Individual research ESR 6

Transcriptional EC heterogeneity of the malforming vasculature in HHT1 – identification of novel targets


Objectives:

  • To identify primary (causative) and secondary effects, of endoglin loss of function in the establishment of AVMs, at a transcriptional level and to relate these to the transcriptional profile of VM/LM
  • Use the above information to propose new targeting strategies
  • To test targeting strategies in in vitro systems with a cellular functional readout
  • To validate therapeutic potential in mouse models of HHT1

Expected Results:

  • Identification of differences in EC transcriptional heterogeneity during normal vascular development compared with abnormal vascular morphogenesis in models of HHT1
  • Identification of key signalling cascades (genes) involved in vascular malformation and validation of targeting to treat disease

Secondments:

  • AstraZeneca
  • Perimed
  • FinnAdvance
  • Uppsala University
  • Institut National de la Sante et de la Recherche Medicale