- Malaria (Parasitology)
- Vaccine development
- Cell and Molecular Biology
Head of the Leiden Malaria Research Group (Associate Professor)
Department of Parasitology, Center of Infectious Diseases
- Development of a malaria vaccine based on genetically attenuated parasites
- Identification and analysis of parasite proteins that are (putative) targets for subunit vaccines
- Identification and analysis of parasite proteins that are (putative) targets for drugs
- Analysis of parasite-host interactions involved in pathology and disease
Zie voor meer informatie: Website of the Leiden Malaria Research Group
The Leiden Malaria Group (LMRG) developed Plasmodium genetic modification in 1995 and continues to innovate and lead research into Plasmodium transgenesis. Gene deletion mutants generated have been used to analyze a wide range of parasite gene functions. In 2005 LMRG were one of the first groups to create genetically attenuated parasites that could serve as a live-parasite vaccine against malaria. In addition to gene-deletion and disruption-mutants, LMRG has created a number of parasites expressing foreign ‘transgenes’ to create reference parasite lines including those expressing fluorescent, bioluminescent, OVA reporter proteins, which have proven to be valuable tools in dissecting parasite-host interactions at the cellular and molecular level and are shared by many different labs world-wide. LMRG has created over 160 transgene expressing mutants and have distributed various mutant- and transgenic lines to more than 50 groups across the world.
Recently, the LMRG applied their expertise of Plasmodium genetic modification to the human parasite P. falciparum and developed a novel method to efficiently generate stable genetically modified P. falciparum that are free of heterologous drug-selectable markers, facilitating sequential genetic modifications. The LMRG have refined the CRISPR-Cas9 genetic modification method for P. falciparum.
The current emphasis of the research is on the development of a human malaria vaccine based on genetically attenuated parasites and on the identification and analysis of parasite proteins that are (putative) targets for subunit vaccines.
The website 'Plasmodium berghei - model of malaria provides general information about the Plasmodium berghei rodent model of malaria. It contains detailed protocols for biological assays, molecular techniques and information about our standard ‘in-house’ plasmids for a variety of genetic modifications in rodent malaria parasites. In addition, the website also provides databases (Excel files) with transcriptome, proteome and genome data. A significant number of standard plasmids for genetic modification and transgenic P. berghei parasite lines from the Leiden Malaria Group are available to the malaria research community.
www.pberghei.eu is a web-based database (RMgmDB) from the Leiden Malaria Group containing information on genetically modified rodent malaria parasite lines generated by many labs worldwide. Specifically, it contains data of three rodent malaria parasite species; Plasmodium berghei, P. yoelii and P. chabaudi. The aim of this database is to provide the research community access to detailed information on the generation (e.g. disruption, tagging, mutation, transgene expression) and phenotype of genetically modified malaria parasites. The information in this database is shared with the ‘Sanger Institute Pathogen Genome Database’ (www.GeneDB.org) and ‘EuPathDB Bioinformatics Resource Center for biodefense and Emerging / Re-emerging Infectious Diseases’ (www.PlasmoDB.org)
Dijk, M.R. van, Waters, A.P. and Janse, C.J. (1995). Stable transfection of malaria parasite blood stages. Science 268, 1358-1362.
Dijk, M.R. van, Janse, C.J. and Waters, A.P. (1996). Expression of a Plasmodium gene introduced into subtelomeric regions of Plasmodium berghei chromosomes. Science 271, 662-665.
Wel, A.M. van der, Tomas, A.M., Kocken, C.H.M., Malhotrall, P., Janse, C.J., Waters, A.P. and A.W. Thomas (1997). Transfection of the primate malaria parasite Plasmodium knowlesi using entirely heterologous constructs. J.Exp.Med. 185, 1499-1503
Menard, R., Sultan, A.A., Cortes, C., Altszuler, R., van Dijk, M.R., Janse, C.J., Waters, A.P., Nussenzweig, R.S. and Nussenzweig, V. (1997). Circumsporozoite protein is required for development of malaria sporozoites in mosquitoes. Nature 385, 336-340.
