Research in the Cao Lab focuses on epigenetic regulation of cancer immunity. We use bioinformatic and high-throughput screen approaches to identify key epigenetic regulators of anti-tumor immune response, validate their functions by cell-based assays and animal models, and aim to develop novel therapeutical strategies to boost anti-tumor immune response.
There are three major layers of epigenetic regulation in mammalian cells: DNA methylation, histone posttranslational modifications, and chromatin structure regulation. Epigenetics determines gene expression patterns and plays central roles in fate determination in development and homeostasis of differentiated tissues. Dysregulation of epigenetic processes contributes significantly to cancer initiation, progression, metastasis, and resistance to drug treatment. The fact that epigenetic alterations are largely reversible and druggable, in contrast to genetic mutations, positions epigenetic regulators attractive drug targets for developing cancer therapies.
Emerging evidences suggested that epigenetic processes are involved in cancer immune regulation, which is the base of the fast-growing field of cancer immunotherapies. In a previous study, we identified KDM5 histone demethylases as suppressors of cGAS-STING-interferon pathway in tumor cells. Inhibition of KDM5 restores cytosolic double-strand DNA-triggered activation of interferon pathway, recruits tumor infiltrating lymphocytes, and suppresses tumor growth. We recently identified a chromatin regulating factor involved in cancer immune escape. The mechanism and potential targeting strategies are under study.
In collaboration with Prof. Dawei Li’s group at University of Vermont, we are developing and applying a bioinformatic approach to identify novel viral etiologies in human cancer.