Dr. Shahid M. Khan (Associate Professor)

Vakgebied(en)

  • Parasitology - Malaria
  • Vaccine Research
  • Parasite Cell and Molecular biology
  • Parasite Genetic Modification

Introductie

Associate Professor


Biography

Shahid Khan is an Associate Professor in the Leiden Malaria Research Group, Leiden University Medical Center, Netherlands. Shahid graduated with a degree in Parasitology from the University of Glasgow, after which he worked as a Research Assistant in the Institute of Molecular Medicine, University of Oxford (in the group of Chris Newbold). For his PhD he moved to the University of Cambridge (Cambridge, UK), where his studies were focused on genetic and physical chromosomal mapping of  the Apicomplexan parasite, Toxoplasma gondii. For post-doctoral research he moved to the National Institute for Medical Research (London, UK) where his research was focussed on malaria, specifically on the expansion and expression of multi-gene families involved in parasite invasion of red blood cells. After this he moved to Leiden, Netherlands and to the group of Chris Janse and Andy Waters, and in collaboration with the group Matthias Mann (then Odense, Denmark), performed in depth and large scale proteome analyses on different stages of the malaria parasite and coupled this with the targeted deletion of parasite genes to uncover novel aspects of the parasite’s biology. He took up a group leader position within the Department of Parasitology in the LUMC in 2008.


Research Interests

I run a group that is working towards a malaria vaccine. Our focus in this area is divided into 2 main activities. First, we are looking to generate and test live-attenuated parasite vaccines; first screening using rodent models and then advancing the best candidates into P. falciparum and clinical evaluation. Second, we are engaged in projects to develop novel vaccine testing platforms that can be used to rapidly down-select sub-unit vaccine candidates and to test different vaccination modalities. These vaccine testing platforms involve generating modified rodent malaria parasites that express proteins from the human malaria parasite, which can then be used to rapidly assess the vaccine potency and efficacy against a human malaria antigen, in vivo (i.e. in mice).

In addition my group also is looking to improve genetic modification of both rodent and human malaria parasites, to create next generation attenuated vaccines and also to create various modified transgenic (rodent and human) parasites that can be used as reporters lines to test different drugs and vaccines.


Papers

Bijker EM, Borrmann S, Kappe SH, Mordmüller B, Sack BK, Khan SM
Novel approaches to whole sporozoite vaccination against malaria.
Vaccine (2015) Oct 12. pii: S0264-410X(15)01385-7. (REVIEW)

Salman AM, Mogollon CM, Lin JW, van Pul FJ, Janse CJ, Khan SM
Generation of Transgenic Rodent Malaria Parasites Expressing Human Malaria Parasite Proteins.
Methods Mol Biol. (2015) 1325:257-86 

Rijpma SR, van der Velden M, González-Pons M, Annoura T, van Schaijk BC, van Gemert GJ, van den Heuvel JJ, Ramesar J, Chevalley-Maurel S, Ploemen IH, Khan SM, Franetich JF, Mazier D, de Wilt JH, Serrano AE, Russel FG, Janse CJ, Sauerwein RW, Koenderink JB, Franke-Fayard BM.
Multidrug ABC transporters are essential for hepatic development of Plasmodium sporozoites.
Cellular Microbiology (2015) Aug 29

Hopp CS, Chiou K, Ragheb DR, Salman A, Khan SM, Liu AJ, Sinnis P.
Longitudinal analysis of Plasmodium sporozoite motility in the dermis reveals component of blood vessel recognition.
Elife (2015) Aug 13;4

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.
Long-term live imaging reveals cytosolic immune responses of host hepatocytes against Plasmodium infection and parasite escape mechanisms.
Autophagy (2015) Sep 2;11(9):1561-79 

Longley RJ, Salman AM, Cottingham MG, Ewer K, Janse CJ, Khan SM, Spencer AJ, Hill AV.
Comparative assessment of vaccine vectors encoding ten malaria antigens identifies two protective liver-stage candidates.
Scientific Reports (2015) Jul 3;5:11820.

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
Replication of Plasmodium in reticulocytes can occur without hemozoin formation, resulting in chloroquine resistance.
Journal of Experimental Medicine (2015) Jun 1;212(6):893-903

De Niz M, Helm S, Horstmann S, Annoura T, Del Portillo HA, Khan SM, Heussler VT.
In vivo and in vitro characterization of a Plasmodium liver stage-specific promoter.
PLoS One (2015) Apr 15;10(4):e0123473

Ramiro RS, Khan SM, Franke-Fayard B, Janse CJ, Obbard DJ, Reece SE.
Hybridization and pre-zygotic reproductive barriers in Plasmodium.
Proceedings of the Royal Society B (2015) May 7;282(1806):20143027

