Deciphering Inflammatory and Placental Mechanisms of Pre-eclampsia in Sickle Cell Disease

Objetivo

In this project, I will investigate the inflammatory and placental mechanisms underlying the high risk of pre-eclampsia in sickle cell disease (SCD), the most common inherited hemoglobinopathy worldwide and a major global health problem. I will employ immunological, vascular, and transcriptomic approaches to characterize how chronic inflammation, oxidative stress, and angiogenic imbalance contribute to pre-eclampsia in SCD pregnancies. Using plasma, PBMCs, and placental samples, I will define immune and vascular signatures, map placental transcriptional programs through single-cell and single-nucleus RNA sequencing, and assess the impact of transfusion and hydroxyurea on trophoblast inflammatory and vascular responses. I will integrate these datasets to identify mechanistic pathways and prioritize candidate biomarkers for clinical translation. My project will provide the first systems-level map of maternal–placental inflammation in SCD pregnancy, generating insights that can guide risk stratification and therapeutic strategies to improve maternal and fetal outcomes. My background in SCD pathophysiology, thrombosis, and oxidative stress is highly complementary to the expertise of my supervisors, Dr. Thiago Maciel, an expert in inflammation and erythropoiesis, and Dr. Sara El Hoss (co-supervisor), an expert in ineffective erythropoiesis, SCD pathophysiology and pregnancy. I will further benefit from a secondment at King’s College London with Dr. Panicos Shangaris, an expert in maternal–fetal medicine, which will provide advanced training in placental functional assays. This fellowship will allow me to expand my research scope into pregnancy complications in SCD, bridging mechanistic biology and clinical translation, and positioning me to develop into an independent investigator.