Dr Laurent DEMBELE, an Assistant Professor at the Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Mali has been awarded an EDCTP career development fellowship reference TMA2017CDF-1892/HypnoBio.
His project is entitled : Understanding the biology of Plasmodium vivax and Plasmodium ovale for the development of a field-based anti-hypnozoite drug screening model.
Dr Laurent DEMBELE’s project aim to investigate the biology of the hepatic stages including hypnozoites of P. vivax and P. ovale in a field setting in Ethiopia and Mali to accelerate drug discovery against malaria relapsing species.
According to Dr Laurent Dembele, research focusing on Plasmodium vivax and Plasmodium ovale has been severely limited by logistical and biological obstacles while most of malaria control program have instead focused on falciparum malaria. P. vivax and P. ovale have unique attribute to cause malaria relapses, resulting from the activation of quiescent hepatic hypnozoites, hinder global efforts to control and eliminate malaria. Currently, Primaquine is the only licensed drug able to eradicate hypnozoite. However primaquine is not a well-tolerated drug. Unfortunately very few tools are available to support biological studies and screen efforts for P. vivax and P. ovale. Specifically, an optimized in vitro liver-stage model supporting biological studies and screen efforts and that would be easily accessible to all researchers is critically needed to enable the discovery of new drugs. We have previously used simian parasite, Plasmodium cynomolgi that is related to P. vivax to establish an in vitro culture system in which we have recapitulated the full liver stage life-cycle of the parasite including the hypnozoite stage. We have now demonstrated that this system could be used for testing candidate drugs or exploring the liver stage biology including hypnozoite. A further unique attribute is the absence of a reliable robust culture system for the blood stage forms of P. vivax and P. ovale, this is also the case for the most closely related simian malaria species, P. cynomolgi. Thus, access to P. vivax and P. ovale becomes depend to field isolates. These major obstacles have critically limited molecular and cellular investigation of P. vivax and P. ovale malaria biology. To leverage these promising results, the objective of this career development fellowship proposal is to accelerate the research toward an optimized drug assay in which to evaluate the anti-hypnozoite activity of candidate drugs toward accelerated drug discovery against malaria relapsing species.
Please refer to Dr Laurent Dembele previous publications on Malaria drug discovery and liver stage biology and technologies.
Laurent Dembélé, Jean-François Franetich, Audrey Lorthiois, Audrey Gego, Anne-Marie Zeeman, Clemens H M Kocken, Roger Le Grand, Nathalie Dereuddre-Bosquet, Geert-Jan van Gemert, Robert Sauerwein, Jean-Christophe Vaillant, Laurent Hannoun, Matthew J Fuchter, Thierry T Diagana, Nicholas A Malmquist, Artur Scherf, Georges Snounou & Dominique Mazier. Persistence and activation of malaria hypnozoites in long-term primary hepatocyte cultures. Nature Medicine 20, 307–312 (2014) 09 February 2014 doi:10.1038/nm.3461
Laurent Dembele, Audrey Gego , Anne-Marie Zeeman, Jean-François Franetich, Olivier Silvie, Armelle Rametti, Roger Le Grand, Nathalie Dereuddre-Bosquet, Robert Sauerwein, Geert-Jan van Gemert, Jean-Christophe Vaillant, Alan W. Thomas, Georges Snounou , Clemens H. M. Kocken , Dominique Mazier. Towards an In Vitro Model of Plasmodium Hypnozoites Suitable for Drug Discovery. PLoS One. 2011 Mar 31; 6(3): https://doi.org/10.1371/journal.pone.0018162
Laurent Dembele* Devendra Kumar Gupta Bamaprasad Dutta Adeline C.Y. Chua Siu Kwan Sze Pablo Bifani. Quantitative Proteomic Analysis of Simian Primary Hepatocytes Reveals Candidate Molecular Markers for Permissiveness to Relapsing Malaria Plasmodium Cynomolgi. Proteomics. Published: 24 August 2019 https://doi.org/10.1002/pmic.201900021
Devendra Kumar Gupta†, Laurent Dembele†, Annemarie Voorberg-van der Wel, Guglielmo Roma, Andy Yip, Vorada Chuenchob, Niwat Kangwanrangsan, Tomoko Ishino, Ashley M Vaughan6, Stefan H Kappe, Erika L Flannery, Jetsumon Sattabongkot, Sebastian Mikolajczak, Pablo Bifani, Clemens HM Kocken, Thierry Tidiane Diagana*. The Plasmodium Liver-Specific Protein 2 (LISP2) is an early marker of liver stage development. eLife 2019-05-16 | ISSN: 2050-084X. DOI: 10.7554/elife.43362
Annemarie M. Voorberg-van der Wel, Anne-Marie Zeeman, Ivonne G. Nieuwenhuis, Nicole M. van der Werff, Els J. Klooster, Onny Klop, Lars C. Vermaat, Devendra Kumar Gupta, Laurent Dembele, Thierry T. Diagana & Clemens H. M. Kocken. A dual fluorescent Plasmodium cynomolgi reporter line reveals in vitro malaria hypnozoite reactivation. COMMUNICATIONS BIOLOGY | https://doi.org/10.1038/s42003-019-0737-3 . Published: 03 January 2020.
Adeline C.Y.Chua, Abhishek Ananthanarayanan, Jessica Jie Ying Ong, Jen Yi Won, AndyYip, Nisha Hari Singh, Yinghua Qu, Laurent Dembele, Michael McMillian, Ratawan Ubalee, Silas Davidson, Anchalee Tungtaeng, Rawiwan Imerbsin, Kapish Gupta, Chiara Andolina, FanLee, Kevin S-W Tan, François Nosten, Bruce Russell, Amber Lange, Thierry T. Diagana, Laurent Rénia, Bryan K.S.Yeung, HanryYudi, Pablo Bifani*. Hepatic spheroids used as an in vitro model to study malaria relapse. Biomaterials 2019-05-22 | ISSN: 0142-9612. DOI: 10.1016/j.biomaterials.2019.05.032
Laurent Dembele, Devendra Kumar Gupta, Michelle Yi-Xiu Lim, Xiaoman Ang, Jeremy J. Selva, Kesinee Chotivanich, Chea Nguon, Arjen M. Dondorp, Ghislain M. C. Bonamy, Thierry T. Diagana, and Pablo Bifani. Imidazolopiperazines (IPZ) kill both rings and dormant rings in wild type and K13 artemisinin resistant Plasmodium falciparum in vitro. Antimicrob Agents Chemother. 2018 Apr 26;62(5). pii: e02235-17. doi: 10.1128/AAC.02235-17.
Laurent Dembele, Ang X, Chavchich M, Bonamy GMC, Selva JJ, Lim MY, Bodenreider C, Yeung BKS, Nosten F, Russell BM, Edstein MD, Straimer J, Fidock DA, Diagana TT, Bifani. The Plasmodium PI(4)K inhibitor KDU691 selectively inhibits dihydroartemisinin-pretreated Plasmodium falciparum ring-stage parasites. Scientific Reports 7, May 24, 2017. Article number: 2325 (2017) doi:10.1038/s41598-017-02440-6