The Mats Wahlgren Group

We hypothesize that by decoding the molecular details of the mechanisms that regulate genetic and non-genetic adaptation of P. falciparum to its host we will increase the understanding role of transcription, translation and switching of genes. This will enable the development of novel drugs that circumvent the parasite’s evasion of detection and elimination.

Group picture of the Mats Wahlgren group

Biology of Plasmodium falciparum

500,000 individuals are infected with P. falciparum malaria each day. Despite a 50% decrease of incidence and prevalence over the years, new approaches to eradicate the disease are still urgently needed. The emergence of drug resistant parasites and their ability to evade the host immune system, which prohibits the development of vaccines inducing sterile immunity, are constant re-occurring obstacles to current efforts in malaria endemic countries. Thus, the lack of success in eradicating malaria is partly due to the parasite’s remarkable ability to adapt to metabolic, immunological and pharmaceutical changes within the human host. Although we know that a high level of genome plasticity and a complex regulatory machinery of gene expression underlie this ability to adapt, the exact mechanisms used by the parasite to circumvent selective pressures are not understood. We hypothesize that by decoding the molecular details of the mechanisms that regulate genetic and non-genetic adaptation of P. falciparum to its host we will increase the understanding role of transcription, translation and switching of genes. This will enable the development of novel drugs that circumvent the parasite’s evasion of detection and elimination.

An archetype anti-rosetting vaccine against severe disease is being developed as is a receptor-based drug, the latter together with a recently funded KI AB company, Dilafor AB. Dilaforette

Our work is carried out in close co-operation with professors Fred Kironde and Florence Mirembe at Makerere University and Tomas Egwang, Medical Biotech Labs, all in Kampala, Uganda. Scientists from China, Denmark, France, Germany, Japan, Papua New Guinea, Spain, Sweden and USA are also part of our network of collaborators.

Projects

Burkitt's lymphoma: PfEMP1 and Epstein-Barr virus

Burkitt's lymphoma, an aggressive B cell malignancy, is the most common cancer in children in the tropics accounting for 30-70% of childhood cancers in Africa.

In the present project we analyze the mechanisms by which chronic malaria infection affects the regulation of the B cell compartment and the relationship between EBV and B-lymphocytes. We have found that that malaria may join forces with EBV to heighten the risk for Burkitt's lymphoma. P. falciparum is highly mitogenic for B cells. The P. falciparum erythrocyte membrane protein 1 (PfEMP1) contains a cysteine-rich inter-domain region 1± (CIDR1±) that acts as a potent activator and stimulator of B lymphocyte proliferation (Chene et al PLoS Path, 2007). It is particularly active against memory B cells (Donati et al J.Immunol, 2005), which, coincidentally, are where EBV persists in vivo.

We hypothesize that in individuals chronically stimulated by the malaria parasites the B-cell compartment is protected from early death, apoptosis. In addition, malaria parasite stimulation disturbs the control of EBV latency leading to an increase in virus production. The combination of the two effects increases the pool of B cells with the potential to oncogenic changes that could lead to the development of BL.

Genome deletions and duplications in P.falciparum

In this project we study the presence of gene copy number polymorphisms (CNPs). Further analysis of the impact of discovered genetic differences and the underlying mechanisms is likely to generate a better understanding of the biology and the virulence of the malaria parasite.

The extent to which duplications and deletions occur in the Plasmodium falciparum genome, outside of the subtelomeres, and their contribution to the virulence of the malaria parasite is not known. We have recently found CNPs covering 82 genes, the most extensive spanning a cumulative size of 110 kilobases (Ribacke et al, MBP 2007). CNPs were identified in both laboratory strains and fresh clinical isolates using a 70-mer oligonucleotide microarray in conjunction with fluorescent in situ hybridizations and real-time quantitative PCR. The CNPs were found on all chromosomes except on chromosomes 6 and 8 and involved a total of 50 genes with increased copy numbers and 32 genes with decreased copy numbers relative to the 3D7 parasite. The genes, amplified in up to six copies, encode molecules involved in cell cycle regulation, cell division, drug resistance, erythrocyte invasion, sexual differentiation and unknown functions. These together with previous findings, suggest that the malaria parasite employs gene duplications and deletions as general strategies to enhance its survival and spread.

