National Cancer Institute 5R00CA255586-04

Exploring O-glycoproteomics to prevent metabolic radioresistance in the tumor microenvironment

The award funds research to explore O-glycoproteomics in the tumor microenvironment to prevent metabolic radioresistance, aiming to improve radiotherapy outcomes in cancer patients with inoperable tumors.

Description

This project focuses on metabolic reprogramming toward the hexosamine biosynthesis pathway (HBP), an understudied glucose pathway leading to protein glycosylation, associated with poor survival in lung adenocarcinoma. The research aims to identify proteins that are O-glycosylated after MR toward HBP and understand how these PTMs affect cellular behavior and modulate radioresistance. The hypothesis is that tumor-stroma crosstalk in the tumor microenvironment, leading to changes in the O-glycoproteome, plays a role in radioresistance. The project involves constructing in-situ maps of tumor compartments using CODEX, deconvoluting cell neighborhoods with machine learning, creating 3D assembloid models, irradiating them, and analyzing the O-glycoproteome to identify targets for restoring radiosensitivity.

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