Wengelnik, K., Spaccapelo, R., Naitza, S., Robson, K.J.H., Janse, C.J., Waters, A.P. & Crisanti, A. (1999). TRAP complementation in Plasmodium berghei and mutation analysis reveals a role of the conserved adhesive domains in the invasion of mosquito salivary glands. EMBO J. 18, 5195-204
Tomas, A.M., Margos, G., Dimopoulos, G., Lin, L.H.M. van, de Koning-Ward, T.F., Sinha, R., Lupetti, P., Beetsma, A.L., Rodriguez, M.C., Karras, M., Hagar, A., Mendoza, J., Butcher, G.A., Kafatos, F.C., Janse, C.J., Waters, A.P. and Sinden, R.E. (2001). The conserved P25/P28 proteins of the malaria ookinete surface have multiple and partially redundant functions. EMBO Journal 20, 3975-83.
Dijk, M.R., Janse, C.J., Thompson, J., Waters, A.P., Braks, J.A.M., Dodemont, H.J., Stunnenberg, H.G., Gemert, G.J. van, Sauerwein, R.W. and Eling, W. (2001). A central role for P48/45 in malaria parasite male gamete fertility. Cell 104, 153-164
Carlton JM, Angiuoli SV, Suh BB, Kooij TW, Pertea M, Silva JC, Ermolaeva MD, Allen JE, Selengut JD, Koo HL, Peterson JD, Pop M, Kosack DS, Shumway MF, Bidwell SL, Shallom SJ, van Aken SE, Riedmuller SB, Feldblyum TV, Cho JK, Quackenbush J, Sedegah M, Shoaibi A, Cummings LM, Florens L, Yates JR, Raine JD, Sinden RE, Harris MA, Cunningham DA, Preiser PR, Bergman LW, Vaidya AB, van Lin LH, Janse CJ, Waters AP, Smith HO, White OR, Salzberg SL, Venter JC, Fraser CM, Hoffman SL, Gardner MJ, Carucci DJ. Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii. Nature. 2002, 419:512-9.
Blandin S, Shiao SH, Moita LF, Janse CJ, Waters AP, Kafatos FC, Levashina EA (2004) Complement-like protein TEP1 is a determinant of vectorial capacity in the malaria vector Anopheles gambiae. Cell. 116: 661-70.
Kooij TW, Carlton JM, Bidwell SL, Hall N, Ramesar J, Janse CJ, Waters AP (2005) A Plasmodium Whole-Genome Synteny Map: Indels and Synteny Breakpoints as Foci for Species-Specific Genes. PLoS Pathog. 23;1(4): e44
van Dijk MR, Douradinha B, Franke-Fayard B, Heussler V, van Dooren MW, van Schaijk B, van Gemert GJ, Sauerwein RW, Mota MM, Waters AP, Janse CJ. (2005). Genetically attenuated, P36p-deficient malarial sporozoites induce protective immunity and apoptosis of infected liver cells. Proc Natl Acad Sci U S A, 102:12194-9
Franke-Fayard B, Janse CJ, Cunha-Rodrigues M, Ramesar J, Buscher P, Que I, Lowik C, Voshol PJ, den Boer MA, van Duinen SG, Febbraio M, Mota MM, Waters AP.(2005). Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration. Proc Natl Acad Sci U S A. 102. 11468-73
Khan, S.M., Franke-Fayard, B., Mair, G.R., Lasonder, E., Janse, C.J, Mann, M. & Waters, A.P. (2005) Proteome analysis of separated male and female gametocytes reveals novel sex specific Plasmodium biology. Cell 121: 675-87
Hall, N., Karras, M., Raine, J.D., Carlton, J.M., Kooij, T.W.A., Berriman, M., Florens, L., Janssen, C., Pain, A., Christophides, C.K., James, K., Rutherford, K., Harris, B., Harris, D., Churcher, C., Quail, M.A., Ormond, D., Doggett, J., Trueman, H.E., Mendoza, J., Bidwell, S., Rajandream, M.A., Carucci, D.A., Yates, J.R. III, Kafatos, F.C., Janse, C.J., Barrell, B., Turner, C.M.R., Waters, A.P., Sinden, R.E. (2005) A comprehensive survey of the Plasmodium life cycle by genomic, transcriptomic and proteomic analyses. Science 307. 82-6.
