratunga C, Lim P, Dhorda M, Miotto O, Woodrow C, Ashley EA, Dondorp AM, White NJ, Wirth D, Fairhurst R, Volkman SK. Artemisinin resistance without pfkelch13 mutations in Plasmodium falciparum isolates from Cambodia. Malar J. 2017 05 12; 16(1):195. PMID: 28494763.
    Citations: 10     Fields:    Translation:Animals
  34. Gunawardena S, Daniels RF, Yahathugoda TC, Weerasooriya MV, Durfee K, Volkman SK, Wirth DF, Karunaweera ND. Case report of Plasmodium ovale curtisi malaria in Sri Lanka: relevance for the maintenance of elimination status. BMC Infect Dis. 2017 04 24; 17(1):307. PMID: 28438137.
    Citations:    Fields:    Translation:HumansAnimals
  35. Ndiaye YD, Diédhiou CK, Bei AK, Dieye B, Mbaye A, Mze NP, Daniels RF, Ndiaye IM, Déme AB, Gaye A, Sy M, Ndiaye T, Badiane AS, Ndiaye M, Premji Z, Wirth DF, Mboup S, Krogstad D, Volkman SK, Ahouidi AD, Ndiaye D. High resolution melting: a useful field-deployable method to measure dhfr and dhps drug resistance in both highly and lowly endemic Plasmodium populations. Malar J. 2017 Apr 19; 16(1):153. PMID: 28420422.
    Citations:    Fields:    Translation:HumansAnimals
  36. Srinivasulu V, Reddy A, Mazitschek R, Lukens AK, Wirth DF, Li L, Naumov P, O'Connor MJ, Al-Tel TH. Intramolecular Diaza-Diels-Alder Protocol: A New Diastereoselective and Modular One-Step Synthesis of Constrained Polycyclic Frameworks. Chemistry. 2017 Mar 23; 23(17):4137-4148. PMID: 27997727.
    Citations:    Fields:    
  37. Wong W, Griggs AD, Daniels RF, Schaffner SF, Ndiaye D, Bei AK, Deme AB, MacInnis B, Volkman SK, Hartl DL, Neafsey DE, Wirth DF. Genetic relatedness analysis reveals the cotransmission of genetically related Plasmodium falciparum parasites in Thiès, Senegal. Genome Med. 2017 01 24; 9(1):5. PMID: 28118860.
    Citations: 5     Fields:    Translation:HumansAnimals
  38. Silterra J, Gillette MA, Lanaspa M, Pellé KG, Valim C, Ahmad R, Acácio S, Almendinger KD, Tan Y, Madrid L, Alonso PL, Carr SA, Wiegand RC, Bassat Q, Mesirov JP, Milner DA, Wirth DF. Transcriptional Categorization of the Etiology of Pneumonia Syndrome in Pediatric Patients in Malaria-Endemic Areas. J Infect Dis. 2017 01 15; 215(2):312-320. PMID: 27837008.
    Citations:    Fields:    Translation:Humans
  39. Daniels RF, Deme AB, Gomis JF, Dieye B, Durfee K, Thwing JI, Fall FB, Ba M, Ndiop M, Badiane AS, Ndiaye YD, Wirth DF, Volkman SK, Ndiaye D. Evidence of non-Plasmodium falciparum malaria infection in Kédougou, Sénégal. Malar J. 2017 01 03; 16(1):9. PMID: 28049489.
    Citations: 7     Fields:    Translation:HumansAnimals
  40. Sakata-Kato T, Wirth DF. A Novel Methodology for Bioenergetic Analysis of Plasmodium falciparum Reveals a Glucose-Regulated Metabolic Shift and Enables Mode of Action Analyses of Mitochondrial Inhibitors. ACS Infect Dis. 2016 12 09; 2(12):903-916. PMID: 27718558.