This summer I was given the opportunity to conduct research with Professor Yi Fan and Dr. Menggui Huang at the Fan Lab of the radiation oncology department at the Perelman school of medicine. My project studies how CRISPR-Cas9 Genome Editing of Target Gene B could Mediate Brain Tumor Angiogenesis In Vivo.

Angiogenesis plays a crucial role in tumor growth because newly formed tumor blood vessels provide oxygen and nutrients to the tumor microenvironment, allowing tumor progression and metastasis. Traditionally, targeting tumor-associated endothelial cells (ECs) has been a fundamental strategy for cancer treatment. However, CAR T cell-based immunotherapy in brain tumor glioblastoma is challenged due to limited T cell infiltration and T cell exhaustion caused by the immunosuppressive nature of the tumor microenvironment.

Our lab’s recent studies have shown that endothelial plasticity in glioblastoma induces vessel abnormality, causing resistance to chemotherapy, anti-angiogenic therapy, and immunotherapy. Our goal for this study is to reprogram tumor vasculature such that CAR T immunotherapy results could be improved. We have identified gene B as a key regulator for endothelial-mesenchymal transformation through whole-genome CRISPR-Cas9 library screening. In this study, we will generate inducible EC-specific gene B knockout mice with Adeno-Associated Virus (AAV)-delivered CRISPR technology. The AAV-delivered sgRNA will be intracranially injected into Cdh5 Cre; Cas9 ROSA-GFP mice to generate EC-specific gene B knockout mice. The accomplishment of this study will provide a novel target and new therapeutic strategy to improve CAR-T therapy in solid tumors.