T E Wellems

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. ncbi request reprint Genome projects, genetic analysis, and the changing landscape of malaria research
    T E Wellems
    Malaria Genetics Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4, Room 126, 4 Center Drive, MSC 0425, Bethesda, MD 20892 0425, USA
    Curr Opin Microbiol 2:415-9. 1999
  2. ncbi request reprint Plasmodium chloroquine resistance and the search for a replacement antimalarial drug
    Thomas E Wellems
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA
    Science 298:124-6. 2002
  3. ncbi request reprint Chloroquine-resistant malaria
    T E Wellems
    Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Infect Dis 184:770-6. 2001
  4. ncbi request reprint Conservation of a novel vacuolar transporter in Plasmodium species and its central role in chloroquine resistance of P. falciparum
    J M Carlton
    National Center for Biotechnology Research, National Library of Medicine, National Institutes of Health, Building 45, 45 Center Drive, Bethesda, MD 20892-6510, USA
    Curr Opin Microbiol 4:415-20. 2001
  5. ncbi request reprint Dissecting the loci of low-level quinine resistance in malaria parasites
    Michael T Ferdig
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4, Room 126, NIH Campus, Bethesda, MD 20892 0425, USA
    Mol Microbiol 52:985-97. 2004
  6. pmc Geographic patterns of Plasmodium falciparum drug resistance distinguished by differential responses to amodiaquine and chloroquine
    Juliana Martha Sá
    Laboratory of Malaria and Vector Research and Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 106:18883-9. 2009
  7. pmc Dictyostelium discoideum expresses a malaria chloroquine resistance mechanism upon transfection with mutant, but not wild-type, Plasmodium falciparum transporter PfCRT
    Bronwen Naudé
    Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Bethesda, Maryland 20892 8132, USA
    J Biol Chem 280:25596-603. 2005
  8. ncbi request reprint Two worlds of malaria
    Thomas E Wellems
    National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA
    N Engl J Med 349:1496-8. 2003
  9. ncbi request reprint Alternative mutations at position 76 of the vacuolar transmembrane protein PfCRT are associated with chloroquine resistance and unique stereospecific quinine and quinidine responses in Plasmodium falciparum
    Roland A Cooper
    National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Pharmacol 61:35-42. 2002
  10. ncbi request reprint Genetic linkage and association analyses for trait mapping in Plasmodium falciparum
    Xinzhuan Su
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike Bethesda, Maryland 20892 8132, USA
    Nat Rev Genet 8:497-506. 2007

Collaborators

Detail Information

Publications40

  1. ncbi request reprint Genome projects, genetic analysis, and the changing landscape of malaria research
    T E Wellems
    Malaria Genetics Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4, Room 126, 4 Center Drive, MSC 0425, Bethesda, MD 20892 0425, USA
    Curr Opin Microbiol 2:415-9. 1999
    ..The genetic blueprint of P. falciparum will ultimately need to be understood at multiple levels of an integrated system and will provide a detailed account of the life processes of the parasite and of the devastating disease it causes...
  2. ncbi request reprint Plasmodium chloroquine resistance and the search for a replacement antimalarial drug
    Thomas E Wellems
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA
    Science 298:124-6. 2002
    ..Drug discovery initiatives are finding new leads that have favorable pharmaceutical properties and efficacy against chloroquine-resistant malaria...
  3. ncbi request reprint Chloroquine-resistant malaria
    T E Wellems
    Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Infect Dis 184:770-6. 2001
    ..Investigation of the resistance mechanisms and of the role of immunity in therapeutic outcomes will support new approaches to drugs that can take the place of chloroquine or augment its efficiency...
  4. ncbi request reprint Conservation of a novel vacuolar transporter in Plasmodium species and its central role in chloroquine resistance of P. falciparum
    J M Carlton
    National Center for Biotechnology Research, National Library of Medicine, National Institutes of Health, Building 45, 45 Center Drive, Bethesda, MD 20892-6510, USA
    Curr Opin Microbiol 4:415-20. 2001
    ..vivax gene. This is consistent with lines of evidence that suggest alternative mechanisms of chloroquine resistance among various malaria parasite species...
  5. ncbi request reprint Dissecting the loci of low-level quinine resistance in malaria parasites
    Michael T Ferdig
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4, Room 126, NIH Campus, Bethesda, MD 20892 0425, USA
    Mol Microbiol 52:985-97. 2004
    ..Dissection of the genes and modifiers involved in QN response will require experimental strategies that can evaluate multiple genes from different chromosomes in combination...
