EDCTP Alumni Network

Fostering excellence and collaboration in the next generation of researchers

Call Career Development Fellowship (CDF)
Programme EDCTP2
Start Date 2018-12-01
End Date 2020-11-30
Project Code TMA2017CDF-1892
Status Active

Title

Understanding the biology of Plasmodium vivax and Plasmodium ovale for the development of a field-based anti-hypnozoite drug screening model (HypnoBio)

Host Organisation

Institution Country
Mali

Current Organisation

Université des Sciences, des Techniques et des Technologies de Bamako

Current Job Title

Master Assistant Professor

Awards

2018 MMV African challenge grant ref RD/18/0056
2019 MMV-USTTB screening project ref PO 18/01123

Students Supervised

Type Name Title University Start Date End Date
Pharmacy student thesis Fanta Sogore Supervisor Université des Sciences, des Techniques et des Technologies de Bamako (faculte de pharmacie) 2019 2020
PhD candidate Biology-entomology Andargie Abate Co-supervisor Addis Ababa University, Aklilu Lemma Institute of Pathobiology, 2019
Master Bio-informatic Aissata Doumbia Supervisor Université des Sciences, des Techniques et des Technologies de Bamako (faculté sciences techniques) 2019 2019

Memberships

Role Committee/board Start Date End Date
reviewer Vaccines and Immunology 2018

Education

Institution Degree Year
UNIVERSITE PARIS 6 (UNIVERSITE PIERRE ET MARIE CURIE (UPMC)), France PhD in Complexity of living organisms 2012-09-12
UNIVERSITE JOSEPH FOURIER (UJF), faculty of pharmacy, Grenoble 1., France Master in biotechnology, health, diagnostic and drug engineering 2008-06-30
UNIVERSITE D’ORAN ES-SENIA, department of biotechnology, Oran., Algeria Engineer degree in biotechnology and microbiology engineering 2007-06-30

Areas Of Specialisation

Malaria Neglected Infectious Diseases (NID)

Grants

Grant Code:
Source of funding:
Merck Master Service Agreement.
Amount:
46000
Role:
Principal Investigator
Start Date:
2021-01-01
End Date:
2022-01-01
Grant Code:
RD/18/0056)
Source of funding:
MMV
Amount:
20000
Role:
Principal Investigator
Start Date:
2018-01-01
End Date:
2018-01-01
Grant Code:
GCA/DD/rnd3/028/006
Source of funding:
Bill and Melinda Gates Foundation
Amount:
100000
Role:
Researcher
Start Date:
2019-01-01
End Date:
2021-01-01
Grant Code:
Source of funding:
Merck Master Service Agreement.
Amount:
46000
Role:
Principal Investigator
Start Date:
2021-01-01
End Date:
2021-01-01
Grant Code:
ID INV-015996
Source of funding:
Bill and Melinda Gates Foundation
Amount:
200000
Role:
Researcher
Start Date:
2020-01-01
End Date:
2022-01-01
Grant Code:
RD-18-0067
Source of funding:
Medicines for Malaria Venture (MMV)
Amount:
80000
Role:
Start Date:
2021-01-01
End Date:
2022-01-01
Grant Code:
Source of funding:
Merck Master Service Agreement.
Amount:
49000
Role:
Principal Investigator
Start Date:
2020-01-01
End Date:
2021-01-01
Grant Code:
RD-18-0067
Source of funding:
Medicines for Malaria Venture (MMV)
Amount:
100000
Role:
Principal Investigator
Start Date:
2020-01-01
End Date:
2021-01-01
Grant Code:
PO/18/01123
Source of funding:
MMV
Amount:
75000
Role:
Principal Investigator
Start Date:
2019-01-01
End Date:
2020-01-01

Publications

Authors:
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.
Date:
2018-04-26
Journal:
Antimicrob Agents Chemother
Content:
Identifiers:
Authors:
Laurent Dembele, Yaw Aniweh, Nouhoum Diallo, Fanta Sogore, Cheick Papa Oumar Sangare, Aboubecrin Sedhigh Haidara, Aliou Traore, Seidina A S Diakité, Mahamadou Diakite, Brice Campo, Gordon A Awandare, Abdoulaye A Djimde
Date:
2021-05-22
Journal:
Journal of Antimicrobial Chemotherapy
Content:

Abstract

Objectives

To evaluate Plasmodium malariae susceptibility to current and lead candidate antimalarial drugs.

