Research

Wnt7a in Pulmonary Angiogenesis

In fall of 2011, within 3 months of the lab’s inception, one simple experiment launched an exciting campaign in exploring the role of Wnt signaling in pulmonary angiogenesis.  In the experiment, we found a 4-fold increase in Wnt7a gene expression in Pulmonary Microvascular Endothelial Cells (PMVECs) that were cultured at semi-confluency, an environment in which the cells are actively growing and moving in an attempt to reach full confluency, such as how they exist in a complete and healthy blood vessel.  In the lung, after injury occurs to the blood vessels, perhaps Wnt7a is important in coordinating angiogenesis, or the repair of damaged vessels, as it involves significant migration and proliferation of PMVECs.  Over the last five years since that early experiment, our lab has gathered a lot of exciting data supporting the hypothesis that Wnt7a coordinates with VEGF signaling in driving the first steps of angiogenesis.  Furthermore, we find that PMVECs from PAH patients have reduced Wnt7a expression, and so our hypothesis expands to say that diseased PMVECs, without Wnt7a, undergo dysfunctional angiogenesis, which ultimately leads to the small vessel loss seen in PAH.  This idea is supported by Wnt7a mouse models where we find recapitulation of disease phenotypes.  Now we are working with collaborators from Stanford BioADD and The University of Illinois at Chicago to develop a deliverable Wnt7a nanoparticle.  With this potential therapy, we hope that Wnt7a can be delivered to damaged lung vessels to restore proper angiogenesis and preserve vascular homeostasis.