The complete genome sequence of the human malaria parasite Plasmodium falciparum has revealed a block of genes (³ 10 kilobases in size) which has been duplicated and transposed on multiple subtelomeres (Mok et al, submitted). We found both inter- and intragenic regions of these SD are highly conserved across species, except for a hypervariable region encoding a surface-exposed loop of the PFMC-2TM. The existing numbers of this SD per genome is here shown to be variable in between different parasite lines, suggesting variable expansion and/or deletions of existing duplicons. The ubiquity and uniqueness of the SDs in the P. falciparum subtelomeres, and the nature of genes within suggests an important role in plasmodia speciation.

Heparan sulphate and other sequestration receptors

Project member: Anna Vogt

PfEMP1-species of infected erythrocytes of children with severe malaria frequently bind to the host receptor heparan sulfate present on both endothelial cells and erythrocytes (Barragan et al Blood 2000, Heddini et al, Inf. Immun. 2001, Vogt et al, Blood, 2003). Heparin, which is similar to heparan sulfate in that it is composed of the same building blocks, was previously used in the treatment of severe malaria but it was discontinued due to the occurrence of serious side effects such as intracranial bleedings.

We recently discovered that de-polymerized heparin that lacks anticoagulant activity blocks up to 80% of infected erythrocytes from binding in the micro-vasculature and releases already sequestered parasites into circulation (Vogt et al PloS Path, 2006). We suggest the modified heparin to be a promising candidate for adjunct therapy in severe malaria and are presently developing the substance it into a drug together with a recently funded KIAB company

Dilaforette

Immunoglobulin-binding and placental malaria

The harmful effects of pregnancy-associated malaria are engendered by the heavy sequestration of Plasmodium falciparum parasitized RBCs in the placenta. It is well documented that this process is mediated by interactions of parasite-encoded variant surface antigens and placental receptors. A P. falciparum erythrocyte membrane protein 1 variant, VAR2CSA, and the placental receptor chondroitin sulfate A (CSA) are currently the focus of PAM research.

We have previously shown a role for immunoglobulins (IgG and IgM) from normal human serum as additional receptors in placental sequestration and in resetting (Scholander et al, Nature Med 1996; Flick et al, Science 2001). In this project we are studying the phenoytypes of parasites eluted from the placenta and parasites in vitro and found (i) that CSA and non immune IgG-IgM binding are linked phenotypes of in vitro-adapted parasites, (ii) that a VAR2CSA variant shown to bind CSA also harbors IgG- and IgM-binding domains (DBL2-X, DBL5-!, and DBL6-!), and (iii) that IgG and IgM binding and adhesion to multiple receptors (IgG/IgM/HA/CSA) rather than the exclusive binding to CSA is a characteristic of fresh Ugandan placental isolates. These findings are of importance for the understanding of the pathogenesis of placental malaria and have implications for the ongoing efforts to develop a global PAM vaccine.

Novel Ag332 at the infected erythrocyte surface?

In this project we are studying a novel part of the Ag332 which we recently identified (Moll et al PLoS One, 2007) using biochemical and molecular tools. An open reading frame representing a hitherto unknown second exon of the Pf332 gene that encodes a cysteine-rich polypeptide with a high degree of similarity to the Duffy-binding-like (DBL) domain of the erythrocyte-binding-ligand (EBL) family was found (Moll et al, PLoS One 2007).

The sequence of this DBL-domain is conserved and expressed in all parasite clones/strains investigated. In addition, the expression level of Pf332 correlates with proliferation efficiency of the parasites in vitro. Antibodies raised against the DBL-domain are able to reduce the invasion efficiency of different parasite clones/strains. Analysis of the DBL-domain revealed its ability to bind to uninfected human RBC, and moreover demonstrated association with the iRBC surface. Thus, Pf332 is a molecule with a potential role to support merozoite invasion. Due to the high level of conservation in sequence, the novel DBL-domain of Pf332 is of possible importance for development of novel anti-malaria drugs and vaccines.

PfEMP1-motifs, rosetting and the pathogenesis of severe malaria

We have previously identified virulence-associated markers of the parasite such as resetting and giant resetting (Udomsangpetch et al JEM, 1989; Carlson et al Lancet, 1990; Carlson et al PNAS 1990). In this project we have been studying var-RNA of Ugandan children with mild or severe malaria in cooperation with professors Fred Kironde and Tom Egwang and other scientists at Makerere University-MBL. We have been using a novel method for sub-sectioning region alignments into homology areas (MOTIFF) developed in the laboratory of Björn Andersson at Karolinska Institutet and we found specific PfEMP1 amino acid motifs to be associated with severe disease. The method is applicable to any family of variant proteins and the results suggest that certain PfEMP1 species are predisposed to inducing severe malaria (Normark et al, PNAS, 2007).

