Ribonucleotides and the Inflammatory Response

Role of ADAR in interferon-activated cancer cells: Our identification of the RNA adenosine deaminase gene ADAR as a genetic dependency in a subset of lung cancer cell lines led to the finding that an elevated interferon gene expression signature is a biomarker for the vulnerability of cancer cells to ADAR loss (Gannon et al, 2018). ADAR deletion causes activation of several double-stranded RNA sensors, leading to inflammatory cytokine production and cancer cell lethality. We are working to understand the relationship between elevated interferon gene expression and ADAR deletion and how ADAR can be exploited as a therapeutic target in cancer cell lines with activated interferon signaling. 

RNA metabolism and innate immunity in cancer cells: We are exploring whether perturbation of cellular RNA metabolism pathways can cause context-specific vulnerabilities in cancer cells. Specifically, we are interrogating whether alterations in cellular RNA metabolism can activate endogenous innate immune signaling pathways to limit cancer cell viability and/or prime an anti-tumor immune response.