Individual research ESR 8

Identification of pathways regulating pathological perivascular ECM remodeling and its importance for pathogenesis of vascular anomalies


  • Investigate alterations in EC-ECM interplay involving the synthesis and modifications of ECM constituents, regulation of cell signaling pathways, and the signaling loops between the ECM, perivascular mural cells, other stromal cells and ECs in TIE2/PIK3CA mutation positive VMs and in other types of VAs
  • To test hypothesis that defective deposition of ECM components and the increase in ECM protease activity remodel the vascular wall thereby contributing to the development of malformed vasculature in VA lesions
  • To generate mouse models allowing advanced microscopic imaging of vascular cells and perivascular ECM molecules to dissect cellular and molecular events in VA lesion formation and responses for therapies

Expected Results:

  • Identification of similarities/differences in molecular and cellular pathways that cause the alterations in VA ECMs
  • Understanding of mechanism and importance of ECM remodeling in VA pathogenesis
  • Identification of means to prevent pathological ECM remodeling in VA lesions in the preclinical models