  6. pmc Geographic patterns of Plasmodium falciparum drug resistance distinguished by differential responses to amodiaquine and chloroquine
    Juliana Martha Sá
    Laboratory of Malaria and Vector Research and Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 106:18883-9. 2009
    ..Increasing use of AQ in Africa poses the threat of a selective sweep of highly AQ-resistant, CQ-resistant parasites with pfcrt and pfmdr1 mutations that are as advantaged and persistent as in South America...
  7. pmc Dictyostelium discoideum expresses a malaria chloroquine resistance mechanism upon transfection with mutant, but not wild-type, Plasmodium falciparum transporter PfCRT
    Bronwen Naudé
    Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Bethesda, Maryland 20892 8132, USA
    J Biol Chem 280:25596-603. 2005
    ..Transformed D. discoideum will be useful for further studies of the chloroquine resistance mechanism and may assist in the development and evaluation of new antimalarial drugs...
  8. ncbi request reprint Two worlds of malaria
    Thomas E Wellems
    National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA
    N Engl J Med 349:1496-8. 2003
  9. ncbi request reprint Alternative mutations at position 76 of the vacuolar transmembrane protein PfCRT are associated with chloroquine resistance and unique stereospecific quinine and quinidine responses in Plasmodium falciparum
    Roland A Cooper
    National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Pharmacol 61:35-42. 2002
    ..The various mutations that have now been documented at PfCRT position 76 (K76T, K76N, K76I) suggest that the loss of lysine is central to the CQR mechanism...
  10. ncbi request reprint Genetic linkage and association analyses for trait mapping in Plasmodium falciparum
    Xinzhuan Su
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike Bethesda, Maryland 20892 8132, USA
    Nat Rev Genet 8:497-506. 2007
    ..Rapidly increasing genetic and genomic information on Plasmodium parasites, mosquitoes and humans will combine as a rich resource for new advances in our understanding of malaria, its transmission and its manifestations of disease...
  11. pmc The impact of malaria parasitism: from corpuscles to communities
    Thomas E Wellems
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892 8132, USA
    J Clin Invest 119:2496-505. 2009
    ..Advances in genetics and genomics are providing fresh insights into the nature of these evolutionary adaptations, processes of parasite transmission and infection, and the difficult challenges of malaria control...
  12. pmc Genetic mapping of targets mediating differential chemical phenotypes in Plasmodium falciparum
    Jing Yuan
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA
    Nat Chem Biol 5:765-71. 2009
    ..This study identifies new leads for antimalarial drugs and demonstrates the utility of a high-throughput chemical genomic strategy for studying malaria traits...
  13. ncbi request reprint PfCG2, a Plasmodium falciparum protein peripherally associated with the parasitophorous vacuolar membrane, is expressed in the period of maximum hemoglobin uptake and digestion by trophozoites
    Roland A Cooper
    Laboratory of Malaria and Vector Research, Twinbrook III, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 8132, USA
    Mol Biochem Parasitol 144:167-76. 2005
    ..PfCG2 interacts with erythrocyte cytoplasm and may be associated with processes of hemoglobin uptake and digestion by erythrocytic-stage parasites...
  14. pmc Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs
    Jianbing Mu
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases NIAID, National Institutes of Health NIH, Bethesda, Maryland, USA
    Nat Genet 42:268-71. 2010
    ..Parasite half-maximum inhibitory concentrations for seven antimalarial drugs were obtained and used in GWAS to identify genes associated with drug responses. This study provides valuable tools and insight into the P. falciparum genome...
  15. ncbi request reprint Plasmodium biology: genomic gleanings
    L Aravind
    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
    Cell 115:771-85. 2003
    ..Plasmodium possesses many cell surface molecules with "animal-like" adhesion modules. Potential genetic footprints of the ancestral eukaryotic algal precursor of the apicoplast are also detectable in its genome...
  16. ncbi request reprint Malaria. Cooperative silencing elements in var genes
    K W Deitsch
    Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0425, USA
    Nature 412:875-6. 2001
    ..This finding should help to clarify the mechanisms by which parasites coordinate the silencing and activation of var genes that are responsible for antigenic variation in malaria...
  17. ncbi request reprint Evidence for different mechanisms of chloroquine resistance in 2 Plasmodium species that cause human malaria
    T Nomura
    Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 0425, USA
    J Infect Dis 183:1653-61. 2001
    ..vivax gene. This is evidence that the molecular events underlying P. vivax CQR differ from those in P. falciparum...