RIFINS/SURFINS at the surface of the infected erythrocyte and merozoite

The rif genes, which encode RIFIN proteins, is the largest family in the P. falciparum genome with ~150 copies per haploid genome. They are small two-exon genes with a conserved domain architecture. Our group, as well as others, has shown that RIFIN proteins are exported from the parasite to the infected cell surface (Helmby et al, Inf.Immun 1992, Fernandez et al, JEM, 1999). We have recently determined that the RIFIN protein family can be subdivided into two major groups (Joannin et al. submitted to BMC Genomics). In addition to demonstrating differential developmental regulation and localization of these sub-families (Petter et al, in press Molecular and Biochemical Parasitology 2007), we have also predicted that these proteins have undergone a functional shift (Joannin et al. submitted to BMC Genomics).

SURFINs are encoded by a family of 10 surf genes, including a predicted pseudogene, located within or close to the sub-telomers of five of the chromosomes. SURFINs show structural and sequence similarities with exported, surface exposed proteins (PvSTP1, PkSICAvar, PvVIR, Pf332, PfEMP1) of several plasmodium species. SURFIN4.2 has been found co-transported with PfEMP1 and RIFIN to the IE surface but also accumulated in the parasitophorous vacuole. In released merozoites SURFIN4.2 was present in an amorphous cap at the parasite apex where it may be involved in the invasion of erythrocytes (Winter et al JEM 2005).

By exposing shared polymorphic antigens on IEs and merozoites the parasite may coordinate the antigenic composition of these attachment-surfaces during growth in the bloodstream.

Vaccine against severe malaria

Building on the sequencing of var genes of children with severe or mild malaria (project: PfEMP1-motifs, rosetting and the pathogenesis of severe malaria) we have in parallel studies created a prototypic anti-severe malaria vaccine composed of a PfEMP1-molecule that harbors such severe malaria amino-acid motifs (Chen et al, Vaccine 2004; Pettersson et al, I&I 2005). Adhesion of infected erythrocyte in the micro-vasculature and the subsequent development of severe malaria is prevented by immunizing animals, including primates, with the PfEMP1- vaccine prior to challenge (Moll et al I&I 2007).

Antibodies are an important component of acquired protective immunity

In our group, we are trying to understand which functions of antibodies that are important for protection against malaria. Basic understanding of how these antibodies work is imperative for creating a functioning vaccine against malaria. We are studying the affinity of antibodies directed against different merozoite antigens, as well as the invasion inhibitory effect, and correlating this to protection. We are also investigating different invasion pathways in wild isolates of parasites, and correlating this to symptoms and severity of disease. We have before developed a method for measuring invasion inhibitory antibodies, and we have also shown that variation in use of invasion pathways (involving the merozoite antigens EBA and Rh proteins) mediates evasion of inhibitory antibodies.

Variation in use of erythrocyte invasion pathways by Plasmodium falciparum mediates evasion of human inhibitory antibodies.
Persson KE, McCallum FJ, Reiling L, Lister NA, Stubbs J, Cowman AF, et al
J Clin Invest 2008 Jan;118(1):342-51

Development and optimization of high-throughput methods to measure Plasmodium falciparum-specific growth inhibitory antibodies.
Persson KE, Lee CT, Marsh K, Beeson JG
J Clin Microbiol 2006 May;44(5):1665-73

Investigation of functionally important antibodies against malaria

Project members: Kristina Persson, Sreenivasulu Reddy, Hodan Ahmed Ismail, Caroline Rönnberg, Allan Lugaajju, Tijani Muyideen Kolapo.

The merozoite form of P. falciparum invades red blood cells and multiplies within the cell, finally causing rupture of the red blood cell with release of daughter merozoites back into the circulation after 48 hours. Those who live in malaria-endemic areas and do not die from the disease at a young age, eventually develop immunity, but only slowly and after repeated exposure. Antibodies are an important component of acquired protective immunity.

