When cancer spreads to the brain, it often establishes hidden reservoirs of dormant tumor cells long before forming detectable metastases. These disseminated tumor cells (DTCs) evade immune clearance in part because the brain’s immune environment is unique—lacking many conventional immune cells and relying instead on specialized brain-resident cells called microglia. Although microglia can detect invading tumor cells, they rarely eliminate them under normal conditions. Dr. Shi Li’s research seeks to understand why these cells remain inactive and how to reawaken their tumor-fighting potential.
Dr. Li has discovered that neighboring support cells in the brain, called astrocytes, send signals that restrain microglial activity against tumor cells. His project will identify these suppressive “checkpoints” and determine how to overcome them by activating a purinergic signaling pathway—an energy-sensing communication system involving molecules such as ATP. Using advanced tools like intravital imaging, spatial transcriptomics, and genetic manipulation, Dr. Li will define how astrocyte and microglial interactions dictate whether tumor cells are ignored or destroyed. He will also test a novel therapeutic approach using nanoparticles that deliver activation signals directly to the tumor niche, potentially preventing brain metastasis before it takes hold.
Dr. Li is a neuroimmunologist and imaging scientist whose background spans nanomedicine, molecular imaging, and brain tumor biology. His work bridges cutting-edge imaging with immune mechanism discovery to reveal how the brain’s own cells can be harnessed to fight cancer.
Sponsor
Cyrus Ghajar, PhD (Sponsor); Even Newell,, PhD (Co-Sponsor)
Projects and Grants
Purinergic checkpoints governing microglial clearance of disseminated tumor cells
