NIH R01 · 2025
Cell intrinsic and extrinsic effects of zinc metabolism in therapy resistant melanoma
Project Summary/Abstract The ultimate goal of this proposal is to address the fundamental gap in knowledge on the mechanisms driving resistance to immune checkpoint blockade (ICB), particularly in melanoma patients who exhibit downregulation or deletion of p16 (~40% of cases). The research plan focuses on elucidating the mechanistic role of p16 loss in regulating zinc (Zn) homeostasis through the Zn transporter SLC39A9. The goal is to explore whether manipu- lating Zn levels enhance the efficacy of current ICB in p16low melanomas. Drawing on a compelling in vivo CRISPR knockout screen, our data reveal that the knockdown of SLC39A9 sensitizes p16low melanomas to anti- PD1 ICB. Additionally,…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.