In our group, we are trying to understand which functions of antibodies that are important for protection against malaria. Basic understanding of how these antibodies work is imperative for creating a functioning vaccine against malaria. We are studying the affinity of antibodies directed against different merozoite antigens, as well as the invasion inhibitory effect, and correlating this to protection. We are also investigating different invasion pathways in wild isolates of parasites, and correlating this to symptoms and severity of disease. We have before developed a method for measuring invasion inhibitory antibodies, and we have also shown that variation in use of invasion pathways (involving the merozoite antigens EBA and Rh proteins) mediates evasion of inhibitory antibodies. We are also investigating the interaction between B-cells and malaria parasites.

Plasmodium falciparum line-dependent association of in vitro growth-inhibitory activity and risk of malaria.
Rono J, Färnert A, Olsson D, Osier F, Rooth I, Persson KE
Infect Immun 2012 May;80(5):1900-8

High affinity antibodies to Plasmodium falciparum merozoite antigens are associated with protection from malaria.
Reddy SB, Anders RF, Beeson JG, Färnert A, Kironde F, Berenzon SK, et al
PLoS One 2012 ;7(2):e32242

Erythrocyte-binding antigens of Plasmodium falciparum are targets of human inhibitory antibodies and function to evade naturally acquired immunity.
Persson KE, Fowkes FJ, McCallum FJ, Gicheru N, Reiling L, Richards JS, et al
J Immunol 2013 Jul;191(2):785-94

Variation in use of erythrocyte invasion pathways by Plasmodium falciparum mediates evasion of human inhibitory antibodies.
Persson KE, McCallum FJ, Reiling L, Lister NA, Stubbs J, Cowman AF, et al
J Clin Invest 2008 Jan;118(1):342-51

Host-parasite interactions in schistosomiasis and virtual microscopy

The excretory-secretory system of intravascular blood flukes, schistosomes is studied as a target for the host immune response. Glycans at the parasite surface have been observed to originate from the parasite protonephridial system, a sophisticated phylogenetically ancient organ. The protonephridial system also seems to be involved in the metabolization of host serum immunoglobulins as part of an unknown transportation system.

Future studies aim at further characterization of the schistosome protonephridia using novel immunohistochemical light and ultrastructural markers.

Studies aiming at education and an improved parasitological diagnostic service at the basic level of health care in developing countries have been initiated (see link below). The idea is to generate a digitalized library of parasitological specimens freely available at the www and consisting of entire specimens scanned in high magnification and permitting viewing in the x, y and z plane at different magnification.

Webmicroscope website

Project Leaders

Anders Björkman Project

Qijun Chen Professorship in Beijing

Akira Kaneko Project

Manuel Patarroyo Project

Ulf Ribacke Project

Group Members

Former Group Members

Former Group Members

Selected publications

Rosette-Disrupting Effect of an Anti-Plasmodial Compound for the Potential Treatment of Plasmodium falciparum Malaria Complications.
Ch'ng JH, Moll K, Quintana Mdel P, Chan SC, Masters E, Moles E, et al
Sci Rep 2016 07;6():29317

Differences in affinity of monoclonal and naturally acquired polyclonal antibodies against Plasmodium falciparum merozoite antigens.
Reddy SB, Anders RF, Cross N, Mueller I, Senn N, Stanisic DI, et al
BMC Microbiol 2015 Jul;15():133

Binding of subdomains 1/2 of PfEMP1-DBL1α to heparan sulfate or heparin mediates Plasmodium falciparum rosetting.
Angeletti D, Sandalova T, Wahlgren M, Achour A
PLoS One 2015 ;10(3):e0118898

Schistosomiasis in Swedish travellers to sub-Saharan Africa: Can we rely on serology?
Thors C, Holmblad P, Maleki M, Carlson J, Linder E
Scand J Infect Dis 2006 ;38(9):794-9

Immunoglobulin uptake and processing by Schistosoma mansoni.
Thors C, Jokiranta TS, Meri T, Kairemo K, Meri S, Linder E
Parasite Immunol 2006 Sep;28(9):421-8

Thomsen-Friedenreich oncofetal antigen in Schistosoma mansoni : localization and immunogenicity in experimental mouse infection.
Thors C, Jansson B, Helin H, Linder E
Parasitology 2006 Jan;132(Pt 1):73-81