  18. ncbi request reprint Modulation of malaria virulence by determinants of Plasmodium falciparum erythrocyte membrane protein-1 display
    Rick M Fairhurst
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20852 8132, USA
    Curr Opin Hematol 13:124-30. 2006
    ..These binding events enable parasitized erythrocytes to sequester and avoid clearance by the spleen, and they also contribute to disease by causing microvascular inflammation and obstruction...
  19. pmc Erythrocyte binding protein PfRH5 polymorphisms determine species-specific pathways of Plasmodium falciparum invasion
    Karen Hayton
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892 8132, USA
    Cell Host Microbe 4:40-51. 2008
    ..nancymaae erythrocytes. Our results also suggest that PfRH5 is a parasite ligand for human infection, and that amino acid substitutions can cause its binding domain to recognize different human erythrocyte surface receptors...
  20. ncbi request reprint Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria
    Rick M Fairhurst
    Laboratory of Malaria and Vector Research, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 435:1117-21. 2005
    ..Haemoglobin C might protect against malaria by reducing PfEMP-1-mediated adherence of parasitized erythrocytes, thereby mitigating the effects of their sequestration in the microvasculature...
  21. ncbi request reprint Hemoglobin C associated with protection from severe malaria in the Dogon of Mali, a West African population with a low prevalence of hemoglobin S
    A Agarwal
    National Institute of Allergy and Infectious Diseases and the National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
    Blood 96:2358-63. 2000
    ..The data also suggest that the protective effect associated with HbC may be greater than that of HbS in this population...
  22. pmc Impaired cytoadherence of Plasmodium falciparum-infected erythrocytes containing sickle hemoglobin
    Rushina Cholera
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 105:991-6. 2008
    ..Coinherited hemoglobin polymorphisms and naturally acquired antibodies to PfEMP-1 may influence the degree of malaria protection in AS children by further weakening cytoadherence interactions...
  23. pmc Disruption of a Plasmodium falciparum gene linked to male sexual development causes early arrest in gametocytogenesis
    Tetsuya Furuya
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 8132, USA
    Proc Natl Acad Sci U S A 102:16813-8. 2005
    ..Mosquito infectivity of the knockout parasites was also greatly reduced but not completely lost. The results suggest that pfmdv-1 plays a key role in gametocyte membrane formation and integrity...
  24. ncbi request reprint Hemoglobin C modulates the surface topography of Plasmodium falciparum-infected erythrocytes
    Takayuki Arie
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
    J Struct Biol 150:163-9. 2005
    ..These data support a model in which large knobs and their aggregates are promoted by hemoglobin C, reducing the adherence of parasitized erythrocytes in the microvasculature and ameliorating the severity of a malaria infection...
  25. ncbi request reprint Band 3 modifications in Plasmodium falciparum-infected AA and CC erythrocytes assayed by autocorrelation analysis using quantum dots
    Fuyuki Tokumasu
    Biochemical and Biophysical Parasitology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 8132, USA
    J Cell Sci 118:1091-8. 2005
    ..Increased band 3 clustering may enhance recognition sites for autoantibodies, which could contribute to the protective effect of hemoglobin C against malaria...
  26. ncbi request reprint Case report: life-threatening hypoglycaemia associated with sulfadoxine-pyrimethamine, a commonly used antimalarial drug
    R M Fairhurst
    Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Trans R Soc Trop Med Hyg 97:595-6. 2003
    ..In this report, we present a case of hypoglycaemic coma associated with SP, an adverse reaction that is likely to be underreported and expected to occur with greater frequency as the use of SP increases...
  27. ncbi request reprint Plasmodium falciparum var genes are regulated by two regions with separate promoters, one upstream of the coding region and a second within the intron
    Michael S Calderwood
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 278:34125-32. 2003
    ..These findings suggest that interactions between the regions of these two promoters and the generation of the sterile transcripts play a significant role in regulating var gene expression...
  28. ncbi request reprint Aberrant development of Plasmodium falciparum in hemoglobin CC red cells: implications for the malaria protective effect of the homozygous state
    Rick M Fairhurst
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 101:3309-15. 2003
    ....
