Robert T. Manguso, PhD

Massachusetts General Hospital

Academic Titles

Associate Professor, Medicine, Harvard Medical School

Research Program Affiliation

Member, Cancer Immunology

Research Abstract

The Manguso lab is working to improve the efficacy of cancer immunotherapy. We use a range of approaches including mouse models, functional genomics, cellular immunology, and single-cell profiling to understand how cancers evade the immune system. Our lab has pioneered the use of in vivo genetic screens with CRISPR to identify new immunotherapy targets and resistance mechanisms. Using these approaches, we identified the tyrosine phosphatase PTPN2, a critical regulator of immunotherapy sensitivity in tumor cells. We also identified the dsRNA-editing enzyme ADAR1 as a checkpoint that regulates the sensing of self-dsRNA by tumor cells. Our results indicate that there are dozens of ways that cancers can be targeted by the immune system, and we are working to understand the new mechanisms revealed by our 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.