Joined the Department in 2022
- B.Sc., Biochemistry and Microbiology, University of Bamako. 2009
- M.Sc., Molecular and Cellular Biology, Pierre and Marie Curie University. 2011
- M.Sc., Genetics, Paris Diderot University. 2012
- Ph.D., Parasitology, Lille 2 University. 2015
- Postdoctoral research, University of California, Davis 2016-2021
Molecular characterization of Toxoplasma gondii in vivo dissemination and its interaction with the placental barrier
The apicomplexan parasite Toxoplasma gondii (Toxoplasma) can infect all warm-blooded animals, and ~30% of humans are chronically infected with this parasite. Toxoplasma belongs to the TORCH pathogens group (Toxoplasma gondii, Other, Rubella, Cytomegalovirus, and Herpes virus 1/2) that causes significant mortality and morbidity in infants worldwide. Congenital toxoplasmosis occurs when the parasite crosses the placenta of an infected pregnant woman and infects the fetus. In the US, approximately 500 to 5000 babies are born every year with congenital toxoplasmosis; additionally, there is an unknown number of acute abortions due to toxoplasmosis. The clinical manifestation of toxoplasmosis on the neonate is generally detected late after the delivery. Most infants will develop mental retardations, motor or cerebellar dysfunction, and chorioretinitis. However, despite the impact of this pathogen on the developing fetus, very little is known about the Toxoplasma-placenta interactions’ molecular basis. Toxoplasma can disseminate from the site of infection to specific tissues where it causes the initial acute stage of the infection. The parasite has specialized organelles called micronemes, rhoptries, and dense granules that secrete proteins, MICs, ROPs, and GRAs, respectively, facilitating the invasion and co-option of the host cell. Those secretory proteins could determinate the capacity of Toxoplasma to colonize the placenta and infect the fetus.
The Sangare lab uses Toxoplasma as a model to determine how pathogens disseminate and cross the placental barrier. We hypothesize that Toxoplasma possesses sets of genes allowing it to disseminate and cross the placental barrier. The rationale of our research program is to characterize the critical steps of Toxoplasma-placenta interaction before the fetus’s infection, which will likely provide new drug and vaccine targets against congenital toxoplasmosis. To attain the overall objective, The Sangare lab investigates three independent projects:
- Characterizing the molecular mechanism of Toxoplasma dissemination to the placenta.
- Understanding the molecular mechanism of Toxoplasma survival in placental tissues.
- Identification and characterization of Toxoplasma gene products that are essential to cross the placental barrier.
The results from this research program would reveal the mechanism by which a Toxoplasma and others TORCH pathogen reach and cross the placental barrier to infect the fetus. In addition, the results will provide a science-based framework for future drug targets and vaccine development to prevent Toxoplasma‘s vertical transmission.
- Paredes-Santos, TC, Bitew, MA, Swale, C, Rodriguez, F, Krishnamurthy, S, Wang, Y et al.. Genome-wide CRISPR screen identifies genes synthetically lethal with GRA17, a nutrient channel encoding gene in Toxoplasma. PLoS Pathog. 2023;19 (7):e1011543. doi: 10.1371/journal.ppat.1011543. PubMed PMID:37498952 PubMed Central PMC10409377.
- Krishnamurthy, S, Maru, P, Wang, Y, Bitew, MA, Mukhopadhyay, D, Yamaryo-Botté, Y et al.. CRISPR Screens Identify Toxoplasma Genes That Determine Parasite Fitness in Interferon Gamma-Stimulated Human Cells. mBio. 2023;14 (2):e0006023. doi: 10.1128/mbio.00060-23. PubMed PMID:36916910 PubMed Central PMC10128063.
- Rahman, Z, Khuroo, T, Mohamed, EM, Dharani, S, Kayalar, C, Kuttolamadom, MA et al.. Pyrimethamine 3D printlets for pediatric toxoplasmosis: design, pharmacokinetics, and anti-toxoplasma activity. Expert Opin Drug Deliv. 2023;20 (2):301-311. doi: 10.1080/17425247.2023.2169272. PubMed PMID:36639201 .
- Sangaré, LO, Wang, Y, Arranz-Solís, D, Saeij, JPJ. CRISPR screen to determine the in vivo fitness of Toxoplasma genes. STAR Protoc. 2021;2 (2):100520. doi: 10.1016/j.xpro.2021.100520. PubMed PMID:34013213 PubMed Central PMC8113973.
- Wang, Y, Sangaré, LO, Paredes-Santos, TC, Hassan, MA, Krishnamurthy, S, Furuta, AM et al.. Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages. Nat Commun. 2020;11 (1):5258. doi: 10.1038/s41467-020-18991-8. PubMed PMID:33067458 PubMed Central PMC7567896.
- Wang, Y, Sangaré, LO, Paredes-Santos, TC, Saeij, JPJ. Toxoplasma Mechanisms for Delivery of Proteins and Uptake of Nutrients Across the Host-Pathogen Interface. Annu Rev Microbiol. 2020;74 :567-586. doi: 10.1146/annurev-micro-011720-122318. PubMed PMID:32680452 PubMed Central PMC9934516.
- Mukhopadhyay, D, Sangaré, LO, Braun, L, Hakimi, MA, Saeij, JP. Toxoplasma GRA15 limits parasite growth in IFNγ-activated fibroblasts through TRAF ubiquitin ligases. EMBO J. 2020;39 (10):e103758. doi: 10.15252/embj.2019103758. PubMed PMID:32293748 PubMed Central PMC7232000.
- Sangaré, LO, Ólafsson, EB, Wang, Y, Yang, N, Julien, L, Camejo, A et al.. In Vivo CRISPR Screen Identifies TgWIP as a Toxoplasma Modulator of Dendritic Cell Migration. Cell Host Microbe. 2019;26 (4):478-492.e8. doi: 10.1016/j.chom.2019.09.008. PubMed PMID:31600500 PubMed Central PMC7060943.
- Sangaré, LO, Yang, N, Konstantinou, EK, Lu, D, Mukhopadhyay, D, Young, LH et al.. Toxoplasma GRA15 Activates the NF-κB Pathway through Interactions with TNF Receptor-Associated Factors. mBio. 2019;10 (4):. doi: 10.1128/mBio.00808-19. PubMed PMID:31311877 PubMed Central PMC6635525.
- Wang, Y, Cirelli, KM, Barros, PDC, Sangaré, LO, Butty, V, Hassan, MA et al.. Three Toxoplasma gondii Dense Granule Proteins Are Required for Induction of Lewis Rat Macrophage Pyroptosis. mBio. 2019;10 (1):. doi: 10.1128/mBio.02388-18. PubMed PMID:30622189 PubMed Central PMC6325250.