M Lanzer

University of São Paulo, São Paulo, Estado de Sao Paulo, Brazil

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Publications (31)236.35 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The malarial parasite Plasmodium vivax causes disease in humans, including chronic infections and recurrent relapses, but the course of infection is rarely fatal, unlike that caused by Plasmodium falciparum. To investigate differences in pathogenicity between P. vivax and P. falciparum, we have compared the subtelomeric domains in the DNA of these parasites. In P. falciparum, subtelomeric domains are conserved and contain ordered arrays of members of multigene families, such as var, rif and stevor, encoding virulence determinants of cytoadhesion and antigenic variation. Here we identify, through the analysis of a continuous 155,711-base-pair sequence of a P. vivax chromosome end, a multigene family called vir, which is specific to P. vivax. The vir genes are present at about 600-1,000 copies per haploid genome and encode proteins that are immunovariant in natural infections, indicating that they may have a functional role in establishing chronic infection through antigenic variation.
    Nature 05/2001; 410(6830):839-42. · 38.60 Impact Factor
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    ABSTRACT: Rapid progress has been made in the study of intracellular ion activities of eukaryotic cells through the recent combination of high-resolution microscopy with fluorimetric ion-specific probes. This technique allows a specific ion concentration within a single living cell to be monitored on-line with high temporal and spatial resolution. In this report, Stefan Wünsch, Paul Horrocks, Michael Gekle and Michael Lanzer evaluate the application of single-cell fluorimetry to the study of transport processes in Plasmodium falciparum.
    Parasitology Today 06/1999; 15(5):198-200. · 5.51 Impact Factor
  • P Horrocks, M Lanzer
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    ABSTRACT: Here we investigated whether the Plasmodium falciparum GBP130 promoter maintains its developmental activity during the intraerythrocytic cycle when located on an episomal plasmid introduced using transient transfection. Comparing its activity with that of the endogenous chromosomally located GBP130 promoter indicates that the episomally located GBP130 promoter looses its developmental restriction, being rendered constitutively active. Loss of developmental restriction coincides with the absence of phased nucleosomal arrays over the episome. These data suggest that epigenetic factors may play a role in developmentally regulated gene expression in P. falciparum.
    Parasitology International 04/1999; 48(1):55-61. · 2.30 Impact Factor
  • Paul Horrocks, Michael Lanzer
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    ABSTRACT: Here we describe the functional characterization of a Plasmodium falciparum promoter region, identifying a discrete five base pair sequence element that is responsible for efficient promoter activity. This sequence element binds nuclear factors in a sequence-specific manner. It shares no homology with any known eukaryotic transcription factor binding site, supporting the notion that the protozoan parasite P. falciparum has evolved a transcriptional machinery distinct from that of its human and mosquito hosts. This report represents the first description of a minimal and necessary cis-acting sequence element for efficient promoter activity in P. falciparum.
    Molecular and Biochemical Parasitology 04/1999; 99(1):77-87. · 2.73 Impact Factor
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    ABSTRACT: Rapid progress has been made in the study of intracellular ion activities of eukaryotic cells through the recent combination of high-resolution microscopy with fluorimetric ion-specific probes. This technique allows a specific ion concentration within a single living cell to be monitored on-line with high temporal and spatial resolution. In this report, Stefan Wünsch, Paul Horrocks, Michael Gekle and Michael Lanzer evaluate the application of single-cell fluorimetry to the study of transport processes in Plasmodium falciparum.
    Parasitology Today - PARASITOL TODAY. 01/1999; 15(5):198-200.
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    ABSTRACT: Several multicopy gene families have been described in Plasmodium falciparum, including the var genes that code for the variant surface antigen PfEMP1, the stevor family of subtelomeric open reading frames and the rif interspersed repetitive elements. This report documents the chromosomal location of stevor genes, their transcription and characteristics of the deduced protein. On 14 chromosomes, 34 stevor copies were identified from the Dd2 parasite line. Most are in subtelomeric regions within 50 kb of the telomere. stevor genes are located close to var genes and rij. All stevor genes sequenced had two exons: a short exon 1 encoding a start codon and a transmembrane domain; exon 2 encoding for the remainder of the approximately 30 kDa protein and including two more transmembrane segments. A similar structure was found for copies of rif and its predicted protein. In both STEVOR and RIF proteins, a highly polymorphic region is predicted to be a loop on the outer side of the membrane. We propose that stevor and rif are members of a larger superfamily. The number of copies of stevor and rif, their location close to the var genes, their extreme polymorphism and the predicted structure of the proteins suggest that stevor and rif code for variant surface antigens.
    Molecular and Biochemical Parasitology 12/1998; 97(1-2):161-76. · 2.73 Impact Factor