Waters, A.P. Mota, M.M., van Dijk, M.R. & Janse C.J. (2005) Malaria Vaccines: Back to the Future? – Perspective. Science 307:528-30
Mair GR, Braks JA, Garver LS, Wiegant JC, Hall N, Dirks RW, Khan SM, Dimopoulos G, Janse CJ, Waters AP (2006). Regulation of sexual development of Plasmodium by translational repression. Science 313: 667-9.
Kooij TW, Janse CJ, Waters AP (2006). Plasmodium post-genomics: better the bug you know? Nat Rev Microbiol. 4: 344-57. Review.
Janse CJ, Franke-Fayard B, Waters AP. Selection by flow-sorting of genetically transformed, GFP-expressing blood stages of the rodent malaria parasite, Plasmodium berghei. Nat Protoc. 2006;1(2):614-23.
Franke-Fayard B, Waters AP, Janse CJ. Real-time in vivo imaging of transgenic bioluminescent blood stages of rodent malaria parasites in mice. Nat Protoc. 2006;1(1):476-85.
Janse CJ, Ramesar J, Waters AP. High-efficiency transfection and drug selection of genetically transformed blood stages of the rodent malaria parasite Plasmodium berghei. Nat Protoc. 2006;1(1):346-56.
van Ooij C, Tamez P, Bhattacharjee S, Hiller NL, Harrison T, Liolios K, Kooij T, Ramesar J, Balu B, Adams J, Waters A, Janse C, Haldar K. The malaria secretome: from algorithms to essential function in blood stage infection. PLoS Pathog. 2008 Jun 13;4(6):e1000084.
Lasonder E, Janse CJ, van Gemert GJ, Mair GR, Vermunt AM, Douradinha BG, van Noort V, Huynen MA, Luty AJ, Kroeze H, Khan SM, Sauerwein RW, Waters AP, Mann M, Stunnenberg HG. Proteomic profiling of Plasmodium sporozoite maturation identifies new proteins essential for parasite development and infectivity. PLoS Pathog. 2008 Oct;4(10):e1000195.
Yu M, Kumar TR, Nkrumah LJ, Coppi A, Retzlaff S, Li CD, Kelly BJ, Moura PA, Lakshmanan V, Freundlich JS, Valderramos JC, Vilcheze C, Siedner M, Tsai JH, Falkard B, Sidhu AB, Purcell LA, Gratraud P, Kremer L, Waters AP, Schiehser G, Jacobus DP, Janse CJ, Ager A, Jacobs WR Jr, Sacchettini JC, Heussler V, Sinnis P, Fidock DAThe fatty acid biosynthesis enzyme FabI plays a key role in the development of liver-stage malarial parasites.. Cell Host Microbe. 2008 4:567-78.
Vega-Rodríguez J, Franke-Fayard B, Dinglasan RR, Janse CJ, Pastrana-Mena R, Waters AP, Coppens I, Rodríguez-Orengo JF, Jacobs-Lorena M, Serrano AE. The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission. PLoS Pathog. 2009, 5(2):e1000302.
Baum J, Papenfuss AT, Mair GR, Janse CJ, Vlachou D, Waters AP, Cowman AF, Crabb BS, de Koning-Ward TF. Molecular genetics and comparative genomics reveal RNAi is not functional in malaria parasites. Nucleic Acids Res. 2009;37(11):3788-98.
Moon RW, Taylor CJ, Bex C, Schepers R, Goulding D, Janse CJ, Waters AP, Baker DA, Billker O. A cyclic GMP signalling module that regulates gliding motility in a malaria parasite. PLoS Pathog. 2009 Sep;5(9):e1000599.
Spaccapelo R, Janse CJ, Caterbi S, Franke-Fayard B, Bonilla JA, Syphard LM, Di Cristina M, Dottorini T, Savarino A, Cassone A, Bistoni F, Waters AP, Dame JB, Crisanti A. Plasmepsin 4-deficient Plasmodiumberghei are virulence attenuated and induce protective immunity against experimental malaria. Am J Pathol. 2010;176(1):205-17.
Iwanaga S, Khan SM, Kaneko I, Christodoulou Z, Newbold C, Yuda M, Janse CJ, Waters AP (2010). Functional identification of the Plasmodium centromere and generation of a Plasmodium artificial chromosome. Cell Host Microbe. 7(3):245-55.
