ANGI-20. ELUCIDATING MOLECULAR AND EPIGENETIC DRIVERS OF PATHOLOGICAL ANGIOGENESIS IN CHOROID PLEXUS TUMORS

Abstract Choroid plexus (ChP) tumors, including atypical choroid plexus papilloma (aCPP) and choroid plexus carcinoma (CPC), are rare, aggressive, and often deadly brain tumors that arise from the ChP, a highly vascular secretory tissue that fills the brain ventricles. ChP tumors are most commonly seen in very young children and often present as large, extremely vascularized masses that can extend into adjacent brain tissue. These factors increase risk of incomplete surgical resection and intraoperative hemorrhage, which in turn create major barriers to treatment. Our overarching hypothesis is that exploitable, tumor-specific vulnerabilities exist in the interplay between epithelial-vascular interactions in aCPP and CPC vs. normal ChP, and our ultimate goal is to uncover novel therapeutic targets for these diseases. Toward this end, we have begun characterizing normal vs. tumor vascular development in the ChP using immunostaining, vascular casting, and multi-omic sequencing approaches. Applying our lab’s robust mouse models of ChP tumors, we have been particularly focused on exploring rates of vascular development, timing of capillary fenestration, and homing of vascular immune cells (e.g., macrophages) to ChP vasculature in tumor vs. non-tumor tissue. Our preliminary data point to differences in the structure and presence of specific vascular anatomical structures and angiogenic factors in the ChP across development and identify a few major targets of interest. Overall, this ongoing project is poised to delineate key divergences between normal and tumor vascular development in the ChP, and holds potential to reveal neoadjuvant treatment strategies for aCPP and CPC.