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© Artur Scherf
Scanning Electron Microscopy of Red Blood Cell infected by Plasmodium falciparum.
Scientific Fields
Diseases
Organisms
Applications
Technique

About

My research experience focuses on antimalarial drug discovery and malaria drug resistance.

During my PhD, I worked on a new chemical series inspired by a natural biflavonoid. I worked in the Laboratory of Therapeutic Innovation (UMR7200, Strasbourg) and in the Institut de Parasitologie et de Pathologie Tropicale de Strasbourg. I characterized the antimalarial properties of the compounds and, together with the chemists from the CERMN (Centre d’Enseignement et de Recherche sur le Médicament en Normandie) and the UMR7200, worked to optimize the hit to a lead drug candidate.

During my PhD, I had the opportunity to spend 6 months in the team of Didier Menard (now headed by Benoit Witkowski) in the Pasteur Institute in Cambodia, thanks to a Pierre-Ledoux and Pasteur International Network fellowship. There, I learnt with experts in the field of malaria drug resistance and assessed the efficacy of antimalarial drug candidates in field isolates of P. falciparum.

This experience in Cambodia allowed me also to obtain a postdoc position in the lab of Artur Scherf, who is renowned worldwide in the field of malaria, notably for his work in the field of malaria antigenic variation. I have now set up my project, aiming at discovering new antimalarial drugs targeting epigenetics.

Malaria is a tropical disease due to the parasite Plasmodium, still causing more than 650.000 deaths each year. The parasite is transmitted to Humans through the bite of an infected Anopheles mosquito. The parasite has a complex life cycle, reaching first the liver and then the blood, where it invades red blood cells. This last phase is responsible for the symptoms and can rapidly evolve in a life-threatening state. Plasmodium is becoming increasingly resistant to the front-line therapy (artemisinin-based combination therapies), especially in South-East Asia and more recently in South-America and Africa. There is thus an urgent need to develop new drugs that kill drug-resistant parasites. This pathogen uses phenotypic plasticity to adapt to changing environment. Epigenetic mechanisms play a major role in stage specific development and switch to different life cycle stages such as transmission stages. We are targeting these mechanisms to kill Plasmodium parasites and block parasite proliferation and transmission. Through a collaboration with the team of P. Arimondo, we already obtained epigenetic inhibitors that kill efficiently drug resistant P. falciparum blood stages. To integrate early the activity against circulating multi-resistant parasites, we collaborate with Benoit Witkowski (IP Cambodia). This project aims at combining chemistry and biology to (1) deliver a new drug candidate with characterized preclinical activity; (2) understand the mode of action. The project aims to develop our new drug candidates following a defined agenda to reach clinical trials, in order to provide urgently needed alternatives to the existing antimalarial therapies. In addition, the project will bring a deeper understanding of the role of epigenetic processes in malaria infection.

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