Publications

In Vitro Methods to Study Colon Release: State of the Art and An Outlook on New Strategies for Better In-Vitro Biorelevant Release Media.
Wahlgren M, Axenstrand M, Håkansson Å, Marefati A, Lomstein Pedersen B
Pharmaceutics 2019 Feb;11(2):

A comparison of emulsion stability for different OSA-modified waxy maize emulsifiers: Granules, dissolved starch, and non-solvent precipitates.
Saari H, Wahlgren M, Rayner M, Sjöö M, Matos M
PLoS One 2019 ;14(2):e0210690

Effect of ABO blood group on asymptomatic, uncomplicated and placental Plasmodium falciparum infection: systematic review and meta-analysis.
Degarege A, Gebrezgi MT, Beck-Sague CM, Wahlgren M, de Mattos LC, Madhivanan P
BMC Infect Dis 2019 Jan;19(1):86

Exploring parasite heterogeneity using single-cell RNA-seq reveals a gene signature among sexual stage Plasmodium falciparum parasites.
Ngara M, Palmkvist M, Sagasser S, Hjelmqvist D, Björklund ÅK, Wahlgren M, et al
Exp Cell Res 2018 10;371(1):130-138

SURGE complex of Plasmodium falciparum in the rhoptry-neck (SURFIN4.2-RON4-GLURP) contributes to merozoite invasion.
Quintana MDP, Ch'ng JH, Zandian A, Imam M, Hultenby K, Theisen M, et al
PLoS One 2018 ;13(8):e0201669

ABO Blood Group Antigen Decorated Giant Unilamellar Vesicles Exhibit Distinct Interactions with Plasmodium falciparum Infected Red Blood Cells.
Vagianou CD, Stuhr-Hansen N, Moll K, Bovin N, Wahlgren M, Blixt O
ACS Chem Biol 2018 09;13(9):2421-2426

Factors influencing the induction of high affinity antibodies to Plasmodium falciparum merozoite antigens and how affinity changes over time.
Tijani MK, Reddy SB, Langer C, Beeson JG, Wahlgren M, Nwuba RI, et al
Sci Rep 2018 06;8(1):9026

A Thioredoxin Homologous Protein of Plasmodium falciparum Participates in Erythrocyte Invasion.
Wang W, Huang P, Jiang N, Lu H, Zhang D, Wang D, et al
Infect Immun 2018 08;86(8):

Characterization of the Catalytic Subunits of the RNA Exosome-like Complex in Plasmodium falciparum.
Jiang N, Yu S, Yang N, Feng Y, Sang X, Wang Y, et al
J Eukaryot Microbiol 2018 11;65(6):843-853

Antibodies in children with malaria to PfEMP1, RIFIN and SURFIN expressed at the Plasmodium falciparum parasitized red blood cell surface.
Quintana MDP, Ch'ng JH, Moll K, Zandian A, Nilsson P, Idris ZM, et al
Sci Rep 2018 02;8(1):3262

Inhibition of merozoite invasion and transient de-sequestration by sevuparin in humans with Plasmodium falciparum malaria.
Leitgeb AM, Charunwatthana P, Rueangveerayut R, Uthaisin C, Silamut K, Chotivanich K, et al
PLoS One 2017 ;12(12):e0188754

An ApiAP2 member regulates expression of clonally variant genes of the human malaria parasite Plasmodium falciparum.
Martins RM, Macpherson CR, Claes A, Scheidig-Benatar C, Sakamoto H, Yam XY, et al
Sci Rep 2017 10;7(1):14042

Acquisition, maintenance and adaptation of invasion inhibitory antibodies against Plasmodium falciparum invasion ligands involved in immune evasion.
Tijani MK, Babalola OA, Odaibo AB, Anumudu CI, Asinobi AO, Morenikeji OA, et al
PLoS One 2017 ;12(8):e0182187

Burden and impact of Plasmodium vivax in pregnancy: A multi-centre prospective observational study.
Bardají A, Martínez-Espinosa FE, Arévalo-Herrera M, Padilla N, Kochar S, Ome-Kaius M, et al
PLoS Negl Trop Dis 2017 Jun;11(6):e0005606

Regulation of PfEMP1-VAR2CSA translation by a Plasmodium translation-enhancing factor.
Chan S, Frasch A, Mandava CS, Ch'ng JH, Quintana MDP, Vesterlund M, et al
Nat Microbiol 2017 May;2():17068

