Mentor Name: Shireen Ganapathi

Effective treatment of pediatric brain tumors is often limited by inadequate drug delivery across the blood–brain tumor barrier (BBTB). Although vascular abnormalities are known to influence treatment response, the biology of tumor associated blood vessels in children remains poorly defined, and most current knowledge is extrapolated from adult studies. A clearer understanding of how vascular structure, permeability, and therapeutic target expression vary across pediatric tumor types is needed to guide the development of more effective therapies. This project aims to systematically characterize vascular features across a broad spectrum of childhood brain and spinal cord tumors by leveraging our institution’s deeply annotated biobank. Working under joint mentorship from pediatric oncologists with expertise in clinical and translational research, we will identify representative tumor cases and regions of interest, incorporating both common and rare diagnoses as well as non cancerous control brain tissue. These specimens will be used to design tissue microarrays (TMAs) that provide an efficient and standardized platform for comparative analysis across tumor classes.

During the summer fellowship, we will perform immunostaining on TMA sections to co-localize endothelial and perivascular markers with a curated panel of therapeutically relevant proteins, including those that represent emerging targets for antibody–drug conjugates and other next generation agents. By quantifying vascular density, morphology, and protein expression across tumor types and then integrating these patterns with available clinical and genomic annotations, we will generate one of the first therapeutic atlases of vascular proteins in pediatric brain tumors. This atlas will highlight how the BBTB differs between tumor subtypes and will identify candidate molecular features that may be exploited to enhance drug delivery. The insights gained from this work will provide foundational knowledge about the vascular microenvironment in childhood brain tumors and will inform the rational design of future treatments that more effectively reach tumor tissue. Ultimately, this project sets the stage for expanding vascular mapping efforts across additional pediatric tumor types and contributes to a growing framework for improving outcomes in children with these devastating diseases.