Catherine LAVAZEC

Information

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. Neveu G, Dupuy F, Ladli M, Barbieri D, Naissant B, Richard C, Martins RM, Lopez Rubio JJ, Bachmann A, Verdier F, Lavazec C. Plasmodium falciparum gametocyte-infected erythrocytes do not adhere to human primary erythroblasts. Scientific Reports 2018 Dec 14;8(1):17886. doi: 10.1038/s41598-018-36148-y

2. Naissant B, Dupuy F, Duffier Y, Lorthiois A, Duez J, Scholz J, Buffet P, Merckx A, Bachmann A, Lavazec C. Plasmodium falciparum STEVOR phosphorylation regulates host erythrocyte deformability enabling malaria parasite transmission. Blood 2016 Jun 16;127(24):e42-53. doi: 10.1182/blood-2016-01-690776

3. Duffier Y, Lorthiois A, Cisteró P, Dupuy F, Jouvion G, Fiette L, Mazier D, Mayor A, Lavazec C#, Moreno-Sabater# A. (# co-last author). A humanized mouse model for sequestration of Plasmodium falciparum sexual stages and in vivo evaluation of gametocytidal drugs. Scientific Reports 2016 Oct 12; 6:35025. doi: 10.1038/srep35025

4. Bargieri DY, Thiberge S, Tay CL, Carey AF, Rantz A, Hischen F, Lorthiois A, Straschil U, Singh P, Singh S, Triglia T, Tsuboi T, Cowman A, Chitnis C, Alano P, Baum J, Pradel G, Lavazec C, Ménard R. Plasmodium Merozoite TRAP Family Protein Is Essential for Vacuole Membrane Disruption and Gamete Egress from Erythrocytes. Cell Host & Microbe 2016 Nov 9;20(5):618-630. doi: 10.1016/j.chom.2016.10.015

5. Ramdani G, Naissant B, Thompson E, Breil F, Lorthiois A, Dupuy F, Cummings R, Duffier Y, Corbett Y, Mercereau-Puijalon O, Vernick K, Taramelli D, Baker D, Langsley G, Lavazec C. cAMP-signalling regulates gametocyte-infected erythrocyte deformability required for malaria parasite transmission. PLoS Pathogens 2015 May 7;11(5):e1004815. doi: 10.1371/journal.ppat.1004815