Mohamed-Ali HAKIMI

Information

Scientific interests and projects

Toxoplasma gondii is a prevalent single-celled eukaryotic parasite causing toxoplasmosis, a food-borne zoonotic disease, with life-threatening potentials in cases of immunesuppressed individuals and of unborn fetuses. As an obligate intracellular parasite, T. gondii deploys sophisticated mechanisms to profoundly modify the host cells to acquire nutrients and to promote parasite persistence. Our project considers the "host-parasite" association as a whole, aiming at filling current gaps of knowledge in the comprehensive understanding of the biology of Toxoplasma gondii and the etiology of Toxoplasmosis. Our long-term goal is to reveal the molecular mechanisms by which T. gondii is orchestrating immune evasion and lifelong persistence in a great range of hosts. Capitalizing on past achievements, we aim at exploring three lines of investigation:

1- We investigate how this single-cell parasite is able to co-opt specific host cell signaling pathways (e.g. MAPK or p53) upon invasion. Along the way, we uncovered a novel subfamily of T. gondii effector proteins that are singularly exported beyond the vacuolecontaining parasites and reach the host cell nucleus to reshape the host (epi)genetic program. We aim to study their modus operandi and particularly their possible implications in immune evasion and parasite persistence.

2- We are also studying the 'epigenetic' mechanisms involved in the regulation of the developmental transition between acute and chronic stages of infection. We thus identified serological markers for Toxoplasma chronic infection in Humans. Our team also uncovers a way to epigenetically reprogram the life cycle and therefore to study the parasite’s sexual development in vitro, as an alternative to the requirement of cat infections.

3- Current drugs for treating toxoplasmosis have been used for decades and have limitations such as the appearance of side-effects, low-to-medium drug efficacy and administration routes. Importantly, there are no drugs that clear chronic infection. Along the way, we discovered new anti-parasitic compounds that efficiently prevent acute toxoplasmosis, but also malaria and Cryptosporidiosis.

Top 5 publications of the last 5 years

1. Cruz-Miron R, Swale C, Liang Q, Yamaryo-Botté Y, Arnold CS, Hakimi MA, Botté CY, Bougdour A, Saeij JPJ. TgSEC14-LTP1 is a vacuole-secreted SEC14/CRAL-TRIO-like protein required for host DAG flux and PC homeostasis in T. gondii. Cell Rep. 2026 May 26;45(5):117299. doi: 10.1016/j.celrep.2026.117299. 

2. Diaz-Martin S, Swale C, Bellini V, Dobrescu I, Wenker J, Brenier-Pinchart MP, Braun L, Tollec A, Corrao C, Couté Y, Mas C, Laurent F, Bowler M, Hakimi MA, Bougdour A. Structural and functional characterization of TgGSK3, a druggable kinase in Toxoplasma gondii. Nat Commun. 2025 Nov 5;16(1):9765. doi: 10.1038/s41467-025-64701-7. 

3. Pachano B, Farhat DC, Shahinas M, von Velsen J, Corrao C, Belmudes L, de Bock PJ, Mas C, Couté Y, Bowler MW, Bougdour A, Swale C, Hakimi MA. An ISWI-related chromatin remodeller regulates stage-specific gene expression in Toxoplasma gondii. Nat Microbiol. 2025 May;10(5):1156-1170. doi: 10.1038/s41564-025-01980-2.

4. Robert MG, Swale C, Pachano B, Dépéry L, Bellini V, Dard C, Cannella D, Corrao C, Belmudes L, Couté Y, Bougdour A, Pelloux H, Chapey E, Wallon M, Brenier-Pinchart MP, Hakimi MA. Uncovering biomarkers for chronic toxoplasmosis detection highlights alternative pathways shaping parasite dormancy. EMBO Mol Med. 2025 Jul;17(7):1686-1715. doi: 10.1038/s44321-025-00252-0. 

5. Antunes AV, Shahinas M, Swale C, Farhat DC, Ramakrishnan C, Bruley C, Cannella D, Robert MG, Corrao C, Couté Y, Hehl AB, Bougdour A, Coppens I, Hakimi MA. In vitro production of cat-restricted Toxoplasma pre-sexual stages. Nature. 2024 Jan;625(7994):366-376. doi: 10.1038/s41586-023-06821-y.