Milner Lab
Principal Investigator: John Justin Milner
Institution: University of North Carolina at Chapel Hill (Chapel Hill, NC)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
PROJECT SUMMARY Oncogenic mutations in KRAS are nearly universal in pancreatic ductal adenocarcinoma (PDAC) and drive disease initiation, progression, and maintenance. Small molecules that inhibit mutant forms of KRAS (KRASi) and both mutant and wildtype RAS proteins (RASi) have recently emerged with the potential to transform the treatment landscape of PDAC. However, the mechanisms dictating efficacy and resistance to RAS inhibitors remain poorly understood. PDAC development and therapeutic response depends on co-evolution and interaction between tumor cells and the tumor immune microenvironment (TIME). This research proposal focuses on a major goal of our laboratories: to determine how remodeling of tumor-immune interactions contributes to efficacy and durability of RAS inhibition. We have developed immunocompetent mouse models that recapitulate seminal features of PDAC heterogeneity and found that while the KRASG12D inhibitor MRTX1133 and the pan-RASGTP inhibitor RMC-6236 both effectively inhibit the MAPK pathway and illicit potent tumor responses in pre-clinical studies, they result in distinct patterns of response and adaptation in tumor cells and the tumor microenvironment. W…
Active NIH Awards
- 1R21CA309360-01: Identifying immune-mediated mechanisms of RAS inhibitor efficacy and resistance in pancreatic cancer (2026)
- 5R01AI177864-03: Epigenetic regulation of T cell differentiation during infection (2026)
- 5R01AI177864-02: Epigenetic regulation of T cell differentiation during infection (2025)
- 1R01AI177864-01A1: Epigenetic regulation of T cell differentiation during infection (2024)
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