Elisa Boscolo, Ph.D.
Department of Experimental Hematology and Cancer Biology
Cincinnati Children's Hospital
Vascular anomalies are birthmarks caused by defects in the vascular system affecting capillaries, arteries, veins or lymphatics (or a combination of these). They involve increased number of vessels and/or vessels that are enlarged and twisting. Elisa Boscolo, PhD is investigating venous malformations (VM). VMs are slow-flow lesions composed of ectatic veins with irregular smooth muscle cell coverage. VMs cause defects, pain, localized intravascular coagulopathy, and they expand with time. Activating mutations in the TIE2 receptor and PIK3CA genes are a common cause of these lesions.
Dr. Boscolo’s lab recently made a mouse model of VM expressing the most frequent VM-causing TIE2 mutation TIE2-L914F to test possible drugs for their ability in stopping lesion growth. The mTOR pathway inhibitor Sirolimus successfully prevented VM growth through its ability to reduce mutant TIE2-induced AKT signaling. This work was translated into a clinical pilot study showing clinical improvement in Sirolimus treated patients with venous malformation, measured by decreases in pain, bleeding, lesion size, function and coagulopathy. Currently Dr. Boscolo’s lab is testing an array of FDA-approved drugs for their effects on patient-derived mutant endothelial cells and on murine VM growth and regression to identify a drug that could be used alone, or in combination with Sirolimus, to increase clinical improvement in patients.
Members of the laboratory:
Yuqi Cai (Research Associate)
Xian Li (Post-doctoral Fellow)
Jillian Goines (Research Assistant III)
- Timothy LeCras (Pulmonary Biology – Cincinnati Children’s Hospital)