Mair GR, Lasonder E, Garver LS, Franke-Fayard BM, Carret CK, Wiegant JC, Dirks RW, Dimopoulos G, Janse CJ, Waters AP. Universal features of post-transcriptional gene regulation are critical for Plasmodium zygote development. PLoS Pathog. 2010;6(2):e1000767.
Dijk MR van, BSchaijk BCL van, Khan SM, Dooren MW van, Ramesar J, Kaczanowski S, Gemert GJ van, Kroeze H, Stunnenberg HG, Eling WM, Sauerwein RW, Waters AP, Janse CJ. Three Members of the 6-cys Protein Family of Plasmodium Play a Role in Gamete Fertility. Plos Pathogens. 2010 Apr 8;6(4):e1000853.
Franke-Fayard B, Fonager J, Braks A, Khan SM, Janse CJ. Sequestration and tissue accumulation of human malaria parasites: can we learn anything from rodent models of malaria? PLoS Pathog. 2010; 6(9). pii: e1001032.
Gueirard P, Tavares J, Thiberge S, Bernex F, Ishino T, Milon G, Franke-Fayard B, Janse CJ, Ménard R, Amino R. Development of the malaria parasite in the skin of the mammalian host. Proc Natl Acad Sci U S A. 2010;107(43):18640-5.
Gomes-Santos CS, Braks J, Prudêncio M, Carret C, Gomes AR, Pain A, Feltwell T, Khan S, Waters A, Janse C, Mair GR, Mota MM. Transition of Plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein pumilio.PLoS Pathog. 2011; 7(5):e1002046.
Wykes MN, Kay JG, Manderson A, Liu XQ, Brown DL, Richard DJ, Wipasa J, Jiang SH, Jones MK, Janse CJ, Waters AP, Pierce SK, Miller LH, Stow JL, Good MF. Rodent blood-stage Plasmodium survive in dendritic cells that infect naive mice. Proc Natl Acad Sci U S A. 2011 108(27):11205-10.
Fonager J, Pasini EM, Braks JA, Klop O, Ramesar J, Remarque EJ, Vroegrijk IO, van Duinen SG, Thomas AW, Khan SM, Mann M, Kocken CH, Janse CJ, Franke-Fayard BM. Reduced CD36-dependent tissue sequestration of Plasmodium-infected erythrocytes is detrimental to malaria parasite growth in vivo. J Exp Med. 2011 16; 209(1): 93-107.
Annoura T, Ploemen IH, van Schaijk BC, Sajid M, Vos MW, van Gemert GJ, Chevalley-Maurel S, Franke-Fayard BM, Hermsen CC, Gego A, Franetich JF, Mazier D, Hoffman SL, Janse CJ, Sauerwein RW, Khan SM. Assessing the adequacy of attenuation of genetically modified malaria parasite vaccine candidates. Vaccine 2012; 30(16): 2662-70.
Sun T, Holowka T, Song Y, Zierow S, Leng L, Chen Y, Xiong H, Griffith J, Nouraie M, Thuma PE, Lolis E, Janse CJ, Gordeuk VR, Augustijn K, Bucala R. A Plasmodium-encoded cytokine suppresses T-cell immunity during malaria. Proc Natl Acad Sci U S A. 2012; 109(31):E2117-26.
The role of animal models for research on severe malaria. Craig AG, Grau GE, Janse C, Kazura JW, Milner D, Barnwell JW, Turner G, Langhorne J; participants of the Hinxton Retreat meeting on Animal Models for Research on Severe Malaria. PLoS Pathog. 2012 Feb;8(2):e1002401
A putative homologue of CDC20/CDH1 in the malaria parasite is essential for male gamete development. Guttery DS, Ferguson DJ, Poulin B, Xu Z, Straschil U, Klop O, Solyakov L, Sandrini SM, Brady D, Nieduszynski CA, Janse CJ, Holder AA, Tobin AB, Tewari R. PLoS Pathog. 2012 Feb;8(2):e1002554.
Genetic engineering of attenuated malaria parasites for vaccination. Khan SM, Janse CJ, Kappe SH, Mikolajczak SA. Curr Opin Biotechnol. 2012 Dec;23(6):908-16.