Variant surface antigens of Plasmodium falciparum and their roles in severe malaria
Mats Wahlren, Suchi Goel and Reetesh R Akhouri
Nature Reviews Microbiology June 2017

Effects of sevuparin on rosette formation and cytoadherence of Plasmodium falciparum infected erythrocytes.
Saiwaew S, Sritabal J, Piaraksa N, Keayarsa S, Ruengweerayut R, Utaisin C, et al
PLoS One 2017 ;12(3):e0172718

Epitopes of anti-RIFIN antibodies and characterization of rif-expressing Plasmodium falciparum parasites by RNA sequencing.
Ch'ng JH, Sirel M, Zandian A, Del Pilar Quintana M, Chun Leung Chan S, Moll K, et al
Sci Rep 2017 02;7():43190

Development of Plasmodium falciparum specific naïve, atypical, memory and plasma B cells during infancy and in adults in an endemic area.
Lugaajju A, Reddy SB, Wahlgren M, Kironde F, Persson KE
Malar J 2017 01;16(1):37

Development of drug-loaded immunoliposomes for the selective targeting and elimination of rosetting Plasmodium falciparum-infected red blood cells.
Moles E, Moll K, Ch'ng JH, Parini P, Wahlgren M, Fernàndez-Busquets X
J Control Release 2016 11;241():57-67

Phagocytosis-inducing antibodies to Plasmodium falciparum upon immunization with a recombinant PfEMP1 NTS-DBL1α domain.
Quintana Mdel P, Angeletti D, Moll K, Chen Q, Wahlgren M
Malar J 2016 08;15(1):416

The TatD-like DNase of Plasmodium is a virulence factor and a potential malaria vaccine candidate.
Chang Z, Jiang N, Zhang Y, Lu H, Yin J, Wahlgren M, et al
Nat Commun 2016 05;7():11537

Architecture of Human IgM in Complex with P. falciparum Erythrocyte Membrane Protein 1
Reetesh Raj Akhouri, Suchi Goel, Hirotoshi Furusho, Ulf Skoglund, Mats Wahlgren
Cell Reports Feb 2016;14:1–14

Evasion of Immunity to Plasmodium falciparum: Rosettes of Blood Group A Impair Recognition of PfEMP1.
Moll K, Palmkvist M, Ch'ng J, Kiwuwa MS, Wahlgren M
PLoS One 2015 ;10(12):e0145120

Novel flow cytometry technique for detection of Plasmodium falciparum specific B-cells in humans: increased levels of specific B-cells in ongoing infection.
Lugaajju A, Reddy SB, Rönnberg C, Wahlgren M, Kironde F, Persson KE
Malar J 2015 Sep;14():370

Differences in affinity of monoclonal and naturally acquired polyclonal antibodies against Plasmodium falciparum merozoite antigens.
Reddy SB, Anders RF, Cross N, Mueller I, Senn N, Stanisic DI, et al
BMC Microbiol 2015 Jul;15():133

HIV-DNA Given with or without Intradermal Electroporation Is Safe and Highly Immunogenic in Healthy Swedish HIV-1 DNA/MVA Vaccinees: A Phase I Randomized Trial.
Nilsson C, Hejdeman B, Godoy-Ramirez K, Tecleab T, Scarlatti G, Bråve A, et al
PLoS One 2015 ;10(6):e0131748

Parasite Specific Antibody Increase Induced by an Episode of Acute P. falciparum Uncomplicated Malaria.
Kaddumukasa M, Lwanira C, Lugaajju A, Katabira E, Persson KE, Wahlgren M, et al
PLoS One 2015 ;10(4):e0124297

RIFINs are adhesins implicated in severe Plasmodium falciparum malaria.
Goel S, Palmkvist M, Moll K, Joannin N, Lara P, Akhouri RR, et al
Nat Med 2015 Apr;21(4):314-7

Subclass responses and their half-lives for antibodies against EBA175 and PfRh2 in naturally acquired immunity against Plasmodium falciparum malaria.
Ahmed Ismail H, Tijani MK, Langer C, Reiling L, White MT, Beeson JG, et al
Malar J 2014 Nov;13():425

