Hayman Lab Research

DNA-damaging therapies such as radiation therapy and chemotherapy (e.g. cisplatin) are primary treatment modalities for the majority of malignancies. However, the development of resistance to these DNA damaging treatments fundamental cause of treatment failure, leading to tumor recurrence and ultimately death. As such the major focus of our lab is understanding mechanisms of resistance to these therapies with the goal of developing novel approaches to neutralize the adaptive response and ultimately to translate the findings to the clinic to improve patient outcomes.

As an approach to uncover novel regulators of the cellular response to DNA-damage we recently performed a whole-genome CRISPR-Cas9 screen using radiation as a selection pressure. Unexpectedly, we identified STING (stimulator of interferon genes) as a regulator of the cell intrinsic response to DNA-damage. Specifically we have shown that STING regulates a transcriptional program responsible for ROS (reactive oxygen species) generation with loss of STING expression altering ROS homeostasis and increasing resistance to DNA-damaging therapies. Lastly from a translational perspective we show that pharmacologic activation of STING using an intravenously available STING agonist enhances the efficacy or radiation in vivo. (Hayman et. al., Nature Communications 2021). This work has described a novel role for tumor STING in regulating the cell intrinsic response to DNA damage that is in addition to its previously described role in regulating the extrinsic (immune-mediated) response to cancer directed therapies.

As such a major focus of our lab will be on defining the role of STING and the STING pathway in regulating the tumor intrinsic response to DNA-damaging therapies. Additionally, given the importance of the STING pathway in regulating the immune response we will utilize genetic techniques to dissect the interaction of tumor STING with the host immune system with regards to modulating the response to cancer directed therapies. We expect these results to uncover novel biology with respect to the cellular DNA damage response and to identify therapeutic strategies to improve anti-tumor effects to cancer-directed therapy.