Proteomic and genetic analyses demonstrate that Plasmodium berghei blood stages export a large and diverse repertoire of proteins. Pasini EM, Braks JA, Fonager J, Klop O, Aime E, Spaccapelo R, Otto TD, Berriman M, Hiss JA, Thomas AW, Mann M, Janse CJ, Kocken CH, Franke-Fayard B. Mol Cell Proteomics. 2013 Feb;12(2):426-48
The utility of Plasmodium berghei as a rodent model for anti-merozoite malaria vaccine assessment. Goodman AL, Forbes EK, Williams AR, Douglas AD, de Cassan SC, Bauza K, Biswas S, Dicks MD, Llewellyn D, Moore AC, Janse CJ, Franke-Fayard BM, Gilbert SC, Hill AV, Pleass RJ, Draper SJ. Sci Rep. 2013;3:1706
Two Plasmodium 6-Cys family-related proteins have distinct and critical roles in liver-stage development. Annoura T, van Schaijk BC, Ploemen IH, Sajid M, Lin JW, Vos MW, Dinmohamed AG, Inaoka DK, Rijpma SR, van Gemert GJ, Chevalley-Maurel S, Kielbasa SM, Scheltinga F, Franke-Fayard B, Klop O, Hermsen CC, Kita K, Gego A, Franetich JF, Mazier D, Hoffman SL, Janse CJ, Sauerwein RW, Khan SM. FASEB J. 2014 Feb 7.
van Schaijk BC, Ploemen IH, Annoura T, Vos MW, Foquet L, van Gemert GJ, Chevalley-Maurel S, van de Vegte-Bolmer M, Sajid M, Franetich JF, Lorthiois A, Leroux-Roels G, Meuleman P, Hermsen CC, Mazier D, Hoffman SL, Janse CJ, Khan SM, Sauerwein RW. A genetically attenuated malaria vaccine candidate based on P. falciparum b9/slarp gene-deficient sporozoites. Elife. 2014 Nov 19;3.
A comprehensive evaluation of rodent malaria parasite genomes and gene expression. Otto TD, Böhme U, Jackson AP, Hunt M, Franke-Fayard B, Hoeijmakers WA, Religa AA, Robertson L, Sanders M, Ogun SA, Cunningham D, Erhart A, Billker O, Khan SM, Stunnenberg HG, Langhorne J, Holder AA, Waters AP, Newbold CI, Pain A, Berriman M, Janse CJ. BMC Biol. 2014 Oct 30;12:86
Guerreiro A, Deligianni E, Santos JM, Silva PA, Louis C, Pain A, Janse CJ, Franke-Fayard B, Carret CK, Siden-Kiamos I, Mair GR. Genome-wide RIP-Chip analysis of translational repressor-bound mRNAs in the Plasmodium gametocyte. Genome Biol. 2014 Nov 3;15(11):493.
Burda PC, Roelli MA, Schaffner M, Khan SM, Janse CJ, Heussler VT. A Plasmodium phospholipase is involved in disruption of the liver stage parasitophorous vacuole membrane. PLoS Pathog. 2015 Mar 18;11(3):e1004760.
Replication of Plasmodium in reticulocytes can occur without hemozoin formation, resulting in chloroquine resistance. Lin JW, Spaccapelo R, Schwarzer E, Sajid M, Annoura T, Deroost K, Ravelli RB, Aime E, Capuccini B, Mommaas-Kienhuis AM, O'Toole T, Prins F, Franke-Fayard BM, Ramesar J, Chevalley-Maurel S, Kroeze H, Koster AJ, Tanke HJ, Crisanti A, Langhorne J, Arese P, Van den Steen PE, Janse CJ, Khan SM. J. Exp Med. 2015 212(6):893-903
Long-term live imaging reveals cytosolic immune responses of host hepatocytes against Plasmodium infection and parasite escape mechanisms. Prado M, Eickel N, De Niz M, Heitmann A, Agop-Nersesian C, Wacker R, Schmuckli-Maurer J, Caldelari R, Janse CJ, Khan SM, May J, Meyer CG, Heussler VT. Autophagy. 2015;11(9):1561-79.
Comparative assessment of vaccine vectors encoding ten malaria antigens identifies two protective liver-stage candidates. Longley RJ, Salman AM, Cottingham MG, Ewer K, Janse CJ, Khan SM, Spencer AJ, Hill AV. Sci Rep. 2015; 5:11820.
