Maintenance of DIPG Blood-Brain Barrier Integrity by Angiopoietin1

Award: $300,000 over three years (Early Career Development Grant)
Principal Investigator: Timothy Phoenix, PhD, University of Cincinnati
Co-mentors: Q. Richard Lu, PhD, and Maryam Fouladi, MD, Cincinnati Children’s Hospital Medical Center

In order to enter brain tissue, molecules and cells in the circulation coursing through the central nervous system (CNS) must first cross a specialized biological border in blood vessel walls called the blood-brain barrier (BBB). Drug penetration across the BBB presents a fundamental challenge to effective treatment of many brain tumors, including diffuse intrinsic pontine gliomas (DIPGs), which are unresectable and only temporarily respond to radiation treatment. Through this Early Career Development grant, Dr. Phoenix will characterize the mechanisms that regulate Angiopoietin-1 (Angpt1) expression and function in DIPG and determine the potential of Angpt1-Tie2 inhibition to effect tumor-specific increases in BBB permeability and drug penetration. Findings will open the door for new approaches to manipulating the BBB in DIPG and ultimately better clinical outcomes for children.