Dudley Lab
Principal Investigator: Andrew Carl Dudley
Institution: University of Virginia (Charlottesville, VA)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
SUMMARY Tumor blood vessels allow anti-tumor immune cells to enter the tumor microenvironment, but abnormalities in the tumor endothelium can impair immune cell entry, resulting in poor responses to immune checkpoint blockade (ICB). We recently found that genetic deletion of the epigenetic gene silencer DNA methyltransferase 1 (Dnmt1) in blood vessels primes the endothelium for cytokine stimulation, resulting in improved responses to ICB. This suggests that epigenetic reprogramming of the tumor vasculature could improve the efficacy of ICB and augment immune surveillance. We have now used melanoma cells with differing tumor mutation burden (TMB) and found that targeting Dnmt1 in the endothelium results in notable regression of TMBhi melanoma, increased CD4/CD8 memory T-cells and granzyme B+ effectors, increased dendritic cells and lymphatic vessels in tumor-draining lymph nodes, and a profound reduction in lung-metastatic burden following combinations of ICB. In this proposal, we aim to test three hypotheses: first, that genetic disruption of Dnmt1 in endothelial cells promotes long-term tumor control via dendritic cell trafficking to draining lymph nodes and recruitment of CD4+ T-…
Active NIH Awards
- 5R01CA177875-13: Targeting the vasculature to enhance anti-tumor immunity (2026)
- 1R03CA308458-01A1: Epigenetic modulation of tumor vasculature to augment immunotherapy (2026)
- 2R01CA177875-12A1: Targeting the vasculature to enhance anti-tumor immunity (2025)
- 5R01CA177875-11: Targeting the vasculature to enhance anti-tumor immunity (2024)
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