Novel Immunotherapies for Cancer

Gladstone-UCSF Institute of Genomic Immunology Seminar

Robert Manguso, PhD

Principal Investigator Robert Manguso, PhD, is an assistant professor of medicine at Massachusetts General Hospital Cancer Center and Harvard Medical School, and an associate member at the Broad Institute. He completed his undergraduate degree at Wheaton College in Norton, MA, and his PhD at Harvard Medical School/Dana-Farber Cancer Institute in Nick Haining’s lab. His work focuses on using functional genomics to improve our understanding of cancer immunology and the treatment of cancer with immunotherapies.

The Manguso Lab uses a range of approaches including mouse models, functional genomics, cellular immunology, and single-cell profiling to understand how cancers evade the immune system. The lab has pioneered the use of in vivo genetic screens with CRISPR to identify new immunotherapy targets and resistance mechanisms. Using these approaches, Manguso’s team identified the tyrosine phosphatase PTPN2, a critical regulator of immunotherapy sensitivity in tumor cells. They also identified the dsRNA-editing enzyme ADAR1 as a checkpoint that regulates the sensing of self-dsRNA by tumor cells. Results indicate there are dozens of ways that cancers can be targeted by the immune system, and the team is working to understand the new mechanisms revealed by their studies. In the long term, these approaches will enable a new understanding of how the immune system interacts with cancerous tissue and how the interaction can be manipulated to destroy tumors.

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