Burda PC, Roelli MA, Schaffner M, Khan SM, Janse CJ, Heussler VT.
A Plasmodium phospholipase is involved in disruption of the liver stage parasitophorousvacuole membrane.
PLoS Pathogens (2015) Mar 18;11(3):e1004760

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

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.
A comprehensive evaluation of rodent malaria parasite genomes and gene expression.
BMC Biology (2014) Oct 30;12:86

Lin JW, Shaw TN, Annoura T, Fougère A, Bouchier P, Chevalley-Maurel S, Kroeze H, Franke-Fayard B, Janse CJ, Couper KN, Khan SM
The subcellular location of ovalbumin in Plasmodium berghei blood stages influences the magnitude of T-cell responses
Infection and Immunity (2014) Nov;82(11):4654-65

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
Two Plasmodium 6-Cys family-related proteins have distinct and critical roles in liver-stage development
FASEB Journal (2014) May;28(5):2158-70

Ezougou CN, Ben-Rached F, Moss DK, Lin JW, Black S, Knuepfer E, Green JL, Khan SM, Mukhopadhyay A, Janse CJ, Coppens I, Yera H, Holder AA, Langsley G.
Plasmodium falciparum Rab5B is an N-terminally myristoylated Rab GTPase that is targeted to the parasite's plasma and food vacuole membranes
PLoS One (2014) Feb 3;9(2):e87695.

Khan SM, Reece SE, Waters AP, Janse CJ, Kaczanowski S.
Why are male malaria parasites in such a rush?: Sex-specific evolution and host-parasite interactions
Evolution, Medicine, and Public Health (2013) Jan;2013(1):3-13.

van Schaijk BC, Kumar TR, Vos MW, Richman A, van Gemert GJ, Li T, Eappen AG, Williamson KC, Morahan BJ, Fishbaugher M, Kennedy M, Camargo N, Khan SM, Janse CJ, Sim KL, Hoffman SL, Kappe SH, Sauerwein RW, Fidock DA, Vaughan AM.
Type II fatty acid biosynthesis is essential for Plasmodium falciparum sporozoite development in the midgut of Anopheles mosquitoes
Eukaryotic Cell (2014) May;13(5):550-9. 

Ferrer M, Martin-Jaular L, De Niz M, Khan SM, Janse CJ, Calvo M, Heussler V, del Portillo HA.
Imaging of the spleen in malaria
Parasitology International (2014) Feb;63(1):195-205 (REVIEW)

Pollitt LC, Churcher TS, Dawes EJ, Khan SM, Sajid M, Basáñez MG, Colegrave N, Reece SE
Costs of crowding for the transmission of malaria parasites.
Evolutionary Applications (2013) Jun;6(4):617-29

Lin JW, Meireles P, Prudêncio M, Engelmann S, Annoura T, Sajid M, Chevalley-Maurel S, Ramesar J, Nahar C, Avramut CMC, Koster AJ, Matuschewski K, Waters AP, Janse CJ, Mair GR,Khan SM
Loss-of-Function Analyses Defines Vital and Redundant Functions of the Plasmodium Rhomboid Protease Family.
Molecular Microbiology (2013) 88(2):318-38.

Lin JW, Sajid M, Ramesar J, Khan SM, Janse CJ, Franke-Fayard B.
Screening inhibitors of P. berghei blood stages using bioluminescent reporter parasites.
Methods Mol Biol. (2013); 923:507-22.

Annoura T, Chevalley S, Janse CJ, Franke-Fayard B, Khan SM
Quantitative analysis of Plasmodium berghei liver stages by bioluminescence imaging.
Methods Mol Biol. (2013); 923:429-43

Khan SM, Kroeze H, Franke-Fayard B, Janse CJ.
Standardization in generating and reporting genetically modified rodent malaria parasites: the RMgmDB database.
Methods Mol Biol. (2013); 923:139-50.

Khan SM*, Reece SE*, Waters AP, Janse CJ, Kaczanowski S*
Why are male malaria parasites in such a rush? Sex-specific evolution and host-parasite interactions
Evolution Medicine and Public Health (2013) (1): 3-13

Ploemen IHJ, Chakravarty S, van Gemert G-J, Annoura T, Khan SM, Janse CJ, Hermsen CC, Hoffman SL, Sauerwein RW
Plasmodium liver load following parenteral sporozoite administration in rodents
Vaccine (2013) Jul 25;31(34):3410-6

Khan SM*, Janse CJ, Kappe SH, Mikolajczak SA*
Genetic engineering of attenuated malaria parasites for vaccination
Current  Opinion in Biotechnology (2012), 23(6):908-16 (REVIEW

Annoura T*, Ploemen IHJ*, van Schaijk BCL*, Sajid M, Vos MW, van Gemert G-J, Chevalley-Maurel S, Franke-Fayard BMD, Hermsen CC, Gego A, Franetich J-F, 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

