Our Research
Viral mimicry in lung cancer
While currently approved cancer immunotherapies utilize the adaptive immune system (T cells and antibodies), it remains unclear whether we can leverage the innate immune system for cancer therapy. We found that loss of the RNA-editing enzyme ADAR1 or the exoribonuclease XRN1 can trigger the activation of innate immune double-stranded (dsRNA) sensors and cell lethality in cancer cells with intrinsic activation of the interferon response pathway. In a collaborative study, we also showed that depletion of the dsRNA-binding protein PACT can inhibit the growth of neuroendocrine lineage lung cancer cells through the activation of the dsRNA sensor protein kinase R (PKR).
We are currently:
Using genome-scale CRISPR screens to identify new regulators of innate immune dsRNA sensors
Leveraging RNA-based therapeutics to trigger dsRNA sensors in specific subtypes of lung cancer
Potential rotation projects:
Characterize novel regulators of the dsRNA sensor PKR
Co-opt dsRNA sensors to target specific subsets of lung cancer
Design your own project!
Interferon signaling in cancer
A substantial number of cancers, including lung cancers, display cell-intrinsic activation of the interferon response pathway. In certain cancers, interferon pathway activation has been associated with therapy-resistance, including to immune checkpoint inhibitors. Therefore, there is a clinical need to develop treatments tailored to this elevated interferon cell state in cancer.
We are approaching this question in the following ways:
Improve our understanding of how cancer cells acquire interferon pathway activation
Performing genome-scale CRISPR screens to identify vulnerabilities unique to this cell state
Potential rotation projects:
Understand how and why the elevated interferon cell state develops in cancer cells
Characterize novel vulnerabilities associated with the activated interferon cell state
Design your own project!
T cells in solid tumors
Solid tumors in human patients harbor T cell populations with reactivity against both cancer neo-antigens and common pathogens. We are using a combination of computational and experimental methods to characterize T cells associated with solid tumors in humans. Through these efforts, we intend to design new therapeutic approaches to utilize tumor-associated T cells to target lung cancer in human patients.
Potential rotation projects:
Characterize the landscape of tumor-associated T cells, particularly in lung cancer
Engineer novel approaches to utilize tumor-associated T cells for cancer therapy
Design your own project!