The main research themes in the De Val group
Enhancer analysis has elucidated multiple independent regulatory cascades governing endothelial behavior.
- Arterial endothelial cells (Sacilotto et al (2013) PNAS) An unknown factor activates SOXF to induce the expression of Notch1 and Dll4, Flk1, Nrp1 to induce arterial endothelial cells. Notch1 also activates Dll4, Flk1, Nrp1.
- Angiogenic endothelial cells (Sacilotto, Chouliaras (2016) Genes Dev): VEGFA activates EP300 that activates MEF2, and inihibits HDAC that inhibits MEF2. MEF2 induces the expression of Hlx, Ets1 and Elk3. Ets1 operates a positive feedback loop to further activate MEF2. MEF2 also activates the expression of Dll4 (which is also partially activated by Ets1 and Elk3). Hlx, Ets1, Elk3 and Dll4 induce angiogenic endothelial cells.
- Venous endothelial cells (Neal et al (2019) Nature Commun): BMP4 activates ALK3 which activates SMAD1/5. SMAD1/5 stimulates the transcription of Ephb4, Nrf2f2 and Emcn to induce venous endothelial cells.