  • P Horrocks, K Dechering, M Lanzer
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    ABSTRACT: Transfection has facilitated a functional analysis of transcriptional processes in the human malarial parasite Plasmodium falciparum, providing the first fascinating glimpses into the mechanisms regulating parasite development and pathogenicity. Here we review our rapidly evolving knowledge of what constitutes a promoter, what factors regulate promoter activity and how this activity affects the manifestation of the disease.
    Molecular and Biochemical Parasitology 10/1998; 95(2):171-81. · 2.73 Impact Factor
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    ABSTRACT: Members of the Plasmodium falciparum var gene family encode clonally variant adhesins, which play an important role in the pathogenicity of tropical malaria. Here we employ a selective panning protocol to generate isogenic P.falciparum populations with defined adhesive phenotypes for CD36, ICAM-1 and CSA, expressing single and distinct var gene variants. This technique has established the framework for examining var gene expression, its regulation and switching. It was found that var gene switching occurs in situ. Ubiquitous transcription of all var gene variants appears to occur in early ring stages. However, var gene expression is tightly regulated in trophozoites and is exerted through a silencing mechanism. Transcriptional control is mutually exclusive in parasites that express defined adhesive phenotypes. In situ var gene switching is apparently mediated at the level of transcriptional initiation, as demonstrated by nuclear run-on analyses. Our results suggest that an epigenetic mechanism(s) is involved in var gene regulation.
    The EMBO Journal 10/1998; 17(18):5418-26. · 9.82 Impact Factor
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    ABSTRACT: As a contribution to the characterization of the parasitophorous vacuolar membrane from Plasmodium falciparum we have begun the identification of vacuolar membrane proteins. Exported protein-2 (EXP-2) is a vacuolar membrane protein exposed into the vacuolar space. To further characterize EXP-2, it was purified, and the 45 N-terminal amino acids were determined by micro-sequencing. Based on this information, partial cDNA and genomic fragments were amplified by PCR and used as probes for the isolation of complete cDNA and genomic DNA clones. The single copy gene is located on chromosome 14, and is transcribed during the ring stage of parasite development. The open reading frame encodes an N-terminal signal sequence which is cleaved from the mature protein. The amino acid composition of EXP-2 is characterized by charged amino acids, with a high abundance of aspartate residues in the C-terminal portion of the protein. In contrast to EXP-1, an integral protein of the vacuolar membrane, EXP-2 lacks a typical hydrophobic transmembrane domain. We suggest that EXP-2 may associate with the vacuolar membrane via an amphipathic helix located in the N-terminal half of the protein.
    Molecular and Biochemical Parasitology 05/1998; 92(1):47-57. · 2.73 Impact Factor
  • C P Sanchez, P Horrocks, M Lanzer
    Cell 03/1998; 92(5):601-2. · 31.96 Impact Factor
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    ABSTRACT: Here we describe the identification and characterization of a physiological marker that is associated with the chloroquine-resistant (CQR) phenotype in the human malarial parasite Plasmodium falciparum. Single cell in vivo pH measurements revealed that CQR parasites consistently have an elevated cytoplasmic pH compared to that of chloroquine-sensitive (CQS) parasites because of a constitutively activated Na+/H+ exchanger (NHE). Together, biochemical and physiological data suggest that chloroquine activates the plasmodial NHE of CQS parasites, resulting in a transitory phase of rapid sodium/hydrogen ion exchange during which chloroquine is taken up by this protein. The constitutively stimulated NHE of CQR parasites are capable of little or no further activation by chloroquine. We propose that the inability of chloroquine to stimulate its own uptake through the constitutively activated NHE of resistant parasites constitutes a minimal and necessary event in the generation of the chloroquine-resistant phenotype.
    The Journal of Cell Biology 02/1998; 140(2):335-45. · 10.82 Impact Factor
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    ABSTRACT: The malaria parasite Plasmodium falciparum that infects humans encodes several extremely large proteins with molecular masses in the hundreds of thousands to megadalton range. Studies on the structure, function and antigenicity of these ;giant proteins' are hindered by the inability to resolve them effectively in conventional polyacrylamide gels. In this report, Jochen Wiesner, Denise Mattei, Artur Scherf and Michael Lanzer describe a convenient gel system, based on a composite polyacrylamide-agarose matrix, which facilitates analysis of giant proteins.
    Parasitology Today 02/1998; 14(1):38-40. · 5.51 Impact Factor
  • Parasitology Today - PARASITOL TODAY. 01/1998; 14(1):38-40.
  • P HORROCKS, M LANZER
    Parasitology International - PARASITOL INT. 01/1998; 47(2):101-106.
  • Paul Horrocks, Michael Lanzer
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    ABSTRACT: The development of a transfection system for the protozoan parasite Plasmodium falciparum hailed a breakthrough in understanding one of the world's most prevalent human pathogens. One hundred years after the discovery by Sir Ronald Ross that the etiological agent of malaria is transmitted to humans by the bite of infected Anopheline mosquitoes, we now have the tools at hand with which to investigate the biology and pathogenicity of P. falciparum, at the molecular level, in an attempt to develop sustainable means to control this important infectious disease. Here we review the recent progress facilitated by transfection in malariology and discuss the future opportunities this technique offers.
