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Investigating Pregnancy in Sickle Cell Disease
Sickle cell disease (SCD) is a severe genetic disorder characterized by chronic hemolysis, vaso-occlusion, and systemic inflammation. Beyond its well-known hematological complications, SCD also affects the immune system, leading to dysregulation and a skewing toward the myeloid lineage at the progenitor level. These immune alterations contribute to a heightened inflammatory state, which poses additional risks during pregnancy.
Pregnancy in individuals with SCD is associated with increased maternal and fetal complications, including vaso-occlusive crises, organ damage, pre-eclampsia, preterm birth, and fetal growth restriction. Despite the well-documented inflammatory profile in SCD, its role in pregnancy remains poorly understood, particularly regarding its effects on fetal hematopoiesis.
In close collaraboration with Necker Hospital, adult hematology and Gynecology departmens, our research aims to elucidate the physiological mechanisms linking maternal inflammation in SCD pregnancies to fetal hematopoietic stem and progenitor cell (HSPC) development. Through a longitudinal cohort study, we analyze inflammation markers, immune cell profiles, and cytokine levels at key pregnancy stages in both SCD and non-SCD groups. Additionally, we investigate how maternal inflammation affects fetal HSPC function at the cellular and molecular levels. To explore potential therapeutic interventions, we assess the impact of anti-inflammatory treatments in preclinical models.
By providing critical insights into the inflammatory mechanisms driving pregnancy complications in SCD, our project seeks to inform new therapeutic and management strategies, ultimately improving maternal and fetal health outcomes in this high-risk population.
Main Publications :
El Hoss S, Shangaris P., Brewin J., Psychogyiou ME., Ng C., Pedler L., Rooks H., Gotardo E., Gushiken L., Brito P., Nicolaides K., Conran N., Rees D., Strouboulis J. Reduced GATA1 levels are associated with ineffective erythropoiesis in sickle cell anemia. Haematologica. 2024. https://pubmed.ncbi.nlm.nih.gov/39633531/ 2. Bouyssou I. *, El Hoss S. *#, Doderer-Lang C., Schoenhals M., Tsikiniaina Rasoloharimanana L., Vigan-Womas I., Ratsimbasoa A., Abate A., Golassa L., Mabilotte S., Kessler P., Guillotte-Blisnick M., Martinez FJ., Chitnis CE., Strouobulis J. #, Ménard D. # The DARC side of vivax malaria in Africa: unveiling invasion pathways into Duffy-negative erythroblasts. Cell Host & Microbe. 2023. https://pubmed.ncbi.nlm.nih.gov/38056460/
Ressources & publications
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Journal (source)Hum. Mol. Genet.
Human IFT52 mutations uncover a novel role for the protein in microtubule dyn...
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Journal (source)Am. J. Hum. Genet.
Mutations in TUBB4B Cause a Distinctive Sensorineural Disease.
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Journal (source)Hum. Mol. Genet.
Constitutively-active FGFR3 disrupts primary cilium length and IFT20 traffick...
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Journal (source)Am J Hum Genet
Mutations in KIAA0586 Cause Lethal Ciliopathies Ranging from a Hydrolethalus ...
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Journal (source)J Med Genet
IFT81, encoding an IFT-B core protein, as a very rare cause of a ciliopathy p...
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Journal (source)Am J Hum Genet
Mutations in TUBB4B Cause a Distinctive Sensorineural Disease.
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Journal (source)Am J Hum Genet
Mutations in TUBB4B Cause a Distinctive Sensorineural Disease.
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Journal (source)Proc Natl Acad Sci U S A
Agonists of prostaglandin E2 receptors as potential first in class treatment ...
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Journal (source)Am J Hum Genet
Mutations in TUBB4B Cause a Distinctive Sensorineural Disease.
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Journal (source)J Med Genet
IFT81, encoding an IFT-B core protein, as a very rare cause of a ciliopathy p...