The machinery underlying malaria parasite virulence is conserved between rodent and human malaria parasites. De Niz M, Ullrich AK, Heiber A, Blancke Soares A, Pick C, Lyck R, Keller D, Kaiser G, Prado M, Flemming S, Del Portillo H, Janse CJ, Heussler V, Spielmann T. Nat Commun. 2016 May 26;7:11659
Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes: molecular insight into sex-specific processes and translational repression. Lasonder E, Rijpma SR, van Schaijk BC, Hoeijmakers WA, Kensche PR, Gresnigt MS, Italiaander A, Vos MW, Woestenenk R, Bousema T, Mair GR, Khan SM, Janse CJ, Bártfai R, Sauerwein RW. Nucleic Acids Res. 2016 Jun 13. pii: gkw536
Maternally supplied S-acyl-transferase is required for crystalloid organelle formation and transmission of the malaria parasite. Santos JM, Duarte N, Kehrer J, Ramesar J, Avramut MC, Koster AJ, Dessens JT, Frischknecht F, Chevalley-Maurel S, Janse CJ, Franke-Fayard B, Mair GR. Proc Natl Acad Sci U S A. 2016 Jun 14. pii: 201522381
Variant Exported Blood-Stage Proteins Encoded by Plasmodium Multigene Families Are Expressed in Liver Stages Where They Are Exported into the Parasitophorous Vacuole. Fougère A, Jackson AP, Paraskevi Bechtsi D, Braks JA, Annoura T, Fonager J, Spaccapelo R, Ramesar J, Chevalley-Maurel S, Klop O, van der Laan AM, Tanke HJ, Kocken CH, Pasini EM, Khan SM, Böhme U, van Ooij C, Otto TD, Janse CJ, Franke-Fayard B. PLoS Pathog. 2016 Nov 16;12(11):e1005917.
CD8+ T Cells Induce Fatal Brainstem Pathology during Cerebral Malaria via Luminal Antigen-Specific Engagement of Brain Vasculature. Swanson PA 2nd, Hart GT, Russo MV, Nayak D, Yazew T, Peña M, Khan SM, Janse CJ, Pierce SK, McGavern DB. PLoS Pathog. 2016 Dec 1;12(12):e1006022.
The use of transgenic parasites in malaria vaccine research.Othman AS, Marin-Mogollon C, Salman AM, Franke-Fayard BM, Janse CJ, Khan SM. Expert Rev Vaccines. 2017 Jul;16(7):1-13.
Malaria parasite LIMP protein regulates sporozoite gliding motility and infectivity in mosquito and mammalian hosts. Santos JM, Egarter S, Zuzarte-Luís V, Kumar H, Moreau CA, Kehrer J, Pinto A, Costa MD, Franke-Fayard B, Janse CJ, Frischknecht F, Mair GR. Elife. 2017 May 2;6. pii: e24109.
Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies.Triller G, Scally SW, Costa G, Pissarev M, Kreschel C, Bosch A, Marois E, Sack BK, Murugan R, Salman AM, Janse CJ, Khan SM, Kappe SHI, Adegnika AA, Mordmüller B, Levashina EA, Julien JP, Wardemann H. Immunity. 2017 Dec 19;47(6):1197-1209.
Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity. Stone WJR, Campo JJ, Ouédraogo AL, Meerstein-Kessel L, Morlais I, Da D, Cohuet A, Nsango S, Sutherland CJ, van de Vegte-Bolmer M, Siebelink-Stoter R, van Gemert GJ, Graumans W, Lanke K, Shandling AD, Pablo JV, Teng AA, Jones S, de Jong RM, Fabra-García A, Bradley J, Roeffen W, Lasonder E, Gremo G, Schwarzer E, Janse CJ, Singh SK, Theisen M, Felgner P, Marti M, Drakeley C, Sauerwein R, Bousema T, Jore MM. Nat Commun. 2018 Feb 8;9(1):558.
