Cancer cells often find ways to hide from the immune system, limiting the effectiveness of today’s most promising immunotherapies. One powerful but poorly understood immune pathway centers on a protein called ZBP1, which acts as an internal alarm sensor. When activated, ZBP1 can trigger inflammation and a specialized form of cell death known as necroptosis. These responses may help the immune system recognize and attack tumors by releasing signals that expose cancer cells to immune surveillance. Yet scientists still do not understand how this pathway is switched on, how it is organized inside cells, or how viruses and other factors can shut it down.
Dr. Yu’s research aims to uncover the molecular “assembly instructions” that govern ZBP1 signaling. Using cutting-edge structural biology, high-resolution imaging, and biochemical approaches, he will determine how ZBP1 and its partner protein, RIPK3, come together to form larger signaling complexes that control inflammatory cell death. The project will also investigate how a herpesvirus protein blocks this process, taking advantage of viral strategies that have evolved to evade immune defenses.
Dr. Yu is uniquely positioned to tackle this challenge. Throughout his training, he has built an impressive track record of revealing how immune systems are activated, regulated, and subverted across diverse biological systems. His discoveries—including a new anti-CRISPR immune evasion protein, a key regulatory mechanism in plant immunity, and the structural basis of a novel antiviral defense system—have been published in leading journals including Nature and Molecular Cell. By revealing how ZBP1 signaling is controlled at the molecular level, his work could identify new strategies to enhance anti-tumor immunity, overcome immune suppression, and improve patient responses to cancer immunotherapies such as checkpoint blockade.
Mentor
Tianmin Fu, PhD
Projects and Grants
Decoding the RHIM signalosome in the ZBP1-RIPK3 pathway for anti-tumor immunity
