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Alliance Française contre les Maladies Parasitaires

  Cetherine Lavazec

Catherine LAVAZEC

Information

microscope Institut Cochin, CNRS UMR 8104, Inserm U1016 
team Biology of Plasmodium transmission 
location Paris
orcid 0000-0003-1533-7282 
email This email address is being protected from spambots. You need JavaScript enabled to view it.
website https://www.institutcochin.fr/la-recherche/3i/equipe-lavazec

Scientific interests and projects


Our team aims to dissect the interactions between Plasmodium falciparum transmission stages (gametocytes) and the human host. Our work is oriented in 4 main axes:

i) Decipher how gametocytes modify the biomechanical properties of their infected host cell
We use novel biophysical and microscopy techniques (microsphiltration, micropipette aspiration, ektacytometry, FRAP, AFM, Super-resolution imaging, Imagestream, patchclamp…) to unravel the mechanisms regulating deformability, stability, permeability and adhesive properties of gametocyte-infected red blood cells.

ii) Unravel the interactions of gametocytes with the bone marrow microenvironment
We focus our attention on interactions of Plasmodium gametocytes with bone marrow erythroid precursors. For this we have access to human primary erythroblasts and we have recently set-up a protocol for producing gametocyte-infected erythroid precursor cells in ex vivo culture of human erythroblasts. A permanent scientist in the team is an expert in human erythropoiesis.

iii) Address in vivo the mechanisms underlying the sequestration and the circulation of gametocytes in their host We perform in vivo imaging in a humanized mouse model that we have recently set up to decipher the mechanisms underlying sequestration and circulation of gametocytes. This mouse model also allows to test in vivo transmission-blocking drugs.

iv) Generate a novel anti-malarial transmission-blocking drug
We propose a novel translational approach based on targeting the mechanical properties of infected host cells rather than parasite metabolic pathways. In this context, we have discovered that the phosphodiesterase (PDE) inhibitor sildenafil (Viagra) increases the stiffness of mature GIE and may thus favor their elimination by the spleen. We have developed collaborations with chemists (Pr B. Deprez, Pasteur Lille) to optimize Plasmodium-specific PDE inhibitors.

Top 5 publications of last 5 years


1. Royer L, Colard-Itté E, Tavella TA, Lorthiois A, Goussin S, N’Dri ME, Sabra R, Deiss A, Thiberge S, Lamarque MH, Lavazec C. Plasmodium falciparum PP1 phosphatase is a key regulator of malaria parasite transmission. mBio 2025 Sep 10;16(9):e0087425.

2. Ali M, Dura R, Guery MA, Colard-Itté E, Cheviet T, Robresco L, Berry L, Lionne C, Lavazec C, Claessens A, Peyrottes S, Wengelnik K, Wein S, Cerdan R. An acyclic nucleoside phosphonate effectively blocks the egress of the malaria parasite by inhibiting the synthesis of cyclic GMP. Science Advances 2025 Nov 21;11(47):eady2859.

3. Seveno M, Loubens M, Berry L, Graindorge A, Lebrun M, Lavazec C, Lamarque MH. The malaria parasite PP1 phosphatase controls the initiation of the egress pathway of asexual blood-stages by regulating the rounding-up of the vacuole. PloS pathogens 2025 Jan 14;21(1):e1012455.

4. N’Dri ME, Tavella TA, Royer L, Dupuy F, Bedault L, Verdier F, Lavazec C. Phosphodiesterase delta governs the mechanical properties of erythrocytes infected with Plasmodium falciparum gametocytes. Microbes and Infection 2023 Jan 25;105102.

5. Barbieri D, Gomez L, Royer L, Dupuy F, Franetich JF, Tefit M, N’Dri ME, Mazier D, Silvie O, Moreno-Sabater A, Lavazec C. The phosphodiesterase inhibitor tadalafil promotes splenic retention of Plasmodium falciparum gametocytes in humanized mice. Frontiers in Cellular and Infection Microbiology 2022 May 25;12:883759.

 

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