Manguso Lab
Principal Investigator: Robert Thomas Manguso
Institution: Broad Institute (Cambridge, MA)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: ✅ Hiring Postdocs
Research Focus
PROJECT SUMMARY Head and Neck Squamous Cell Carcinoma (HNSCC) is a deadly malignancy with few effective treatment options for patients with advanced disease. While immunotherapy with anti-PD-1 and CTLA-4 have been highly effective in cancers such as melanoma and NSCLC, responses in HNSCC remain low despite a similar tumor mutational burden and features of an inflamed tumor microenvironment. Thus, additional strategies to enhance immune- mediated control of HNSCC are urgently needed. PTPN2 is a phosphatase that inhibits JAK-STAT signaling in tumor cells and immune cells. We previously identified PTPN2 inhibition (PTPN2i) as a therapeutic approach that renders tumor cells highly sensitive to interferon. We recently described the development of the first small molecule inhibitor of PTPN2 and described its efficacy and mechanism of action as an immunotherapy in tumor models. In preliminary studies, we discovered that inhibition of PTPN2 in HNSCC cells treated with IFNg dramatically increases the expression of STING and that combination treatment of tumor cells with PTPN2i and STING agonist led to synergistic activation of type I IFN responses and cell death. Further, our preliminary da…
Active NIH Awards
- 1R01CA312510-01: Unleashing IFN signal transduction to prime HNSCC immunogenicity (2026)
- 1R21CA309357-01A1: High-throughput identification of transcription factors that enhance CAR T cell efficacy in solid tumors. (2026)
- 5R01CA285582-02: Investigating CREB5-driven mechanisms of immune therapy resistance (2026)
- 1R01CA285582-01A1: Investigating CREB5-driven mechanisms of immune therapy resistance (2025)
Explore 700+ US Biology Labs on FindBioLabs.com