Grant: Project Grant

Vascular malformations are very common in humans and include arteriovenous malformations (connections of arteries and veins directly), capillary malformations (dilated, disorganized vessels with abnormally fast or slow circulation) and vascular tumors such as hemangioma. Rasa1 is a gene that causes capillary and arteriovenous malformations (CM-AVM) when mutated in humans and was one of the first vascular malformation genes identified. In the past 5 years we have found that many human vascular malformations and tumors are caused by mutations in genes that function in a pathway related to Rasa1. Surprisingly, benign malformations and vascular tumors can be caused by mutations in the same genes; we do not understand why some are benign and some malignant. Also, the only treatments currently available are not based on scientific evidence but are 'best guesses. Our goals in this project are to identify mechanisms and possible therapeutics for vascular malformations, focusing on Rasa1. We will study this gene in an animal model where Rasa1 is lost. We will test its role in the blood vessel wall and identify small molecules that improve malformations.