  29. pmc A silenced Plasmodium falciparum var promoter can be activated in vivo through spontaneous deletion of a silencing element in the intron
    Laila Gannoun-Zaki
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 8132, USA
    Eukaryot Cell 4:490-2. 2005
    ..The resulting promoter activation does not affect the transcription of chromosomal var genes...
  30. pmc Mechanisms underlying mutually exclusive expression of virulence genes by malaria parasites
    Ron Dzikowski
    Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, Box 62, New York, New York 10021, USA
    EMBO Rep 8:959-65. 2007
    ....
  31. ncbi request reprint Mutations in transmembrane domains 1, 4 and 9 of the Plasmodium falciparum chloroquine resistance transporter alter susceptibility to chloroquine, quinine and quinidine
    Roland A Cooper
    Department of Biological Sciences, Old Dominion University, Norfolk, VA 23529, USA
    Mol Microbiol 63:270-82. 2007
    ..Charge-affecting mutations within these segments may affect the ability of PfCRT to bind different quinoline drugs and determine their net accumulation in the DV...
  32. ncbi request reprint Expression and function of pvcrt-o, a Plasmodium vivax ortholog of pfcrt, in Plasmodium falciparum and Dictyostelium discoideum
    Juliana Martha Sá
    Departamento de Parasitologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Av Lineu Prestes 1374, Sao Paulo 05508 900, SP, Brazil
    Mol Biochem Parasitol 150:219-28. 2006
    ..Our data support an effect of PvCRT-o on chloroquine transport and/or accumulation by P. vivax, independent of the K76T amino acid substitution...
  33. ncbi request reprint Decreased prevalence of the Plasmodium falciparum chloroquine resistance transporter 76T marker associated with cessation of chloroquine use against P. falciparum malaria in Hainan, People's Republic of China
    Xinhua Wang
    Tropical Medicine Institute, Guangzhou University of Traditional Chinese Medicine, Guangzhou, People s Republic of China
    Am J Trop Med Hyg 72:410-4. 2005
    ..Monitoring for continued decreases will provide valuable information for future drug-use policies in China...
  34. ncbi request reprint Clearance of drug-resistant parasites as a model for protective immunity in Plasmodium falciparum malaria
    Abdoulaye A Djimde
    Bandiagara Malaria Project, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali
    Am J Trop Med Hyg 69:558-63. 2003
    ..Age-adjusted comparison of subjects able to clear resistant parasites and those unable to do so provides a new phenotype for identifying host immune and genetic factors responsible for protective immunity against malaria...
  35. ncbi request reprint Plasmodium vivax: allele variants of the mdr1 gene do not associate with chloroquine resistance among isolates from Brazil, Papua, and monkey-adapted strains
    Juliana Martha Sá
    Departamento de Parasitologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Av Lineu Prestes 1374, Sao Paulo SP, 05508 900, Brazil
    Exp Parasitol 109:256-9. 2005
    ..Similarity and dendrogram analyses revealed that sequences could be grouped according to their geographical origin. Within each geographical group however, no correlation was found between chloroquine resistance and specific mutations...
  36. ncbi request reprint Transporter of a malaria catastrophe
    Thomas E Wellems
    Nat Med 10:1169-71. 2004
  37. pmc X-linked G6PD deficiency protects hemizygous males but not heterozygous females against severe malaria
    Aldiouma Guindo
    Malaria Research and Training Center, Faculty of Medicine, Pharmacy, and Odontostomatology, University of Bamako, Mali
    PLoS Med 4:e66. 2007
    ..These proposals are paradoxical, and they are not consistent with currently hypothesized mechanisms of protection...
  38. ncbi request reprint Malaria-protective traits at odds in Africa?
    Thomas E Wellems
    Nat Genet 37:1160-2. 2005
  39. ncbi request reprint Community permission for medical research in developing countries
    Dapa A Diallo
    Department of Hematology, Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Mali
    Clin Infect Dis 41:255-9. 2005
    ..Far from competing with the individual informed consent process, the process of obtaining community permission both initiated and facilitated the process of disclosure for individual informed consent...
  40. ncbi request reprint A comparison of anemia in hemoglobin C and normal hemoglobin A children with Plasmodium falciparum malaria
    Dapa A Diallo
    faculté de médecine de pharmacie et d odontostomatologie, University of Bamako, Bamako, Mali
    Acta Trop 90:295-9. 2004
    ..By this measure, HbC, a malaria-protective polymorphism with few deleterious consequences, does not appear to be associated with more frequent anemia than normal HbA in episodes of uncomplicated P. falciparum malaria...