Common PIEZO1 Allele in African Populations Causes RBC Dehydration and Attenuates Plasmodium Infection. Ma S, Cahalan S, LaMonte G, Grubaugh ND, Zeng W, Murthy SE, Paytas E, Gamini R, Lukacs V, Whitwam T, Loud M, Lohia R, Berry L, Khan SM, Janse CJ, Bandell M, Schmedt C, Wengelnik K, Su AI, Honore E, Winzeler EA, Andersen KG, Patapoutian A. Cell. 2018 Mar 8
Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection. Baeza Garcia A, Siu E, Sun T, Exler V, Brito L, Hekele A, Otten G, Augustijn K, Janse CJ, Ulmer JB, Bernhagen J, Fikrig E, Geall A, Bucala R. Nat Commun. 2018; 9(1):2714.
A Plasmodium berghei sporozoite-based vaccination platform against human malaria. Mendes AM, Machado M, Gonçalves-Rosa N, Reuling IJ, Foquet L, Marques C, Salman AM, Yang ASP, Moser KA, Dwivedi A, Hermsen CC, Jiménez-Díaz B, Viera S, Santos JM, Albuquerque I, Bhatia SN, Bial J, Angulo-Barturen I, Silva JC, Leroux-Roels G, Janse CJ, Khan SM, Mota MM, Sauerwein RW, Prudêncio M. NPJ Vaccines. 2018; 3:33.
Prime and target immunization protects against liver-stage malaria in mice. Gola A, Silman D, Walters AA, Sridhar S, Uderhardt S, Salman AM, Halbroth BR, Bellamy D, Bowyer G, Powlson J, Baker M, Venkatraman N, Poulton I, Berrie E, Roberts R, Lawrie AM, Angus B, Khan SM, Janse CJ, Ewer KJ, Germain RN, Spencer AJ, Hill AVS. Sci Transl Med. 2018 Sep 26;10(460).
Pre-clinical evaluation of a P. berghei-based whole-sporozoite malaria vaccine candidate.Mendes AM, Reuling IJ, Andrade CM, Otto TD, Machado M, Teixeira F, Pissarra J, Gonçalves-Rosa N, Bonaparte D, Sinfrónio J, Sanders M, Janse CJ, Khan SM, Newbold CI, Berriman M, Lee CK, Wu Y, Ockenhouse CF, Sauerwein RW, Prudêncio M. NPJ Vaccines. 2018 Nov 27;3:54.
Monocyte-Derived CD11c+ Cells Acquire Plasmodium from Hepatocytes to Prime CD8 T Cell Immunity to Liver-Stage Malaria. Kurup SP, Anthony SM, Hancox LS, Vijay R, Pewe LL, Moioffer SJ, Sompallae R, Janse CJ, Khan SM, Harty JT. Cell Host Microbe. 2019 Apr 10;25(4):565-577.
A tracer-based method enables tracking of Plasmodium falciparum malaria parasites during human skin infection. Winkel BMF, de Korne CM, van Oosterom MN, Staphorst D, Bunschoten A, Langenberg MCC, Chevalley-Maurel SC, Janse CJ, Franke-Fayard B, van Leeuwen FWB, Roestenberg M. Theranostics. 2019 Apr 13;9(10):2768-2778.
Genome-Scale Identification of Essential Metabolic Processes for Targeting the Plasmodium Liver Stage. Stanway RR, Bushell E, Chiappino-Pepe A, Roques M, Sanderson T, Franke-Fayard B, Caldelari R, Golomingi M, Nyonda M, Pandey V, Schwach F, Chevalley S, Ramesar J, Metcalf T, Herd C, Burda PC, Rayner JC, Soldati-Favre D, Janse CJ, Hatzimanikatis V, Billker O, Heussler VT. Cell. 2019 Nov 14;179(5):1112-1128.
A double-blind, placebo-controlled phase 1/2a trial of the genetically attenuated malaria vaccine PfSPZ-GA1. oestenberg M, Walk J, van der Boor SC, Langenberg MCC, Hoogerwerf MA, Janse JJ, Manurung M, Yap XZ, García AF, Koopman JPR, Meij P, Wessels E, Teelen K, van Waardenburg YM, van de Vegte-Bolmer M, van Gemert GJ, Visser LG, van der Ven AJAM, de Mast Q, Natasha KC, Abebe Y, Murshedkar T, Billingsley PF, Richie TL, Sim BKL, Janse CJ, Hoffman SL, Khan SM, Sauerwein RW. Sci Transl Med. 2020 May 20;12(544):eaaz5629.
