Project description
Overcoming erythropoiesis issues in sickle cell disease
Sickle cell disease is caused by a mutation in the gene encoding the beta-chain of haemoglobin, the oxygen carrier in our body. Under certain conditions, patients present with sickle-shaped irregular red blood cells that are sticky and can block the smaller blood vessels causing episodes of severe pain. The EU-funded InEr-SICKLE project will investigate the contribution of defective red blood cell production (erythropoiesis) to sickle cell disease severity. The focus will be on a critical red cell regulator, GATA1, as a target in alleviating sickle cell disease, by restoring normal erythropoiesis in these patients. Project results will generate important insight into the pathogenesis of sickle cell disease and may unveil novel therapeutic targets.
Objective
In this project, I will investigate ineffective erythropoiesis as a contributing factor and potential therapeutic target in the pathogenesis of sickle cell disease (SCD), one of the most prevalent genetic disorders in man and a global health problem. I will employ cutting-edge proteomic and genomic approaches to investigate in detail deregulation of the master erythroid transcription factor GATA1 as a result of oxidative stress in sickle red blood cells, as the basis for ineffective erythropoiesis in SCD. I will also investigate whether restoring GATA1 functions can alleviate ineffective erythropoiesis, thus providing alternative therapeutic opportunities in treating SCD. Lastly, I will generate novel cellular models for SCD from patients that can be used in dissecting the pathophysiology of SCD and in screening for agents that can alleviate IE and sickling. My project will generate novel insight into SCD pathogenesis and tools that can lead to the development of novel therapeutic approaches. My background in SCD cellular pathophysiology is highly complementary to those of my supervisors, Prof. John Strouboulis who is an expert in GATA1 functions in molecular erythropoiesis and Prof. David Rees, who is a world leading clinician in pediatric sickle cell disease. I stand to benefit greatly by receiving excellent training in -omics, functional assays in molecular erythropoiesis and in clinical aspects of SCD, that will enable me to progress into a career as an independent investigator.
Fields of science
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
WC2R 2LS London
United Kingdom