Dr. Li’s lab studies DNA mismatch repair (MMR), an important cellular mechanism that ensures replication fidelity. His work has contributed to the understanding of MMR and its role in cancer susceptibility and therapy. He discovered MMR defects as the genetic basis of hereditary non-polyposis colorectal cancer and sporadic colorectal cancers displaying microsatellite instability. He identified and characterized the majority of components required for human MMR, and reconstituted the human MMR reaction in vitro. His laboratory discovered epigenetic factors as important MMR components/regulators, including histone modifications and mutations. He is also responsible for discovering the apoptotic function of MMR, in which MMR proteins recognize chemically and physically adducted DNA and trigger a futile repair cycle to induce cell death, implicating MMR in cancer therapy. Recently, his laboratory has elucidated the molecular basis on which MMR deficiency benefits checkpoint blockade immunotherapy by activating the cGAS-STING pathway. In addition, he also studies the mechanism of MMR in promoting (CAG)•(CTG) repeat expansions that cause many neurodegenerative disorders.