Methods

We conducted cross-sectional screening and detection of all Plasmodium species malaria cases, which were nested within a longitudinal prospective study, and an ex vivo assessment of efficacy of a panel of antimalarials against P. malariae and Plasmodium falciparum, both PCR-confirmed mono-infections. Reference compounds tested included chloroquine, lumefantrine, artemether and piperaquine, while candidate antimalarials included the imidazolopiperazine GNF179, a close analogue of KAF156, and the Plasmodium phosphatidylinositol-4-OH kinase (PI4K)-specific inhibitor KDU691.

Results

We report a high frequency (3%–15%) of P. malariae infections with a significant reduction in ex vivo susceptibility to chloroquine, lumefantrine and artemether, which are the current frontline drugs against P. malariae infections. Unlike these compounds, potent inhibition of P. malariae and P. falciparum was observed with piperaquine exposure. Furthermore, we evaluated advanced lead antimalarial compounds. In this regard, we identified strong inhibition of P. malariae using GNF179, a close analogue of KAF156 imidazolopiperazines, which is a novel class of antimalarial drug currently in clinical Phase IIb testing. Finally, in addition to GNF179, we demonstrated that the Plasmodium PI4K-specific inhibitor KDU691 is highly inhibitory against P. malariae and P. falciparum.

Conclusions

Our data indicated that chloroquine, lumefantrine and artemether may not be suitable for the treatment of P. malariae infections and the potential of piperaquine, as well as new antimalarials imidazolopiperazines and PI4K-specific inhibitor, for P. malariae cure.

Identifiers:
Authors:
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*.
Date:
2019-05-22
Journal:
Biomaterials
Content:
Identifiers:
Authors:
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*.
Date:
2019-05-16
Journal:
eLife
Content:
Identifiers:
Authors:
Laurent Dembélé 1 2 3, Jean-François Franetich 1, Valérie Soulard 1, Nadia Amanzougaghene 1, Shahin Tajeri 1, Teun Bousema 4, Geert-Jan van Gemert 4, Roger Le Grand 5, Nathalie Dereuddre-Bosquet 5, J Kevin Baird 6 7, Dominique Mazier # 1, Georges Snounou # 1 5
Date:
2020-12-16
Journal:
Antimicrob Agents Chemothe
Content:

For a long while, 8-aminoquinoline compounds have been the only therapeutic agents against latent hepatic malaria parasites. These have poor activity against the blood-stage plasmodia causing acute malaria and must be used in conjunction with partner blood schizontocidal agents. We examined the impacts of one such agent, chloroquine, upon the activity of primaquine, an 8-aminoquinoline, against hepatic stages of Plasmodium cynomolgiPlasmodium yoeliiPlasmodium berghei, and Plasmodium falciparum within several ex vivo systems-primary hepatocytes of Macaca fascicularis, primary human hepatocytes, and stably transformed human hepatocarcinoma cell line HepG2. Primaquine exposures to formed hepatic schizonts and hypnozoites of P. cynomolgi in primary simian hepatocytes exhibited similar 50% inhibitory concentration (IC50) values near 0.4 μM, whereas chloroquine in the same system exhibited no inhibitory activities. Combining chloroquine and primaquine in this system decreased the observed primaquine IC50 for all parasite forms in a chloroquine dose-dependent manner by an average of 18-fold. Chloroquine also decreased the primaquine IC50 against hepatic P. falciparum in primary human hepatocytes, P. berghei in simian primary hepatocytes, and P. yoelii in primary human hepatocytes. Chloroquine had no impact on primaquine IC50 against P. yoelii in HepG2 cells and, likewise, had no impact on the IC50 of atovaquone (hepatic schizontocide) against P. falciparum in human hepatocytes. We describe important sources of variability in the potentiation of primaquine activity by chloroquine in these systems. Chloroquine potentiated primaquine activity against hepatic forms of several plasmodia. We conclude that chloroquine specifically potentiated 8-aminoquinoline activities against active and dormant hepatic-stage plasmodia in normal primary hepatocytes but not in a hepatocarcinoma cell line.