Label-free microfluidic enrichment of ring-stage Plasmodium falciparum-infected red blood cells using non-inertial hydrodynamic lift.
Geislinger TM, Chan S, Moll K, Wixforth A, Wahlgren M, Franke T
Malar J 2014 Sep;13():375

A comparative study on the heparin-binding proteomes of Toxoplasma gondii and Plasmodium falciparum.
Zhang Y, Jiang N, Jia B, Chang Z, Zhang Y, Wei X, et al
Proteomics 2014 Aug;14(15):1737-45

Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria.
Bachmann J, Burté F, Pramana S, Conte I, Brown BJ, Orimadegun AE, et al
PLoS Pathog 2014 Apr;10(4):e1004038

Improved in vitro culture of Plasmodium falciparum permits establishment of clinical isolates with preserved multiplication, invasion and rosetting phenotypes.
Ribacke U, Moll K, Albrecht L, Ahmed Ismail H, Normark J, Flaberg E, et al
PLoS One 2013 ;8(7):e69781

Acquired antibodies to merozoite antigens in children from Uganda with uncomplicated or severe Plasmodium falciparum malaria.
Ahmed Ismail H, Ribacke U, Reiling L, Normark J, Egwang T, Kironde F, et al
Clin Vaccine Immunol 2013 Aug;20(8):1170-80

Malaria: Molecular secrets of a parasite.
Venkatesh S, Workman JL, Wahlgren M, Bejarano MT
Nature 2013 Jul;499(7457):156-7

High expression of p63 is correlated to poor prognosis in squamous cell carcinoma of the tongue.
Loljung L, Coates PJ, Nekulova M, Laurell G, Wahlgren M, Wilms T, et al
J Oral Pathol Med 2014 Jan;43(1):14-9

Rosetting in Plasmodium vivax: a cytoadhesion phenotype associated with anaemia.
Marín-Menéndez A, Bardají A, Martínez-Espinosa FE, Bôtto-Menezes C, Lacerda MV, Ortiz J, et al
PLoS Negl Trop Dis 2013 ;7(4):e2155

Proteomic analysis of Plasmodium falciparum schizonts reveals heparin-binding merozoite proteins.
Zhang Y, Jiang N, Lu H, Hou N, Piao X, Cai P, et al
J Proteome Res 2013 May;12(5):2185-93

Genetic diversity of Plasmodium falciparum infections in mild and severe malaria of children from Kampala, Uganda.
Kiwuwa MS, Ribacke U, Moll K, Byarugaba J, Lundblom K, Färnert A, et al
Parasitol Res 2013 Apr;112(4):1691-700

Elevated levels of high-mobility group box-1 (HMGB1) in patients with severe or uncomplicated Plasmodium falciparum malaria.
Angeletti D, Kiwuwa MS, Byarugaba J, Kironde F, Wahlgren M
Am J Trop Med Hyg 2013 Apr;88(4):733-5

Analysis of antibody induction upon immunization with distinct NTS-DBL1α-domains of PfEMP1 from rosetting Plasmodium falciparum parasites.
Angeletti D, Albrecht L, Wahlgren M, Moll K
Malar J 2013 Jan;12():32

A sequence in subdomain 2 of DBL1α of Plasmodium falciparum erythrocyte membrane protein 1 induces strain transcending antibodies.
Blomqvist K, Albrecht L, Quintana Mdel P, Angeletti D, Joannin N, Chêne A, et al
PLoS One 2013 ;8(1):e52679

Plasmodium falciparum rosetting epitopes converge in the SD3-loop of PfEMP1-DBL1α.
Angeletti D, Albrecht L, Blomqvist K, Quintana Mdel P, Akhter T, Bächle SM, et al
PLoS One 2012 ;7(12):e50758

Detection of copy number variation and single nucleotide polymorphisms in genes involved in drug resistance and other phenotypic traits in P. falciparum clinical isolates collected from Uganda.
Kiwuwa MS, Byarugaba J, Wahlgren M, Kironde F
Acta Trop 2013 Mar;125(3):269-75

Plasmodium falciparum antigen 332 is a resident peripheral membrane protein of Maurer's clefts.
Nilsson S, Angeletti D, Wahlgren M, Chen Q, Moll K
PLoS One 2012 ;7(11):e46980

Placental infection with Plasmodium vivax: a histopathological and molecular study.
Mayor A, Bardají A, Felger I, King CL, Cisteró P, Dobaño C, et al
J Infect Dis 2012 Dec;206(12):1904-10

