Deciphering the role of ephrin B2 mutation in the pathogenesis of central conducting lymphatic anomaly
Awardee: Shoshana Greenberger
Institution: Newcastle University
Grant Amount: $62,398
Funding Period: February 1, 2025 - January 31, 2026
Summary:
Summary of the project: Recently, we have identified a novel mutation in a gene Ephrin-B2 (EFNB2) that causes a change in amino acid sequence of the protein, resulting in a severe lymphatic anomaly (CCLA) in a child patient. This child shows several severe symptoms, all linked to the function of the lymphatic system. We assume that the mutation in EFNB2 causes the disease by the disruption of the structure and function of lymphatic vessels through the erratic activity of the important signal transduction pathways. We were able to isolate the lymphatic endothelial cells (LEC) from this patient. Thus we have a unique opportunity to study the effect of this mutation on both structure and function of the lymphatic vessels. Herein we propose to study a novel genetic cause of this central conducting lymphatic anomaly by: (1) characterizing the effect of EFNB2 mutation on the cellular function and signaling in patient-derived lymphatic cells, and (2) creating a zebrafish model, with mutant EFNB2 in order to decipher the effect of the mutation on lymphatic system development, creating a tool that could be used in future drug screening. We believe that this study will expand our knowledge of the role of EFNB2 in the lymphatic disease, towards our better understanding of the underlying pathogenic processes, bringing about the possibility to find a remedy for the disease.