Research That Leads to Innovation
Scientific study of hemangiomas, other rare vascular tumors and vascular malformations is an important and growing area of research. Breakthroughs in the laboratory will help the medical community better understand the conditions, develop new treatments and improve the quality of life for patients.
Laboratory research at Cincinnati Children’s provides the foundation for innovative treatments. Once a month, researchers from the lab get together with researchers and physicians in the clinic to discuss the latest findings during the Vascular Clinical Basic Science Research Conference.
Current areas of focus in the lab include:
- Learning more about venous malformation (VM): Vascular anomalies are birthmarks caused by defects in the vascular system affecting capillaries, arteries, veins or lymphatics (or a combination of these) and involve increased number or vessels and / or vessels that are enlarged and sinuous. Our laboratory is investigating venous malformation (VM). VMs are slow-flow lesions composed of ectatic veins with irregular smooth muscle cell coverage. VMs cause deformity, pain, local intravascular coagulopathy, and they expand with time. Activating mutations in the endothelial cell tyrosine kinase receptor TIE2 and PIK3CA genes are a common cause of these lesions. We recently generated a model of VM by injecting human umbilical vein endothelial cells (HUVECs) expressing the most frequent VM-causing TIE2 mutation TIE2-L914F into immune-deficient mice. TIE2-L914F-expressing HUVECs formed VMs with ectatic blood-filled channels that enlarged over time.
Targeted pharmacological therapies are not available for the treatment of VM, therefore we used our murine VM model to test candidate drugs for their efficacy in preventing lesion growth. The mTOR inhibitor rapamycin effectively prevented VM growth through its ability to reduce mutant TIE2-induced AKT signaling.
Our VM model allows evaluation of potential therapeutic strategies; an ongoing prospective clinical pilot study demonstrated that rapamycin provides clinical improvement in patients with venous malformation. In six patients with difficult–to-treat venous anomalies, rapamycin reduced pain, bleeding, lesion size, functional and esthetic impairment, and intravascular coagulopathy. Read the full article.
Currently we are testing an array of FDA-approved drugs for their effects on TIE2 mutant endothelial cells and on murine VM growth and regression to identify a drug that can be used alone, or in combination with rapamycin, to increase clinical improvement in patients. Learn more about the Boscolo Lab.
- Learning more about vascular development: Knowing how genes regulate normal development of the vascular system will help us to understand genetic causes and possible treatments for human vascular disorders. Researcher Saulius Sumanas uses zebrafish embryos as a model system to study how vascular systems develop. (Similar genes control both human and zebrafish vascular development.) Sumanas is investigating detailed mechanisms of blood vessel formation and identifying new genes participating in these processes. Ultimately, he hopes to find new genes that can be targeted for treatment of vascular disorders.