Identifiers:
Authors:
Désiré N, Ngo Y, Franetich JF, Laurent Dembele, Mazier D, Vaillant JC, Poynard T, Thibault V.
Date:
2015-09-22
Journal:
J Viral Hepat
Content:
Identifiers:
Authors:
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.

Date:
2014-02-09
Journal:
Nature Medicine
Content:
Identifiers:
Authors:
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.

Date:
2017-05-24
Journal:
Scientific Reports
Content:
Identifiers:
Authors:
Devendra Kumar Gupta,#1,2,† Laurent Dembele,#2,3,† Annemarie Voorberg-van der Wel,4 Guglielmo Roma,5 Andy Yip,2 Vorada Chuenchob,6 Niwat Kangwanrangsan,7 Tomoko Ishino,8 Ashley M Vaughan,6 Stefan H Kappe,6 Erika L Flannery,6 Jetsumon Sattabongkot,9 Sebastian Mikolajczak,1,6 Pablo Bifani,2,10,11 Clemens HM Kocken,4 and Thierry Tidiane Diagana1,2
Date:
2019-05-16
Journal:
eLife.
Content:

Plasmodium vivax hypnozoites persist in the liver, cause malaria relapse and represent a major challenge to malaria elimination. Our previous transcriptomic study provided a novel molecular framework to enhance our understanding of the hypnozoite biology (Voorberg-van der Wel A, et al., 2017). In this dataset, we identified and characterized the Liver-Specific Protein 2 (LISP2) protein as an early molecular marker of liver stage development. Immunofluorescence analysis of hepatocytes infected with relapsing malaria parasites, in vitro (P. cynomolgi) and in vivo (P. vivax), reveals that LISP2 expression discriminates between dormant hypnozoites and early developing parasites. We further demonstrate that prophylactic drugs selectively kill all LISP2-positive parasites, while LISP2-negative hypnozoites are only sensitive to anti-relapse drug tafenoquine. Our results provide novel biological insights in the initiation of liver stage schizogony and an early marker suitable for the development of drug discovery assays predictive of anti-relapse activity.

Identifiers:
Authors:
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.
Date:
2011-03-31
Journal:
PLoS One
Content:
Identifiers:
Authors:
Laurent Dembele* Devendra Kumar Gupta Bamaprasad Dutta Adeline C.Y. Chua Siu Kwan Sze Pablo Bifani.
Date:
2019-08-24
Journal:
PROTEOMICS
Content:
Identifiers:
Authors:
Annemarie M. Voorberg-van der Wel 1, Anne-Marie Zeeman1, Ivonne G. Nieuwenhuis1, Nicole M. van der Werff1, Els J. Klooster1, Onny Klop1, Lars C. Vermaat1, Devendra Kumar Gupta2, Laurent Dembele2,3, Thierry T. Diagana2 & Clemens H.M. Kocken1*
Date:
2020-01-03
Journal:
COMMUNICATIONS BIOLOGY
Content:

Plasmodium vivax malaria is characterized by repeated episodes of blood stage infection (relapses) resulting from activation of dormant stages in the liver, so-called hypnozoites. Transition of hypnozoites into developing schizonts has never been observed. A barrier for studying this has been the lack of a system in which to monitor growth of liver stages. Here, exploiting the unique strengths of the simian hypnozoite model P. cynomolgi, we have developed green-fluorescent (GFP) hypnozoites that turn on red-fluorescent (mCherry) upon activation. The transgenic parasites show full liver stage development, including merozoite release and red blood cell infection. We demonstrate that individual hypnozoites actually can activate and resume development after prolonged culture, providing the last missing evidence of the hypnozoite theory of relapse. The few events identified indicate that hypnozoite activation in vitro is infrequent. This system will further our understanding of the mechanisms of hypnozoite activation and may facilitate drug discovery approaches.

Identifiers:

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