Project Overview

In 2023, over 3,000 Canadians were newly diagnosed as brain tumor, and around 2,500 succumbed to this disease. Despite strenuous efforts to fight against this serious illness, brain tumor is still hard to be cured, and more than half of the patients die within five years of diagnosis. Brain is usually protected from the tumor by brain-resident immune system, called microglia, that can take away cancerous/abnormal cells and debris from brain. However, during tumor progression, the cancer cells alter microglia functions to restrict their anti-tumor activity, and eventually escape their immune attack and clearance. Furthermore, the altered microglia produce enzymes and growth factors that are favorable for tumor proliferation and spread. Therefore, to protect the patients from this invasive disease, it is important to better understand how the cancer cells reprogram the microglia to undermine their immune activity and endow the tumor-promoting functions.

To address this question, we will develop high-throughput genetic screening system by employing two state-of-the-art techniques: lab-grown brains (termed brain organoid) and genetic screening (termed CRISPR interference). The brain organoids are miniature brains cultured in laboratory dish, and closely mimics real human brains. The CRISPR interference is a genetic perturbation technique, and advantageous for the high-throughput screening. Here, we will model the brain tumor environment using the brain organoids, and perform the CRISPR interference screening to identify genes that controls i) microglia migration into the brain tumor and ii) the immune escape of the brain tumor. Collectively, the proposed project will provide essential insights to restore the anti-tumor functions of microglia, and have a significant impact in revolutionizing the therapy of the brain cancer.

Principal Investigator

Yoshiaki Tanaka , Universite de Montreal