Validity of self-reported use of sulphadoxine-pyrimethamine intermittent presumptive treatment during pregnancy (IPTp): a cross-sectional study.
Namusoke F, Ntale M, Wahlgren M, Kironde F, Mirembe F
Malar J 2012 Sep;11():310

TLRs innate immunereceptors and Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) CIDR1α-driven human polyclonal B-cell activation.
Simone O, Bejarano MT, Pierce SK, Antonaci S, Wahlgren M, Troye-Blomberg M, et al
Acta Trop 2011 Aug;119(2-3):144-50

Low anticoagulant heparin disrupts Plasmodium falciparum rosettes in fresh clinical isolates.
Leitgeb AM, Blomqvist K, Cho-Ngwa F, Samje M, Nde P, Titanji V, et al
Am J Trop Med Hyg 2011 Mar;84(3):390-6

RSpred, a set of Hidden Markov Models to detect and classify the RIFIN and STEVOR proteins of Plasmodium falciparum.
Joannin N, Kallberg Y, Wahlgren M, Persson B
BMC Genomics 2011 Feb;12():119

var gene transcription and PfEMP1 expression in the rosetting and cytoadhesive Plasmodium falciparum clone FCR3S1.2.
Albrecht L, Moll K, Blomqvist K, Normark J, Chen Q, Wahlgren M
Malar J 2011 Jan;10():17

Carolus Linnaeus, the ash, worm-wood and other anti-malarial plants.
Aydin-Schmidt B, Thorsell W, Wahlgren M
Scand J Infect Dis 2010 Dec;42(11-12):941-2

Co-infections with Plasmodium knowlesi and other malaria parasites, Myanmar.
Jiang N, Chang Q, Sun X, Lu H, Yin J, Zhang Z, et al
Emerg Infect Dis 2010 Sep;16(9):1476-8

varDB: a database of antigenic variant sequences--current status and future prospects.
Diez D, Hayes N, Joannin N, Normark J, Kanehisa M, Wahlgren M, et al
Acta Trop 2010 Jun;114(3):144-51

Differential recognition of P. falciparum VAR2CSA domains by naturally acquired antibodies in pregnant women from a malaria endemic area.
Brolin KJ, Persson KE, Wahlgren M, Rogerson SJ, Chen Q
PLoS One 2010 Feb;5(2):e9230

Malaria research--diversity and control: a Sweden-Japan joint seminar.
Kaneko A, Wahlgren M
Acta Trop 2010 Jun;114(3):129-30

Review: Molecular pathogenesis of severe malaria” Nature Rev Microbiol

Variant surface antigens of Plasmodium falciparum and their roles in severe malaria
Mats Wahlren, Suchi Goel and Reetesh R Akhouri
Nature Reviews Microbiology June 2017

Thesis

Fingani Annie Mphande

Towards understanding the SURFIN protein family and var genes in Plasmodium falciparum (Pdf file, 994 Kb)

Arnaud Chêne

Impact of malaria on B-cell homeostasis and Epstein-Barr virus reactivation. Endemic Burkitt's lymphoma pathogenesis (Pdf file, 1 Mb)

Bobo Mok

Genomic and transcripto variation in blood stage Plasmodium falciparum (Pdf file, 5 Mb)

Andreas Heddini

Endothelial cytoadherence, rosetting and virulence in Plasmodium falciparum malaria (Pdf file, 33 Mb)

Carl Johan Treutiger

Host cell adhesion of Plasmodium falciparum-infected erythrocytes (Pdf file, 38 Mb)

Methods in Malaria Research 6th Edition

View Methods in Malaria Research 6th Edition Online

Links

Protocols Hybridization

Download Lucidea application protocol

Plasmodium and anopheles databases

PlasmoDB

AnoBase

Malaria Research and Reference Reagent Resource Center - MR4

Malaria centers, International agencies and initiatives

EDCTP

EMVI - European Malaria Vaccine Initiative

Roll Back Malaria

WHO/TDR

MIM - Multilateral Initiative on Malaria

AMANET - African Malaria Network Trust

The Wellcome Trust

Global fund to fight, AIDS, Tuberculosis and Malaria

Center for Disease Control and Prevention

MFI - Malaria Foundation International

Bill and Melinda Gates Foundation

MW
Content reviewer:
28-03-2023