Research interest

The central objective of our research is to understand the role of endothelial cell (EC) gene expression in vessel wall homeostasis and the genesis of vascular diseases. We are pursing the thrombin- and cytokine-activated intracellular signaling pathways and transcription factors responsible for induction of leukocyte adhesion to EC in vivo and in vitro. We are currently focused on the relative importance of the two tumor necrosis factor (TNF)-alpha receptors in EC activation. We are also testing the hypothesis that homeobox (HOX) genes, a family of master-control transcription factors, are involved in the process of cytokine-induced activation of EC. We have shown that HOXA9 is required for cytokine-induced expression of the EC-leukocyte adhesion molecule E-selectin. We are identifying other EC genes that are regulated by HOXA9 and we are pursuing binding partners of HOXA9 in the EC nucleus. Finally, we are characterizing regulatory pathways involved in the expression of inflammatory genes by EC in response to the protease thrombin and the angiogenic factor VEGF and defining the induction and functions of the dual-specificity nuclear phosphatase MKP-1 (MAP kinase phosphatase-1).