Fonager J, Pasini EM, Braks JAM, Klop O, Ramesar J, Remarque EJ, Vroegrijk IO, van Duinen SG, Thomas AW, Khan SM, Mann M, Kocken CHM, Janse CJ, Franke-Fayard BM
Reduced CD36-dependent tissue sequestration of Plasmodium-infected erythrocytes is detrimental to malaria parasite growth in vivo
Journal of Experimental Medicine (2012), 16;209(1):93-107

Lin J-W*, Annoura T*, Sajid M, Chevalley-Maurel S, Ramesar J, Klop O, Franke-Fayard BMD, Janse CJ, Khan SM
A Novel ‘Gene Insertion/Marker Out’ (GIMO) Method for Transgene Expression and Gene Complementation in Rodent Malaria Parasites.
PLoS ONE (2011) 6(12): e29289. doi:10.1371/journal.pone.0029289

Douradinha B, van Dijk M, van Gemert G-J, Khan SM, Janse CJ, Waters AP, Sauerwein RW, Luty AJF, Silva-Santos B, Mota MM, Epiphanio S
Immunization with genetically attenuated P52-deficient Plasmodium berghei sporozoites induces a long-lasting effector memory CD8+ T cell response in the liver
Journal of Immune Based Therapies and Vaccines (2011), Oct; 9(1):6

Laurentino EC, Taylor S, Mair GR, Lasonder E, Bartfai R, Stunnenberg HG, Kroeze H, Ramesar J, Franke-Fayard B, Khan SM, Janse CJ, Waters AP
Experimentally controlled down regulation of the histone chaperone FACT in Plasmodium berghei reveals that it is critical to male gamete fertility
Cellular Microbiology (2011) Dec;13(12):1956-1974

Balu B, Maher SP, Pance A, Chauhan C, Naumov AV, Andrews RM, Ellis PD, Khan SM, Lin JW, Janse CJ, Rayner JC, Adams JH.
CCR4-Associated Factor-1 Coordinates Expression of Plasmodium falciparum Egress and Invasion Proteins.
Eukaryotic Cell (2011) Sep;10(9):1257-63

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 Pathogens (2011) May;7(5):e1002046 

Barker RH Jr, Urgaonkar S, Mazitschek R, Celatka C, Skerlj R, Cortese JF, Tyndall E, Liu H, Cromwell M, Sidhu AB, Guerrero-Bravo JE, Crespo-Llado KN, Serrano AE, Lin JW, Janse CJ, Khan SM, Duraisingh M, Coleman BI, Angulo-Barturen I, Jiménez-Díaz MB, Magán N, Gomez V, Ferrer S, Santos Martínez M, Wittlin S, Papastogiannidis P, O'Shea T, Klinger JD, Bree M, Lee E, Levine M, Wiegand RC, Munoz B, Wirth DF, Clardy J, Bathurst I, Sybertz E.
Aminoindoles: a Novel Scaffold with Potent Activity against Plasmodium falciparum.
Antimicrobial Agents and Chemotherapy (2011) June; 55(6):2612-22.

Fonager J, Franke-Fayard BM, Adams JH, Ramesar J, Klop O, Khan SM, Janse CJ, Waters AP
Development of the piggyBac transposable system for Plasmodium berghei and its application for random mutagenesis in malaria parasites.
BMC Genomics. (2011) Mar 20;12(1):155

van Schaijk BC, Vos MW, Janse CJ, Sauerwein RW, Khan SM
Removal of heterologous sequences from Plasmodium falciparum mutants using FLPe-recombinase.
PLoS One (2010) Nov 30;5(11):e15121. 

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 Pathogens (2010) Sep 30;6(9). pii: e1001032 (REVIEW)

Booker ML, Bastos CM, Kramer ML, Barker RH Jr, Skerlj R, Bir Sidhu A, Deng X, Celatka C, Cortese JF, Guerrero Bravo JE, Krespo Llado KN, Serrano AE, Angulo-Barturen I, Jimenez-Diaz MB, Viera S, Garuti H, Wittlin S, Papastogiannidis P, Lin JW, Janse CJ, Khan SM, Duraisingh M, Coleman B, Goldsmith EJ, Phillips MA, Munoz B, Wirth DF, Klinger JD, Wiegand R, Sybertz E.
Novel inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase with anti-malarial activity in the mouse model.
Journal of Biological Chemistry (2010) Aug 11.

Janse CJ, Kroeze H, van Wigcheren A, Mededovic S, Fonager J, Franke-Fayard B, Waters AP, Khan SM
A genotype and phenotype database of genetically modified malaria-parasites
Trends in Parasitology (2010) Jul 19 (REVIEW)

van Dijk MR, van Schaijk BC, Khan SM, van Dooren MW, Ramesar J, Kaczanowski S, van Gemert GJ, 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.  