    Parasitology International 01/1998; 47(2):101-106. · 2.30 Impact Factor
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    ABSTRACT: Here we demonstrate that components of the entire complement cascade are fixed on the surface of erythrocytes infected with the human malarial parasite Plasmodium falciparum. Despite the activation of lytic complement factors, no complement-mediated lysis of P. falciparum-infected erythrocytes occurred only in the absence of functional intrinsic CD59. These data suggest that the restriction of the complement attack of P. falciparum-infected erythrocytes is principally mediated by intrinsic host cell factors, in particular CD59.
    European Journal of Immunology 11/1997; 27(10):2708-13. · 4.97 Impact Factor
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    ABSTRACT: Plasmodium falciparum var genes encode a diverse family of proteins, located on the surfaces of infected erythrocytes, which are implicated in the pathology of human malaria through antigenic variation and adhesion of infected erythrocytes to the microvasculature. We have constructed a complete representative telomere-to-telomere yeast artificial chromosome (YAC) contig map of the P. falciparum chromosome 8 for studies on the chromosomal organization, distribution, and expression of var genes. Three var gene loci were identified on chromosome 8, two of which map close to the telomeres at either end of the chromosome. Analysis of the previously described chromosome 2 contig map and random P. falciparum telomeric YAC clones revealed that most, if not all, 14 P. falciparum chromosomes contain var genes in a subtelomeric location. Mapping the chromosomal location of var genes expressed in a long-term culture of the P. falciparum isolate Dd2 revealed that four of the five different expressed var genes identified map within subtelomeric locations. Expression of var genes from a chromosomal domain known for frequent rearrangements has important implications for the mechanism of var gene switching and the generation of novel antigenic and adhesive phenotypes.
    Molecular and Cellular Biology 08/1997; 17(7):3679-86. · 5.04 Impact Factor
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    ABSTRACT: Here we describe the construction of a representative YAC library for the human malarial parasite Plasmodium vivax. As P. vivax cannot be maintained continuously under laboratory conditions, the P. vivax DNA necessary for the library construction was isolated from a single human patient presenting himself with vivax malaria to a local hospital in the Brazilian Amazon. Thus, this YAC library is the first of its kind to be generated from patient-derived material. The YAC library consists of 560 clones with an average insert size of 180 kb. Of 9 published P. vivax genes, 8 were found to be present in the library. In addition, 12 P. vivax telomeric YAC clones were identified.
    Genomics 07/1997; 42(3):467-73. · 3.01 Impact Factor
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    ABSTRACT: Here we describe a novel methodology for the investigation of the intracellular pH of P. falciparum. This method is based on a fluorescent dye with pH-dependent spectral properties, which can be monitored using a digital imaging system. This non-invasive method allows the cytoplasmic pH of single, living P. falciparum parasites to be measured while still within the host erythrocyte. It was found that schizonts from the P. falciparum clone D10 have a cytoplasmic pH of 7.18 to 7.23, differing slightly on the buffering system used. The pH of uninfected erythrocytes is 7.10 +/- 0.05. This method offers an opportunity to study the parasite's physiology and define transport mechanisms essential for parasite growth.
    Behring Institute Mitteilungen 04/1997;
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    ABSTRACT: Large genomic DNA fragments from the Plasmodium falciparum clone Dd2 have been cloned as artificial chromosomes in yeast (YAC). The resulting library has a 10-fold redundancy for single-copy genes and consists of 1440 individual clones, including 240 telomeric clones, with an average insert size of 150 kb. A novel hybridization method was developed for the rapid and cost-effective screening of protozoan YAC libraries. The Dd2 YAC clones will facilitate a positional approach to the parasite's genes and aid in the dissection of genetic loci associated with the virulence and pathogenicity of P. falciparum.
    Parasitology Research 02/1997; 83(1):87-9. · 2.85 Impact Factor

Publication Stats

1k Citations
236.35 Total Impact Points

Institutions

  • 2001
    • University of São Paulo
      • Department of Parasitology (ICB)
      São Paulo, Estado de Sao Paulo, Brazil
  • 1999
    • Universität Heidelberg
      • Department of Parasitology
      Heidelberg, Baden-Wuerttemberg, Germany
  • 1994–1999
    • University of Wuerzburg
      • Research Center for Infectious Diseases
      Würzburg, Bavaria, Germany
  • 1998
    • Institut Pasteur
      Lutetia Parisorum, Île-de-France, France
  • 1992–1994
    • Memorial Sloan-Kettering Cancer Center
      • Division of Molecular Biology
      New York City, NY, United States
    • Cornell University
      • Department of Molecular Biology
      Ithaca, NY, United States