Final Report Summary - EXPLORE (Exploring novel pathways governing immunity and leukemia by studying the genetic basis of human myeloid cell defects - from genetics to gene therapy)
The ERC Advanced Grant EXPLORE awarded a research initiative aiming to improve diagnosis and fundamental understanding of rare blood and immune diseases in children. Based on a global clinical network, the so called Care-for-Rare alliance, clinicians and scientists have been working together to decipher the genetic causes of rare diseases of neutrophil granulocytes, a subtype of white blood cells critical for elimination of invading bacteria and tissue homeostasis. This knowledge has been further expanded by functional experiments in cells and model organisms such as mice and zebrafish. As a result of these investigations, several previously unrecognized diseases could be discovered and categorized (e.g. JAGN1-deficiency, VPS45-deficiency, CSF3R-deficiency, SMARCD2-deficiency). In the future, affected patients will have access to a rapid molecular diagnosis, highly relevant for genetic counselling. Furthermore, novel signalling units and pathways that orchestrate the development and function of neutrophil granulocytes have been discovered. In the future, this knowledge is important to define targeted therapies which may help not only patients with very rare disorders but also patients with much more common diseases.