The University of Texas MD Anderson Cancer Center
Department of Immunology
Killer cell-mediated tumor cell killing is a key, final step of anti-tumor immune protection. CD8 cytotoxic T cells and Natural Killer (NK) cells use the cytotoxic proteases granzymes (Gzms) to eliminate tumor cells. Gzms, delivered by the pore-forming protein perforin (PFN), cleave a number of substrates in target cells to induce cell death. Like apoptosis, killer cell-mediated target cell death has always been thought of as noninflammatory. However, recent studies suggest an emerging role of the inflammatory cell death, called pyroptosis, in killer cell-mediated tumor elimination.
Pyroptosis is a gasdermin-mediated programmed necrotic cell death that activates immune responses. Gasdermin (GSDM) family proteins, which include GSDM A-E, trigger pyroptosis after their N-terminal (NT) active domains are cleaved by proteases from their C-terminal inhibitory domains and form pores on the plasma membrane. Inflammasome-activated caspase-1/4/5/11 cleave and activate GSDMD while apoptotic caspase-3 processes and activates GSDME. Our recent study shows that killer cell GzmB activates pyroptosis in GSDME-expressing target cells by both directly cleaving GSDME and indirectly activating caspase-3. The resulting pyroptosis further increases the number and functions of tumor infiltrating CD8 T cells and NK cells, thus enhancing killer cell-mediated anti-tumor immunity and leading to tumor suppression.
Our lab is using biochemical, molecular biological, cellular biological and mouse genetic tools to further explore roles of pyroptosis in anti-tumor immunity and discover new ways to manipulate pyroptosis in order to enhance anti-tumor responses. We aim to 1) Investigate novel mechanisms underlying killer cell-triggered pyroptosis. 2) Understand how pyroptosis induces anti-tumor protection. 3) Discover novel regulatory mechanisms of pyroptosis. 4) Develop pyroptosis-based therapeutic interventions for tumor treatment.
Education & Training
PhD – National Institute of Biological Science & Beijing Normal University - 2014