Iwanaga S, Khan SM, Kaneko I, Christodoulou Z, Newbold C, Yuda M, Janse CJ, Waters AP
Functional identification of the Plasmodium centromere and generation of a Plasmodiumartificial chromosome.
Cell Host and Microbe (2010) Mar 18;7(3):245-55.

Ploemen IH, Prudêncio M, Douradinha BG, Ramesar J, Fonager J, van Gemert GJ, Luty AJ, Hermsen CC, Sauerwein RW, Baptista FG, Mota MM, Waters AP, Que I, Lowik CW, Khan SM, Janse CJ, Franke-Fayard BM
Visualisation and quantitative analysis of the rodent malaria liver stage by real time imaging.
PLoS ONE (2009) Nov 18;4(11):e7881

Tufet-Bayona M, Janse CJ, Khan SM, Waters AP, Sinden RE, Franke-Fayard B
Localisation and timing of expression of putative Plasmodium berghei rhoptry proteins in merozoites and sporozoites
Molecular and Biochemical Parasitology (2009) 166(1):22-31

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 Pathogens (2008) Oct;4(10):e1000195 

van Schaijk BC, Janse CJ, van Gemert GJ, van Dijk MR, Gego A, Franetich JF, van de Vegte-Bolmer M, Yalaoui S, Silvie O, Hoffman SL, Waters AP, Mazier D, Sauerwein RW, Khan SM
Gene disruption of Plasmodium falciparum p52 results in attenuation of malaria liver stage development in cultured primary human hepatocytes
PLoS ONE (2008); 3(10):e3549

Deitsch K, Duraisingh M, Dzikowski R, Gunasekera A, Khan S, Le Roch K, Llinas M, Mair G, McGovern V, Roos D, Shock J, Sims J, Wiegand R, Winzeler E, Wirth D.
Mechanisms of gene regulation in Plasmodium
American Journal of Tropical Medicine and Hygiene (2007) Aug;77(2):201-8 

Mair GR, Braks JA, Garver LS, Wiegant JC, Hall N, Dirks RW, Khan SM, Dimopoulos G, Janse CJ, Waters AP.
Regulation of sexual development of Plasmodium by translational repression.
Science (2006) Aug; 313(5787):667-9. 

Khan SM, Franke-Fayard B, Mair GR, Lasonder E, Janse CJ, Mann M & Waters AP.
Proteome analysis of separated male and female gametocytes reveals novel sex specific Plasmodium biology
Cell (2005) June; 121 675-87 

Khan SM, Waters AP
Malaria parasite transmission stages: an update.
Trends in Parasitology (2004) Dec; 20(12):575-80 (REVIEW)

Kaviratne M, Khan SM, Jarra W, Preiser PR.
Small variant STEVOR antigen is uniquely located within Maurer's clefts in Plasmodium falciparum-infected red blood cells.
Eukaryotic Cell (2002) Dec; 1(6):926-35.

Preiser PR, Khan S, Costa FT, Jarra W, Belnoue E, Ogun S, Holder AA, Voza T, Landau I, Snounou G, Renia L.
Stage-specific transcription of distinct repertoires of a multigene family during Plasmodiumlife cycle.
Science (2002) Jan 11;  295(5553):342-5. 

Di Ruberto C, Dempster A, Khan S, Jarra W.
Analysis of infected blood cell images using morphological operators
Image and Vision Computing (2002) Feb 20 (2):133-146

Khan SM, Jarra W, Preiser PR.
The 235 kDa rhoptry protein of Plasmodium (yoelii) yoelii: function at the junction.
Molecular and  Biochemical Parasitology (2001) Sep 28; 117(1):1-10 (REVIEW

Khan SM, Jarra W, Bayele H, Preiser PR.
Distribution and characterisation of the 235 kDa rhoptry multigene family within the genomes of virulent and avirulent lines of Plasmodium yoelii.
Molecular and Biochemical Parasitology (2001) May; 114(2):197-208. 

Preiser P, Kaviratne M, Khan S, Bannister L, Jarra W.
The apical organelles of malaria merozoites: host cell selection, invasion, host immunity and immune evasion.
Microbes and Infection (2000) Oct; 2(12):1461-77 (REVIEW)

Craig AG, Pinches R, Khan S, Roberts DJ, Turner GD, Newbold CI, Berendt AR.
Failure to block adhesion of Plasmodium falciparum-infected erythrocytes to ICAM-1 with soluble ICAM-1.
Infection and Immunity (1997) Nov; 65(11):4580-5.

All publications can be found at Google Scholar


Contactgegevens

Leids Universitair Medisch Centrum
Gebouw 1
Kamer P4-31

Albinusdreef 2
2333 ZA Leiden
Tel: +31 71 526 1405

Postzone P4-Q
Postbus 9600
2300 RC Leiden

E-mail: s.m.khan@lumc.nl