The Scientific and Medical Advisory Board and Board of Directors of CLOVES Syndrome Community are pleased to award Dr. Wen Yih Aw of The University of North Carolina/Chapel Hill a $50,000 grant for her project titled “Non-canonical signaling and therapeutic targets for vascular anomalies in CLOVES.”
Dr. Aw has provided a summary of her project for our community below. Thank you Dr. Aw!
A characteristic condition of CLOVES is the development of vascular malformations, abnormal blood vessels that do not allow the proper transport of blood, nutrients, and oxygen. Improved treatment of CLOVES thus requires a better understanding of how vascular malformations develop and what genes and proteins can be targeted to revert vascular malformations to healthy, normal vasculature. However, it is difficult to study vascular malformations because the current experimental toolset is limited: mice have different genes and proteins that govern key processes in vascular development, and it is difficult to induce vascular malformations at a time and place that allows for well-controlled experiments, while traditional cultures of human cells do not form vessels. We have sought to address these shortcomings by developing a tissue engineered model of blood vessels using human cells. We have shown this micro-scale model of vascular physiology (microphysiological model) reproduces the development of vascular malformations when using cells that express a mutant version of the gene that leads to CLOVES, PIK3CA. In this project, we are going to test two drugs that have been used to treat other forms of vascular malformations and to treat certain cancers. Each drug inhibits a specific protein, so by testing these drugs in our microphysiological model, we can look at how inhibiting each protein affects individual cells and how the cells affect blood vessel formation. Thus, the results of our work will not only explore these drugs as treatments for vascular malformations in CLOVES but will also inform us about how vascular malformations arise, hopefully leading to the development of new drugs and interventions. Furthermore, by continuing to develop the microphysiological model, we will establish a platform for eventually testing drugs and personalized treatments for individual patients.