Short professional biosketch Dr. Chris J. Janse (2021)
1976-1982: Leiden University, The Netherlands
The undergraduate/graduate studies were performed at the Faculty of Science (Biology) of the Leiden University, The Netherlands. Graduate research involved studies on the ecology and host-seeking behavior of parasitic wasps, ecology of bird populations (relationships between species diversity and forest management) and cell-biology of malaria parasites (genetic and environmental factors underlying sexual differentiation).
1983-1986: Leiden University / Utrecht University, The Netherlands
The PhD studies (‘cum Laude), funded by the Netherlands Organization for Scientific Research (NWO), were carried out jointly between the Utrecht University and the Leiden University. These PhD studies involved the development of technologies for use of the rodent model of malaria Plasmodium berghei to investigate sexual differentiation and DNA replication in malaria parasites. For example, technologies for in vitro cultivation of blood stages and sexual stages of the parasite. These technologies have significantly increased the relevance of P. berghei as a model for human malaria and improved the understanding of the biology of malaria parasites at the cellular and molecular level; for example, novel insights into the processes of DNA replication during parasite sexual development. Technologies were developed that allowed the first identification, separation and characterization of the chromosomes of rodent malaria parasites.
1986-2005: Leiden University / Leiden University Medical Center, The Netherlands
After the PhD studies, research in the Department of Parasitology (Leiden, LUMC) focused on the further development of rodent malaria models to investigate the biology of malaria parasites. This research has contributed to the introduction and application of advanced molecular techniques in malaria research, such as genomics (genome sequencing) and post-genomic (transcriptome, proteome) technologies. A major breakthrough was the implementation of technologies that permit genetic modification of rodent malaria parasites; technologies that allowed, for the first time, the generation of malaria parasites that retain stable genetic modifications. These and other technologies we developed have opened up new avenues in malarial research and have greatly aided studies on the basic biology of the parasite, studies on host-parasite interaction involved in pathology and contributed to the functional analysis of genes (including potential novel vaccine and drug targets), molecular processes such as translational gene regulation and real-time in vivo imaging of parasite-host interactions. These studies included genomic- and post-genomic analyses of malaria parasites, contributing to the complete genome sequencing of different malaria parasites and genome-wide studies of gene expression (microarrays, RNAseq analyses, proteome analyses). In 2005 these studies led to the development of the concept of vaccination with genetically attenuated parasites (GAP) and it was shown in rodent malaria models that GAP immunization can effectively protect against malaria infection.
2005-2021: Leiden University / Leiden University Medical Center, The Netherlands
Head of the Leiden Malaria Research Group (Department of Parasitology, LUMC): The current emphasis of the research is on the development of a human malaria vaccine based on genetically attenuated parasites (GAP) and on the identification and analysis of parasite proteins that are (putative) targets for improving current subunit vaccines that are in development (in collaboration with different international research groups, for example at the Jenner Institute, Oxford). For preclinical evaluation of novel vaccine candidates, the optimized rodent models of malaria are used, followed by the translation into human malaria vaccines and clinical evaluation (for example, viral-vectored vaccines targeting pre-erythrocytic stages of the human parasite). This research is based on the generation of a variety of gene-deletion and transgenic parasites, expressing reporter proteins (such as fluorescent, bioluminescent and OVA proteins), which have proven to be valuable tools in dissecting parasite biology and screening for vaccine candidate antigens. These genetically modified, transgenic parasites are shared by many different labs worldwide; in 2018 more than 170 transgene expressing parasites have been distributed by the Leiden malaria research group to more than 50 scientific groups across the world. In addition, CRISPR-Cas9 genetic modification of the human malaria parasite P. falciparum has been optimized for the creation of mutant (gene deletion and insertion) parasite lines, free of genes encoding drug resistance proteins.
The studies on a GAP vaccine led to the generation of the first malaria vaccine (GA1-Pfspz) consisting of genetically attenuated P. falciparum parasites and the preclinical and clinical evaluation of this vaccine (2015-2020; in collaboration with the biotech company Sanaria, US and Radboudumc, The Netherlands). This vaccine was safe and induced protective immune responses in human volunteers. Current studies are focused on enhancing the efficacy/immunogenicity of a genetically attenuated malaria vaccine and a clinical study testing a second-generation GAP vaccine (GA2) developed in Leiden is planned for 2021.
Leids Universitair Medisch Centrum
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